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Dear Patients,

I created this forum to welcome any questions you have on the topic of infertility, IVF, conception, testing, evaluation, or any related topics. I do my best to answer all questions in less than 24 hours. I know your question is important and, in many cases, I will answer within just a few hours. Thank you for taking the time to trust me with your concern.

– Geoffrey Sher, MD

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19,522 Comments

Mia H

Hello Dr Sher

I am 42 years old; diagnosed with PCOS. We had two of FET ; 5day blastocyst (one was already hatched before transfer) however failed on implantation. My Dr. performed endometrial scratch and I injected progesterone, and also orally took estradiol, but apparently did not help.
We did not do any PGD test on our embryos as my blood work shows I was not karyotype female.
My doctor and nurse thought I had a good chance (even mentioned over 90% chance) since embryo in appearance look good.
I am trying to recruit more eggs to do embryo banking again; fresh cycle update appointment with my current doctor is next Friday.

Do I still have hope? Would I still have a good chance of getting pregnant doing exactly the same process that I did for the first failed attempt? I still can’t get wrap around my head as to why this cycle was failed when everything looked good. would you recommend to do something different this time to increase the chance?
Please help!!

reply
Dr. Geoffrey Sher

Contingent upon your ovarian reserve and the ideal selection of the ideal protocol for ovarian stimulation and you select optimal quality embryos by using PGS, you could still have a reasonable chance. Please consider the following:

The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.

While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.

I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy

Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly

• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
• Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• IVF Egg Donation: A Comprehensive Overview
___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Priya

Hi Dr sher. Am 33 old having a 8 yr old daughter. I concieved naturally tat time. Now I have beaded tubes hence not able to conceive. Embryo transfer done on 23rd Feb 2019. 2 embryos transferred. Today day 15dp transfer upt negative. Waiting for beta test results.. No symptoms of pregnancy…what r the chances of positivity.

reply
Dr. Geoffrey Sher

The negative urine test at this stage is discouraging. Get the blood test done on Monday. No need (in my opinion to wait until the 23rd.

___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Jessaca

What are your guidelines for potential surrogates? Age? # of pregnancies? Csecs?
Thank you

reply
Dr. Geoffrey Sher

IVF surrogacy involves the transfer of one or more embryos into the uterus of a surrogate, who provides a host womb and carries the baby to term, but does not contribute genetically to the baby. Typically, the intended mother provides the eggs and her partner (the intended father) provides the sperm. However, at times eggs and/or sperm may be derived from gamete donors. While ethical, moral, and medico legal issues still apply, IVF surrogacy appears to have gained social acceptance. We offer IVF surrogacy as an option at most SIRM programs.
Candidates for IVF surrogacy can be divided into two groups: (1) women who are not capable of carrying a pregnancy to full term due to: their uterus having been surgically removed (hysterectomy), disease, or developmental absence of the uterus (from birth) and (2) women who have been advised against undertaking a pregnancy because of systemic illnesses such as diabetes, heart disease, hypertension, etc.
As in preparation for other assisted reproductive techniques, the biological/intended parents, the surrogate and/or donors undergo a thorough clinical, psychological, and laboratory assessment prior to embarking on the process. The purpose is to exclude sexually transmitted diseases that might damage eggs, sperm and embryos, or be carried to the surrogate with embryo transfer. They are also counseled on issues faced by all IVF participants such as the possibility of multiple gestation, miscarriage and ectopic pregnancy.
All legal issues pertaining to custody and the rights of the biological parents and the surrogate should be discussed in detail and the appropriate consent forms completed following full disclosure. We recommend that the surrogate and biological/intended parents get separate legal counsel to avoid any conflict of interest that could arise were one attorney to counsel both parties.
Selecting a Surrogate
Couples with the necessary financial resources will usually retain a surrogacy agency to find a suitable IVF surrogacy candidate. We direct our patients to reputable surrogacy agencies who have access to quality surrogates. Because the surrogate gives birth, it is rarely possible or even realistic for her to remain anonymous.
Since recruiting a gestational surrogate from an agency can be very expensive, many infertile couples who qualify for IVF surrogate parenting solicit the assistance of empathic friends or family members to act as surrogates.
Other couples independently seek surrogates by advertising in the media.
Screening the Surrogate
Once the surrogate has been selected, she will undergo thorough medical and psychological evaluations, including:
1. Cervical cultures and/or blood tests to screen for infection with sexually transmitted bacteria such chlamydia, ureaplasma, gonococcus and syphilis or viruses such as cytomegalic virus, HIV, HTLV, and hepatitis.
2. A variety of blood hormone tests, such as the measurement of plasma prolactin and thyroid stimulating hormone (TSH) and tests to ensure that the surrogate is immune to the development of rubella (German measles).
3. Physical evaluation
4. Psychological assessment
When friends or family members serve as IVF surrogates they should be be carefully assessed to ascertain whether they might have been coerced to paricipate. This is especially important when a young family member is being recruited.
The surrogate should also be counseled on issues such as risks and consequences of multiple pregnancies. Such discussions should include agreement on the number of embryos to be transferred and the delicate issue of selective pregnancy reduction , in the event of a high order multiple pregnancy (triplets or greater).
The surrogate should visit with her designated IVF physician who should take her medical history and perform a thorough physical examination. Thereupon she should have a full consultation with the nurse coordinator charged with oversight of her treatment. The coordinator will outline the exact IVF-surrogacy process step by step, will make certain that the surrogate understands that she has full right of access to the clinic staff and that her concerns will be addressed promptly at all times. The surrogate should also be informed that if pregnancy occurs, she will be referred to a qualified obstetrician or perinatologist for prenatal care and delivery.
Once a viable pregnancy is confirmed by ultrasound recognition of a fetal heartbeat (at the 6th-7th week), there is a better than 85% chance that the pregnancy will proceed normally to term. Once the pregnancy has progressed beyond the 12th week, the chance of a healthy baby being born is upward of 95%.
At SIRM, depending on the age of the egg provider (under 39 years) and her having normal ovarian reserve, we would anticipate approximately a 40%-50% birthrate every time good quality advanced embryos (expanded blastocysts) are transferred. The birthrate falls with further advancement in the age of the egg provider and with diminishing ovarian reserve. It is important to note that there is no convincing evidence to suggest an increase in the incidence of spontaneous miscarriage or birth defects as a direct result of IVF surrogacy.
If the surrogate’s blood pregnancy tests are negative, treatment with estrogen, progesterone and corticosteroids is discontinued, and she can expect to menstruate within four to 10 days. In the event that the pregnancy test is positive, estrogen, progesterone and steroid therapy are continued till the 10th week of pregnancy.
After the evaluation and counseling of both the couple and the surrogate has been completed, the three parties should meet. And, once all the evaluations have been completed, the intended parents will select a date to begin treatment.

Synchronizing the Cycles of Surrogate and Aspiring Mother
Both the surrogate and the egg provider are placed on monophasic birth control pills (BCP) for 10-25 days. The objective ist to insure that they both start menstruating around the same date so as to launch their cycle of treatment together. Thus the duration that each would remain on the BCP will depend on the desired timing of the start of the IVF treatment cycle. At some point while taking the BCP, both parties will overlapped the BCP with a GnRH agonist (GnRHa) such as Lupron for a period of approximately 2-3 days, whereupon the BCP will be stopped and the Lupron continued. Menstruation will follow (in both) within a few days.
At this point the egg provider begins controlled ovarian stimulation (COS) with gonadotropins while the IVF surrogate commences corticosteroid (dexamethasone or prednisone) therapy and either, twice weekly injections of estradiol valerate (Delestrogen) or daily estradiol skin patches. Blood estradiol measurements are taken twice weekly and the dosage of administered estradiol is adjusted so as to attain a blood estradiol level of between 500 and 1,000pg/ml. Then, as soon as the egg provider (based on hormonal testing and ultrasound follicle assessment) receives the hCG “trigger shot” the surrogate starts receiving daily intramuscular progesterone injections ( while continuing estradiol therapy). In the case of day 3 embryo transfers, this continues for 4 days prior to the embryo transfer and in the case of blastocyst transfers, for 6 days.
Preimplantation Genetic Sampling (PGS) Selection-the Ideal Approach for Gestational Surrogacy
PGS of embryos via next generation gene sequencing (NGS) requires that the woman’s IVF cycle be broken into two parts – the first involving stimulation, egg retrieval, fertilization, and removal of a cell from the embryo for testing. Because CGH testing requires 4-5 weeks to obtain results, the embryos are frozen while the testing is performed on the removed cell. The woman then returns at a later date for her embryo transfer. We call this process “Staggered IVF “. The same approach to ET can be used with gestational surrogacy and the same 60+% birth rate can be anticipated when CGH-normal embryos are transferred. In fact, Staggered IVF lends itself to Gestational Surrogacy because it is possible in this way to completely segregate the ovarian stimulation process from the ET. This allows couples seeking gestational surrogacy to delay identifying and recruiting a surrogate until they are assured of having “competent” embryos available for transfer.
Management and Follow up after the Embryo Transfer
Following embryo transfer, the surrogate will be given daily progesterone injections and bi-weekly estradiol valerate injections and/or suppositories in order to sustain an optimal environment for implantation. Approximately 10 days after the embryo transfer, she will undergo a pregnancy test. A positive test indicates that implantation is taking place. In such an event, the hormone injections will be continued for an additional four to six weeks. In the interim, an ultrasound examination will be performed to definitively diagnose a clinical pregnancy. If the test is negative, all hormonal treatment is discontinued, and menstruation will ensue within three to 10 days. If the surrogate does not conceive, the aspiring mother may have her remaining embryos frozen, to be thawed and transferred to the uterus of the surrogate at a later date. If, in spite of both the initial attempt and subsequent transfer of thawed embryos the surrogate does not conceive, the infertile couple may schedule a new cycle of treatment.
Toward the Bioethics of IVF Surrogacy
The determination of ethical guidelines has not kept pace with the exploding growth and development in IVF. However, some leaders in the field are working together, sharing experiences and advice, in an attempt to formulate a code of ethics.
The genetic combination of the male and the female provide two of the essential elements which, along with gestation, are necessary to produce a human being. The two out of three rule basically looks at these three elements: the egg, the sperm, and the gestational component. If at all possible, I recommend that at least two of these three components be contributed by the intended parents. If they can only contribute one, it is important to make every effort not to have the other two contributed by the same person (i.e., the egg provider should not also be the surrogate) as this can cause a variety of problems.

___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Anil

What is sucess rate 5BC frozen blastosys and after birth the kid was normal or any complication we face

reply
Dr. Geoffrey Sher

That is possible to answer authoritatively without much more specific information regarding age; cause of infertility, whether or not PGS was done and the clinic you underwent treatment with.

___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Priya

Hi Dr sher… Am 33 yr old I have a 8 yr old daughter. I had conceived naturally.tat time . Now my tubes r beaded… Had embryo transfer on 23 Feb 2019…. 2 embryos r transferred.. Today is day 15 post 5d blastocyst.. Waiting for beta hcg results. My doc to take upt which is negative… What are the chances…

reply
Dr. Geoffrey Sher

You should have a very good chance of conception. I wish you good lucK!

___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Kelly

Hello. I have done 10 IVF cycles and had 9 retrievals over the past 2 years. I’m now 37. My AMH at the beginning of this was 0.53. As of 6 months ago it was 0.15. Since last summer the majority of my cycles have yielded empty follicles. I usually only get one or two follicles. I’ve been doing mini Ivf with clomid and triggering with Lupron or Ovidrel. Most recently I triggered at 18mm with ovidrel. I also had a small 12mm which was 17 at the time of retrieval.
The larger follicle (which was 22 at time of retrieval) was empty. But the smaller one which was 17 had a follicle and I found out today it fertilized. I have also noticed during ALL of these cycles my LH never ever rises. It’s always around 2 or 3. And in some cases even drops. The only stims I’ve used during these cycles are either low dose clomid (1/4 pill every day). Or 75 gonal f (which is what I did this past cycle).
I’m just very concerned and frustrated and don’t understand why my LH never rises on its own, and if that’s indicative of having empty follicles. And WHY do I have sooo many cycles with empty follicles???
Thank you so much!!

reply
Dr. Geoffrey Sher

There is in my opinion no such entity as “Empty Follicle Syndrome”. All follicles contain eggs. Failure to access those eggs at ER can often be a result of the protocol used for controlled ovarian stimulation (COS.

Not infrequently, when following vigorous and often repeated flushing of follicles at egg retrieval they fail to yield eggs, it is ascribed to the “empty follicle syndrome”. This is a gross misnomer because all follicles contain eggs so it did not happen because the follicles were “empty”. Most likely it was because they would/could not yield the eggs they harbored. This situation is most commonly seen in older women, women who have severely diminished ovarian reserve and in women with polycystic ovarian syndrome and in my opinion, it often preventable when an optimal, individualized and strategic protocol for controlled ovarian stimulation (COS) is employed and the correct timing and dosage is applied to the “hCG trigger” shot.

Normally, following optimal ovarian stimulation, the hCG “trigger shot” is given for the purpose of it triggering meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG “trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse such that the egg can detach and readily be captured at egg retrieval (ER). Ordinarily, normal eggs (and even those with only one or two chromosomal irregularities) will readily detach and be captured with the very first attempt to empty of a follicle. Eggs that have several chromosomal numerical abnormalities (i.e., are “complex aneuploid”) are often unable to facilitate this process. This explains why when the egg is complex aneuploid its follicle will not yield an egg…and why, when it requires repeated flushing of a follicle to harvest an egg, it is highly suggestive of it being aneuploid and thus “incompetent” (i.e., incapable of subsequently propagating a normal embryo).

Older women, women with diminished ovarian reserve and those with polycystic ovarian syndrome, tend to have more biologically active LH in circulation. LH cause production of male hormone (androgens, predominantly testosterone, by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced oogenesis’ (egg development. Too much LH activity compromises the latter and eggs so affected, are far more likely to be aneuploid, following meiosis. Women with the above conditions have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH elevations or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the “hCG trigger” leading to failed and the so called “empty follicle syndrome”

Since the developing eggs of women who have increased LH activity [older women, women with diminished ovarian reserve (DOR) and those with PCOS] are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Also, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole) and drugs that contain LH or hCG (e.g., Menopur; or protocols of ovarian stimulation the provoke increase exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols” and the use of “late pituitary blockade (antagonists) protocols can be prejudicial. The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used and the timing of its administration in such cases, cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG(hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG can by compromising meiosis, increase the risk of egg aneuploidy and thus of IVF outcome.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
• Implications of “Empty Follicle Syndrome and “Premature Luteinization”
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• Fertility Preservation (FP) Through Freezing/Banking Human Eggs
• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
• Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.
• IVF: The first Choice for Infertile Women 40 to 43 Years of Age!
• IVF Egg Donation: A Comprehensive Overview
_______________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Olesja

Dear Dr. Sher,

For 5 long years me and my husband have been trying for a successful pregnancy. We are both 32 years old.
8 very early pregnancy losses at max 4.5 weeks confirmed only with BHCG.
No difficulties in conceiving.

I have MTHFR mutation homozigote and my husband V Leiden heterozigote.
Positive beta2 glycoprotein
Insuline resitant. 5 years ago diagnozed with PCO and endometriosis with laparoscopy and AMH 2.4. Removed subseptum. Weight gain and BMi 32. Intolerant of gluten, lactose and conservants.
Doctors suggest IVF with PGS. What if it happens again? What do you suggest for my case? Which might be the adequate protocol for the treatment and IVF?

Thank you

reply
Dr. Geoffrey Sher

When it comes to reproduction, humans are the poorest performers of all mammals. In fact we are so inefficient that up to 75% of fertilized eggs do not produce live births, and up to 30% of pregnancies end up being lost within 10 weeks of conception (in the first trimester). RPL is defined as two (2) or more failed pregnancies. Less than 5% of women will experience two (2) consecutive miscarriages, and only 1% experience three or more.

Pregnancy loss can be classified by the stage of pregnancy when the loss occurs:
• Early pregnancy loss (first trimester)
• Late pregnancy loss (after the first trimester)
• Occult “hidden” and not clinically recognized, (chemical) pregnancy loss (occurs prior to ultrasound confirmation of pregnancy)
• Early pregnancy losses usually occur sporadically (are not repetitive).

In more than 70% of cases the loss is due to embryo aneuploidy (where there are more or less than the normal quota of 46 chromosomes). Conversely, repeated losses (RPL), with isolated exceptions where the cause is structural (e.g., unbalanced translocations), are seldom attributable to numerical chromosomal abnormalities (aneuploidy). In fact, the vast majority of cases of RPL are attributable to non-chromosomal causes such as anatomical uterine abnormalities or Immunologic Implantation Dysfunction (IID).

Since most sporadic early pregnancy losses are induced by chromosomal factors and thus are non-repetitive, having had a single miscarriage the likelihood of a second one occurring is no greater than average. However, once having had two losses the chance of a third one occurring is double (35-40%) and after having had three losses the chance of a fourth miscarriage increases to about 60%. The reason for this is that the more miscarriages a woman has, the greater is the likelihood of this being due to a non-chromosomal (repetitive) cause such as IID. It follows that if numerical chromosomal analysis (karyotyping) of embryonic/fetal products derived from a miscarriage tests karyotypically normal, then by a process of elimination, there would be a strong likelihood of a miscarriage repeating in subsequent pregnancies and one would not have to wait for the disaster to recur before taking action. This is precisely why we strongly advocate that all miscarriage specimens be karyotyped.

There is however one caveat to be taken into consideration. That is that the laboratory performing the karyotyping might unwittingly be testing the mother’s cells rather than that of the conceptus. That is why it is not possible to confidently exclude aneuploidy in cases where karyotyping of products suggests a “chromosomally normal” (euploid) female.

Late pregnancy losses (occurring after completion of the 1st trimester/12th week) occur far less frequently (1%) than early pregnancy losses. They are most commonly due to anatomical abnormalities of the uterus and/or cervix. Weakness of the neck of the cervix rendering it able to act as an effective valve that retains the pregnancy (i.e., cervical incompetence) is in fact one of the commonest causes of late pregnancy loss. So also are developmental (congenital) abnormalities of the uterus (e.g., a uterine septum) and uterine fibroid tumors. In some cases intrauterine growth retardation, premature separation of the placenta (placental abruption), premature rupture of the membranes and premature labor can also causes of late pregnancy loss.

Much progress has been made in understanding the mechanisms involved in RPL. There are two broad categories:

1. Problems involving the uterine environment in which a normal embryo is prohibited from properly implanting and developing. Possible causes include:
• Inadequate thickening of the uterine lining
• Irregularity in the contour of the uterine cavity (polyps, fibroid tumors in the uterine wall, intra-uterine scarring and adenomyosis)
• Hormonal imbalances (progesterone deficiency or luteal phase defects). This most commonly results in occult RPL.
• Deficient blood flow to the uterine lining (thin uterine lining).
• Immunologic implantation dysfunction (IID). A major cause of RPL. Plays a role in 75% of cases where chromosomally normal preimplantation embryos fail to implant.
• Interference of blood supply to the developing conceptus can occur due to a hereditary clotting disorder known as Thrombophilia.

2. Genetic and/or structural chromosomal abnormality of the embryo.Genetic abnormalities are rare causes of RPL. Structural chromosomal abnormalities are slightly more common but are also occur infrequently (1%). These are referred to as unbalanced translocation and they result from part of one chromosome detaching and then fusing with another chromosome. Additionally, a number of studies suggest the existence of paternal (sperm derived) effect on human embryo quality and pregnancy outcome that are not reflected as a chromosomal abnormality. Damaged sperm DNA can have a negative impact on fetal development and present clinically as occult or early clinical miscarriage. The Sperm Chromatin Structure Assay (SCSA) which measures the same endpoints are newer and possibly improved methods for evaluating.

IMMUNOLOGIC IMPLANTATION DYSFUNCTION
Autoimmune IID: Here an immunologic reaction is produced by the individual to his/her body’s own cellular components. The most common antibodies that form in such situations are APA and antithyroid antibodies (ATA).

But it is only when specialized immune cells in the uterine lining, known as cytotoxic lymphocytes (CTL) and natural killer (NK) cells, become activated and start to release an excessive/disproportionate amount of TH-1 cytokines that attack the root system of the embryo, that implantation potential is jeopardized. Diagnosis of such activation requires highly specialized blood test for cytokine activity that can only be performed by a handful of reproductive immunology reference laboratories in the United States.

Alloimmune IID, i.e., where antibodies are formed against antigens derived from another member of the same species, is believed to be a relatively common immunologic cause of recurrent pregnancy loss.

Autoimmune IID is often genetically transmitted. Thus it should not be surprising to learn that it is more likely to exist in women who have a family (or personal) history of primary autoimmune diseases such as lupus erythematosus (LE), scleroderma or autoimmune hypothyroidism (Hashimoto’s disease), autoimmune hyperthyroidism (Grave’s disease), rheumatoid arthritis, etc. Reactionary (secondary) autoimmunity can occur in conjunction with any medical condition associated with widespread tissue damage. One such gynecologic condition is endometriosis. Since autoimmune IID is usually associated with activated NK and T-cells from the outset, it usually results in such very early destruction of the embryo’s root system that the patient does not even recognize that she is pregnant. Accordingly the condition usually presents as “unexplained infertility” or “unexplained IVF failure” rather than as a miscarriage.

Alloimmune IID, on the other hand, usually starts off presenting as unexplained miscarriages (often manifesting as RPL). Over time as NK/T cell activation builds and eventually becomes permanently established the patient often goes from RPL to “infertility” due to failed implantation. RPL is more commonly the consequence of alloimmune rather than autoimmune implantation dysfunction.

However, regardless, of whether miscarriage is due to autoimmune or alloimmune implantation dysfunction the final blow to the pregnancy is the result of activated NK cells and CTL in the uterine lining that damage the developing embryo’s “root system” (trophoblast) so that it can no longer sustain the growing conceptus. This having been said, it is important to note that autoimmune IID is readily amenable to reversal through timely, appropriately administered, selective immunotherapy, and alloimmune IID is not. It is much more difficult to treat successfully, even with the use of immunotherapy. In fact, in some cases the only solution will be to revert to selective immunotherapy plus using donor sperm (provided there is no “match” between the donor’s DQa profile and that of the female recipient) or alternatively to resort to gestational surrogacy.

DIAGNOSING THE CAUSE OF RPL
In the past, women who miscarried were not evaluated thoroughly until they had lost several pregnancies in a row. This was because sporadic miscarriages are most commonly the result of embryo numerical chromosomal irregularities (aneuploidy) and thus not treatable. However, a consecutive series of miscarriages points to a repetitive cause that is non-chromosomal and is potentially remediable. Since RPL is most commonly due to a uterine pathology or immunologic causes that are potentially treatable, it follows that early chromosomal evaluation of products of conception could point to a potentially treatable situation. Thus I strongly recommend that such testing be done in most cases of miscarriage. Doing so will avoid a great deal of unnecessary heartache for many patients.

Establishing the correct diagnosis is the first step toward determining effective treatment for couples with RPL. It results from a problem within the pregnancy itself or within the uterine environment where the pregnancy implants and grows. Diagnostic tests useful in identifying individuals at greater risk for a problem within the pregnancy itself include:

• Karyotyping (chromosome analysis) both prospective parents
• Assessment of the karyotype of products of conception derived from previous miscarriage specimens
• Ultrasound examination of the uterine cavity after sterile water is injected or sonohysterogram, fluid ultrasound, etc.)
• Hysterosalpingogram (dye X-ray test)
• Hysteroscopic evaluation of the uterine cavity
• Full hormonal evaluation (estrogen, progesterone, adrenal steroid hormones, thyroid hormones, FSH/LH, etc.)
• Immunologic testing to include:
a) Antiphospholipid antibody (APA) panel
b) Antinuclear antibody (ANA) panel
c) Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies)
d) Reproductive immunophenotype
e) Natural killer cell activity (NKa) assay (i.e., K562 target cell test)
f) Alloimmune testing of both the male and female partners

TREATMENT OF RPL
Treatment for Anatomic Abnormalities of the Uterus: This involves restoration through removal of local lesions such as fibroids, scar tissue, and endometrial polyps or timely insertion of a cervical cerclage (a stitch placed around the neck of the weakened cervix) or the excision of a uterine septum when indicated.

Treatment of Thin Uterine Lining: A thin uterine lining has been shown to correlate with compromised pregnancy outcome. Often this will be associated with reduced blood flow to the endometrium. Such decreased blood flow to the uterus can be improved through treatment with sildenafil and possibly aspirin.

Sildenafil (Viagra) Therapy. Viagra has been used successfully to increase uterine blood flow. However, to be effective it must be administered starting as soon as the period stops up until the day of ovulation and it must be administered vaginally (not orally). Viagra in the form of vaginal suppositories given in the dosage of 25 mg four times a day has been shown to increase uterine blood flow as well as thickness of the uterine lining. To date, we have seen significant improvement of the thickness of the uterine lining in about 70% of women treated. Successful pregnancy resulted in 42% of women who responded to the Viagra. It should be remembered that most of these women had previously experienced repeated IVF failures.

Use of Aspirin: This is an anti-prostaglandin that improves blood flow to the endometrium. It is administered at a dosage of 81 mg orally, daily from the beginning of the cycle until ovulation.

Treating Immunologic Implantation Dysfunction with Selective Immunotherapy: Modalities such as IL/IVIg, heparinoids (Lovenox/Clexane), and corticosteroids (dexamethasone, prednisone, prednisolone) can be used in select cases depending on autoimmune or alloimmune dysfunction.

The Use of IVF in the Treatment of RPL
In the following circumstances, IVF is the preferred option:
1. When in addition to a history of RPL, another standard indication for IVF (e.g., tubal factor, endometriosis, and male factor infertility) is superimposed.
2. In cases where selective immunotherapy is needed to treat an immunologic implantation dysfunction.
3.
The reason for IVF being a preferred approach in such cases is that in order to be effective, the immunotherapy needs to be initiated well before spontaneous or induced ovulation. Given the fact that the anticipated birthrate per cycle of COS with or without IUI is at best about 15%, it follows that short of IVF, to have even a reasonable chance of a live birth, most women with immunologic causes of RPL would need to undergo immunotherapy repeatedly, over consecutive cycles. Conversely, with IVF, the chance of a successful outcome in a single cycle of treatment is several times greater and, because of the attenuated and concentrated time period required for treatment, IVF is far safer and thus represents a more practicable alternative

Since embryo aneuploidy is a common cause of miscarriage, the use of preimplantation genetic diagnosis (PGD), with tests such as CGH, can provide a valuable diagnostic and therapeutic advantage in cases of RPL. PGD requires IVF to provide access to embryos for testing.

There are a few cases of intractable alloimmune dysfunction due to absolute DQ alpha matching where Gestational Surrogacy or use of donor sperm could represent the only viable recourse, other than abandoning treatment altogether and/or resorting to adoption. Other non-immunologic factors such as an intractably thin uterine lining or severe uterine pathology might also warrant that last resort consideration be given to gestational surrogacy.

The good news is that if a couple with RPL is open to all of the diagnostic and treatment options referred to above, a live birthrate of 70%–80% is ultimately achievable.

I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF

___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Vanessa

Hello Dr. Sher, I am 40 yrs old going in for my 6th low stimulation mini IVF. I also have MTHMR C677T gene.
Cycle 1: BC 1/2 tablet for 14 days stopped a few days then started with Clomid 75mg Letrozole 2.5mg and Gonal F 75 for 5 days. Rechecked and cont for 1 day Clomid and Gonal F 150 cont a few days clomid decreased Gonal to 75 and Ovidrel 250mcg Total 3 eggs Results 1 Euploid 1Abnormal Aneuploid Del of 5qter
Cycle 2: BCP 1/2 tablet 14 days Clomid 50 Gonal 75 went back and forth with increase and decrease of both Clomid and Gonal Lupron trigger no eggs made Blast.
Cycle 3: 1/2 tablet 3 days Again Gonal 150 Clomid 50 Lupron 3 eggs retrieved 1 blast PGS/NGS tested Tri 21
Cycle 4: BCP 1/2 for 14 days Clomid 50 Gonal 75 towards end 1/3 cetrotide and Lupron trigger 15 units. Total 5 eggs 1 made blast and waiting for PGS/NGS report. It has been same medication but I was wondering if it should be tweaked even as a low stim cycle?
Is the Aneuploid worth transferring? What about the Tri 21 Would these two self correct?

reply
Dr. Geoffrey Sher

First, I am against mini-IVF . The very people (older women) who it is more commonly recommended to are the one’s who in my opinion it is the least suited to. Second, triggering with Ovidrel 250mcg is too low a dosage It should be doubles in my opinion. Third, I would need more information before I can authoritatively recommend the transfer of specific aneuploid embryos.

Mini-IVF is a procedure that involves ovarian stimulation using low dosage medications (often oral drugs like clomiphene and Letrozole) under the premise that it is a “safer” and less expensive than conventional gonadotropin stimulation regimes while yielding comparable success. …….. Nothing could be further from the truth. The fact is that success rates per fresh mini-IVF cycle ranges between 10% and 12%s (i.e., about one third of that which reported national average for conventional IVF performed on women under 39y of age) ). And when it comes to older women and those with diminished ovarian reserve (DOR), the success rate with mini-IVF is usually much lower still.

There can be little doubt that aside from a woman’s age, the method used for ovarian stimulation represents the most important determinant of egg/embryo quality and thus of IVF outcome. There is no single stimulation protocol that is suitable for all IVF patients. It must be individualized…. especially when it comes to women who, regardless of their age have diminished ovarian reserve (DOR) and for women over >40y of age. The reason for this is that in such cases, the pituitary gland often over-produces LH which in turn causes the ovarian stroma/theca (connective tissue) to thicken (stromal hyperplasia/hyperthecosis) and over-produce male hormones (mainly testosterone). This in turn adversely influences egg and follicle growth, resulting in poor egg/embryo “competency” and compromised IVF outcome.
So let us examine the validity of the claims made in support of mini-IVF:

1. Milder stimulation using oral agents such as clomiphene, letrozole (alone or in combination with low dosage gonadotropins (Follistim/Gonal-F/Puregon/Menopur) reduces stress on the ovaries and overall risk associated with IVF. This argument while perhaps having some merit when applied to mini-IVF conducted in younger women who also have normal ovarian reserve, does not hold water for older women and those with DOR who (s stated above) often already have excessive LH-induced ovarian testosterone production. Furthermore, addition of clomiphene and letrozole by further increasing pituitary LH (and thus ovarian testosterone) only serves to add “fuel to the fire” in such cases and Menopur which contains both LH and hCG ( that both have similar effects on ovarian testosterone production), if administered in large amounts (>75U per day) can also do harm in my opinion.

2. Women with DOR will respond better to “milder stimulation” and egg quality will so be enhanced. This assertion borders on the ridiculous. It is like saying that applying less force to a heavier object will increase the likelihood of moving it”. That is simply not how FSH stimulates follicle development. You see…the cell membranes that envelop the follicular granulosa cells that line the inside surface of ovarian follicles have on their surfaces, a finite number of FSH receptors. FSH molecules attach to these receptors and mediate intracellular events that lead to granulosa cell proliferation with production of estradiol and the concurrent development of the egg (oogenesis) that is attached to the inner wall of the follicle. Once all the FSH receptors on the cell membranes are saturated, any residual FSH is discarded. This is why, when it comes to older women and women with DOR whose granulose cell membranes harbor fewer FSH receptors, it is virtually impossible to overstimulate them. Excessive FSH will simply be rejected and discarded.

3. Use of fewer drugs translates into lower cost. This would be true, were it not for the fact that success rates with mini-IVF across the board are much lower than with conventional ovarian stimulation. More important is the fact that the cost of IVF should be expressed in terms of “the cost of having a baby” rather than “cost per cycle of treatment”. When this is taken into account the cost associated with mini-IVF will b be significantly higher than conventional IVF. Then there is the additional emotional cost associated with a much higher IVF failure rate with mini-IVF.
4. Mini-IVF is less technology driven, less stressful and easier to execute. This assertion is in my opinion also without merit. Aside from reduced cost of medications, the same monitoring and laboratory procedures are needed for mini-IVF as with conventional treatment.

What is the best approach? When it comes to older women and those with DOR, it is in my opinion preferable to use a long pituitary down-regulation protocol with conversion from an I.M agonist (e.g. Lupron or Buserelin) to an antagonist such as Cetrotide/Orgalutron or Ganirelix (the agonist/antagonist conversion protocol) augmented with human growth hormone (HGH) and/or estrogen priming and combing this “embryo banking” over several cycles. In such cases preimplantation genetic screening (PGS) can be incorporated to help select the most “competent” embryos for transfer.

What about younger women with normal or increased ovarian reserve? If mini-IVF has any role at all, it could be in young women who have normal or increased ovarian reserve. I do not o not advocate aggressively stimulating the ovaries of younger women who have normal or increased ovarian reserve (as assessed by basal FSH, AMH and estradiol) simply to try and access more eggs. In fact, such an approach is neither safe nor acceptable. In such women it is often wiser to use lower dosage stimulation to try and prevent the development of severe ovarian hyperstimulation syndrome (OHSS) which aside from putting the woman at severe risk of (sometimes) life-endangering complications, can also compromise egg/embryo quality. However, it is my fervent belief that in such women, the preferred approach to ovarian stimulation is through the use of low dosage FSHr-dominant gonadotropins (rather than oral agents such as clomiphene or Letrozole and/or high dosage Menopur). This approach is referred to as Micro-IVF.

I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• A Fresh Look at the Indications for IVF
• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• IVF and the use of Supplementary Human Growth Hormone (HGH) : Is it Worth Trying and who needs it?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• Why did my IVF Fail
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
• Implications of “Empty Follicle Syndrome and “Premature Luteinization”
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• Micro-IVF: Often Preferable to Ovarian Stimulation with or Without IUI

ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Karen Carroll

Hi dr.sher I’m 53 years old I am interested in having ivf but would like to use my own eggs if possible!

reply
Dr. Geoffrey Sher

Hi Karen,

Respectfully, in my opinion it will be an exercise in Futility.

Geoff Sher

reply
Flores

Hi Dr Sher, I am 6 weeks + 5 days after a FET of a genetically tested embryo. I had a scan at 6+2 and seen a heart beat and all looked okay. Today I started bleeding and I feel like I am coming on my period. Surely all the meds I’m taking would stop my period from coming? I don’t get it?

reply
Dr. Geoffrey Sher

Unfortunately only time will tell. I suggest that you have another ultrasound early next week or sooner if the bleeding increases in amount. There is really nothing else to be done at this stage.

Good luck and G-d bless!

Geoff Sher

reply
Dr. Geoffrey Sher

In my opinion…depending on the type,of progesterone, probably not but I do not personally see a benefit in doing so.

Geoff Sher

reply
Katrin

Dear Dr.Sher,
I wrote to you a couple of times and every time you helped me a lot.Now I have 2 very important questions.I am 43 years old, in 17 week of pregnancy after an IVF.My doctor wants me to continue taking folic acid and progesteron(vaginal).But I have read these both are not good to be taken after 12 th week.What is your advice and opinion?

reply
Dr. Geoffrey Sher

In my opinion, you might take the FA but I would not continue on progesterone.

Geoff Sher

reply
Ekta

Dr. Sher, Based on your feedback on the skype consultation, awaiting for the immune testing before the next transfer, we went ahead with a retrieval to bank some embryos. We used exactly the same protocol as the first cycle of retrieval, but the response has been drastically different when the two retrievals were planned within a period of 5 months. Can you please advise why was there such a huge difference in the response, and what best we can do next time? We both are 35 years old and I have an AMH of 2.33 ng/ml as tested in Oct 2018
Retrieval #1 : Oct 2018
Day 2 Levels: P4: 0.45 ng/ml, E2: 31 pg/ml, FSH: 4.39 mIU/ml, AFC: 15
Stimulation plan: 150IU Gonal F + 150IU Menopur(8 days) with 50mg Clomid (7 days)
Results: 13 Oocytes retrieved, 11 mature, 9 fertilised, 2 day-5 and 5 day-6 blastocysts (total 7).

Retrieval #2: March 2019
Day 2 Levels: P4: 0.41 ng/ml, E2: 37 pg/ml, FSH: 8.9 IU/L, AFC = 7
Stimulation plan: 150IU Gonal F + 150IU Menopur(8 days) with 50mg Clomid (7 days)
Results: Cycle CANCELLED due to poor response.
Response to stimulation:
After 5 days: E2: 1037.4 pg/ml, P4: 0.36 ng/ml, follicle count(Rt Ovary: 14mm,8,7,4,4 ; Lt Ovary: 18,13,11,7,7,2)
After 7 days: E2: 1493 pg/ml, P4: 0.765 ng/ml, follicle count( Rt Ovary: 16mm, 11, 10 ; Lt Ovary: 21,13,12,9,8)

Would really appreciate if you can advise the potential cause of such variation? Our doctor still wants to use the same protocol given our response in the first cycle of retrieval.

reply
Dr. Geoffrey Sher

I am personally against the use of clomiphene in IVF stimulation. In my opinion, it can compromise follicle growth and egg development.T

The potential for a woman’s eggs to undergo orderly development and maturation, while in large part being genetically determined can be profoundly influenced by the woman’s age, her “ovarian reserve” and proximity to menopause. It is also influenced by the protocol used for controlled ovarian stimulation (COH) which by fashioning the intra-ovarian hormonal environment, profoundly impacts egg development and maturation.

After the menarche (age at which menstruation starts) a monthly process of repeatedly processing eggs continues until the menopause, by which time most eggs will have been used up, and ovulation and menstruation cease. When the number of eggs remaining in the ovaries falls below a certain threshold, ovarian function starts to wane over a 5 to10-years. This time period is referred to as the climacteric. With the onset of the climacteric, blood Follicle Stimulating Hormone (FSH) and later also Luteinizing Hormone (LH) levels begin to rise…. at first slowly and then more rapidly, ultimately culminating in the complete cessation of ovulation and menstruation (i.e. menopause).

One of the early indications that the woman has entered the climacteric and that ovarian reserve is diminishing DOR) , is the detection of a basal blood FSH level above 9.0 MIU/ml and/ or an AMH level og <2.0ng/ml.

Prior to the changes that immediately precede ovulation, virtually all human eggs have 23 pairs (i.e. 46) of chromosomes. Thirty six to forty hours prior to ovulation, a surge occurs in the release of LH by the pituitary gland. One of the main e purposes of this LH surge is to cause the chromosomes in the egg to divide n half (to 23 in number) in order that once fertilized by a mature sperm ends up having 23 chromosomes) the resulting embryo will be back to having 46 chromosomes. A “competent” mature egg is one that has precisely 23 chromosomes, not any more or any less. It is largely the egg, rather than the sperm that determines the chromosomal integrity of the embryo and only an embryo that has a normal component of 46 chromosomes (i.e. euploid) is “competent” to develop into a healthy baby. If for any reason the final number of chromosomes in the egg is less or more than 23 (aneuploid), it will be incapable of propagating a euploid, “competent” embryo. Thus egg/embryo aneuploidy (“incompetence”) is the leading cause of human reproductive dysfunction which can manifest as: arrested embryo development and/or failed implantation (which often presents as infertility), early miscarriage or chromosomal birth defects (e.g. Down’s syndrome). While most aneuploid (“incompetent”) embryos often fail to produce a pregnancy, some do. However, most such pregnancies miscarry early on. On relatively rare occasions, depending on the chromosome pair involved, aneuploid embryos can develop into chromosomally defective babies (e.g. Down’s syndrome).

Up until a woman reaches her mid- thirties, at best, 1:2 of her eggs will likely be chromosomally normal. As she ages beyond her mid-thirties there will be a a progressive decline in egg quality such that by age 40 years only about 15%-20% of eggs are euploid and, by the time the woman reaches her mid-forties, less than 10% of her eggs are likely to be chromosomally normal. While most aneuploid embryos do appear to be microscopically abnormal under the light microscope, this is not invariably so. In fact, many aneuploid embryos a have a perfectly normal appearance under the microscope. This is why it is not possible to reliably differentiate between competent and incompetent embryos on the basis of their microscopic appearance (morphologic grade) alone.

The process of natural selection usually precludes most aneuploid embryos from attaching to the uterine lining. Those that do attach usually do so for such only a brief period of time. In such cases the woman often will not even experience a postponement of menstruation. There will be a transient rise in blood hCG levels but in most cases the woman will be unaware of even having conceived (i.e. a “chemical pregnancy”). Alternatively, an aneuploid embryo might attach for a period of a few weeks before being expelled (i.e. a “miscarriage”). Sometimes (fortunately rarely) an aneuploid embryo will develop into a viable baby that is born with a chromosomal birth defect (e.g. Down’s syndrome).
The fact that the incidence of embryo aneuploidy invariably increases with advancing age serves to explain why reproductive failure (“infertility”, miscarriages and birth defects), also increases as women get older.

It is an over-simplification to represent that diminishing ovarian reserve as evidenced by raised FSH blood levels (and other tests) and reduced response to stimulation with fertility drugs is a direct cause of “poor egg/ embryo quality”. This common misconception stems from the fact that poor embryo quality (“incompetence”) often occurs in women who at the same time, because of the advent of the climacteric also have elevated basal blood FSH/LH levels and reduced AMH. But it is not the elevation in FSH or the low AMH that causes embryo “incompetence”. Rather it is the effect of advancing age (the “biological clock”) resulting a progressive increase in the incidence of egg aneuploidy, which is responsible for declining egg quality. Simply stated, as women get older “wear and tear” on their eggs increases the likelihood of egg and thus embryo aneuploidy. It just so happens that the two precipitating factors often go hand in hand.

The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by those IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome in patients at risk – particularly those with diminished ovarian reserve (“poor responders”) and those who are “high responders” (women with PCOS , those with dysfunctional or absent ovulation, and young women under 25 years of age).

While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.

During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) that are produced by the ovarian stroma (the tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (cells that line the inner walls of follicles), and egg maturation.

However, over-production of testosterone can adversely influence the same processes. It follows that protocols for controlled ovarian stimulation (COS should be geared toward optimizing follicle growth and development (without placing the woman at risk from overstimulation), while at the same time avoiding excessive ovarian androgen production. Achievement of such objectives requires a very individualized approach to choosing the protocol for COS with fertility drugs as well as the precise timing of the “trigger shot” of hCG.

It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed towards the cells lining the inside of the follicle that are responsible for estrogen production. LH, on the other hand, acts primarily on the ovarian stroma to produce male hormones/ androgens (e.g. androstenedione and testosterone). A small amount of testosterone is necessary for optimal estrogen production. Over-production of such androgens can have a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.

In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often a feature of this condition. The use of LH-containing preparations such as Menopur further aggravates this effect. Thus we recommend using FSH-dominant products such as Follistim, Puregon, and Gonal-F in such cases. While it would seem prudent to limit LH exposure in all cases of COS, this appears to be more vital in older women, who tend to be more sensitive to LH

It is common practice to administer gonadotropin releasing hormone agonists (GnRHa) agonists such as Lupron, and, GnRH-antagonists such as Ganirelix and Orgalutron to prevent the release of LH during COS. GnRH agonists exert their LH-lowering effect over a number of days. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in the LH level falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. GnRH Antagonists, on the other hand, act very rapidly (within a few hours) to block pituitary LH release, so as achieve the same effect.

Long Agonist (Lupron/Buserelin) Protocols: The most commonly prescribed protocol for Lupron/gonadotropin administration is the so-called “long protocol”. Here, Lupron is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to near zero. It is followed by uterine withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the long protocol which I prefer using in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a Lupron-induced bleed , this agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I supplement with human growth hormone (HGH) to try and further enhance response and egg development.

Lupron Flare/Micro-Flare Protocol: Another approach to COS is by way of so-called “(micro) flare protocols”. This involves initiating gonadotropin therapy simultaneous with the administration of GnRH agonist (e.g. Lupron/Buserelin). The intent here is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” represents “a double edged sword” because while it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal androgen production which could potentially compromise egg quality, especially in older women and women with PCOS, whose ovaries have increased sensitivity to LH. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe them at all.

Estrogen Priming – My approach for “Poor Responders” Our patients who have demonstrated reduced ovarian response to COS as well as those who by way of significantly raised FSH blood levels are likely to be “poor responders”, are treated using a “modified” long protocol. The approach involves the initial administration of GnRH agonist for a number of days to cause pituitary down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered and the woman is given twice-weekly injections of estradiol for a period of 8. COS is thereupon initiated using a relatively high dosage of FSH-(Follistim, Bravelle, Puregon or Gonal F) which is continued along with daily administration of GnRH agonist until the “hCG trigger.” By this approach we have been able to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients”.

The “Trigger”: hCG (Profasi/Pregnyl/Novarel) versus Lupron: With ovulation induction using fertility drugs, the administration of 10,000U hCGu (the hCG “trigger”) mimics the LH surge, sending the eggs (which up to that point are immature (M1) and have 46 chromosomes) into maturational division (meiosis) This process is designed to halve the chromosome number , resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes it had prior to the “trigger”. Such a chromosomally normal, M2 egg, upon being fertilized by mature sperm (that following maturational division also has 23 chromosomes) will hopefully propagate embryos that have 46 chromosomes and will be “:competent” to propagate viable pregnancies. The key is to trigger with no less than 10,000U of hCGu (Profasi/Novarel/Pregnyl) and if hCGr (Ovidrel) is used, to make sure that 500mcg (rather than 250mcg) is administered. In my opinion, any lesser dosage will reduce the efficiency of meiosis, and increase the risk of the eggs being chromosomally abnormal. . I also do not use the agonist (Lupron) “trigger”. This approach which is often recommended for women at risk of overstimulation, is intended to reduce the risk of OHSS. The reason for using the Lupron trigger is that by inducing a surge in the release of LH by the pituitary gland it reduces the risk of OHSS. This is true, but this comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the percentage of chromosomally abnormal and of immature (M1) eggs. The use of “coasting” in such cases) can obviate this effect

.I strongly recommend that you visit www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
• Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.
___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Moti

Hi Dr. Sher.
I have a question for you regarding poor egg quality and low number of mature eggs. I am 33. I live in California. My AMH is 3.2, FSH: 11, and LH is 9 (all day 4 cycle). I have long time history of irregular menstruation, hirsutism, and ovarian cysts. Some doctors believe I am PCOS, some don’t.
I did my first IVF cycle on long lupron plus 300 Gonal-F and 75 Menopur for 10 days. 17 eggs retrieved and only 4 mature (3 fertilized), and all 3 developed to blastocyst AA. No PGS. Transferred one, and it was BFN. Frozen 2 blastocysts. IVF #2: antagonist protocol. 300 unit Gonal-F and 150 unit Menopur. Trigger with Novorel 2 vials after 11 days. On day of trigger I had 11 eggs between 17-21 mm. My doctor was happy. But, unfortunately, out of 13 retrieved, 5 were mature, 4 were m1 and 4 were GV. out of 5 mature eggs, 3 fertilized, and I currently have 3 day 3 embryos (waiting for day 5 results). I am going to send the frozen and new embryos for PGS testing (not sure if refreezing would hurt the frozen blastocysts).
My doctor said he is frustrated with the result, and he believes that the problem is quality of my eggs. He told me to think about egg donor. I am 33 and I don’t know if I should just give it up and move on to egg donor? Based on my studies on your website and watching your youtube video, I am confident that you are the best person to ask this question from. I highly appreciate it if you could kindly help me and provide me with your professional opinion!

reply
Dr. Geoffrey Sher

Very respectfully, I doubt that at 33, even if you do have PCOS, this translates into intractable egg issues that would require OD. In my opinion, it is more likely to be a matter of selecting the optimal protocol for ovarian stimulation and then optimally implementing it.

The potential for a woman’s eggs to undergo orderly development and maturation, while in large part being genetically determined can be profoundly influenced by the woman’s age, her “ovarian reserve” and proximity to menopause. It is also influenced by the protocol used for controlled ovarian stimulation (COH) which by fashioning the intra-ovarian hormonal environment, profoundly impacts egg development and maturation.

After the menarche (age at which menstruation starts) a monthly process of repeatedly processing eggs continues until the menopause, by which time most eggs will have been used up, and ovulation and menstruation cease. When the number of eggs remaining in the ovaries falls below a certain threshold, ovarian function starts to wane over a 5 to10-years. This time period is referred to as the climacteric. With the onset of the climacteric, blood Follicle Stimulating Hormone (FSH) and later also Luteinizing Hormone (LH) levels begin to rise…. at first slowly and then more rapidly, ultimately culminating in the complete cessation of ovulation and menstruation (i.e. menopause).

One of the early indications that the woman has entered the climacteric and that ovarian reserve is diminishing DOR) , is the detection of a basal blood FSH level above 9.0 MIU/ml and/ or an AMH level og <2.0ng/ml.

Prior to the changes that immediately precede ovulation, virtually all human eggs have 23 pairs (i.e. 46) of chromosomes. Thirty six to forty hours prior to ovulation, a surge occurs in the release of LH by the pituitary gland. One of the main e purposes of this LH surge is to cause the chromosomes in the egg to divide n half (to 23 in number) in order that once fertilized by a mature sperm ends up having 23 chromosomes) the resulting embryo will be back to having 46 chromosomes. A “competent” mature egg is one that has precisely 23 chromosomes, not any more or any less. It is largely the egg, rather than the sperm that determines the chromosomal integrity of the embryo and only an embryo that has a normal component of 46 chromosomes (i.e. euploid) is “competent” to develop into a healthy baby. If for any reason the final number of chromosomes in the egg is less or more than 23 (aneuploid), it will be incapable of propagating a euploid, “competent” embryo. Thus egg/embryo aneuploidy (“incompetence”) is the leading cause of human reproductive dysfunction which can manifest as: arrested embryo development and/or failed implantation (which often presents as infertility), early miscarriage or chromosomal birth defects (e.g. Down’s syndrome). While most aneuploid (“incompetent”) embryos often fail to produce a pregnancy, some do. However, most such pregnancies miscarry early on. On relatively rare occasions, depending on the chromosome pair involved, aneuploid embryos can develop into chromosomally defective babies (e.g. Down’s syndrome).

Up until a woman reaches her mid- thirties, at best, 1:2 of her eggs will likely be chromosomally normal. As she ages beyond her mid-thirties there will be a a progressive decline in egg quality such that by age 40 years only about 15%-20% of eggs are euploid and, by the time the woman reaches her mid-forties, less than 10% of her eggs are likely to be chromosomally normal. While most aneuploid embryos do appear to be microscopically abnormal under the light microscope, this is not invariably so. In fact, many aneuploid embryos a have a perfectly normal appearance under the microscope. This is why it is not possible to reliably differentiate between competent and incompetent embryos on the basis of their microscopic appearance (morphologic grade) alone.

The process of natural selection usually precludes most aneuploid embryos from attaching to the uterine lining. Those that do attach usually do so for such only a brief period of time. In such cases the woman often will not even experience a postponement of menstruation. There will be a transient rise in blood hCG levels but in most cases the woman will be unaware of even having conceived (i.e. a “chemical pregnancy”). Alternatively, an aneuploid embryo might attach for a period of a few weeks before being expelled (i.e. a “miscarriage”). Sometimes (fortunately rarely) an aneuploid embryo will develop into a viable baby that is born with a chromosomal birth defect (e.g. Down’s syndrome).
The fact that the incidence of embryo aneuploidy invariably increases with advancing age serves to explain why reproductive failure (“infertility”, miscarriages and birth defects), also increases as women get older.

It is an over-simplification to represent that diminishing ovarian reserve as evidenced by raised FSH blood levels (and other tests) and reduced response to stimulation with fertility drugs is a direct cause of “poor egg/ embryo quality”. This common misconception stems from the fact that poor embryo quality (“incompetence”) often occurs in women who at the same time, because of the advent of the climacteric also have elevated basal blood FSH/LH levels and reduced AMH. But it is not the elevation in FSH or the low AMH that causes embryo “incompetence”. Rather it is the effect of advancing age (the “biological clock”) resulting a progressive increase in the incidence of egg aneuploidy, which is responsible for declining egg quality. Simply stated, as women get older “wear and tear” on their eggs increases the likelihood of egg and thus embryo aneuploidy. It just so happens that the two precipitating factors often go hand in hand.

The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by those IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome in patients at risk – particularly those with diminished ovarian reserve (“poor responders”) and those who are “high responders” (women with PCOS , those with dysfunctional or absent ovulation, and young women under 25 years of age).

While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.

During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) that are produced by the ovarian stroma (the tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (cells that line the inner walls of follicles), and egg maturation.

However, over-production of testosterone can adversely influence the same processes. It follows that protocols for controlled ovarian stimulation (COS should be geared toward optimizing follicle growth and development (without placing the woman at risk from overstimulation), while at the same time avoiding excessive ovarian androgen production. Achievement of such objectives requires a very individualized approach to choosing the protocol for COS with fertility drugs as well as the precise timing of the “trigger shot” of hCG.

It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed towards the cells lining the inside of the follicle that are responsible for estrogen production. LH, on the other hand, acts primarily on the ovarian stroma to produce male hormones/ androgens (e.g. androstenedione and testosterone). A small amount of testosterone is necessary for optimal estrogen production. Over-production of such androgens can have a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.

In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often a feature of this condition. The use of LH-containing preparations such as Menopur further aggravates this effect. Thus we recommend using FSH-dominant products such as Follistim, Puregon, and Gonal-F in such cases. While it would seem prudent to limit LH exposure in all cases of COS, this appears to be more vital in older women, who tend to be more sensitive to LH

It is common practice to administer gonadotropin releasing hormone agonists (GnRHa) agonists such as Lupron, and, GnRH-antagonists such as Ganirelix and Orgalutron to prevent the release of LH during COS. GnRH agonists exert their LH-lowering effect over a number of days. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in the LH level falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. GnRH Antagonists, on the other hand, act very rapidly (within a few hours) to block pituitary LH release, so as achieve the same effect.

Long Agonist (Lupron/Buserelin) Protocols: The most commonly prescribed protocol for Lupron/gonadotropin administration is the so-called “long protocol”. Here, Lupron is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to near zero. It is followed by uterine withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the long protocol which I prefer using in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a Lupron-induced bleed , this agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I supplement with human growth hormone (HGH) to try and further enhance response and egg development.

Lupron Flare/Micro-Flare Protocol: Another approach to COS is by way of so-called “(micro) flare protocols”. This involves initiating gonadotropin therapy simultaneous with the administration of GnRH agonist (e.g. Lupron/Buserelin). The intent here is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” represents “a double edged sword” because while it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal androgen production which could potentially compromise egg quality, especially in older women and women with PCOS, whose ovaries have increased sensitivity to LH. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe them at all.

Estrogen Priming – My approach for “Poor Responders” Our patients who have demonstrated reduced ovarian response to COS as well as those who by way of significantly raised FSH blood levels are likely to be “poor responders”, are treated using a “modified” long protocol. The approach involves the initial administration of GnRH agonist for a number of days to cause pituitary down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered and the woman is given twice-weekly injections of estradiol for a period of 8. COS is thereupon initiated using a relatively high dosage of FSH-(Follistim, Bravelle, Puregon or Gonal F) which is continued along with daily administration of GnRH agonist until the “hCG trigger.” By this approach we have been able to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients”.

The “Trigger”: hCG (Profasi/Pregnyl/Novarel) versus Lupron: With ovulation induction using fertility drugs, the administration of 10,000U hCGu (the hCG “trigger”) mimics the LH surge, sending the eggs (which up to that point are immature (M1) and have 46 chromosomes) into maturational division (meiosis) This process is designed to halve the chromosome number , resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes it had prior to the “trigger”. Such a chromosomally normal, M2 egg, upon being fertilized by mature sperm (that following maturational division also has 23 chromosomes) will hopefully propagate embryos that have 46 chromosomes and will be “:competent” to propagate viable pregnancies. The key is to trigger with no less than 10,000U of hCGu (Profasi/Novarel/Pregnyl) and if hCGr (Ovidrel) is used, to make sure that 500mcg (rather than 250mcg) is administered. In my opinion, any lesser dosage will reduce the efficiency of meiosis, and increase the risk of the eggs being chromosomally abnormal. . I also do not use the agonist (Lupron) “trigger”. This approach which is often recommended for women at risk of overstimulation, is intended to reduce the risk of OHSS. The reason for using the Lupron trigger is that by inducing a surge in the release of LH by the pituitary gland it reduces the risk of OHSS. This is true, but this comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the percentage of chromosomally abnormal and of immature (M1) eggs. The use of “coasting” in such cases) can obviate this effect

.I strongly recommend that you visit www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
• Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.
___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
SG

Dr Sher,

I wrote to you a few weeks ago about another matter and am very grateful for the advice you provide. I terminated a pregnancy at 14 weeks for trisomy 18 at the age of 39 (I have two remaining embryos from this cycle that are not PGS tested). I have just turned 41 and want to bank at least 3-5 euploid embryos total in order to have more than one child. From the 5 cycles completed at age 40,

May 2018 : no blastocysts
June 2018: 6 Blastocysts; 1 euploid, 1 inconclusive
Sept 2018: 1 Blastocysts; aneuploid
Nov 2018: 3 Blastocysts; 1 euploid, 1 inconclusive
Jan 2019: no blastocysts

Thus I have 2 euploid, 2 inconclusive and 2 untested embryos frozen (produced age 39). I just had another egg retrieval today. There were many follicles but only 6 eggs retrieved. In the previous cycles I had 10-13 eggs retrieved. Depending on the outcome of the fertilization my doctor suggests preparing for fresh transfer without testing. He said he had a few cases of women my age who had only one embryo and successfully transferred on day 2. If not successful and if it were not to implant, or if I had an early miscarriage that would be ok by me. My fear is losing a great deal of time (not to mention the trauma) due to another termination (it took 3 months for my periods to start again and thus I lost 7 months) or later miscarriage when I still might be able to produce viable embryos, especially when I am at the cusp of when fertility drastically declines for women. My doctor also recommended considering donor eggs for future cycles if the transfers of my existing embryos are not successful.

In November my tests were:
FSH 9.68 mUI/ml
LH 2.76 mUI/mL
Prolactine 26.6 ng/ml
AMH 1.91 ng/ml
T4 12,30 pg/ml
TSH 1,53/ uUI/ml

Protocol was as follows for the last 3 cycles (previous cycles the same except slightly varying doses of Gonal-F): 18 days lucette birth control (not used in every cycle), 350 iu Gonal F starting day 2; Day 7 200 iu Gonal f and 150 menopur; day 8 add Orgulatran; trigger with Ovitrelle 250.

A few questions:

1. Based on a poor result last cycle and likely this cycle, should I give up on trying to bank embryos using my own eggs and just do a fresh transfer this cycle? I do have some concern over the long term effects of doing so many cycles however considering my response in the last year and the test results, I still feel like I might be able to produce viable embryos on my own. In my gut, I feel like it is not quite the time to transfer just yet if I would like the chance for more than one child.
2. Is it possible that my body has just gotten used to the medication and will continue to respond less well to the medications? Should I have a break?
3. Should I try a different protocol? What protocol would you recommend? I’ve made enquiries with other clinics and my own about different protocols. I don’t know which protocol to chose. My clinic and another clinic suggested that staying on this protocol for the last cycle was not unreasonable considering I have been responsive to it thus far although my current clinic said they could offer another protocol. Another clinic suggested a long protocol with Decapeptyl 0.1mg Injection + then Menopur 375 + 375 + 300

Thanks so much for your time. It is so difficult to make an informed decision.

reply
Dr. Geoffrey Sher

1. Based on a poor result last cycle and likely this cycle, should I give up on trying to bank embryos using my own eggs and just do a fresh transfer this cycle? I do have some concern over the long term effects of doing so many cycles however considering my response in the last year and the test results, I still feel like I might be able to produce viable embryos on my own. In my gut, I feel like it is not quite the time to transfer just yet if I would like the chance for more than one child.

A: In my opinion, since you still have a good ovarian reserve, you could use own eggs. I do not see a reason to go to DE. However, I would review and revise the protocol for ovarian stimulation. I believe this could be improved upon and if so…could yield a better result. I would not do the FET now. Rather I would try to “make hay while the sun still shines” and try to bank/stockpile more euploid blastocysts while you still have the potential to do so!

2. Is it possible that my body has just gotten used to the medication and will continue to respond less well to the medications? Should I have a break?

A: You do not need > 1 cycle break and besides you do not have time to do so.

3. Should I try a different protocol? What protocol would you recommend? I’ve made enquiries with other clinics and my own about different protocols. I don’t know which protocol to chose. My clinic and another clinic suggested that staying on this protocol for the last cycle was not unreasonable considering I have been responsive to it thus far although my current clinic said they could offer another protocol. Another clinic suggested a long protocol with Decapeptyl 0.1mg Injection + then Menopur 375 + 375 + 300

A:Here is the protocol I advise for women who have adequate ovarian reserve.
My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur—no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
• Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
• A personalized, stepwise approach to IVF
• “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist
___________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
SG

Thank you Dr. Sher. So the result of my last cycle was one blastocyst that has been sent off for PGS and we are awaiting the results. For these last two cycles (the previous one resulting in many follicles but no blastocysts) I had been taking DHEA and I wonder if that may have been detrimental, thus I have stopped it. I asked my clinic for a new protocol and asked if they would consider the one you suggested above. They said yes they could try a new protocol. They could either give me one they use at the clinic or implement the one you suggested but I would need the specific dosages to be prescribed by you. I said I would go ahead with what they use at the clinic since they have my full medical records and have been reviewing them over many cycles for over a year. I’ve just received the new protocol which is very similar to what I was doing before although now I begin with synarel from day 22 of the cycle prior to stimulation and continue until the triggering with Ovitrelle 250+ Gonal F 300 until day 6; from day 7 gonal f 150 + menopur 150. (previously I was on a short protocol, began with Gonal F 350 until day 6; Day 7 200 Gonal F + 150 Menopur + Orgulatran; trigger with Ovitrelle 250).

Questions:

1. Will the use of Synarel make a substantial difference in the outcome when the rest of the drugs are very similar to what I used before?

2. After 2 consecutive poor cycles on a higher dosage of Gonal F and the same dosage of Menopur as the new protocol suggested I am keen to try something substantially different. If I wanted you to prescribe the protocol for my clinic to implement how could I go about that and would it be possible to do this for this cycle? I am on Day 3 of the cycle prior to stimulatation.

3. Will stopping DHEA possibly change the result? I noticed that for these two past cycles during which I took 75mg DHEA per day, I had a higher number of follicles in each cycle but also a larger number that did not yield any eggs. Over all a lower number of eggs were retrieved during these cycles when I used DHEA than in the previous ones, despite the higher number of follicles. Could this be because of the DHEA?

Thank you.

reply
Dr. Geoffrey Sher

I THINK WE SHOULD TALK!!

1. Will the use of Synarel make a substantial difference in the outcome when the rest of the drugs are very similar to what I used before?

A: Probably not, but I prefer injectable agonists for better absorbtion.

2. After 2 consecutive poor cycles on a higher dosage of Gonal F and the same dosage of Menopur as the new protocol suggested I am keen to try something substantially different. If I wanted you to prescribe the protocol for my clinic to implement how could I go about that and would it be possible to do this for this cycle? I am on Day 3 of the cycle prior to stimulatation.

A: Probably too late

3. Will stopping DHEA possibly change the result? I noticed that for these two past cycles during which I took 75mg DHEA per day, I had a higher number of follicles in each cycle but also a larger number that did not yield any eggs. Over all a lower number of eggs were retrieved during these cycles when I used DHEA than in the previous ones, despite the higher number of follicles. Could this be because of the DHEA?

A: Dehydroepiandrosterone (DHEA), is steroid hormone produced by the adrenal glands and ovary. It is involved in producing the male hormones, androstenedione testosterone and also estrogen. DHEA blood levels tend to decline naturally with age.
Under the effect if luteinizing hormone (LH), DHEA is metabolized to testosterone in ovarian connective tissue (theca/stroma). Thereupon the testosterone is transported to the granulosa cells that form the innermost layer of the ovarian follicles where, under the influence of follicle stimulating hormone (FSH)-induced desmolase and aromatase enzymatic activity the testosterone is converted to estradiol. As this happens, granulosa cells multiply, follicle fluid volume increases along with estrogen output and egg development is promoted.
It is recognition of the essential/indispensable role that male hormones (mainly testosterone) play in follicle and egg development that prompted the belief that by giving DHEA and boosting ovarian testosterone production might benefit follicle/egg development. This belief was given some credence by an Israeli study that in 2010 reported on improved fertility when a group of infertile women were given the administration of 75mg of oral DHEA for 5 months. However, this study was seriously flawed by the fact that it did not separate out women who had diminished ovarian reserve, older women and those with PCOS, all of whom have increased LH-induced production of testosterone. In fact, we recently completed a study (currently being processed for publication) where we conclusively showed that when follicular fluid testosterone levels exceeded a certain threshold, egg quality was seriously prejudiced as evidenced by a marked increase in the incidence of egg chromosomal defects (aneuploidy).
Consider the following: Ovarian testosterone is needed for follicular development. However, the amount required is small. Too much ovarian testosterone spills over into the follicular fluid and has a deleterious effect on egg/follicle development. Some women (women with diminished ovarian reserve –DOR, older women and those with polycystic ovarian syndrome-PCOS) who tend to have increased LH biological activity, already over-produce testosterone. To such women, the administration of DHEA to such women, by “adding fuel to the fire” can be decidedly prejudicial, in my opinion. Young women with normal ovarian reserve do not over produce LH-induced ovarian testosterone, and are thus probably not at significant risk from DHEA supplementation. It is noteworthy that to date, none of the studies that suggest a benefit from DHEA therapy have differentiated between young healthy normal women with normal ovarian reserve on the one hand and older women, those with DOR and women with PCOS on the other hand.

In Some countries DHEA treatment requires a medical prescription and medical supervision. Not so in the U.S.A where it can be bought over the counter. Since DHEA is involved in sex hormone production, including testosterone and estrogen, individuals with malignant conditions that may be hormone dependent (certain types of breast cancer or testicular cancer) should not receive DHEA supplementation. Also, if overdosed with DHEA some “sensitive women” might so increase their blood concentrations of testosterone that they develop increased aggressive tendencies or male characteristics such as hirsuites (increased hair growth) and a deepening voice. DHEA can also interact other medications, such as barbiturates, corticosteroids, insulin and with other oral diabetic medications.
BUT the strongest argument against the use of routine DHEA supplementation is the potential risk of compromising egg quality in certain categories of women and since there is presently no convincing evidence of any benefit, why take the risk in using it on anyone.
Finally, for those who in spite of the above, still feel compelled to take DHEA, the best advice I can give is to consult their health care providers before starting the process.

Addendum: One potential advantage of DHEA therapy if used appropriately came from a study conducted by Washington University School of Medicine in St. Louis, MI and reported in the November 2004 issue of the “Journal of the American Medical Association” which showed that judicious (selective) administration of 50mg DHEA daily for 6 months resulted in a significant reduction of abdominal fat and blood insulin in elderly women.

The potential for a woman’s eggs to undergo orderly development and maturation, while in large part being genetically determined can be profoundly influenced by the woman’s age, her “ovarian reserve” and proximity to menopause. It is also influenced by the protocol used for controlled ovarian stimulation (COH) which by fashioning the intra-ovarian hormonal environment, profoundly impacts egg development and maturation.

After the menarche (age at which menstruation starts) a monthly process of repeatedly processing eggs continues until the menopause, by which time most eggs will have been used up, and ovulation and menstruation cease. When the number of eggs remaining in the ovaries falls below a certain threshold, ovarian function starts to wane over a 5 to10-years. This time period is referred to as the climacteric. With the onset of the climacteric, blood Follicle Stimulating Hormone (FSH) and later also Luteinizing Hormone (LH) levels begin to rise…. at first slowly and then more rapidly, ultimately culminating in the complete cessation of ovulation and menstruation (i.e. menopause).

One of the early indications that the woman has entered the climacteric and that ovarian reserve is diminishing DOR) , is the detection of a basal blood FSH level above 9.0 MIU/ml and/ or an AMH level og <2.0ng/ml.

Prior to the changes that immediately precede ovulation, virtually all human eggs have 23 pairs (i.e. 46) of chromosomes. Thirty six to forty hours prior to ovulation, a surge occurs in the release of LH by the pituitary gland. One of the main e purposes of this LH surge is to cause the chromosomes in the egg to divide n half (to 23 in number) in order that once fertilized by a mature sperm ends up having 23 chromosomes) the resulting embryo will be back to having 46 chromosomes. A “competent” mature egg is one that has precisely 23 chromosomes, not any more or any less. It is largely the egg, rather than the sperm that determines the chromosomal integrity of the embryo and only an embryo that has a normal component of 46 chromosomes (i.e. euploid) is “competent” to develop into a healthy baby. If for any reason the final number of chromosomes in the egg is less or more than 23 (aneuploid), it will be incapable of propagating a euploid, “competent” embryo. Thus egg/embryo aneuploidy (“incompetence”) is the leading cause of human reproductive dysfunction which can manifest as: arrested embryo development and/or failed implantation (which often presents as infertility), early miscarriage or chromosomal birth defects (e.g. Down’s syndrome). While most aneuploid (“incompetent”) embryos often fail to produce a pregnancy, some do. However, most such pregnancies miscarry early on. On relatively rare occasions, depending on the chromosome pair involved, aneuploid embryos can develop into chromosomally defective babies (e.g. Down’s syndrome).

Up until a woman reaches her mid- thirties, at best, 1:2 of her eggs will likely be chromosomally normal. As she ages beyond her mid-thirties there will be a a progressive decline in egg quality such that by age 40 years only about 15%-20% of eggs are euploid and, by the time the woman reaches her mid-forties, less than 10% of her eggs are likely to be chromosomally normal. While most aneuploid embryos do appear to be microscopically abnormal under the light microscope, this is not invariably so. In fact, many aneuploid embryos a have a perfectly normal appearance under the microscope. This is why it is not possible to reliably differentiate between competent and incompetent embryos on the basis of their microscopic appearance (morphologic grade) alone.

The process of natural selection usually precludes most aneuploid embryos from attaching to the uterine lining. Those that do attach usually do so for such only a brief period of time. In such cases the woman often will not even experience a postponement of menstruation. There will be a transient rise in blood hCG levels but in most cases the woman will be unaware of even having conceived (i.e. a “chemical pregnancy”). Alternatively, an aneuploid embryo might attach for a period of a few weeks before being expelled (i.e. a “miscarriage”). Sometimes (fortunately rarely) an aneuploid embryo will develop into a viable baby that is born with a chromosomal birth defect (e.g. Down’s syndrome).
The fact that the incidence of embryo aneuploidy invariably increases with advancing age serves to explain why reproductive failure (“infertility”, miscarriages and birth defects), also increases as women get older.

It is an over-simplification to represent that diminishing ovarian reserve as evidenced by raised FSH blood levels (and other tests) and reduced response to stimulation with fertility drugs is a direct cause of “poor egg/ embryo quality”. This common misconception stems from the fact that poor embryo quality (“incompetence”) often occurs in women who at the same time, because of the advent of the climacteric also have elevated basal blood FSH/LH levels and reduced AMH. But it is not the elevation in FSH or the low AMH that causes embryo “incompetence”. Rather it is the effect of advancing age (the “biological clock”) resulting a progressive increase in the incidence of egg aneuploidy, which is responsible for declining egg quality. Simply stated, as women get older “wear and tear” on their eggs increases the likelihood of egg and thus embryo aneuploidy. It just so happens that the two precipitating factors often go hand in hand.

The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by those IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome in patients at risk – particularly those with diminished ovarian reserve (“poor responders”) and those who are “high responders” (women with PCOS , those with dysfunctional or absent ovulation, and young women under 25 years of age).

While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.

During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) that are produced by the ovarian stroma (the tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (cells that line the inner walls of follicles), and egg maturation.

However, over-production of testosterone can adversely influence the same processes. It follows that protocols for controlled ovarian stimulation (COS should be geared toward optimizing follicle growth and development (without placing the woman at risk from overstimulation), while at the same time avoiding excessive ovarian androgen production. Achievement of such objectives requires a very individualized approach to choosing the protocol for COS with fertility drugs as well as the precise timing of the “trigger shot” of hCG.

It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed towards the cells lining the inside of the follicle that are responsible for estrogen production. LH, on the other hand, acts primarily on the ovarian stroma to produce male hormones/ androgens (e.g. androstenedione and testosterone). A small amount of testosterone is necessary for optimal estrogen production. Over-production of such androgens can have a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.

In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often a feature of this condition. The use of LH-containing preparations such as Menopur further aggravates this effect. Thus we recommend using FSH-dominant products such as Follistim, Puregon, and Gonal-F in such cases. While it would seem prudent to limit LH exposure in all cases of COS, this appears to be more vital in older women, who tend to be more sensitive to LH

It is common practice to administer gonadotropin releasing hormone agonists (GnRHa) agonists such as Lupron, and, GnRH-antagonists such as Ganirelix and Orgalutron to prevent the release of LH during COS. GnRH agonists exert their LH-lowering effect over a number of days. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in the LH level falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. GnRH Antagonists, on the other hand, act very rapidly (within a few hours) to block pituitary LH release, so as achieve the same effect.

Long Agonist (Lupron/Buserelin) Protocols: The most commonly prescribed protocol for Lupron/gonadotropin administration is the so-called “long protocol”. Here, Lupron is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to near zero. It is followed by uterine withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the long protocol which I prefer using in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a Lupron-induced bleed , this agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I supplement with human growth hormone (HGH) to try and further enhance response and egg development.

Lupron Flare/Micro-Flare Protocol: Another approach to COS is by way of so-called “(micro) flare protocols”. This involves initiating gonadotropin therapy simultaneous with the administration of GnRH agonist (e.g. Lupron/Buserelin). The intent here is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” represents “a double edged sword” because while it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal androgen production which could potentially compromise egg quality, especially in older women and women with PCOS, whose ovaries have increased sensitivity to LH. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe them at all.

Estrogen Priming – My approach for “Poor Responders” Our patients who have demonstrated reduced ovarian response to COS as well as those who by way of significantly raised FSH blood levels are likely to be “poor responders”, are treated using a “modified” long protocol. The approach involves the initial administration of GnRH agonist for a number of days to cause pituitary down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered and the woman is given twice-weekly injections of estradiol for a period of 8. COS is thereupon initiated using a relatively high dosage of FSH-(Follistim, Bravelle, Puregon or Gonal F) which is continued along with daily administration of GnRH agonist until the “hCG trigger.” By this approach we have been able to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients”.

The “Trigger”: hCG (Profasi/Pregnyl/Novarel) versus Lupron: With ovulation induction using fertility drugs, the administration of 10,000U hCGu (the hCG “trigger”) mimics the LH surge, sending the eggs (which up to that point are immature (M1) and have 46 chromosomes) into maturational division (meiosis) This process is designed to halve the chromosome number , resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes it had prior to the “trigger”. Such a chromosomally normal, M2 egg, upon being fertilized by mature sperm (that following maturational division also has 23 chromosomes) will hopefully propagate embryos that have 46 chromosomes and will be “:competent” to propagate viable pregnancies. The key is to trigger with no less than 10,000U of hCGu (Profasi/Novarel/Pregnyl) and if hCGr (Ovidrel) is used, to make sure that 500mcg (rather than 250mcg) is administered. In my opinion, any lesser dosage will reduce the efficiency of meiosis, and increase the risk of the eggs being chromosomally abnormal. . I also do not use the agonist (Lupron) “trigger”. This approach which is often recommended for women at risk of overstimulation, is intended to reduce the risk of OHSS. The reason for using the Lupron trigger is that by inducing a surge in the release of LH by the pituitary gland it reduces the risk of OHSS. This is true, but this comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the percentage of chromosomally abnormal and of immature (M1) eggs. The use of “coasting” in such cases) can obviate this effect

.I strongly recommend that you visit www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
• Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.
___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

.

reply
R

Hi Dr Sher, I recently suffered a missed miscarriage, I conceived quickly and had no issues during my pregnancy. I haemorrhaged during the D&C procedure though. I’m awaiting results from tissue samples taken but I had my full thyroid panel checked and it was found that my anti thyroid antibody levels were very high – 181. My other results including T4, T3 and TSH were all normal. I’m waiting an appointment with Endocrinology but I wonder what your thoughts are regarding this result – could this high level have contributed to my miscarriage? And is there any other issues I should be concerned about when trying to conceive again?

Many thanks
R

reply
Dr. Geoffrey Sher

In 50% of cases where thyroid antibodies are present there will be activation of uterine NK cells with resultant immunologic implantation failure. This can lead to miscarriage (among other things). In my opinion, this t needs to be thoroughly evaluated and addressed as a priority.

Unless tests for immunologic implantation dysfunction (IID) are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful. . In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of reliable Reproductive Immunology Laboratories in the world and most are in the U.S.A. Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by suboptimal laboratories. Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID (autoimmune IID versus alloimmune) be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented.

WHO SHOULD UNDERGO IID TESTING?

When it comes to who should be evaluated, the following conditions should in always raise a suspicion of an underlying IID, and trigger prompt testing:

• A diagnosis of endometriosis or the existence of symptoms suggestive of endometriosis (heavy/painful menstruation and pain with ovulation or with deep penetration during intercourse) I would however emphasize that a definitive diagnosis of endometriosis requires visualization of the lesions at laparoscopy or laparotomy)
• A personal or family history of autoimmune disease such as hyper/hypothyroidism (as those with elevated or depressed TSH blood levels, regardless of thyroid hormonal dysfunction), Lupus erythematosus, Rheumatoid arthritis, dermatomyositis, scleroderma etc.)
• “Unexplained” infertility
• Recurrent pregnancy loss (RPL)
• A history of having miscarried a conceptus that, upon testing of products of conception, was found to have a normal numerical chromosomal configuration (euploid).
• Unexplained IVF failure
• “Unexplained” intrauterine growth retardation due to placental insufficiency or late pregnancy loss of a chromosomally normal baby

What Parameters should be tested?
In my opinion, too many Reproductive Immunologists unnecessarily unload a barrage of costly IID tests on unsuspecting patients. In most cases the initial test should be for NK cell activation, and only if this is positive, is it necessary to expand the testing.

The parameters that require measurement include:
o For Autoimmune Implantation Dysfunction: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are: a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6, Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity (in my opinion).
o For Alloimmune implantation Dysfunction: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in IID when there is concomitant NK/CTL activation (see elsewhere on this blog).

How should results be interpreted?
Central to making a diagnosis of an immunologic implantation dysfunction is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. Then there is the interpretation of reported results. The most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In my opinion, trying to interpret the effect of adding IVIG or Intralipid to the sample in order assess whether and to what degree the use of these products would have a therapeutic benefit is seriously flawed and of little benefit. Clinically relevant NK cell deactivation can only be significantly effected in vivo and takes more than a week following infusion to occur. Thus what happens in the laboratory by adding these products to the sample prior to K-562 target cell testing is in my opinion likely irrelevant.

There exists a pervasive but blatant misconception on the part of many, that the addition of Intralipid (IL) /immunoglobulin-G IVIG) can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL. However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells, which takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, in reality it would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory, by which time it would be far too late to be of practical advantage.

Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus, it should be infused 10-14 several prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later. In addition, to be effective, IL/IVIG therapy needs to be combined with steroid (dexamethasone/prednisone/prednisolone) therapy to down-regulates (often) concomitantly activated T-cells.

I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID) Why did my IVF Fail
• Recurrent Pregnancy Loss (RPL): Why do I keep losing my PregnanciesGenetically Testing Embryos for IVF
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
• Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
• A personalized, stepwise approach to IVF
_______________________________________________________

ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Emily

I just had an IVF cycle in January 2019. I had 15 eggs retrieved after 12 days of stimulation with menopur and follistim. Of the 15, 8 were mature and 7 fertilized through ICSI. 4 of the 7 fertilized grew out to 5/6 day blastocysts 1 5AA, 1 6 AA, and 2 5 AB. I did a FET this month. I was on BC prior to starting estrogen supplementation due to travel. This basically caused me to have my period twice in a 2.5 week span once the birth control was stopped. My protocol was 2 mg estrace BID and 1 baby asprin daily. My lining was not thickening properly and a Vivelle Dot patch was added and changed every 3 days. I was also increased to 2 mg estrace TID for about a week. My FET was delayed by 5 days until my lining was thick enough. I was started on PIO 5 days prior to transfer. The 5 AA blast was transferred. I continued with PIO every morning, estrace BID and baby asprin until by beta test 9dp5dt. I started cramping and spotting days 4-6 after transfer. I was having an issue with the PIO leaking a bit after getting the IM shot in my buttocks. The team didn’t seem concerned at all. My progesterone level was 80 the day of the transfer. I guess my question is what went wrong? What could we do differently next time to prevent another failed transfer.

reply
Dr. Geoffrey Sher

Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.

It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:

1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.

We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).

3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.

4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:

a. A“ thin uterine lining”
b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c. Immunologic implantation dysfunction (IID)
d. Endocrine/molecular endometrial receptivity issues
e. Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.

Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF?

ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Sharon

Hello Dr. Sher. I am 41 years old. Started my IVF journey in May 2018. My numbers were:

AMH 1.1
FSH 8.6
My protocol was: estrogen priming them lupron twice a day, 225 Gonal F, 225 Menopur

4 eggs retrieved, 1 fertilized but arrested at day 5

Fast forward to February 2019:

AMH 0.5
FSH 8.7

My protocol was: birth control pills for 5 days, 300 Gonal F, 150 menopur. Both times I triggered with 10,000 of pregnyl

6 eggs retrieved, 0 fertilized.

Doc says it’s my age. Donor eggs are not an option. Has anyone had success with similar age, numbers? Should I just throw in the towel?

reply
Dr. Geoffrey Sher

Hi Sharon,

Given your age and diminishing ovarian reserve, there is little doubt that egg donation will resolve your problem. However, if you feeel strongly about still trying with own eggs then please consider the following:

The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.

While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.

I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy

Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly

• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
• Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• IVF Egg Donation: A Comprehensive Overview
___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Ellen

Hi Dr. Sher!

I recently asked my RE about this but he kinda brushed it off. I’m 37 and had my second round of ivf stims in December. I have two remaining PGS normal embryos. In all, I had one fresh transfer in August, a FET in November and then another in February. I had three failed iuis and etc. I don’t ovulate on my own. I have never been pregnant.

Here’s my question… in 2015 I began experiencing g what I thought was the worst yeast infection of my life. It was soon followed my numbness and joint pain. I developed Uveitis several months later and a rheumatologist suspected I had Behçet’s Disease. There is no test for it but all signs pointed to it. I took Colchicine for a while but discontinued it when we began trying for a baby. I have not had a flare up since Dec 2015.

I have seen people mention NK cells and that they are related to AU diseases. Is it remotely possible that something related to my Behçet’s disease could be preventing embryos from implanting in my uterus?

I believe my RE dismissed this question because I have not has miscarriages. We are doing a hysteroscopy to check for lesions Etc in the uterus.

But because Behçet’s is SO rare and random, I feel like I have to at least do my due diligence to make sure it isn’t possible.

Is there a blood test I could have done to rule this out?

reply
Dr. Geoffrey Sher

Very respectfully, I do not agree with the premise that in order to evaluate for immunologic implantation dysfunction there has to be a history of recurrent pregnancy loss! In my opinion that is ludicrous!

Unless tests for immunologic implantation dysfunction (IID) are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful. . In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of reliable Reproductive Immunology Laboratories in the world and most are in the U.S.A. Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by suboptimal laboratories. Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID (autoimmune IID versus alloimmune) be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented.

WHO SHOULD UNDERGO IID TESTING?

When it comes to who should be evaluated, the following conditions should in always raise a suspicion of an underlying IID, and trigger prompt testing:

• A diagnosis of endometriosis or the existence of symptoms suggestive of endometriosis (heavy/painful menstruation and pain with ovulation or with deep penetration during intercourse) I would however emphasize that a definitive diagnosis of endometriosis requires visualization of the lesions at laparoscopy or laparotomy)
• A personal or family history of autoimmune disease such as hyper/hypothyroidism (as those with elevated or depressed TSH blood levels, regardless of thyroid hormonal dysfunction), Lupus erythematosus, Rheumatoid arthritis, dermatomyositis, scleroderma etc.)
• “Unexplained” infertility
• Recurrent pregnancy loss (RPL)
• A history of having miscarried a conceptus that, upon testing of products of conception, was found to have a normal numerical chromosomal configuration (euploid).
• Unexplained IVF failure
• “Unexplained” intrauterine growth retardation due to placental insufficiency or late pregnancy loss of a chromosomally normal baby

What Parameters should be tested?
In my opinion, too many Reproductive Immunologists unnecessarily unload a barrage of costly IID tests on unsuspecting patients. In most cases the initial test should be for NK cell activation, and only if this is positive, is it necessary to expand the testing.

The parameters that require measurement include:
o For Autoimmune Implantation Dysfunction: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are: a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6, Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity (in my opinion).
o For Alloimmune implantation Dysfunction: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in IID when there is concomitant NK/CTL activation (see elsewhere on this blog).

How should results be interpreted?
Central to making a diagnosis of an immunologic implantation dysfunction is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. Then there is the interpretation of reported results. The most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In my opinion, trying to interpret the effect of adding IVIG or Intralipid to the sample in order assess whether and to what degree the use of these products would have a therapeutic benefit is seriously flawed and of little benefit. Clinically relevant NK cell deactivation can only be significantly effected in vivo and takes more than a week following infusion to occur. Thus what happens in the laboratory by adding these products to the sample prior to K-562 target cell testing is in my opinion likely irrelevant.

There exists a pervasive but blatant misconception on the part of many, that the addition of Intralipid (IL) /immunoglobulin-G IVIG) can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL. However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells, which takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, in reality it would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory, by which time it would be far too late to be of practical advantage.

Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus, it should be infused 10-14 several prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later. In addition, to be effective, IL/IVIG therapy needs to be combined with steroid (dexamethasone/prednisone/prednisolone) therapy to down-regulates (often) concomitantly activated T-cells.

I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID) Why did my IVF Fail
• Recurrent Pregnancy Loss (RPL): Why do I keep losing my PregnanciesGenetically Testing Embryos for IVF
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
• Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
• A personalized, stepwise approach to IVF

___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Katrina Spry

Hello Dr Sher,

I am from Canads and just turned 35 in Nov(2018). I did my initial IVF in Aug/sept for Male factor infertility(my husband had a vasectomy in early 2013, had it reversed in late 2016 without success). All my testing came back normal in May 2018
AMH 16.85
AFC 22
FSH 5
BMI 21.4

I had 17 eggs retrieved, 13 mature and 9 fertilized. 7 made it to day 5 blasts but only 2 were frozen. They watched the rest and only 1 was frozen on day 6. The rest they said didnt grow big enough. “They were like raspberries instead of strawberries” my sonohysterogram done in Jan showed everything was good.

I had a fresh transfer with a 4bb embryo with success but unfortunately had a missed misscarriage st 9.5 weeks. Heart stopped and no growth after my 7 week US.

I have just recently started my FET protocol. Birth control for 14 days, daily lupron started 3 days before birth control stops, then blood word, and will start estrace and then PIO. I am on prenatal vit, 1000iu vit D, 600mg calcium, 4mg folic acid, 400mg magnesium glycinate.

My concern is that i have had increasing pelvic discomfort/pain. It’s like a burning type of feeling over the past 6 weeks(since after my sono in jan). A UTI has been ruled out. Also, lower back pain, and most recently very intense pain just prior to having a bowel movement(I have been taking magnesium to keep things really soft since then and it seems to help with pain of stool moving down) I went to see my GP last week and he thinks I may have endometriosis. He has referred me to a surgeon to look into my rectum/lower bowel. I have had very painful periods for a couple years. My flow is not heavy though last 4 days. I sometimes have pain with intercourse although not all the time. I have recently been spotting, sometimes old blood but sometimes fresh(could be from the birth control I guess but never had that happen before).

What would you advise me to do given my current situation? Should I postpone my FET? I know endo does effect fertility and ive been fortunate enough to have been pregnant that one time but would a flare up effect things more(if that is what this is)? My doctor does not test for NK cells nor will they use intralipids 🙁 where would you suggest I go from here? I’m terrified of ‘waisting’ an embryo when I only have 2 left.

Thank you so much for your time. I very much appreciate your advice and knowledge. 🙂

reply
Dr. Geoffrey Sher

It could be that you have endometriosis. If this is endometriosis then you need to be aware that in 1/3 of cases (regardless of severity) there will be an immunologic implantation dysfunction (IID) linked to activation of uterine natural killer cells, that would need to be addressed prior to FET.

However, it is also possible that you had retained products of conception after your loss at 9 weeks and that this became infected causing intrauterine scarring. Dis you have a sonohysterogram or hysteroscopy since the loss.

Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.

It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:

1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.

We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).

3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.

4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:

a. A“ thin uterine lining”
b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c. Immunologic implantation dysfunction (IID)
d. Endocrine/molecular endometrial receptivity issues
e. Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.

Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF?

___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Jessica Nightingale

Hello, I am 29 years old and my Husband is 31. We are both in good health and have had unexplained fertility for 7 + years. My AMH is 18.6 and AFC 16. My husband has a very high sperm count, high motility and 3% morphology.
We are on round 2 of IVF, both have been short protocol-
Round 1 Sept 2018: 225iu of Menopur for 13 days (4 follicles at the right size at the last scan). Trigger was Gonasi 5000 plus 5ml Suprecur. 12 eggs collected, 10 mature, 5 fertilised with normal IVF. I had a day 3 transfer of 4 cell & 5 cell embryos- both fragmented. The other embryos stopped developing at day 2 and it was a Negative pregnancy test.
I started taking 300mg of CoQ10 after this failed round.
Round 2- 300iu of Bemfola for 10 days (6 follicles at the right size at the last scan). Trigger was Gonasi 10000. 10 eggs collected, 8 mature, 5 fertilised with ICSI. I had a day 3 transfer of 6 cell & 7 cell embryos, both grade 3. The other embryos stopped developing at day 2 again. I am currently on the 2ww but I have been spotting & bleeding the same as last time so I don’t think it has worked again.

Please can you offer me your opinion on what our issue could be with embryo development, is this down to the egg, sperm or both? Is there anything that we can do / change to improve this? Would changing to the long protocol make any difference?

Thank you in advance,

Jessica x

reply
Dr. Geoffrey Sher

Hi Jessica,

The potential for a woman’s eggs to undergo orderly development and maturation, while in large part being genetically determined can be profoundly influenced by the woman’s age, her “ovarian reserve” and proximity to menopause. It is also influenced by the protocol used for controlled ovarian stimulation (COH) which by fashioning the intra-ovarian hormonal environment, profoundly impacts egg development and maturation.

After the menarche (age at which menstruation starts) a monthly process of repeatedly processing eggs continues until the menopause, by which time most eggs will have been used up, and ovulation and menstruation cease. When the number of eggs remaining in the ovaries falls below a certain threshold, ovarian function starts to wane over a 5 to10-years. This time period is referred to as the climacteric. With the onset of the climacteric, blood Follicle Stimulating Hormone (FSH) and later also Luteinizing Hormone (LH) levels begin to rise…. at first slowly and then more rapidly, ultimately culminating in the complete cessation of ovulation and menstruation (i.e. menopause).

One of the early indications that the woman has entered the climacteric and that ovarian reserve is diminishing DOR) , is the detection of a basal blood FSH level above 9.0 MIU/ml and/ or an AMH level og <2.0ng/ml.

Prior to the changes that immediately precede ovulation, virtually all human eggs have 23 pairs (i.e. 46) of chromosomes. Thirty six to forty hours prior to ovulation, a surge occurs in the release of LH by the pituitary gland. One of the main e purposes of this LH surge is to cause the chromosomes in the egg to divide n half (to 23 in number) in order that once fertilized by a mature sperm ends up having 23 chromosomes) the resulting embryo will be back to having 46 chromosomes. A “competent” mature egg is one that has precisely 23 chromosomes, not any more or any less. It is largely the egg, rather than the sperm that determines the chromosomal integrity of the embryo and only an embryo that has a normal component of 46 chromosomes (i.e. euploid) is “competent” to develop into a healthy baby. If for any reason the final number of chromosomes in the egg is less or more than 23 (aneuploid), it will be incapable of propagating a euploid, “competent” embryo. Thus egg/embryo aneuploidy (“incompetence”) is the leading cause of human reproductive dysfunction which can manifest as: arrested embryo development and/or failed implantation (which often presents as infertility), early miscarriage or chromosomal birth defects (e.g. Down’s syndrome). While most aneuploid (“incompetent”) embryos often fail to produce a pregnancy, some do. However, most such pregnancies miscarry early on. On relatively rare occasions, depending on the chromosome pair involved, aneuploid embryos can develop into chromosomally defective babies (e.g. Down’s syndrome).

Up until a woman reaches her mid- thirties, at best, 1:2 of her eggs will likely be chromosomally normal. As she ages beyond her mid-thirties there will be a a progressive decline in egg quality such that by age 40 years only about 15%-20% of eggs are euploid and, by the time the woman reaches her mid-forties, less than 10% of her eggs are likely to be chromosomally normal. While most aneuploid embryos do appear to be microscopically abnormal under the light microscope, this is not invariably so. In fact, many aneuploid embryos a have a perfectly normal appearance under the microscope. This is why it is not possible to reliably differentiate between competent and incompetent embryos on the basis of their microscopic appearance (morphologic grade) alone.

The process of natural selection usually precludes most aneuploid embryos from attaching to the uterine lining. Those that do attach usually do so for such only a brief period of time. In such cases the woman often will not even experience a postponement of menstruation. There will be a transient rise in blood hCG levels but in most cases the woman will be unaware of even having conceived (i.e. a “chemical pregnancy”). Alternatively, an aneuploid embryo might attach for a period of a few weeks before being expelled (i.e. a “miscarriage”). Sometimes (fortunately rarely) an aneuploid embryo will develop into a viable baby that is born with a chromosomal birth defect (e.g. Down’s syndrome).
The fact that the incidence of embryo aneuploidy invariably increases with advancing age serves to explain why reproductive failure (“infertility”, miscarriages and birth defects), also increases as women get older.

It is an over-simplification to represent that diminishing ovarian reserve as evidenced by raised FSH blood levels (and other tests) and reduced response to stimulation with fertility drugs is a direct cause of “poor egg/ embryo quality”. This common misconception stems from the fact that poor embryo quality (“incompetence”) often occurs in women who at the same time, because of the advent of the climacteric also have elevated basal blood FSH/LH levels and reduced AMH. But it is not the elevation in FSH or the low AMH that causes embryo “incompetence”. Rather it is the effect of advancing age (the “biological clock”) resulting a progressive increase in the incidence of egg aneuploidy, which is responsible for declining egg quality. Simply stated, as women get older “wear and tear” on their eggs increases the likelihood of egg and thus embryo aneuploidy. It just so happens that the two precipitating factors often go hand in hand.

The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by those IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome in patients at risk – particularly those with diminished ovarian reserve (“poor responders”) and those who are “high responders” (women with PCOS , those with dysfunctional or absent ovulation, and young women under 25 years of age).

While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.

During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) that are produced by the ovarian stroma (the tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (cells that line the inner walls of follicles), and egg maturation.

However, over-production of testosterone can adversely influence the same processes. It follows that protocols for controlled ovarian stimulation (COS should be geared toward optimizing follicle growth and development (without placing the woman at risk from overstimulation), while at the same time avoiding excessive ovarian androgen production. Achievement of such objectives requires a very individualized approach to choosing the protocol for COS with fertility drugs as well as the precise timing of the “trigger shot” of hCG.

It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed towards the cells lining the inside of the follicle that are responsible for estrogen production. LH, on the other hand, acts primarily on the ovarian stroma to produce male hormones/ androgens (e.g. androstenedione and testosterone). A small amount of testosterone is necessary for optimal estrogen production. Over-production of such androgens can have a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.

In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often a feature of this condition. The use of LH-containing preparations such as Menopur further aggravates this effect. Thus we recommend using FSH-dominant products such as Follistim, Puregon, and Gonal-F in such cases. While it would seem prudent to limit LH exposure in all cases of COS, this appears to be more vital in older women, who tend to be more sensitive to LH

It is common practice to administer gonadotropin releasing hormone agonists (GnRHa) agonists such as Lupron, and, GnRH-antagonists such as Ganirelix and Orgalutron to prevent the release of LH during COS. GnRH agonists exert their LH-lowering effect over a number of days. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in the LH level falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. GnRH Antagonists, on the other hand, act very rapidly (within a few hours) to block pituitary LH release, so as achieve the same effect.

Long Agonist (Lupron/Buserelin) Protocols: The most commonly prescribed protocol for Lupron/gonadotropin administration is the so-called “long protocol”. Here, Lupron is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to near zero. It is followed by uterine withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the long protocol which I prefer using in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a Lupron-induced bleed , this agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I supplement with human growth hormone (HGH) to try and further enhance response and egg development.

Lupron Flare/Micro-Flare Protocol: Another approach to COS is by way of so-called “(micro) flare protocols”. This involves initiating gonadotropin therapy simultaneous with the administration of GnRH agonist (e.g. Lupron/Buserelin). The intent here is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” represents “a double edged sword” because while it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal androgen production which could potentially compromise egg quality, especially in older women and women with PCOS, whose ovaries have increased sensitivity to LH. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe them at all.

Estrogen Priming – My approach for “Poor Responders” Our patients who have demonstrated reduced ovarian response to COS as well as those who by way of significantly raised FSH blood levels are likely to be “poor responders”, are treated using a “modified” long protocol. The approach involves the initial administration of GnRH agonist for a number of days to cause pituitary down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered and the woman is given twice-weekly injections of estradiol for a period of 8. COS is thereupon initiated using a relatively high dosage of FSH-(Follistim, Bravelle, Puregon or Gonal F) which is continued along with daily administration of GnRH agonist until the “hCG trigger.” By this approach we have been able to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients”.

The “Trigger”: hCG (Profasi/Pregnyl/Novarel) versus Lupron: With ovulation induction using fertility drugs, the administration of 10,000U hCGu (the hCG “trigger”) mimics the LH surge, sending the eggs (which up to that point are immature (M1) and have 46 chromosomes) into maturational division (meiosis) This process is designed to halve the chromosome number , resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes it had prior to the “trigger”. Such a chromosomally normal, M2 egg, upon being fertilized by mature sperm (that following maturational division also has 23 chromosomes) will hopefully propagate embryos that have 46 chromosomes and will be “:competent” to propagate viable pregnancies. The key is to trigger with no less than 10,000U of hCGu (Profasi/Novarel/Pregnyl) and if hCGr (Ovidrel) is used, to make sure that 500mcg (rather than 250mcg) is administered. In my opinion, any lesser dosage will reduce the efficiency of meiosis, and increase the risk of the eggs being chromosomally abnormal. . I also do not use the agonist (Lupron) “trigger”. This approach which is often recommended for women at risk of overstimulation, is intended to reduce the risk of OHSS. The reason for using the Lupron trigger is that by inducing a surge in the release of LH by the pituitary gland it reduces the risk of OHSS. This is true, but this comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the percentage of chromosomally abnormal and of immature (M1) eggs. The use of “coasting” in such cases) can obviate this effect

.I strongly recommend that you visit www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
• Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.
___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Malinda

Hi Dr. Sher,

I came across your website when I was searching for information regarding Menopur only IVF protocols.

Here’s a little background about myself. I’m 32 with PCOS and extremely irregular/rare periods. I started fertility treatments over a year ago. We were successful getting pregnant with a hybrid cycle that involved Femara, Gonal F, and TI. Unfortunately, we never saw anything on ultrasound and my betas were all over the place. After receiving methotrexate for an ectopic pregnancy, we did an HSG and were told both tubes were blocked.

Moving on to IVF, I was sent to a different RE due to insurance coverage. I took 2 weeks Provera to induce a cycle. I waited 2 weeks from the last pill for a menses that never came and went in to the office for an ultrasound and labs, which showed I had ovulated. My menses started February15th, we started meds for our first IVF cycle on the 16th, and our cycle ended up canceled on the 24th.

I was on an antagonist protocol. CD 2-4 involved 150 iu Gonal F. My E2 on CD5 was 777, so they adjusted my meds to 75 iu Menopur only with 250 mcg Cetrotide CD 5-8. On CD 7, my E2 was 1,151 and on CD 8 was 1,218. CD 9, my E2 dropped to 811. I was told to take 75 iu Gonal F along with the same doses of Menopur and Cetrotide. The next day, CD 10, my E2 dropped to 546 and my cycle was canceled.

During the whole process, I had daily monitoring appointments from CD 5 and on. They expressed how worried they were about overstimulation. They counted/estimated 80+ follicles, half of which were growing too fast initially, so they changed my meds. I seemed to be doing ok on the menopur and cetrotide only, but after a few days, they told me my follicle growth had slowed/stalled. They stated it wouldn’t be worth it continue to stim, trigger. And retrieve the few follicles that were large enough. They feared the quality may not be good and they didn’t want to risk OHSS.

Since cancelling the cycle, they’ve updated me with a new protocol. Their plan is to have me start birth control with my next menses. After the pills are finished, they will start me on 75 iu Menopur on CD2 and then add Cetrotide later in the cycle. They plan to use Lupron as a co-trigger to Novarel.

I’ve never heard of using Menopur only before. I know Menopur has both FSH and LH and I’m concerned about impact the LH may have on egg quality. I’m worried about another canceled cycle or poor outcomes from the cycle.

Here’s some helpful information: My CD 2 labs (drawn prior to this cycle) – AMH = 14, AFC = 52, FSH = 4.8, LH = 2.4, TSH = 1.42, testosterone is normal, hgb A1C, fasting glucose, and insulin level are all normal. The only meds I take are a Prenatal Vitamin, 81 mg ASA, and 1500 mg Metformin once daily. I’m 5’2 and weigh about 127 lbs.

reply
Dr. Geoffrey Sher

Polycystic ovary syndrome (PCOS) is a common hormonal system disorder among women affecting between 5% and 10% of women of reproductive age worldwide. Women with PCOS may have enlarged ovaries that contain multiple small collections of fluid (subcapsular microcysts) that are arranged like a “string of pearls” immediately below the ovarian surface (capsule).interspersed by an overgrowth of ovarian connective tissue (stroma). The condition is characterized by abnormal ovarian function (irregular or absent periods, abnormal or absent ovulation and infertility, androgenicity (increased body hair or hirsutism, acne) and increased body weight –body mass index or BMI.
Women with PCOS are at increased risk that ovarian stimulation with gonadotropins will result in the, of development of severe ovarian hyperstimulation syndrome (OHSS), a life-endangering condition that is often accompanied by a profound reduction in egg “competency” and on fertilization often yield an inordinately high percentage of “incompetent” embryos which have a reduced potential to propagate viable pregnancies.
Concern and even fear that their PCOS patients will develop of OHSS often leads the treating RE to take measures aimed at reducing the risk of this life-endangering condition. One such measures is to “trigger” egg maturation prematurely in the hope of arresting further follicular growth and the other, is to initiate the “trigger” with a reduced dosage of hCG (i.ed. 5,000U rather than the usual 10,000U of of Pregnyl/Profasi/Novarel, to use or 250mcg rather than 500mcg of Ovidrel or to supplant the hCG “trigger” with a Lupron “trigger” which causes a prompt LH surge from the woman’s pituitary gland to take place. While such measures do indeed reduce the risk of OHSS to the mother, this often comes at the expense of egg quantity and “competency”. Fewer than the anticipated number of eggs are harvested and those that are retrieved are far more likely to be “immature” and chromosomally abnormal (aneuploid”), or “immature” , thereby significantly compromising IVF outcome.
Against this background, It is my considered opinion that when it comes to performing IVF in women with PCOS, the most important consideration must be the selection and proper implementation of an individualized or customized ovarian stimulation protocol. Thereupon, rather than prematurely initiating the “trigger” to arrest further follicle growth, administering a reduced dosage of hCG or “triggering with a GnRH agonist (e.g. Lupron/Buserelin) that can compromise egg “competency”….. use of one of the following techniques will often markedly reduce the risk of OHSS while at the same time protecting egg quality:
1. PROLONGED COASTING…my preferred approach: My preferred approach is to use a long pituitary down-regulation protocol coming off the BCP which during the last 3 days is overlapped with the agonist, Lupron/Buserelin/Superfact. The BCP is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling LH-induced ovarian androgen (predominantly, testosterone) production and release. I then stimulate my PCOS patients using a low dosage of recombinant FSH-(FSHr) such as Follistim/Gonal-F/Puregon. On the 3rd day of such stimulation a smidgeon of LH/hCG (Luveris/Menopur) is added. Thereupon, starting on day 7 of ovarian stimulation, I perform serial blood estradiol (E2) and ultrasound follicle assessments, watching for the number and size of the follicles and the blood estradiol concentration [E2]. I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. At this point, provided the [E2] reaches at least >2,500pg/ml, I stop the agonist as well as gonadotropin stimulation and track the blood E2 concentration daily. The [E2] will almost invariably increase for a few days. I closely monitor the [E2] as it rises, plateaus and then begins to decline. As soon as the [E2] drops below 2500pg/ml (and not before then), I administer a “trigger” shot of 10,000U Profasi/ Novarel/Pregnyl or 500mcg Ovidrel/Ovitrel. This is followed by an egg retrieval, performed 36 hours later. Fertilization is accomplished using intracytoplasmic sperm injection (ICSI) because “coasted” eggs usually have little or no cumulus oophoris enveloping them and eggs without a cumulus will not readily fertilize naturally. Moreover, they also tend to have a “hardened” envelopment (zona pellucida), making spontaneous fertilization problematic in many cases. All fertilized eggs are cultured to the blastocyst stage (up to day 5- 6 days) and thereupon are either vitrified and preserved for subsequent transfer in later hormone replacement cycles or (up to 2) blastocysts are transferred to the uterus, transvaginally under transabdominal ultrasound guidance. The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If started too early, follicle growth will arrest and the cycle will be lost. If commenced too late, too many follicles will be post-mature/cystic (>22mm) and as such will usually harbor abnormal or dysmature eggs. Use of “Coasting” almost always prevents the development of severe OHSS, optimizes egg/embryo quality and avoids unnecessary cycle cancellation. If correctly implemented, the worst you will encounter is moderate OHSS and this too is relatively uncommon.
2. EMBRYO FREEZING AND DEFERMENT OF EMBRYO TRANSFEDR (ET): OHSS is always a self-limiting condition. In the absence of continued exposure to hCG, symptoms and signs as well as the risk of severe complications will ultimately abate. Thus, in the absence of pregnancy, all symptoms, signs and risks associated with OHSS will disappear within about 10-14 days of the hCG trigger. Conversely, since early pregnancy is always accompanied by a rapid and progressive rise in hCG , the severity of OHSS will increase until about the 9th or tenth gestational week whereupon a transition from ovarian to placental hormonal dominance occurs, the severity of OHSS rapidly diminishes and the patient will be out of risk. Accordingly, in cases where in spite of best effort to prevent OHSS, the woman develops symptoms and signs of progressive overstimulation prior to planned ET, all the blastocysts should be vitrified and cryostored for FET in a subsequent hormone replacement cycle. In this way women with OHSS can be spared the risk of the condition spiraling out of control.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com . Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
· The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
· Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
· IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
· The Fundamental Requirements For Achieving Optimal IVF Success
· Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
· Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
· Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
· Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
· Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
· The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
· Taking A Fresh Look at Ovarian Hyperstimulation Syndrome (OHSS), its Presentation, Prevention and Management
· Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
· Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
· “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
· The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?
• .Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Implications of “Empty Follicle Syndrome and “Premature Luteinization”
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”

___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Nichelle

Hello Dr! I am hoping you can give me some advice. I just turned 42. My first IVF cycle was not successful. During stimulation, I
had 13 follicles measured on ultrasound. On the day of trigger they measured as followed:

Right Ovary: 22.1, 18, 19.2, 16.9, 19.4, 15.6, 17.2, 16.5
Left Ovary: 19.4, 15.2, 15.1, 13.7, 8.4

I had 19 eggs retrieved but only 7 were mature and only 1 fertilized with ICSI. I was told that due to egg quality the eggs fell a part during the ICSI process. The embryologist recommended Conventional IVF (natural fertilization) next cycle. So only 7 were MII and 9 were GV. Do you believe this was a quality problem or a problem with the protocol or skill of embryologist? Protocol listed below. I would love to know what could be done differently

Took Birth control pills for 2 weeks. After stopping pills, 5 days later starting stimulation. I stimmed for 9 days using the following injections and oral medications

25 units of omnitrope
40 units of Lo Dose HCG
300 units of Gonal F
1 dexamethasone pill for 10 days
2 letrozole pills for 5 days
2 doxycycline pills for 7 days
On day 5 of stimming, I started cetricide until the trigger day.
Trigger day: Gonal F of 450 units, 2 ovidrel prefilled syringes and 1 Lupron acetate trigger.

reply
Dr. Geoffrey Sher

Very respectfully, I think this was likely largely a protocol issue.

The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.

While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.

I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy

Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly

• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
• Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• IVF Egg Donation: A Comprehensive Overview
___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Nichelle

Thank you Dr for your reply! The fertility clinic wants to do a Lupron Lead in for my second IVF cycle. (10 units, starting 8 days after ovulation). They have removed the Letrozole and Dexamethasone from my protocol. Also, I will be using a lower dosage of the Lupron (5 units) the entire time of stimulation rather than the cetricide. Also, the trigger will be with Pregnel. The remaining stimulation will be the same. Gonal F 350 units, Lo Dose HCG 40 units, Omintrope 25 units with the Lupron at 5 units. Do you think this will help with maturing more eggs, increasing fertilization and more blastocysts? With the failed cycle last time, the only fertilized egg developed to a blastocyst of A/B quality. The clinic only checks on them at day 5. Unfortunately, it was PGS tester and determined to not be normal. Just wanted your thoughts on whether this new protocol has a better chance of yielding more favorable results. Do you think I should try ICSI again, conventional IVF or a mixture?

reply
Dr. Geoffrey Sher

It sounds like a reasonable approach. However, here is the protocol I advise for women who have adequate ovarian reserve.

I use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur—no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.

I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
• Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
• A personalized, stepwise approach to IVF
• “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:

Geoff Sher
___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Tihelia Hunter

Hello. I really want to have baby. I’m 37 years old with a 19 year old. I just left my doctor office for follow up. I had a laparoscopy procedure done on 2/01/2019. Today I found out my only tube that I have left is blocked and I have severe adhesion. He basically said everything is stuck together but that my uterus looks good. He also said my ovaries looks good but its stuck to my tube. My question is will I be a good candidate for the IVF treatment?

reply
Dr. Geoffrey Sher

Indeed! IVF is really your only realistic option. We should talk!

Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Nicole

Hello,

My name is Nicole and I am from Bulgaria. I have struggled 5 miscarriages from which the first one was done by my decission with tablets (June 2016) – stopping the baby development at 7th week and then started bleeding (this was the biggest mistake in my Life for which I believe I am getting what I deserve) . The 2nd MC happened in December 2016 at 5th week, no heartbeat detected and then I just started bleeding, so it was like a late period. We went to our doctor and did some blood tests for Trombofilia. I came up with 4g/4g PAI for which I was told that next pregnancy I should be on aspirin and Clexane (injections). I also got tested for NK cells which were very lightly higher and been told to go on an Intralipid therapy during O and then after positive pregnancy test. I also had higher TSH (3.14) for which I took L-Tirox and successfully got it to 1.90. I also has polycystic ovaries and my period appears every now and then but the first 4 pregnancies happened after stopping the contraception pills. Actually my 4th pregnancy happened after the 2nd cycle after stopping the contraceptions so it was on a natural period.

So the next year – 2017 I got pregnant again for the 3rd time. I was on Intralipid, Aspirin, Clexan, L-Tirox and Folid acid. I went to see a heartbeat at around 6 week, which we saw and have been told that this is a god sign and 90% of the pregnancies come to a happy ending… But I started spotting from around 6th week and despite all the examinations, the doctors could not find what was the reason of the bleeding. And then one day I started bleeding heavily and we ran to the hospital where they told us that the HB has stopped. We did DC and actually tested the embryo for genetic disorders and it came positive with Polyploidy. They said this happens and next time is almost 100% sure that would be a healthy embryo. We decided to karyotype ourselves and see if we have any genetic disorder but our results came out normal. We believed it is a very bad luck and decided to keep going. I got pregnant again and conceived in December 2017 after a natural period. I was following the same therapy like last pregnancy – Clexan, aspirin, fluid acid, Vitamin D(was added due to being on the low range), again Intralipid through my O and then after positive pregnancy test.

Actually the things were almost the same. Started spotting from around 5-6 week and then 8th week we found out the HB has stopped. This time we did embryo genetic analysis again but this time the embryo was perfectly healthy (it was a girl). We were devastated…

We have tested my husbands sperm all this times and they told us that it is perfectly healthy.

Then for the 5th pregnancy we were sent to Istanbul (Memorial Hospital) to do IVF (in vitro fertilization) and do PGD to our embryos. Also they tested me for any hereditary diseases which if me and my husband have – then it`s 50% risk of giving it to our embryo and killing it. We waited 2 months for the results. They did the examination in Spain. (they are doing this examination only in USA and Spain). My results came out normal so our next step was to do the IVF. They also wanted me to be tested for full ANA profile and antiphospholipid syndrome. Everything was fine with the results. AGAIN everything was fine. And they collected 22 eggs from me, 10 of which reached day 5. We frozed them all and do PGD for 3 of them (it is very expensive). 2 came up 6AA quality and 1 with Trizomia. I did hysteroskopy on December 17th because one of my tubes was clogged. Also I have been told that after this kind of surgery it is very easy to get pregnant.

Then I got my Frozen embryo transfer on January 28th. Excellent embryo with 6AA quality on 5th day stage…

So what happened here is that I was on Crinon gel twice a day, folid acid, Estrofem, Vitmin E, Clexane and aspirin every day… I was feeling like all the other pregnancies – no pregancy symptoms but I was very positive because there was no thing that could mess this time. days ago on Feb 14th I misscarried again… All the doctors say nothing. I had perfect ureterus I did histeroskopy in December(this was done in order the embryo to implant better), all was fine…

I was checking my HCG and it was increasing every 30 hours. I was on clexan, aspirin, crinone gel twice a day, vitamin e, estrofem and folid acid.

And out of the sudden on Feb 14th in the middle of the day at work I started having strong pain (just like before period) around lunch time and saw pink blood when I went to the toilet. I ran to my doctor where they saw the yolk sac and said all looks perfect for this week. It was 4 weeks and 6 days – no detachment – perfectly at the place where it should have been.

I went home but the pain didn’t stop and 2 hours later I started bleeding heavy… I ran to the hospital and everything was gone…. There was no embryo, no baby. My body has done its part again and has killed it and thrown away.

We are desperate and we don’t know what to do. We have tested everything possible, we have taken all the measures, we do not drink, we do nt smoke, we are 2 healthy people. I am almost 27, my husband will be 34 and the result is 0 live born babies.

The scariest thing is that we have been speaking to the best doctors for the past 3 years and they remain silent…

I read a lot about prednisone and feel that I do have to try it. I don’t know when to start it actually and what dosage and who to ask…

I will discuss it with my doctors although I know they will 100% disagree…

I look forward to your response, because I am not sure if I have to continue with the IVF. We waited 1 year before the FET and actually got pregnant on the 1st try but the result was the same. Neither here in Bulgaria, nor the doctors in Istanbul could think of a reason for this MC. And they do not know what else to examine me for and to be honest I feel that I have examined anything that is possible.

Kind Regards,

Nicole

reply
Dr. Geoffrey Sher

When it comes to reproduction, humans are the poorest performers of all mammals. In fact we are so inefficient that up to 75% of fertilized eggs do not produce live births, and up to 30% of pregnancies end up being lost within 10 weeks of conception (in the first trimester). RPL is defined as two (2) or more failed pregnancies. Less than 5% of women will experience two (2) consecutive miscarriages, and only 1% experience three or more.
Pregnancy loss can be classified by the stage of pregnancy when the loss occurs:
• Early pregnancy loss (first trimester)
• Late pregnancy loss (after the first trimester)
• Occult “hidden” and not clinically recognized, (chemical) pregnancy loss (occurs prior to ultrasound confirmation of pregnancy)
• Early pregnancy losses usually occur sporadically (are not repetitive).
In more than 70% of cases the loss is due to embryo aneuploidy (where there are more or less than the normal quota of 46 chromosomes). Conversely, repeated losses (RPL), with isolated exceptions where the cause is structural (e.g., unbalanced translocations), are seldom attributable to numerical chromosomal abnormalities (aneuploidy). In fact, the vast majority of cases of RPL are attributable to non-chromosomal causes such as anatomical uterine abnormalities or Immunologic Implantation Dysfunction (IID).
Since most sporadic early pregnancy losses are induced by chromosomal factors and thus are non-repetitive, having had a single miscarriage the likelihood of a second one occurring is no greater than average. However, once having had two losses the chance of a third one occurring is double (35-40%) and after having had three losses the chance of a fourth miscarriage increases to about 60%. The reason for this is that the more miscarriages a woman has, the greater is the likelihood of this being due to a non-chromosomal (repetitive) cause such as IID. It follows that if numerical chromosomal analysis (karyotyping) of embryonic/fetal products derived from a miscarriage tests karyotypically normal, then by a process of elimination, there would be a strong likelihood of a miscarriage repeating in subsequent pregnancies and one would not have to wait for the disaster to recur before taking action. This is precisely why we strongly advocate that all miscarriage specimens be karyotyped.
There is however one caveat to be taken into consideration. That is that the laboratory performing the karyotyping might unwittingly be testing the mother’s cells rather than that of the conceptus. That is why it is not possible to confidently exclude aneuploidy in cases where karyotyping of products suggests a “chromosomally normal” (euploid) female.
Late pregnancy losses (occurring after completion of the 1st trimester/12th week) occur far less frequently (1%) than early pregnancy losses. They are most commonly due to anatomical abnormalities of the uterus and/or cervix. Weakness of the neck of the cervix rendering it able to act as an effective valve that retains the pregnancy (i.e., cervical incompetence) is in fact one of the commonest causes of late pregnancy loss. So also are developmental (congenital) abnormalities of the uterus (e.g., a uterine septum) and uterine fibroid tumors. In some cases intrauterine growth retardation, premature separation of the placenta (placental abruption), premature rupture of the membranes and premature labor can also causes of late pregnancy loss.
Much progress has been made in understanding the mechanisms involved in RPL. There are two broad categories:
1. Problems involving the uterine environment in which a normal embryo is prohibited from properly implanting and developing. Possible causes include:
• Inadequate thickening of the uterine lining
• Irregularity in the contour of the uterine cavity (polyps, fibroid tumors in the uterine wall, intra-uterine scarring and adenomyosis)
• Hormonal imbalances (progesterone deficiency or luteal phase defects). This most commonly results in occult RPL.
• Deficient blood flow to the uterine lining (thin uterine lining).
• Immunologic implantation dysfunction (IID). A major cause of RPL. Plays a role in 75% of cases where chromosomally normal preimplantation embryos fail to implant.
• Interference of blood supply to the developing conceptus can occur due to a hereditary clotting disorder known as Thrombophilia.
2. Genetic and/or structural chromosomal abnormality of the embryo.Genetic abnormalities are rare causes of RPL. Structural chromosomal abnormalities are slightly more common but are also occur infrequently (1%). These are referred to as unbalanced translocation and they result from part of one chromosome detaching and then fusing with another chromosome. Additionally, a number of studies suggest the existence of paternal (sperm derived) effect on human embryo quality and pregnancy outcome that are not reflected as a chromosomal abnormality. Damaged sperm DNA can have a negative impact on fetal development and present clinically as occult or early clinical miscarriage. The Sperm Chromatin Structure Assay (SCSA) which measures the same endpoints are newer and possibly improved methods for evaluating.

IMMUNOLOGIC IMPLANTATION DYSFUNCTION
Autoimmune IID: Here an immunologic reaction is produced by the individual to his/her body’s own cellular components. The most common antibodies that form in such situations are APA and antithyroid antibodies (ATA).
But it is only when specialized immune cells in the uterine lining, known as cytotoxic lymphocytes (CTL) and natural killer (NK) cells, become activated and start to release an excessive/disproportionate amount of TH-1 cytokines that attack the root system of the embryo, that implantation potential is jeopardized. Diagnosis of such activation requires highly specialized blood test for cytokine activity that can only be performed by a handful of reproductive immunology reference laboratories in the United States.
Alloimmune IID, i.e., where antibodies are formed against antigens derived from another member of the same species, is believed to be a relatively common immunologic cause of recurrent pregnancy loss.
Autoimmune IID is often genetically transmitted. Thus it should not be surprising to learn that it is more likely to exist in women who have a family (or personal) history of primary autoimmune diseases such as lupus erythematosus (LE), scleroderma or autoimmune hypothyroidism (Hashimoto’s disease), autoimmune hyperthyroidism (Grave’s disease), rheumatoid arthritis, etc. Reactionary (secondary) autoimmunity can occur in conjunction with any medical condition associated with widespread tissue damage. One such gynecologic condition is endometriosis. Since autoimmune IID is usually associated with activated NK and T-cells from the outset, it usually results in such very early destruction of the embryo’s root system that the patient does not even recognize that she is pregnant. Accordingly the condition usually presents as “unexplained infertility” or “unexplained IVF failure” rather than as a miscarriage.

Alloimmune IID, on the other hand, usually starts off presenting as unexplained miscarriages (often manifesting as RPL). Over time as NK/T cell activation builds and eventually becomes permanently established the patient often goes from RPL to “infertility” due to failed implantation. RPL is more commonly the consequence of alloimmune rather than autoimmune implantation dysfunction.
However, regardless, of whether miscarriage is due to autoimmune or alloimmune implantation dysfunction the final blow to the pregnancy is the result of activated NK cells and CTL in the uterine lining that damage the developing embryo’s “root system” (trophoblast) so that it can no longer sustain the growing conceptus. This having been said, it is important to note that autoimmune IID is readily amenable to reversal through timely, appropriately administered, selective immunotherapy, and alloimmune IID is not. It is much more difficult to treat successfully, even with the use of immunotherapy. In fact, in some cases the only solution will be to revert to selective immunotherapy plus using donor sperm (provided there is no “match” between the donor’s DQa profile and that of the female recipient) or alternatively to resort to gestational surrogacy.
DIAGNOSING THE CAUSE OF RPL
In the past, women who miscarried were not evaluated thoroughly until they had lost several pregnancies in a row. This was because sporadic miscarriages are most commonly the result of embryo numerical chromosomal irregularities (aneuploidy) and thus not treatable. However, a consecutive series of miscarriages points to a repetitive cause that is non-chromosomal and is potentially remediable. Since RPL is most commonly due to a uterine pathology or immunologic causes that are potentially treatable, it follows that early chromosomal evaluation of products of conception could point to a potentially treatable situation. Thus I strongly recommend that such testing be done in most cases of miscarriage. Doing so will avoid a great deal of unnecessary heartache for many patients.
Establishing the correct diagnosis is the first step toward determining effective treatment for couples with RPL. It results from a problem within the pregnancy itself or within the uterine environment where the pregnancy implants and grows. Diagnostic tests useful in identifying individuals at greater risk for a problem within the pregnancy itself include:

• Karyotyping (chromosome analysis) both prospective parents
• Assessment of the karyotype of products of conception derived from previous miscarriage specimens
• Ultrasound examination of the uterine cavity after sterile water is injected or sonohysterogram, fluid ultrasound, etc.)
• Hysterosalpingogram (dye X-ray test)
• Hysteroscopic evaluation of the uterine cavity
• Full hormonal evaluation (estrogen, progesterone, adrenal steroid hormones, thyroid hormones, FSH/LH, etc.)
• Immunologic testing to include:
a) Antiphospholipid antibody (APA) panel
b) Antinuclear antibody (ANA) panel
c) Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies)
d) Reproductive immunophenotype
e) Natural killer cell activity (NKa) assay (i.e., K562 target cell test)
f) Alloimmune testing of both the male and female partners
TREATMENT OF RPL
Treatment for Anatomic Abnormalities of the Uterus: This involves restoration through removal of local lesions such as fibroids, scar tissue, and endometrial polyps or timely insertion of a cervical cerclage (a stitch placed around the neck of the weakened cervix) or the excision of a uterine septum when indicated.
Treatment of Thin Uterine Lining: A thin uterine lining has been shown to correlate with compromised pregnancy outcome. Often this will be associated with reduced blood flow to the endometrium. Such decreased blood flow to the uterus can be improved through treatment with sildenafil and possibly aspirin.
Sildenafil (Viagra) Therapy. Viagra has been used successfully to increase uterine blood flow. However, to be effective it must be administered starting as soon as the period stops up until the day of ovulation and it must be administered vaginally (not orally). Viagra in the form of vaginal suppositories given in the dosage of 25 mg four times a day has been shown to increase uterine blood flow as well as thickness of the uterine lining. To date, we have seen significant improvement of the thickness of the uterine lining in about 70% of women treated. Successful pregnancy resulted in 42% of women who responded to the Viagra. It should be remembered that most of these women had previously experienced repeated IVF failures.

Use of Aspirin: This is an anti-prostaglandin that improves blood flow to the endometrium. It is administered at a dosage of 81 mg orally, daily from the beginning of the cycle until ovulation.
Treating Immunologic Implantation Dysfunction with Selective Immunotherapy: Modalities such as IL/IVIg, heparinoids (Lovenox/Clexane), and corticosteroids (dexamethasone, prednisone, prednisolone) can be used in select cases depending on autoimmune or alloimmune dysfunction.
The Use of IVF in the Treatment of RPL
In the following circumstances, IVF is the preferred option:
1. When in addition to a history of RPL, another standard indication for IVF (e.g., tubal factor, endometriosis, and male factor infertility) is superimposed.
2. In cases where selective immunotherapy is needed to treat an immunologic implantation dysfunction.
The reason for IVF being a preferred approach in such cases is that in order to be effective, the immunotherapy needs to be initiated well before spontaneous or induced ovulation. Given the fact that the anticipated birthrate per cycle of COS with or without IUI is at best about 15%, it follows that short of IVF, to have even a reasonable chance of a live birth, most women with immunologic causes of RPL would need to undergo immunotherapy repeatedly, over consecutive cycles. Conversely, with IVF, the chance of a successful outcome in a single cycle of treatment is several times greater and, because of the attenuated and concentrated time period required for treatment, IVF is far safer and thus represents a more practicable alternative
Since embryo aneuploidy is a common cause of miscarriage, the use of preimplantation genetic diagnosis (PGD), with tests such as CGH, can provide a valuable diagnostic and therapeutic advantage in cases of RPL. PGD requires IVF to provide access to embryos for testing.
There are a few cases of intractable alloimmune dysfunction due to absolute DQ alpha matching where Gestational Surrogacy or use of donor sperm could represent the only viable recourse, other than abandoning treatment altogether and/or resorting to adoption. Other non-immunologic factors such as an intractably thin uterine lining or severe uterine pathology might also warrant that last resort consideration be given to gestational surrogacy.
The good news is that if a couple with RPL is open to all of the diagnostic and treatment options referred to above, a live birthrate of 70%–80% is ultimately achievable.

I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF

____________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Ekta

Dear Dr. Sher, I had a Skype consultation with you and was looking to have another round of retrieval this month. My FSH levels have been always under 5mIU/ml and afc count of 7 each ovary. However, for this cycle, the day 2 FSH level is at 8.9IU/L and the afc count reported is only 3 and 4 in the two ovaries. My last retrieval was in October. Can the results drop this quickly or it could be a variation due to different labs. Also, would you be worried with these levels and suggest to wait for a cycle or these levels are good enough to start the stimulation and expect similar results like last oct?

reply
Dr. Geoffrey Sher

I do not believe that the FSH/ AFC is always accurate. I would go ahead!

Geoff Sher

ADDENDUM

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.

For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Kat V Dall

hi there, I had a 5 day frozen embryo transfer- one healthy, genetically tested embryo. I went in on Thursday the 21st and my levels were at 210 (9 days past transfer), then again today and my levels were at 247. I was told to continue the meds and retest on Monday. From what it appears, it seems that I’m losing the baby. Any thoughts?

reply
Dr. Geoffrey Sher

Repeat the hCG test 2 days after the last one. It should be 500MIU/ml. If not, things would not look so good , I am afraid!

Geoff Sher

reply
Olga

Dear Doctor! We have three embryos that are abnormal (PGS). Any of them would be ok to transfer?
A) 46, XY, -10,+22
B) 47, XX, +22
C) 45, XY, -5

Thank you!!!

reply
Dr. Geoffrey Sher

The 45(-5) monosomy and the 47 (+22) trisomy might be worth considering.

Human embryo development occurs through a process that encompasses reprogramming, sequential cleavage divisions and mitotic chromosome segregation and embryonic genome activation. Chromosomal abnormalities may arise during germ cell and/or preimplantation embryo development and represents a major cause of early pregnancy loss. About a decade ago, I and my associate, Levent Keskintepe PhD were the first to introduce full embryo karyotyping (identification of all 46 chromosomes) through preimplantation genetic sampling (PGS) as a method by which to selectively transfer only euploid embryos (i.e. those that have a full component of chromosomes) to the uterus. We subsequently reported on a 2-3-fold improvement in implantation and birth rates as well as a significant reduction in early pregnancy loss, following IVF. Since then PGS has grown dramatically in popularity such that it is now widely used throughout the world.

Most IVF programs that offer PGS services, require that all participating patients consent to all their aneuploid embryos (i.e. those with an irregular quota of chromosomes) be disposed of. However, there is now growing evidence to suggest that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrection”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases occurring within our IVF network. So clearly, summarily discarding all aneuploid embryos as a matter of routine we are sometimes destroying some embryos that might otherwise have “autocorrected” and gone on to develop into normal offspring.

Thus, by discarding aneuploid embryos the possibility exists that we could be denying some women the opportunity of having a baby. This creates a major ethical and moral dilemma for those of us that provide the option of PGS to our patients. On the one hand, we strive “to avoid knowingly doing harm” (the Hippocratic Oath) and as such would prefer to avoid or minimize the risk of miscarriage and/or chromosomal birth defects and on the other hand we would not wish to deny patients with aneuploid embryos, the opportunity to have a baby.

The basis for such embryo “autocorrection” lies in the fact that some embryos found through PGS-karyotyping to harbor one or more aneuploid cells (blastomeres) will often also harbor chromosomally normal (euploid) cells (blastomeres). The coexistence of both aneuploid and euploid cells coexisting in the same embryo is referred to as “mosaicism.”

It is against this background, that an ever-increasing number of IVF practitioners, rather than summarily discard PGS-identified aneuploid embryos are now choosing to cryobanking (freeze-store) certain of them, to leave open the possibility of ultimately transferring them to the uterus. In order to best understand the complexity of the factors involved in such decision making, it is essential to understand the causes of embryo aneuploidy of which there are two varieties:
1. Meiotic aneuploidy” results from aberrations in chromosomal numerical configuration that originate in either the egg (most commonly) and/or in sperm, during preconceptual maturational division (meiosis). Since meiosis occurs in the pre-fertilized egg or in and sperm, it follows that when aneuploidy occurs due to defective meiosis, all subsequent cells in the developing embryo/blastocyst/conceptus inevitably will be aneuploid, precluding subsequent “autocorrection”. Meiotic aneuploidy will thus invariably be perpetuated in all the cells of the embryo as they replicate. It is a permanent phenomenon and is irreversible. All embryos so affected are thus fatally damaged. Most will fail to implant and those that do implant will either be lost in early pregnancy or develop into chromosomally defective offspring (e.g. Down syndrome, Edward syndrome, Turner syndrome).
2. “Mitotic aneuploidy” occurs when following fertilization and subsequent cell replication (cleavage), some cells (blastomeres) of a meiotically normal (euploid) early embryo mutate and become aneuploid. This is referred to as “mosaicism”. Thereupon, with continued subsequent cell replication (mitosis) the chromosomal make-up (karyotype) of the embryo might either comprise of predominantly aneuploid cells or euploid cells. The subsequent viability or competency of the conceptus will thereupon depend on whether euploid or aneuploid cells predominate. If in such mosaic embryos aneuploid cells predominate, the embryo will be “incompetent”). If (as is frequently the case) euploid cells prevail, the mosaic embryo will likely be “competent” and capable of propagating a normal conceptus.

Since some mitotically aneuploid (“mosaic”) embryos can, and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to reliably differentiate between these two varieties of aneuploidy would potentially be of considerable clinical value. The recent introduction of a variety of preimplantation genetic screening (PGS) known as next generation gene sequencing (NGS) has vastly improved the ability to reliably and accurately karyotype embryos and thus to diagnose embryo “mosaicism”.

The ability of mosaic embryos to autocorrect is influenced by the stage at which the condition is diagnosed as well as the percentage of mosaic cells. Many embryos diagnosed as being mosaic while in the earlier cleaved state of development, subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) during the process of undergoing subsequent mitotic cell to the blastocyst stage. Similarly, mosaic blastocysts can also undergo autocorrection after being transferred to the uterus. The lower the percentage of mosaic cells in the blastocyst the greater the propensity to autocorrect and propagate chromosomally normal (euploid) offspring. By comparison, a blastocyst with 10% mosaicism could yield a 30% healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

Aneuploidy involves the addition (trisomy) or subtraction (monosomy) of one or part of one chromosome in any given pair. As previously stated, some aneuploidies are meiotic in origin while others are mitotic “mosaics”. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve several pairs (i.e. complex aneuploidy). Aside from monosomy involving the absence of the y-sex chromosome (i.e. XO) which can result in a live birth (Turner syndrome) of a compromised baby, virtually all monosomies involving autosomes (non-sex chromosomes) are likely to be lethal and will rarely result in viable offspring. Some autosomal meiotic aneuploidies, especially trisomies 13, 18, 21, can propagate viable and severely chromosomally defective babies. Other meiotic autosomal trisomies will almost invariably, either not attach to the uterine lining or upon attachment, will soon be rejected. All forms of meiotic aneuploidy are irreversible while as stated, mitotic aneuploidy (“mosaicism) can autocorrect, yielding healthy offspring. Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies.

Since certain “mosaic” meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can potentially result in aneuploid concepti. For this reason, it is my opinion that unless the woman/couple receiving such embryos is willing to commit to terminating a resulting pregnancy found through amniocentesis or chorionic villus sampling (CVS) to be so affected, she/they are probably best advised not to transfer have them transferred to the uterus. Embryos harboring other autosomal mosaic trisomic embryos, should they not autocorrect in-utero will hardly ever produce a baby and as such there is hardly any risk at all…in transferring such embryos. However, it is my opinion that in the event of an ongoing pregnancy, amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, when it comes to mosaic autosomal monosomy, given that virtually no autosomal monosomy embryos are likely to propagate viable pregnancies, the transfer of such mosaic embryos is virtually risk free. Needless to say, in any such cases , it is absolutely essential to make full disclosure to the patient (s) , and to insure the completion of a detailed informed consent agreement which would include a commitment by the patient (s) to undergo prenatal genetic testing (amniocentesis/CVS) aimed at excluding a chromosomal defect in the developing baby and/or a willingness to terminate the pregnancy should a serious birth defect be diagnosed.

I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
• A Fresh Look at the Indications for IVF
• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Hereditary Clotting Defects (Thrombophilia)
• Blastocyst Embryo Transfers done 5-6 Days Following Fertilization are Fast Replacing Earlier day 2-3 Transfers of Cleaved Embryos.
• Embryo Transfer Procedure: The “Holy Grail in IVF.
• Timing of ET: Transferring Blastocysts on Day 5-6 Post-Fertilization, Rather Than on Day 2-3 as Cleaved Embryos.
• IVF: Approach to Selecting the Best Embryos for Transfer to the Uterus.
• Fresh versus Frozen Embryo Transfers (FET) Enhance IVF Outcome
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.

Geoff Sher
_______________________________________________________
ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.

For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
KSHAH

Hi Dr. Sher,

I had my pgs normal embryo transfer on sat and had a low grade fever and now getting dry cough. I took tylenol, but fever still comes and goes. In your opinion, does this affect with implantation process or outcome of pregnancy

reply
Melissa Jane

Hi Dr Sher, my husband has 69% binding sperm antibodies. Is it okay to use his frozen sperm (from ejaculation) for ICSI with IVF or isn it best to use fresh with his antibody issues?
Thank you

reply
Dr. Geoffrey Sher

You could use his frozen sperm for ICSI.

Antisperm antibodies (ASA) are immunoglobulins that attach to sperm. They are most commonly encountered in semen, blood, cervical mucous and follicular fluid. Not all ASA bind to sperm. However, those that do so can inhibiting fertilization. Methods used to detect for the presence of SAs in blood, in the seminal plasma of the ejaculate or in the cervical mucus only measure those immunoglobulins that bind to sperm components.
ASAs are related to the stimulation of sperm antigen. Detection of ASA requires access to standard sperm antigens that are associated with fertilization. An ideal sperm antigen should be sperm specific, accessible to the antibody and play a key role in fertilization..

In about 1-4% of infertility cases the presence of antisperm antibodies (ASA) in the male or female appear to be the cause. While the presence of ASA reduces both male and fertility significantly, it does not necessarily always prevent conception altogether. Rather, the effects are graduated; i.e., the larger the immunologic response (concentration of antibodies), the less likely it is that a pregnancy will occur and when the blood level rises above 40%, natural conception is highly unlikely to occur.

Like any other kind of antibody manufactured by the body, sperm antibodies are formed in response to antigens. These antigens are proteins, which appear on the outer sperm membranes as the young sperm cells, develop within the male testes. In the man’s own body, his sperm are regarded as foreign invading proteins and as such would normally be targeted for attack However, under normal conditions, direct contact between the man’s blood and sperm is prevented by a cellular structure in the testes called the blood/testis barrier. This barrier is formed by so-called, Sertoli cells, which abut very closely against each other, forming tight junctions that separate the developing sperm cells from the blood and prevent immunologic stimulation. However, the blood/ testis barrier can be broken by physical or chemical injury or by infection. When this barrier is breached, sperm antigens escape from their immunologically protected environment and come in direct contact with blood elements that launch an immunologic attack.

Once sperm and blood come in contact, whether in the male or female, specific antibodies are produced against them by specialized blood cells call T- and B-lymphocytes. The three main types of sperm antibodies produced are Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin M (IgM). These antibodies bind to the proteins (antigens) on the sperm head, midpiece or tail. The antibodies formed may be of the circulatory type (in the blood serum) or secretory type (in the tissue). This is important because high levels of antibodies in the blood serum do not invariably mean that the antibodies will find their way to the semen where they can affect the sperm. For example, the concentration of IgG is much lower in secretions of the reproductive tract that it is in the blood. Conversely, the local level of IgA is higher in the reproductive secretions than in the blood. This is an important point, which we will return to later.

Once sperm antibodies have formed, they can affect sperm in several different ways. Some antibodies will cause sperm to stick together or agglutinate. Agglutinated sperm clump together in dense masses and thus are unable to migrate through the cervix into the uterus. Other antibodies mark the sperm for attack by Natural killer (NK) cells of the body’s immune system (ie; opsonizing antibodies). Some antibodies cause reactions between the sperm membrane and the cervical mucus preventing the sperm from swimming through the cervix (ie; immobilizing antibodies). Antibodies can also block the sperm’s ability to bind to the zona pellucida of the egg, a prerequisite for fertilization (ie; blocking antibodies). Finally, there is recent evidence that the fertilized egg shares some of the same antigens that are found on the sperm. It is possible that sperm antibodies present in the mother can react with the early embryo, resulting in its destruction by phagocytic (ie; phagocytic antibodies) cells.

In my opinion, ASA tests are best performed on blood. There are a number of diagnostic tests available to detect the presence of sperm antibodies. There are several methods for the diagnosis These tests are performed by flow cytometry and the ELISA (enzyme-linked immunoabsorbent assay), the Franklin-Dukes sperm agglutination assay or the Immunobead Binding Test (IBT).the indirect immunofluorescence (IIF) assay, to name a few. My preference is the IBT.

In the male, IgA and IgG are found in the semen although there is controversy as to whether they originate locally (secreted by testicular cells) or cross over from the circulation. Antibodies of the IgM class are not found in semen.

Like the source of some antibodies, the question of the critical levels of sperm antibodies is also hotly debated among clinicians. There seems to be general agreement that blood levels above 30% by the IBT are associated with significant fertility problems.

Studiers have shown that pregnancy is highly unlikely following natural intercourse or intrauterine insemination when either the woman or the man harbors significant antisperm antibodies.

Attempts have to try and remove antibodies from sperm by allowing the sperm to swim through a column of beads are by and large unsuccessful. And, while there have been isolated reports that administration of corticosteroids (eg; prednisone) will temporarily suppress antibody production pregnancy rates are poor. Besides, corticosteroid therapy carries with it the risk of significant side, some of which (although infrequent) can be serious. As an example, in the man spontaneous fractures (especially of the neck of the femur) have been reported in 2 % of cases. I do not recommend this treatment.

In Vitro Fertilization (IVF) with intracytoplasmic Sperm injection (ICSI) is the best option. Here each egg is injected with a single sperm and whether there are antibodies attached to the outer surface of the sperm becomes irrelevant.. In fact, pregnancy and birth rates are the same as in cases where IVF is performed for reasons other than male factor infertility. IVF/ICSI success rates are also .not unaffected by the concentration of antisperm antibodies.

ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure ; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.

For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Jen

Do you think a mosaic embryo with trisomy 3 has a good chance of self-correcting? It’s my only somewhat viable embryo, as all others came back abnormal after two retrievals.

Is there anything I can do after FET to improve my chances?

reply
Dr. Geoffrey Sher

Yes! It has a chance of being mosaic and auto correcting….and no, there is nothing you could do to augment this process.
Human embryo development occurs through a process that encompasses reprogramming, sequential cleavage divisions and mitotic chromosome segregation and embryonic genome activation. Chromosomal abnormalities may arise during germ cell and/or preimplantation embryo development and represents a major cause of early pregnancy loss. About a decade ago, I and my associate, Levent Keskintepe PhD were the first to introduce full embryo karyotyping (identification of all 46 chromosomes) through preimplantation genetic sampling (PGS) as a method by which to selectively transfer only euploid embryos (i.e. those that have a full component of chromosomes) to the uterus. We subsequently reported on a 2-3-fold improvement in implantation and birth rates as well as a significant reduction in early pregnancy loss, following IVF. Since then PGS has grown dramatically in popularity such that it is now widely used throughout the world.

Most IVF programs that offer PGS services, require that all participating patients consent to all their aneuploid embryos (i.e. those with an irregular quota of chromosomes) be disposed of. However, there is now growing evidence to suggest that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrection”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases occurring within our IVF network. So clearly, summarily discarding all aneuploid embryos as a matter of routine we are sometimes destroying some embryos that might otherwise have “autocorrected” and gone on to develop into normal offspring.

Thus, by discarding aneuploid embryos the possibility exists that we could be denying some women the opportunity of having a baby. This creates a major ethical and moral dilemma for those of us that provide the option of PGS to our patients. On the one hand, we strive “to avoid knowingly doing harm” (the Hippocratic Oath) and as such would prefer to avoid or minimize the risk of miscarriage and/or chromosomal birth defects and on the other hand we would not wish to deny patients with aneuploid embryos, the opportunity to have a baby.

The basis for such embryo “autocorrection” lies in the fact that some embryos found through PGS-karyotyping to harbor one or more aneuploid cells (blastomeres) will often also harbor chromosomally normal (euploid) cells (blastomeres). The coexistence of both aneuploid and euploid cells coexisting in the same embryo is referred to as “mosaicism.”

It is against this background, that an ever-increasing number of IVF practitioners, rather than summarily discard PGS-identified aneuploid embryos are now choosing to cryobanking (freeze-store) certain of them, to leave open the possibility of ultimately transferring them to the uterus. In order to best understand the complexity of the factors involved in such decision making, it is essential to understand the causes of embryo aneuploidy of which there are two varieties:
1. Meiotic aneuploidy” results from aberrations in chromosomal numerical configuration that originate in either the egg (most commonly) and/or in sperm, during preconceptual maturational division (meiosis). Since meiosis occurs in the pre-fertilized egg or in and sperm, it follows that when aneuploidy occurs due to defective meiosis, all subsequent cells in the developing embryo/blastocyst/conceptus inevitably will be aneuploid, precluding subsequent “autocorrection”. Meiotic aneuploidy will thus invariably be perpetuated in all the cells of the embryo as they replicate. It is a permanent phenomenon and is irreversible. All embryos so affected are thus fatally damaged. Most will fail to implant and those that do implant will either be lost in early pregnancy or develop into chromosomally defective offspring (e.g. Down syndrome, Edward syndrome, Turner syndrome).
2. “Mitotic aneuploidy” occurs when following fertilization and subsequent cell replication (cleavage), some cells (blastomeres) of a meiotically normal (euploid) early embryo mutate and become aneuploid. This is referred to as “mosaicism”. Thereupon, with continued subsequent cell replication (mitosis) the chromosomal make-up (karyotype) of the embryo might either comprise of predominantly aneuploid cells or euploid cells. The subsequent viability or competency of the conceptus will thereupon depend on whether euploid or aneuploid cells predominate. If in such mosaic embryos aneuploid cells predominate, the embryo will be “incompetent”). If (as is frequently the case) euploid cells prevail, the mosaic embryo will likely be “competent” and capable of propagating a normal conceptus.

Since some mitotically aneuploid (“mosaic”) embryos can, and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to reliably differentiate between these two varieties of aneuploidy would potentially be of considerable clinical value. The recent introduction of a variety of preimplantation genetic screening (PGS) known as next generation gene sequencing (NGS) has vastly improved the ability to reliably and accurately karyotype embryos and thus to diagnose embryo “mosaicism”.

The ability of mosaic embryos to autocorrect is influenced by the stage at which the condition is diagnosed as well as the percentage of mosaic cells. Many embryos diagnosed as being mosaic while in the earlier cleaved state of development, subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) during the process of undergoing subsequent mitotic cell to the blastocyst stage. Similarly, mosaic blastocysts can also undergo autocorrection after being transferred to the uterus. The lower the percentage of mosaic cells in the blastocyst the greater the propensity to autocorrect and propagate chromosomally normal (euploid) offspring. By comparison, a blastocyst with 10% mosaicism could yield a 30% healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

Aneuploidy involves the addition (trisomy) or subtraction (monosomy) of one or part of one chromosome in any given pair. As previously stated, some aneuploidies are meiotic in origin while others are mitotic “mosaics”. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve several pairs (i.e. complex aneuploidy). Aside from monosomy involving the absence of the y-sex chromosome (i.e. XO) which can result in a live birth (Turner syndrome) of a compromised baby, virtually all monosomies involving autosomes (non-sex chromosomes) are likely to be lethal and will rarely result in viable offspring. Some autosomal meiotic aneuploidies, especially trisomies 13, 18, 21, can propagate viable and severely chromosomally defective babies. Other meiotic autosomal trisomies will almost invariably, either not attach to the uterine lining or upon attachment, will soon be rejected. All forms of meiotic aneuploidy are irreversible while as stated, mitotic aneuploidy (“mosaicism) can autocorrect, yielding healthy offspring. Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies.

Since certain “mosaic” meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can potentially result in aneuploid concepti. For this reason, it is my opinion that unless the woman/couple receiving such embryos is willing to commit to terminating a resulting pregnancy found through amniocentesis or chorionic villus sampling (CVS) to be so affected, she/they are probably best advised not to transfer have them transferred to the uterus. Embryos harboring other autosomal mosaic trisomic embryos, should they not autocorrect in-utero will hardly ever produce a baby and as such there is hardly any risk at all…in transferring such embryos. However, it is my opinion that in the event of an ongoing pregnancy, amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, when it comes to mosaic autosomal monosomy, given that virtually no autosomal monosomy embryos are likely to propagate viable pregnancies, the transfer of such mosaic embryos is virtually risk free. Needless to say, in any such cases , it is absolutely essential to make full disclosure to the patient (s) , and to insure the completion of a detailed informed consent agreement which would include a commitment by the patient (s) to undergo prenatal genetic testing (amniocentesis/CVS) aimed at excluding a chromosomal defect in the developing baby and/or a willingness to terminate the pregnancy should a serious birth defect be diagnosed.

I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
• A Fresh Look at the Indications for IVF
• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Hereditary Clotting Defects (Thrombophilia)
• Blastocyst Embryo Transfers done 5-6 Days Following Fertilization are Fast Replacing Earlier day 2-3 Transfers of Cleaved Embryos.
• Embryo Transfer Procedure: The “Holy Grail in IVF.
• Timing of ET: Transferring Blastocysts on Day 5-6 Post-Fertilization, Rather Than on Day 2-3 as Cleaved Embryos.
• IVF: Approach to Selecting the Best Embryos for Transfer to the Uterus.
• Fresh versus Frozen Embryo Transfers (FET) Enhance IVF Outcome
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.

Geoff Sher
_______________________________________________________
ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.

For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Ali

Dr. Sher,

My history: hypothyroidism, microadenoma(hyperprolactin), MThFR heterozygous, slightly elevated anticardiolpin (IgA only)

I had my first FET in November 2018 with a PGS normal embryo which ended in a chemical pregnancy. I had a hysteroscopy D&C and everything came back normal. For my second FET with a normal PGS embryo I was on a heparin, baby aspirin, and prednisone 10mg (couldn’t tolerate 20mg due to shaking and increased heart rate). I also take Folgard and L- methylfolate, Vitamin d and co q 10 and levothyroxine 75mcg. I was on 1ml PIO and 8mg estradiol daily. Also, I stopped my bromocriptine the day of transfer. I began miscarrying at approximately 5 weeks 3 days. The gestational sac and yolk sac were visible on ultrasound the day I started to miscarry and everything measuring right on time.

I feel like I have done every test. I’ve done HSG, RPL, hysteroscopy. What am I missing? Is there any hope for me? Any suggestions?

Thank you!

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Dr. Geoffrey Sher

Most hypothyroidism in women is due to an autoimmune process. Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.

Couples from throughout the United States of America and from more than 40 different other countries have sought advice and care regarding IVF treatment through consultation with me (or) at SIRM and more recently through Sher-IVF. In fact, currently about 65% of my patient consultations emanate from out-of-state or from abroad. Most such patients tend to be are older, have had repeated pregnancy losses or have complex reproductive issues, having experienced numerous “unexplained” IVF failures. Such patients have been able to access seamless care in a caring and non-stressful environment, under my guidance and supervision. In one case, after experiencing 22 consecutive IVF failures, a couple who journeyed from Melbourne, Australia, had a baby following a single IVF attempt. My approach is to orchestrate and oversee individualize care, targeting those factors that often adversely affect IVF outcome.

INTRODUCING SHER FERTILITY SOLUTIONS (SFS). Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will now take on a new role. In future, rather than having hands-on involvement with IVF procedures I will instead provide fertility consultations (via SKYPE) to many more of the ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance. In this way I will be able to advise, and (in many cases) become involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Patients seeking access me through SFS for a Skype consultation can: go online to http://www.SherIVF.com and enroll there; call 1-800-780-7437 or 702-533-2691; or email SFS at (sher@sherivf.com / concierge@SherIVF.com).
There is a onetime fee of $400.00, which provides enrollees with access to:
• A full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me;
• Additional SKYPE consultations (as might be required);
• A written medical report (which will include a recommended plan of action) that can be shared with a Physician(s) of choice. I would, subject to patient(s)’ approval and a request by such Physician(s), also be willing to discuss your case with him/her/them.
I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for patients who are considering traveling to Las Vegas for their IVF treatment….PATIENTS ENROLLED WITH SFS WHO WISH TO TRAVEL TO LAS VEGAS FOR IVF CAN HAVE ME OVERSEE THEIR TREATMENT AND CAN REST ASSURED THAT THE TEAM AT SIRM-LV ARE COMMITTED TO CONTINUE PROVIDING THE TOP NOTCH CARE THAT MY PATIENTS HAVE GROWN ACCUSTOMED TO!.
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TREATMENT OF SFS PATIENTS BY DR. FOULK AT SIRM-LAS VEGAS:

I have worked closely over the past year with Dr. Russell Foulk, Medical Director of SIRM-LV, who intends to work with me to maintain the high level of excellence I plan to provide. Dr Foulk and I will work together by direct communication and collegial interaction to provide our patients the best in reproductive medicine. I have known Dr Foulk for nearly 25 years and highly recommend him to those patients who, following consultation with me, wish to have me remain involved in the construct of their treatment. Dr Foulk openly states he is somewhat of a protégé of mine having been heavily influenced by my career. This having been said, the final say in any management decision is always up to the treating physician.

Following an initial consultation with me at SFS and a subsequent decision to undergo IVF with Dr Foulk at SIRM-LV, I will help facilitate a full consultation by Skype/Phone with Dr Foulk and forward a full report with my recommended treatment strategy for him to take under advisement. Ultimately however, management decisions are always the sole responsibility of the treating physician.

HOW SIRM-LV PROVIDES OPTIMAL CARE AT A DISTANCE:

a) THE INITIAL CONSULTATION WITH DR. FOULK: Dr Foulk will, upon receipt, carefully review my report and recommendations. Thereupon, following an initial (detailed) consultation (and possibly further testing) he might require additional phone/Skype consultations with him, whereupon he will make a recommendation which would likely include scheduling schedule the patient for a cycle of treatment. It is customary at SIRM-LV to perform IVF treatments in ten to twelve pre-scheduled, 1-2 week cycle batches per year (dependent on whether fresh embryo transfers or frozen embryo transfers (FET) are required). This means that patients will know well in advance of treatment, when they need to be present in Las Vegas for IVF. This also allows for optimal convenience, quality assurance, care and outcome.

b) CONSULTATION WITH AN OFFICE ADMINISTRATOR: Within days of the initial consultation with Dr Foulk, patients will be contacted by the SIRM-LV office to set up a free consultation with an office administrator (who will provide logistic and financial information) who will discuss logistics, cost, time constraints, structure, and processes involved in an IVF cycle at SIRM-LV. At this point, patients will be asked to think matters through and then to make a firm decision/commitment as to whether/when to undergo treatment conducted and overseen by Dr Foulk (with my input-as needed). Thereupon, the patients will be asked to make a financial commitment which is needed to secure a place on the IVF calendar at a designated and mutually agreed upon time.

c) CONSULTATION WITH A NURSE COORDINATOR: A specific Clinical-Nurse Coordinator will be assigned to each patient/couple for their entire experience. She/he will interact with patients and (as needed) with their primary care OB/GYN) to facilitate seamless preparation and testing (where possible) in their home setting. The NC and her team will in effect, hand-hold and triage the patient/couple through all required steps and thereupon will schedule follow-up consultations (as needed). Patients will also be provided with contact information by which to reach the NC at will. The NC will develop and forward (in advance of a scheduled Skype or telephone consultation), a color-coded electronic calendar detailing all treatment and investigative actions needed to take the patient to and through a full cycle of treatment. This approach enables patients to plan their treatment with precision, even months in advance. Almost all testing and preparation can be done in the patient’s home setting. Individualized protocols used to perform IVF during the 1-2 week cycle-batches throughout the year will be discussed Patients will rarely need to spend more than two (2) weeks away from home to complete a full cycle of treatment.

d) FOLLOW-UP CONSULTATION WITH DR. FOULK: Once all records are available, test results are in, and the IVF cycle is scheduled, patients may again consult with Dr. Foulk, if needed, at which time everything will be reviewed in detail and final adjustments will be made. Thereupon additional follow-up consultations may be scheduled on an as-needed basis.

e) INVOLVEMENT OF SFS’: While Dr. Foulk has graciously agreed to take my input into consideration for all SFS-patients referred to him for treatment, it is important to re-emphasize here, that in the final analysis, treatment and management decisions, will be between the patient(s) and the treating physician (i.e. Dr. Foulk). I will however, make myself available for advice, to all SFS-referred patients and will at all times, make myself available to discuss SFS-referred patients, one-on-one with Dr Foulk.

f) ONGOING INTERACTION WITH SIRM-LV: SIRM-LV staff will, at all times, be affable and will make themselves available upon request. They will maintain regular contact with all SFS-referred patients, throughout. However, we are all human, and thus are capable of erring at times. So, if anything is not in keeping with expectations, patients should immediately bring the matter(s) to Dr Foulk’s attention so that any/all issues can be addressed in a timely manner.

g) HOW TO REACH SIRM-LV AND WHERE TO STAY WHILE IN LAS VEGAS: The staff at both SFS and SIRM-LV will gladly assist patients in obtaining suitable and affordable transportation to and accommodations in Las Vegas. Being that Las Vegas is a tourist hub, couples who elect to undergo IVF here, will find accommodation and airfare (especially if scheduled well in advance) to be very reasonably priced and of very high quality. Moreover, we may even be able to assist when it comes to obtaining affordable quality accommodations in close proximity to SIRM-LV.

Please to visit http://www.SherIVF.com. Then go to Dr Sher’s Blog and access the “search bar”. Type in the titles of any/all of the articles listed below,. “Click” and select the one’s of interest.
• A Fresh Look at the Indications for IVF
• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• IVF and the use of Supplementary Human Growth Hormone (HGH) : Is it Worth Trying and who needs it?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• Why did my IVF Fail
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• IVF & Diminished Ovarian Reserve (DOR): A Rational Basis for COS Protocol Selection.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Recurrent Pregnancy Loss (RPL): Why do I keep losing my Pregnancies
• Fresh versus Frozen Embryo Transfers (FET) Enhance IVF Outcome
• Genetically Testing Embryos for IVF
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• IVF: The first Choice for Infertile Women 40 to 43 Years of Age!
• IVF Failure and Implantation Dysfunction:
• Management of Immunologic Implantation Dysfunction (IID).
• Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
• Male Factor Infertility
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
• IVF Egg Donation: A Comprehensive Overview
• Gestational Surrogacy
• Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
• Having Realistic Expectations Regarding IVF Outcome: When is it Time to stop or Change Course?

Geoffrey Sher MD

ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.

For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

reply
Jenny

Dear dr Sher,

I tested positive on Tuesday 12 Feb at 18 days post ovulation.
Went to EPU on 26 dpo (5w4d LMP – Wednesday 20th) after 3 days heavy spotting/light bleeding & cramping & lower back pain. Urine test positive but No sign of pregnancy seen on transvaginal U/s – diagnosis PUL – hcg 550, progesterone 25.
Cramps & bleeding continues with some dark red blood & very tiny clots. 2 days later (today – 28 dpo) hcg is 869, progesterone 20.
From everything I’ve been reading it’s most likely either a miscarriage already happened or waiting to happen or low risk ectopic pregnancy which may ‘resolve’ on its own…. what are the chances of it being a viable pregnancy do you think?
I have another scan on Monday which will be over 6 weeks from LMP.

reply
Dr. Geoffrey Sher

It could be too early. I would do a quantitative blood hCG test and if +ve, I would do another US in 7-10 days.

That will give a definitive answer.

Geoff Sher

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UAAT

Dear Dr. Sher,

In 2015 I became pregnant with a frozen embryo after 4 failed fresh cycles. That embryo is now my 3 & 1/2 year old daughter whom I think I never would have had if it wasn’t for your advice. Thank you so much from the bottom of my heart. I am hoping for another baby now and would love to hear your thoughts.

I have elevated FSH which I think the highest reading was 11.2. When I learned this I was 27 and told I could never have a baby with my own eggs. Later that year I learned that my AMH was awesome and above average, and also my day 3 follicle count was really good, and I could make 5/6 eggs of 50mg of clomid – so the fsh thing didn’t make sense. With a lot of research I found out about reproductive immunology, found out I had endometriosis, high natural killer cells etc. I also found you.

My problem with the first 3 IVF cycles was: premature luteinization and dysmature eggs the first cycle…second cycle I lost all the eggs before retrieval, then the third cycle I had premature luteinization, lost eggs half the eggs before retrieval and dysmature eggs. A complete mess. From what I’ve learned from you, all those issues are caused by too much LH. Following your advice, my 4th cycle I used your agonist/antagonist conversion protocol with a full dose of certrotide starting day one of the cycle. My P4 stayed low the whole cycle as well as my LH. I didn’t get pregnant with the embryos they transferred that cycle, but my daughter was conceived from a dysmature egg from that cycle that they “matured” in the lab and froze as a day 5 embryo. I know pregnancy from dysmature eggs is rare. Between that and the immune issues I know I’m blessed.

I also had to do IVIg before my FET and all through out the pregnancy. Itralipids never lowers my NK cells. For my transfer I was also on 20mg of prednisone, lovenox twice a day, letrozole, clyndamacin, doxycycline… I’m sure you know the immune protocol. It worked…

I am reaching out to you now because I think I may be ovulating dysmature eggs in my regular cycles. I think this because when I was trying to conceive before, I often would get two LH surges on the test sticks, but I would eventually release the egg on cycle day 14ish. I really want to try to get pregnant without ivf. Do you think it’s possible or is it a waste of time? I’m going to be 36 in 6 months and I’m wondering what you would recommend for a protocol in a natural cycle for someone you suspected was indeed releasing dysmature eggs.

Thank you so much for taking the time to read my question.

Bless you

reply
Dr. Geoffrey Sher

First, If you are indeed ovulating on your own, I doubt you are ovulating “dysmature eggs”. It is more likely that in the past this (along with your premature luteinization” was due to a suboptimal protocol for ovarian stimulation. It is more likely that your underlying immunologic implantation issue still persists and this would likely require treatment with IL or IVIG. The fact that IL failed to loere NKa in the lab does NOT mean that it is ineffective for you. This is a misconception.

You need to consider doing IVF again. More importantly, perhaps we should talk.

Geoff Sher

reply
UAAT

Really sorry to bother you again. I booked a consultation with you and asked your Vegas office to give me a list of doctors that you would possibly Co-manage me with if I were to do ivf again. I think Co-managing is a service you offer now that you’re retired right?

My question is: What does it mean when someone is getting two LH surges, several days apart? This cycle, for the first time in 4 years, I’ve started started tracking ovulation again with the urine tests. I have very sensitive ovaries… I can feel activity/pinching/aching in my ovary around the time of ovulation. Ive been like this for most of my adult life. As usual, around cycle day 10 (28 day cycles) I got the aching, and then cycle day 12 the OPK was flaming positive. I tested the next two days just to see that the LH was undetectable and the tests were negative . Today, 5 days after the original positive, I felt the aching again and took another OPK. This was the clear blue digital, and the same box as the other tests. It was positive.

As stated in my first question, this has happened before. Not a lot, but it’s not unheard of with me. Once in the past, with the second OPK a little blood came out. That’s only happened once though.

Anyways I have had my ovulation tracked via blood tests and ultrasound when I first started the infertility testing in 2012. There were collapsed follicles on the ultrasound. I know every cycle
Is different but in the past, I was ovulating and the P4 was high after the LH surge, so I think the eggs were being released.

What do you think is going on? Am I not releasing the egg the first LH surge, then getting another surge to release it again? Is this ruining the eggs I release naturally? I’m just so confused. Could I please have your opinion?

Kind regards

Dr. Geoffrey Sher

In my opinion there is no such thing as 2 surges. You might have 1st tested the urine when you were somewhat dehydrated (perhaps early morning, giving you a n+ve. Then again 2 days later as part of the same (perhaps somewhat prolonged ) surge. Bleeding at the time of ovulation is not uncommon and has no significance.

Please call 800-780-7437 on Tuesday and talk or leave a message for Patti Converse (“concierge”. She will set you up with a consultation with me through SFS (see below). We are in the process of me transitioning to SFS at the present time.

___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

PLEASE HELP SPREAD THE WORD ABOUT SFS!

Geoff Sher

Qwendaline

Goodmorning Dr.Sher,
My question is concerning my embryo result.
I was told an abnormal monosomy 12 ( missing 1 of the pair off chromosome 12).
I am just wondering how often this type of abnormality becomes a real pregnancy? Or is it very rare to become a pregnancy?
Also if I transfer can it implant for a few weeks & miscarry or will I just get a négative pregnancy test after day 11
transfer. ?
I have had 4 cycles & 3 cancelled, I had good pre test last year 8 folicles prior to starting &AMH 3.8. Embryos roughly 4/5 each Egg collection but deteriorate day 4/5-6. So far this is the only embryo that has made NGS
testing. I changed my protocol myself to EPP as i had been given same standard menopur protocol last few cycles & finally got one to test with EPP. I have turned 44 yrs & realise in all my commitment that I was not advised to do transfer with day 3 before all my embryos died. I feel maybe PGD is what I should of been advised to do & all my effort has been in vain & have lost 1.5 yrs !What is your opinion? On all the above questions? & what is youre advice for me from here is there anything you can suggest to get me better results?
Many thanks

reply
Dr. Geoffrey Sher

I am sure you are aware of the fact that after the mid-30’s, egg competency (primarily chromosomal integrity) declines with advancing age. At 44y, probably less than 7% of a woman’s eggs are numerically, chromosomally normal. While eggs that are autosomally monosomic are the one’s that are most likely to be “mosaic”, the likelihood of monosomy also declines with advancing age. It is hard to say what the chance of “mosaicism would be in the case of your -12, monosomic embryo would be but my educated guess at 44y is that it is south of 20%. If it were to be mosaic, the best case scenario would be a pregnancy potential of 30-405 which means that going in to an ET, the overall best chance of a baby would be 30% of 25-30%…i.e…<10%.

In my opinion, at 44y, the only rational strategy would be to do egg donation-IVF. However, if that is not acceptable to you, then please consider the following:

The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically "incompetent" (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.

While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.

I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy

Please visit my new Blog on this very site, www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly

• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
• Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• IVF Egg Donation: A Comprehensive Overview

ADDENDUM:
Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
betty

Hi, i was diagnosed with low ovarian reserve and thin linings (5mm). Is thre any hope to improve lining?

reply
Dr. Geoffrey Sher

Women who (regardless of age) have diminished ovarian reserve (DOR) have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This in turn can have a deleterious effect on egg/embryo “competency”.

While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.

I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy

Please visit my new Blog on this very site, www. SherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly

• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
• Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• IVF Egg Donation: A Comprehensive Overview
______________________________________________________
ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Emily

I did one cycle of IVF that resulted in only 2 Day 5 embryos, one of which is completely abnormal and the other is a low level mosaic +22. We are planning to do a second retrieval to see if we can get more embryos (for multiple children/back ups) but are debating about transferring this mosaic +22 5 days after my retrieval or waiting to see if the next retrieval results in any “normal” embryos. For what it’s worth my AMH is 1.84 and my RE is switching me to a micro-dose Lupron protocol for this coming cycle. What do you recommend? Thank you for taking the time to read this!

reply
Dr. Geoffrey Sher

Very respectfully, I am not a fan of “flare protocols”. In some cases (especially in older women and those with diminished ovarian reserve), it is my opinion that it can only make matters worse. I am of the same opinion when it comes to the use of DHEA.

The potential for a woman’s eggs to undergo orderly development and maturation, while in large part being genetically determined can be profoundly influenced by the woman’s age, her “ovarian reserve” and proximity to menopause. It is also influenced by the protocol used for controlled ovarian stimulation (COH) which by fashioning the intra-ovarian hormonal environment, profoundly impacts egg development and maturation.

After the menarche (age at which menstruation starts) a monthly process of repeatedly processing eggs continues until the menopause, by which time most eggs will have been used up, and ovulation and menstruation cease. When the number of eggs remaining in the ovaries falls below a certain threshold, ovarian function starts to wane over a 5 to10-years. This time period is referred to as the climacteric. With the onset of the climacteric, blood Follicle Stimulating Hormone (FSH) and later also Luteinizing Hormone (LH) levels begin to rise…. at first slowly and then more rapidly, ultimately culminating in the complete cessation of ovulation and menstruation (i.e. menopause).

One of the early indications that the woman has entered the climacteric and that ovarian reserve is diminishing DOR) , is the detection of a basal blood FSH level above 9.0 MIU/ml and/ or an AMH level og <2.0ng/ml.

Prior to the changes that immediately precede ovulation, virtually all human eggs have 23 pairs (i.e. 46) of chromosomes. Thirty six to forty hours prior to ovulation, a surge occurs in the release of LH by the pituitary gland. One of the main e purposes of this LH surge is to cause the chromosomes in the egg to divide n half (to 23 in number) in order that once fertilized by a mature sperm ends up having 23 chromosomes) the resulting embryo will be back to having 46 chromosomes. A “competent” mature egg is one that has precisely 23 chromosomes, not any more or any less. It is largely the egg, rather than the sperm that determines the chromosomal integrity of the embryo and only an embryo that has a normal component of 46 chromosomes (i.e. euploid) is “competent” to develop into a healthy baby. If for any reason the final number of chromosomes in the egg is less or more than 23 (aneuploid), it will be incapable of propagating a euploid, “competent” embryo. Thus egg/embryo aneuploidy (“incompetence”) is the leading cause of human reproductive dysfunction which can manifest as: arrested embryo development and/or failed implantation (which often presents as infertility), early miscarriage or chromosomal birth defects (e.g. Down’s syndrome). While most aneuploid (“incompetent”) embryos often fail to produce a pregnancy, some do. However, most such pregnancies miscarry early on. On relatively rare occasions, depending on the chromosome pair involved, aneuploid embryos can develop into chromosomally defective babies (e.g. Down’s syndrome).

Up until a woman reaches her mid- thirties, at best, 1:2 of her eggs will likely be chromosomally normal. As she ages beyond her mid-thirties there will be a a progressive decline in egg quality such that by age 40 years only about 15%-20% of eggs are euploid and, by the time the woman reaches her mid-forties, less than 10% of her eggs are likely to be chromosomally normal. While most aneuploid embryos do appear to be microscopically abnormal under the light microscope, this is not invariably so. In fact, many aneuploid embryos a have a perfectly normal appearance under the microscope. This is why it is not possible to reliably differentiate between competent and incompetent embryos on the basis of their microscopic appearance (morphologic grade) alone.

The process of natural selection usually precludes most aneuploid embryos from attaching to the uterine lining. Those that do attach usually do so for such only a brief period of time. In such cases the woman often will not even experience a postponement of menstruation. There will be a transient rise in blood hCG levels but in most cases the woman will be unaware of even having conceived (i.e. a “chemical pregnancy”). Alternatively, an aneuploid embryo might attach for a period of a few weeks before being expelled (i.e. a “miscarriage”). Sometimes (fortunately rarely) an aneuploid embryo will develop into a viable baby that is born with a chromosomal birth defect (e.g. Down’s syndrome).
The fact that the incidence of embryo aneuploidy invariably increases with advancing age serves to explain why reproductive failure (“infertility”, miscarriages and birth defects), also increases as women get older.

It is an over-simplification to represent that diminishing ovarian reserve as evidenced by raised FSH blood levels (and other tests) and reduced response to stimulation with fertility drugs is a direct cause of “poor egg/ embryo quality”. This common misconception stems from the fact that poor embryo quality (“incompetence”) often occurs in women who at the same time, because of the advent of the climacteric also have elevated basal blood FSH/LH levels and reduced AMH. But it is not the elevation in FSH or the low AMH that causes embryo “incompetence”. Rather it is the effect of advancing age (the “biological clock”) resulting a progressive increase in the incidence of egg aneuploidy, which is responsible for declining egg quality. Simply stated, as women get older “wear and tear” on their eggs increases the likelihood of egg and thus embryo aneuploidy. It just so happens that the two precipitating factors often go hand in hand.

The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by those IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome in patients at risk – particularly those with diminished ovarian reserve (“poor responders”) and those who are “high responders” (women with PCOS , those with dysfunctional or absent ovulation, and young women under 25 years of age).

While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.

During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) that are produced by the ovarian stroma (the tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (cells that line the inner walls of follicles), and egg maturation.

However, over-production of testosterone can adversely influence the same processes. It follows that protocols for controlled ovarian stimulation (COS should be geared toward optimizing follicle growth and development (without placing the woman at risk from overstimulation), while at the same time avoiding excessive ovarian androgen production. Achievement of such objectives requires a very individualized approach to choosing the protocol for COS with fertility drugs as well as the precise timing of the “trigger shot” of hCG.

It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed towards the cells lining the inside of the follicle that are responsible for estrogen production. LH, on the other hand, acts primarily on the ovarian stroma to produce male hormones/ androgens (e.g. androstenedione and testosterone). A small amount of testosterone is necessary for optimal estrogen production. Over-production of such androgens can have a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.

In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often a feature of this condition. The use of LH-containing preparations such as Menopur further aggravates this effect. Thus we recommend using FSH-dominant products such as Follistim, Puregon, and Gonal-F in such cases. While it would seem prudent to limit LH exposure in all cases of COS, this appears to be more vital in older women, who tend to be more sensitive to LH

It is common practice to administer gonadotropin releasing hormone agonists (GnRHa) agonists such as Lupron, and, GnRH-antagonists such as Ganirelix and Orgalutron to prevent the release of LH during COS. GnRH agonists exert their LH-lowering effect over a number of days. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in the LH level falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. GnRH Antagonists, on the other hand, act very rapidly (within a few hours) to block pituitary LH release, so as achieve the same effect.

Long Agonist (Lupron/Buserelin) Protocols: The most commonly prescribed protocol for Lupron/gonadotropin administration is the so-called “long protocol”. Here, Lupron is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to near zero. It is followed by uterine withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the long protocol which I prefer using in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a Lupron-induced bleed , this agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I supplement with human growth hormone (HGH) to try and further enhance response and egg development.

Lupron Flare/Micro-Flare Protocol: Another approach to COS is by way of so-called “(micro) flare protocols”. This involves initiating gonadotropin therapy simultaneous with the administration of GnRH agonist (e.g. Lupron/Buserelin). The intent here is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” represents “a double edged sword” because while it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal androgen production which could potentially compromise egg quality, especially in older women and women with PCOS, whose ovaries have increased sensitivity to LH. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe them at all.

Estrogen Priming – My approach for “Poor Responders” Our patients who have demonstrated reduced ovarian response to COS as well as those who by way of significantly raised FSH blood levels are likely to be “poor responders”, are treated using a “modified” long protocol. The approach involves the initial administration of GnRH agonist for a number of days to cause pituitary down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered and the woman is given twice-weekly injections of estradiol for a period of 8. COS is thereupon initiated using a relatively high dosage of FSH-(Follistim, Bravelle, Puregon or Gonal F) which is continued along with daily administration of GnRH agonist until the “hCG trigger.” By this approach we have been able to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients”.

The “Trigger”: hCG (Profasi/Pregnyl/Novarel) versus Lupron: With ovulation induction using fertility drugs, the administration of 10,000U hCGu (the hCG “trigger”) mimics the LH surge, sending the eggs (which up to that point are immature (M1) and have 46 chromosomes) into maturational division (meiosis) This process is designed to halve the chromosome number , resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes it had prior to the “trigger”. Such a chromosomally normal, M2 egg, upon being fertilized by mature sperm (that following maturational division also has 23 chromosomes) will hopefully propagate embryos that have 46 chromosomes and will be “:competent” to propagate viable pregnancies. The key is to trigger with no less than 10,000U of hCGu (Profasi/Novarel/Pregnyl) and if hCGr (Ovidrel) is used, to make sure that 500mcg (rather than 250mcg) is administered. In my opinion, any lesser dosage will reduce the efficiency of meiosis, and increase the risk of the eggs being chromosomally abnormal. . I also do not use the agonist (Lupron) “trigger”. This approach which is often recommended for women at risk of overstimulation, is intended to reduce the risk of OHSS. The reason for using the Lupron trigger is that by inducing a surge in the release of LH by the pituitary gland it reduces the risk of OHSS. This is true, but this comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the percentage of chromosomally abnormal and of immature (M1) eggs. The use of “coasting” in such cases) can obviate this effect

.I strongly recommend that you visit www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
• Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.
_________________________________________________________

ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Misha

Please help. My cycle has been canceled 3 times due to poor lining of 4.8-5. We transferred in January on a 5 but the transfer failed. We just tried a cycle of vaginal viagra 100mg 4x perday, vaginal estrace 2 times per day and 3 patches 100mg each. My lining got to a 5 and then my last scan it was 4.8. What do you suggest? We have 5 frozen embryos left.

reply
Dr. Geoffrey Sher

This might be an intractable lining issue leaving Gestational surrogacy as the only option.

Sorry!

Geoff Sher

reply
Kalvin

Hi There. I am 42 year old with 4 failed cycles, two with my own eggs and two with donor eggs. My issue is implantation, out of all these 4 failed cycles none of the embryos implanted. In one cycle doctor even put the PGS tested embryo but that also failed. I have done all the tests available like Yale biopsy, receptivity test, NK cells test. All test results came fine. My uterine lining is also great like 10mm-11mm everytime.Can you please advise what should I do different so that my embryo can implant. I am also considering using Embryo glue but not sure if that would change anything. Kindly advise.

reply
Dr. Geoffrey Sher

Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.

It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:

1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.

We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).

3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.

4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:

a. A“ thin uterine lining”
b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c. Immunologic implantation dysfunction (IID)
d. Endocrine/molecular endometrial receptivity issues
e. Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.

Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF?

Geoff Sher

ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Martina

Dear Mr Sher,
I am almost 37 and 4 months ago I discovered I have low AMH, around 0.9ng/ml. I never tried to conceive and currently do not have a partner. I do not want to miss any chance of having a baby and although I know it is already too late I want to do whatever I can do to improve my chances.
1. Does my AMH show that I am near menopause?
2. I was taking yasmin contraceptives for 6weeks to change my cycle and would start stimulation some days ago but another doctor told me that it will be difficult to retrieve eggs after first withdrawal, that my ovaries are very small and I cancelled it. Is it true? I would get two injections of daronda for the 1st and 2nd day of cycle and then stimulation. Now I will start in 1.5 months again. Do you think I did the right thing?
3. Do you have any suggestions for me? I saw that you do not recommend egg freezing after 35y

reply
Dr. Geoffrey Sher

1. Does my AMH show that I am near menopause?

AQ: You certainly have diminishing ovarian reserve (see below)

2. I was taking yasmin contraceptives for 6weeks to change my cycle and would start stimulation some days ago but another doctor told me that it will be difficult to retrieve eggs after first withdrawal, that my ovaries are very small and I cancelled it. Is it true?

A: Not necessarily so

Women who (regardless of age) have diminished ovarian reserve (DOR) have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production, and/or biological activity, of LH. This can result in excessive ovarian male hormone (predominantly testosterone) production. This in turn can have a deleterious effect on egg/embryo “competency”.

While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.

I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy

Please visit my new Blog on this very site, www. SherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly

• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
• Preimplantation Genetic Testing (PGS) in IVF: It Should be Used Selectively and NOT be Routine.
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• IVF Egg Donation: A Comprehensive Overview
______________________________________________________
ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

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Heather

You’ve said before that you don’t believe in the ERA test. Could you explain your thoughts on ERA and why you are not a fan?
Thanks!

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Dr. Geoffrey Sher

With ERA you are attempting to evaluate endometrial receptivity in one cycle and using this to predict receptivity in another. I know of no convincing evidence that this premise holds true.

Geoff Sher

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Monica

Hello and thanks for this question board!
I am 37 (so is my husband). He has CABVD so we have to do IVF. Neither of us have had pregnancies before. My BMI is 25 and due to changes in cycles and a history of intermittent ovarian cysts I have been evaluated for PCOS many times since I was a teen. I was always told “maybe borderline”. For the last year my periods were regular, q33-37 days with predictable positive OPKs. My fsh/oh wasn’t impressive, normal testosterone and high end of normal estrogen. I do not have any androgen-excess symptoms. I do have a fmhx of DM2 however. My AMH is 9.24 which seems to point to PCOS. I just finished my first IVF which unfortunately was not successful. I was on 3 weeks of OCPs then started 225 of Follistim with 75u of Menopur at night. I also was on Femara 5mg in AM b/c I have migraines with auras and trying to prevent super high estrogen levels related to that. About Day 7 I added Ganirelix in Am and increased FSH to 300. I was told I had 24 follicles that were growing at that time the largest being 12mm. I also had one pre-cycle cyst about 2cm prior as well.
I keep on this until day 11 when I triggered with HCG and Lupron. I was never told what my estrogen levels were. Retrieval day 13-had 27 eggs, 25 mature, 18 fertilized with ICSI (his thawed sperm from PESA). I was told 7 days later none of them made it. The clinic does not do updates in between those days and I was not told what day they arrested on. I was bloated but did not have OHSS.

My questions are related to my (suspected) poor egg quality and my (suspected) PCOS. What protocol changes would you recommend to potentially improve egg quality (quality over quantity) Regarding egg quality I started CoQ10 and am trying to work on weight and sugar. I am continuing a low carb diet however should I ask about metformin? (I have very mild IR with A1C around 5.5 and occasional FBS of low 100s. )

Thank you in advance for your help!

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Dr. Geoffrey Sher

Polycystic ovary syndrome (PCOS) is a common hormonal system disorder among women affecting between 5% and 10% of women of reproductive age worldwide. Women with PCOS may have enlarged ovaries that contain small collections of fluid — called follicles — located in each ovary as seen during an ultrasound. The condition is characterized by abnormal ovarian function (irregular or absent periods, abnormal or absent ovulation and infertility), androgenicity (increased body hair or hirsutism, acne) and increased body weight –body mass index or BMI. The ovaries of women with PCOS characteristically contain multiple micro-cysts often arranged like a “string of pearls” immediately below the ovarian surface (capsule).interspersed by an overgrowth of ovarian connective tissue (stroma).

PCOS is one of the most common causes of menstrual irregularities, infertility, and hirsutism, Despite an enormous effort to define its cause, the etiology of PCOS remains unclear, and there is no definite cure at this time. PCOS is clearly a heterogeneous disorder which often has a familial (genetic) basis. Infertility associated with PCOS has been attributed to numerous factors, including dysfunctional gonadotropin pituitary secretion, peripheral insulin resistance, elevated adrenal and/or ovarian androgen (male hormone) levels, and dysfunction of several growth factors. Women with this condition are often obese and insulin resistant. The compensatory hyperinsulinemia further stimulates ovarian androgen production which may be detrimental to egg maturation and there is a clear link between the degree of insulin resistance and anovulation. PCOS is also a significant long-term health risk for women, thus necessitating vigilance through regular annual examinations (non-insulin dependent diabetes mellitus, hypertension, hypercholesterolemia, cardiovascular disease and endometrial cancer). Whereas PCOS-related infertility is usually manageable through the use of fertility drugs, lifestyle changes (diet and exercise) remain a mainstay of long-term therapy. More recently, ovulation rates, circulating androgens, pregnancy rates and perhaps even first-trimester miscarriage rates have been shown to improve when insulin sensitizers like metformin are used to correct the underlying insulin resistance.

Most patients with PCOS are young and have excellent pregnancy rates with oral clomiphene. Those that require more aggressive treatments with injectable medications probably represent a subgroup of PCOS patients with severe ovarian dysfunction. These women often have explosive response to gonadotropins which can result in serious complications like Severe Ovarian Hyperstimulation Syndrome (OHSS…see below) and high order multiple births. In those women, the ability to perform “prolonged coasting” (see below) and selectively transfer fewer embryos during IVF offers a clear advantage over standard gonadotropin injections.

Egg quality in PCOS

The potential for a woman’s eggs to undergo orderly maturation, successful fertilization and subsequent progression to “good quality embryos” is in large part genetically determined. However, the expression of such potential is profoundly susceptible to numerous influences, especially intra-ovarian hormonal changes during the pre-ovulatory phase of the cycle. Proper follicular stimulation as well as precise timing of egg maturation with LH (Luteinizing Hormone) or hCG (human chorionic gonadotropin) is crucial to optimal egg maturation, fertilization and ultimately embryo quality. Both pituitary gonadotropins, LH and FSH (follicle stimulating hormone) play a pivotal but different role in follicular development. The action of FSH is mainly directed toward granulosa cell (cells lining the inside of the follicle) proliferation and estrogen production (E2). LH, on the other hand, acts primarily on the ovarian stroma (the connective tissue that surrounds the follicle) to produce androgens. While small amounts of ovarian androgens, such as testosterone, enhance egg and follicle development, over-exposure to them can have a deleterious effect. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.

Suppressing pituitary secretion of LH with gonadotropin releasing hormone (GnRH) agonists such as Lupron®, is particularly useful in PCOS. In that condition, serum LH levels are elevated, leading to stromal overgrowth, follicular arrests (so-called cysts) and high levels of androgens synthesis. It is therefore not surprising that these follicles often yield poorly developed (“immature”) eggs” at the time of egg retrieval (ET) and that “poor egg/embryo quality”, inadequate endometrial development and high miscarriage rates are common features of this condition. However, contrary to popular belief, this is not due to an intrinsic deficit in “egg quality”. Stimulation protocols geared toward optimizing follicle and egg development and avoiding over exposure to androgens correct these problems ad result in pregnancy rates similar to those of non-PCOS women. Whereas the overuse of LH-containing preparations such as Menopur® and Luveris® further aggravates this effect. In conclusion, to maximize ultimate oocyte maturation, we strongly recommend against the exclusive use of such products in PCOS patients, preferring FSH-dominant products such as Folistim®, Gonal F® or Bravelle® over a period of at least 9 days following pituitary suppression with Lupron®.

PCOS women often have a family history of diabetes and demonstrable insulin resistance (evidenced by high blood insulin levels and an abnormal 2-hour glucose tolerance test).This underlying Diabetes mellitus tendency could play a role in the development of PCOS and contribute to the development of obesity, an abnormal blood lipid profile, and a predisposition to coronary vascular disease. Women with PCOS are slightly more at risk of developing uterine, ovarian and possibly also breast cancer in later life and accordingly should be evaluated for these conditions on a more frequent basis than would ordinarily be recommended to non-PCOS women.

Most women with PCOS either do not ovulate at all or they ovulate irregularly. As a consequence thereof they in addition usually experience delayed, absent or irregular menstruation. In addition, an inordinate percentage of the eggs produced by PCOS women following ovulation induction, tend to be chromosomally abnormal (aneuploid). Rather than being due to an intrinsic egg defect being inherent in PCOS women, the poor egg quality more than likely the result of over-exposure to male hormones (predominantly, testosterone) produced by the ovarian stroma. These two factors (ovulation dysfunction and poor egg quality) are the main reasons for the poor reproductive performance (infertility and an increased miscarriage rate) in PCOS women.

PCOS patients are at an inordinate risk of severely over-responding fertility drugs, both oral varieties (e.g. Clomiphene, Serophene & Femara) and especially the injectables (e.g. Follistim, Puregon, Gonal F, Menopur and Bravelle) by forming large numbers ovarian follicles. This can lead to life endangering complications associated with sever ovarian hyperstimulation (OHSS). In addition PCOS women receiving fertility drugs often experience multiple ovulations putting them at severe risk (40%+) of high order multiple pregnancy (i.e. triplets or greater) with often devastating consequences.

VARIETIES OF POLYCYSTIC OVARIAN SYNDROME:

1) Hypothalamic-pituitary-PCOS: This is the commonest form of PCOS and is often genetically transmitted and is characteristically associated with a blood concentration of Luteinizing Hormone (LH) that is uncharacteristically much higher than the Follicle Stimulating Hormone (FSH) level (FSH is normally higher than the LH concentration) as well as high-normal or blood androgen ( male) hormone concentrations (e.g. androstenedione, testosterone and dehydroepiandrosterone -DHEA).Hypothalamic-pituitary-ovarian PCOS is also often associated with insulin resistance and in about 40%-50% of the cases.

2) Adrenal PCOS: Here the excess of male hormones are derived from overactive adrenal glands rather than from the ovaries. Blood levels of testosterone and/or androstenedione raised but here, but here, the blood level of dehydroepiandrosterone (DHEAS) is also raised, clinching the diagnosis.

3) Severe pelvic adhesive disease secondary to severe endometriosis, chronic pelvic inflammatory disease and/or extensive pelvic surgery: Women who have this type of PCOS tend to less likely to hyperstimulate in response to ovulation induction . Their. DHEAS is also is not raised.

TREATMENT OF INFERTILITY DUE TO ASSOCIATED OVULATION DYSFUNCTION:

Hypothalamic-pituitary-/ovarian PCOS: Ovulation induction with fertility drugs such as clomiphene citrate, Letrozole (Femara) or gonadotropins, with or without intrauterine insemination (IUI) is often highly successful in establishing pregnancies in PCOS women. However, IVF is fast becoming a treatment of choice (see below).

In about 40% of cases, 3-6 months of oral Metformin (Glucophage) treatment results in a significant reduction of insulin resistance, lowering of blood androgen levels, an improvement in ovulatory function, and/or some amelioration of androgenous symptoms and signs.

Surgical treatment by “ovarian drilling” of the many small ovarian cysts lying immediately below the envelopment (capsule) of the ovaries, is often used, but is less successful than alternative non-surgical treatment and is only temporarily effective. The older form of surgical treatment, using ovarian wedge resection is rarely used any longer as it can produce severe pelvic adhesion formation.

Adrenal PCOS is treated with steroids such as prednisone or dexamethasone which over a period of several weeks will suppress adrenal androgen production, allowing regular ovulation to take place spontaneously. This is often combined with clomiphene, Letrozole and/or gonadotropin therapy to initiate ovulation.

PCOS attributable to Pelvic Adhesive Disease is one variety which often is associated with compromised ovarian reserve, a raised FSH blood level and ovarian resistance to fertility drugs. In many such cases, high dosage of gonadotropins (FSH-dominant) with “estrogen priming” will often elicit an ovarian response necessary for successful ovulation induction and/or IVF. Neither steroids nor Metformin are helpful in the vast majority of such cases.

PCOS women undergoing ovulation induction usually release multiple eggs following the hCG trigger and are thus at inordinate risk of twin or higher order multiple pregnancies. They are also at risk of developing OHSS. Many now believe that IVF should be regarded as a primary and preferential treatment for PCOS. The reason is that it is only through this approach that the number of embryos reaching the uterus can be controlled and in this manner the risk of high-order multiples can be minimized and it is only in the course of IVF treatment that a novel treatment method known as “prolonged coasting” ( see below) which prevents OHSS, can be implemented

SEVERE OVARIAN HYPERSTIMULATION SYNDROME (OHSS):

As indicated above, there is an inordinate propensity for women with PCOS to hyper-respond to gonadotropin fertility drugs and in the process produce large numbers of ovarian follicles. If left unchecked this can lead to OHSS, a potentially life endangering condition. The onset of OHSS is signaled by the development of a large number of ovarian follicles (usually more than 25 in number). This is accompanied by rapidly rising plasma estradiol (E2) levels, often exceeding 3000pg/ml within 7 or 9 days of stimulation, often rapidly peaking above 6,000 pg/ml prior to hCG administration. When this happens, the risk of OHSS developing is above 80%.

Symptoms and signs of OHSS include: abdominal distention due to fluid collection (ascites), fluid in the chest cavity (hydrothorax), rapid weight gain (of a pound or more per day) due to tissue fluid retention, abdominal pain, lower back ache, nausea, diarrhea, vomiting, visual disturbances such as blurred vision and spots in front of the eyes (scotomata), a rapidly declining urine output, cardiovascular collapse and failure of blood to clot which sometimes results in severe bruising (echymosis) and frank bleeding. These symptoms and signs may appear before pregnancy can be diagnosed. If pregnancy occurs, the condition is likely to worsen progressively over a period of 3-5 weeks whereupon it rapidly resolves spontaneously over a few days. If no pregnancy occurs, the symptoms and signs all disappear spontaneously within 10-12 days of the hCG injection.

When increasing fluid collection in the abdominal cavity (ascites) starts to compromise breathing raising the head of the bed rose slightly by placing a 4-6 inch block at the base of each head post and using a few additional pillows, will sometimes help ameliorate the problem. In cases where this does not help or symptoms become severe, all or most of the fluid can readily and safely be drained through t transvaginal sterile needle aspiration (vaginal paracentesis-performed once or sometimes twice a week) can be performed once or twice weekly . The problem will usually self corrects within 10-12 days of the hCG shot if pregnancy does not occur or, by the 8th week of pregnancy.

Urine output should be monitored daily to see if it drops below about 500ml a day (about two cups and a half). A chest X-ray, to evaluate for fluid collection in the chest and around the heart should be done weekly along with blood tests for hematocrit, BUN, electrolytes, creatinine, platelet count and fibrin split products (FSP). If indicated on the basis of a deteriorating clinical situation, hospitalization might be needed for close observation and if necessary, to provide intensive care.

In all case of OHSS, the ovaries will invariably be considerably enlarged. This is irrelevant to the final outcome, unless ovarian torsion (twisting of the ovary on its axis), an extremely rare complication occurs. The latter would usually require surgical emergency surgical intervention.

It is important to know that symptoms and signs of OHSS are severely aggravated by rising hCG levels. Thus such patients should not receive additional hCG injections.

Does PCOS cause poor egg/embryo quality? It is an undeniable fact that women with PCOS undergoing IVF are commonly found to have poorly developed (“dysmorphic”) eggs, with reduced fertilization potential and yielding “poor quality embryos”. However, in the author’s opinion (which admittedly runs contrary to popular opinion), this is unlikely to be due to an intrinsic deficit in egg quality. Rather, it more likely relates to intra-ovarian hormonal changes brought about by hyperstimulation and which compromise egg development. This effect, in the author’s opinion, can often be significantly reduced through implementation of an individualized or customized ovarian stimulation protocols that minimize exposure of the developing follicles and eggs to excessive LH-induced ovarian androgens. This can be best achieved by limiting the use of LH-containing gonadotropins such as Menopur through selective institution of “prolonged coasting” (see below).

In the past, the onset of OHSS, heralded by the presence of large numbers of developing ovarian follicles and rapidly rising plasma estradiol levels often led the treating physician to prematurely administer hCG in an attempt to abruptly arrest the process and prevent escalation of risk to the patient. However the premature administration of hCG, while abruptly arresting further proliferation of estrogen producing granulosa cells in the follicles, unfortunately also prematurely arrests egg development. Since the ability of an egg to achieve optimal maturation upon hCG triggering is largely predicated upon it having achieved prior optimal development, the untimely administration of hCG which triggers meiosis, probably increases the risk of numerical chromosomal abnormalities (aneuploidy) of the egg. This in turn would lead to reduced fertilization potential, poor egg/embryo quality and low embryo implantation potential.

In women with PCOS the connective tissue that surrounding the follicles (ovarian stroma) is often characteristically overgrown (stromal hyperplasia). It is the stroma that produces androgens (mainly testosterone) in response to LH. It is this, coupled with the fact that PCOS women also often have elevated blood LH concentrations (see above) results in the excessive production of androgen hormones, which is so characteristic in PCOS. While excessive exposure of developing eggs to ovarian androgens compromises follicle and egg growth it also impairs endometrial response to estrogen, which could explain the common finding of poor endometrial thickening in many PCOS women undergoing IVF.
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The obvious remedy for these adverse effects on egg and endometrial development is to employ stimulation protocols that limit ovarian over-exposure to LH and allowing the time necessary for the follicles/eggs to develop optimally, prior to administering hCG through the judicious implementation of “Prolonged coasting” (PC).

“PROLONGED COASTING”:

In the early 90’s we were the first to report on “prolonged coasting” (PC), a novel approach that protects egg quality while preventing the development of OHSS. PC has since, gained widespread acceptance as a method of choice for preventing OHSS and has established itself as the “standard of care”. It involves withholding gonadotropin therapy while continuing the administration of the GnRHa and waiting until the plasma estradiol concentration drops below 2,500 pg/ml. Thereupon hCG is administered. In such cases, regardless of the number of developed follicles or the number of eggs retrieved, these women rarely, if ever develop OHSS. It has been reported that while PC virtually eliminates the risk of life-endangering complications associated with OHSS, there are reports in the literature that “the price to pay with PC” is often a poorer fertilization rate and reduced embryo implantation potential, compromising the pregnancy”. It is the author’s opinion an experience in the development of PC that egg/embryo quality deficit likely has little to do with the process of PC, itself and can be explained as follows: When PC is initiated too early, follicle growth and development may cease (as evidenced by the estradiol level plateauing or falling immediately, rather than showing an initial continued increase), and when PC is started too late, the follicles will often become cystic, measuring >21mm by the time the estradiol level falls below the safe threshold of 250000pg/ml, and so harbor dysmorphic eggs. Thus precise timing of the initiation of PC is critical. It should in pact be initiated preemptively in all cases when there are more than 25 follicles and the plasma estradiol reaches or exceeds 2,500pg/ml in association, provided that at least 50% of the follicles measuring 14-16mm in mean diameter. Not a day sooner or a day later. If PC is initiated with precise timing, it will usually be followed by a further progressive rise in the estradiol concentration. After a few days, the estradiol level will plateau and then it will start to fall (often rapidly). The temptation to trigger with hCG before the estradiol level falls below 3000picogtrams per milliliter must be resisted …even if the level falls below 1,000pg/ml by the time hCG is given.

Since when using agonist ( Cetrotide/Ganirelix/Orgalutron) pituitary suppression throughout the stimulation phase with gonadotropins, the plasma estradiol level often under expressed follicle growth, this method of pituitary blockade should not be used in cases ( such as with PCOS) where PC might be required.,

Prolonged coasting prevents canceled cycles and with it, canceled dreams.

I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
• A Fresh Look at the Indications for IVF
• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• IVF and the use of Supplementary Human Growth Hormone (HGH) : Is it Worth Trying and who needs it?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Embryo Transfer: The “Holy Grail in IVF.
• IVF: Approach to Selecting the Best Embryos for Transfer to the Uterus.
• Fresh versus Frozen Embryo Transfers (FET) Enhance IVF Outcome
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Genetically Testing Embryos for IVF
• Staggered IVF
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• Sher Fertility Solutions (SFS): An Exciting New Chapter….
• Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• Avoiding High Order Multiple Pregnancies (Triplets or Greater) with IVF
• The Role of Nutritional Supplements in Preparing for IVF
• Ovarian Hyperstimulation Syndrome (OHS): Its Evolution & Reducing itsIncumbent Risks
• Taking A Fresh Look at Ovarian Hyperstimulation Syndrome (OHSS), its Presentation, Prevention and Management
• Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
• IVF Outcome in Patients with Polycystic Ovarian Syndrome (PCOS): Minimizing the Risk of Severe Ovarian Hyperstimulation Syndrome (OHSS) and optimizing Egg/Embryo Quality.
• Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
• IVF & Polycystic Ovarian Syndrome (PCOS): Reducing the Risk of Severe Ovarian Hyperstimulation Syndrome (OHSS), Improving Egg Quality and Optimizing Outcome.

Geoff Sher

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.

For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Alina

Dear Mr. Sher,

I am so happy that I could get some information about sperm antibodies through your website as this is really difficult to find (beside some very basic stuff) – so thank you for that. My question is concerning exactly those antibodies. My husband has them (lg(G): 98% and lg(A): 15%) and we had trouble with the blastocyst development. 1. ICSI (GONAL-F 150): We did 6 of my eggs with IVF (none fertilized) and the 8 with ICSI (7 fertilized). All looked good until day 3, we froze 6 eggs as the clinic did not work on the weekend (one got transferred) – that is why they were developed to blastocysts after unfreezing. Only 1 was of a good enough quality (but also only 2 AB). No pregnancy. 2. ICSI – we were hopeful, because we changed clinic which works also on the weekend so that we had the chance for seeing how they develop without the freezing (old clinic said there was no egg issue). Unfortunately, 2. ICSI (Pergoveris: 1. day 225 2. day 150 from day 7 187.5) my follicles were from the beginning on very unequal (some bigger, some smaller) and that’s why we got only 9 mature eggs out of 19 as the other ones were just too small. 8 eggs fertilized and all looked good again until day 3… we ended up with one blastocyst (fair quality grade 4 2 2). Another one was grade 232 but was not frozen. The doctor said my eggs looked like having particles in it and was wondering if it is an egg quality as my AMH-value is low for my age – soon 28 years old- (though still normal 1.6 ug/l as well as the FSH 7.1 IU/l ). I need to say in the 3 month before the 2. ICSI I took antibiotics for the vagina, had 1 mammography and 1 röntgen of the back (just 1 day apart from each other). I was reinsured it would not matter – maybe it did? In other words, I am confused, panicked and I do not know whether I should put hope into a new ICSI with my own eggs. The big question I just have is how much the antibodies of my husband are impacting all of this? However, I am extremely stressed for a longer period of time (unemployment, living abroad, infertility) so that could have an impact as well?!

Thanks a lot for taking the time to answer!

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Dr. Geoffrey Sher

Hi Alina,

Respectfully, ICSI will overcome the effects of spem antibodies. I think the likely explanation for your egg/embryo quality issue relates more to the protocol used for ovarian stimulation than anything else.

One of the commonest questions asked by patients undergoing IVF relates to the likelihood of their eggs fertilizing and the likely “quality of their embryos. This is also one of the most difficult questions to answer. On the one hand many factors that profoundly influence egg quality; such as the genetic recruitment of eggs for use in an upcoming cycle, the woman’s age and her ovarian reserve, are our outside of our control. On the other hand the protocol for controlled ovarian stimulation (COS) can also profoundly influence egg/embryo development and this is indeed chosen by the treating physician.

First; it should be understood that the most important determinant of fertilization potential, embryo development and blastocyst generation, is the numerical chromosomal integrity of the egg (While sperm quality does play a role, in the absence of moderate to severe sperm dysfunction this is (moderate or severe male factor infertility a relatively small one). Human eggs have the highest rate of numerical chromosomal irregularities (aneuploidy) of all mammals. In fact only about half the eggs of women in their twenties or early thirties, have the required number of chromosomes (euploid), without which upon fertilization the cannot propagate a normal pregnancy. As the woman advances into and beyond her mid-thirties, the percentage of eggs euploid eggs declines progressively such that by the age of 40 years, only about one out of seven or eight are likely to be chromosomally normal and by the time she reaches her mid-forties less than one in ten of her eggs will be euploid.

Second; embryos that fail to develop into blastocysts are almost always aneuploid and not worthy of being transferred to the uterus because they will either not implant, will miscarry or could even result in a chromosomally abnormal baby (e.g. Down syndrome). However, it is incorrect to assume that all embryos reaching the blastocyst stage will be euploid (“competent”). ). It is true that since many aneuploid embryos are lost during development and that those failing to survive to the blastocyst stage are far more likely to be competent than are earlier (cleaved) embryos. What is also true is that the older the woman who produces the eggs, the less likely it is that a given blastocyst will be “competent”. As an example, a morphologically pristine blastocyst derived from the egg of a 30-year-old woman would have about a 50:50 chance of being euploid and a 30% chance of propagating a healthy, normal baby, while a microscopically comparable blastocyst-derived through fertilization of the eggs from a 40-year-old, would be about half as likely to be euploid and/or propagate a healthy baby.

While the effect of species on the potential of eggs to be euploid at ovulation is genetically preordained and nothing we do can alter this equation, there is, unfortunately, a lot we can (often unwittingly) do to worsen the situation by selecting a suboptimal protocol of controlled ovarian stimulation (COS). This, by creating an adverse intraovarian hormonal environment will often disrupt normal egg development and lead to a higher incidence of egg aneuploidy than otherwise might have occurred. Older women, women with diminished ovarian reserve (DOR) and those with polycystic ovarian syndrome are especially vulnerable in this regard.

During the normal, ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone), that are produced by the ovarian stroma (tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (that line the inner walls of follicles), and egg maturation. However, over-production of testosterone can adversely influence the same processes. It follows that COS protocols should be individualized and geared toward optimizing follicle growth and development time while avoiding excessive ovarian androgen (testosterone) production and that the hCG “trigger shot” should be carefully timed.

In summary, it is important to understand the influence species, age of the woman as well as the effect of the COS protocol can have on egg/embryo quality and thus on IVF outcome. The selection of an individualized protocol for ovarian stimulation is one of the most important decisions that the RE has to make and this becomes even more relevant when dealing with older women, those with DOR and women with PCOS. Such factors will in large part determine fertilization potential, the rate of blastocyst generation and indeed IVF outcome.
I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
• Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.

ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Becca

Dear Dr Sher

You have been recommended to me by a friend and I would be grateful for your advice. I am 41 and my husband is 46, I have never been pregnant but my husband has 2 children from his previous marriage. We have been TTC for 2 years with no obvious issues, the only thing we’ve not had checked is whether or not my tubes are blocked. I have an AMH of 16.2 and a follicle count of 18. My husbands sperm analysis results were good with no issues at all.

We did our first IVF in September 2018 and they collected 19 eggs, 9 fertilised and 3 made it to Day 5. We did a FET of 2 embryos in November which failed. Due to my age we decided to do another egg collection rather than transfer our last embryo. My egg collection was last Friday and they collected 19 eggs again. As my husband was diagnosed with cancer in November and has now started chemotherapy we froze his sperm prior to treatment and decided to use ICSI to improve fertilisation. 10 eggs were considered immature so they were fertilised using IVF and non fertilised. The other 9 eggs were fertilised by ICSI, 1 rejected the sperm and of the other 8 only 1 has fertilised.

I was surprised as my expectation was that ICSI would achieve a higher fertilisation rate? When we saw the embryologist after the egg collection she said she’d defrosted 1 of my husbands samples when actually all 3 were for this cycle. She said if she’d known that it would have made a difference. Does this potentially mean that the sperm she had to select from wasn’t of good enough quality?

I’ve done mild stimulation IVF with Bemfola 225 and Letrozole.

Any advice or suggestions you can give would be appreciated. With thanks.

reply
Dr. Geoffrey Sher

One of the commonest questions asked by patients undergoing IVF relates to the likelihood of their eggs fertilizing and the likely “quality of their embryos. This is also one of the most difficult questions to answer. On the one hand many factors that profoundly influence egg quality; such as the genetic recruitment of eggs for use in an upcoming cycle, the woman’s age and her ovarian reserve, are our outside of our control. On the other hand the protocol for controlled ovarian stimulation (COS) can also profoundly influence egg/embryo development and this is indeed chosen by the treating physician.

First; it should be understood that the most important determinant of fertilization potential, embryo development and blastocyst generation, is “competency” of the embryo that is mostly affected by the numerical chromosomal integrity (ploidy) of the egg. While sperm quality does play a role, in the absence of moderate to severe sperm dysfunction this is (moderate or severe male factor infertility a relatively small one). Human eggs have the highest rate of numerical chromosomal irregularities (aneuploidy) of all mammals. In fact only about half the eggs of women in their twenties or early thirties, have the required number of chromosomes (euploid), without which upon fertilization they cannot propagate a normal pregnancy. As the woman advances into and beyond her mid-thirties, the percentage of eggs euploid eggs declines progressively such that by the age of 40 years, only about one out of six are likely to be chromosomally normal. By her mid-only about forties one in ten of her eggs will be euploid and by 4r years of age, fewer than one in twenty will be euploid.

Second; embryos that fail to develop into blastocysts are almost always aneuploid and not worthy of being transferred to the uterus because they will either not implant, will miscarry or could even result in a chromosomally abnormal baby (e.g. Down syndrome). However, it is incorrect to assume that all embryos reaching the blastocyst stage are will be euploid (“competent”). ). It is true that since many aneuploid embryos are lost during development and that those failing to survive to the blastocyst stage are far more likely to be competent than are earlier (cleaved) embryos. What is also true is that the older the woman who produced the eggs, the less likely it is that a given blastocyst will be “competent”. As an example, a morphologically pristine blastocyst derived from the egg of a 30 year old woman would have about a 50:50 chance of being euploid and such a microscopically normal embryo would have 25%-30% chance of propagating a healthy, normal baby, while a microscopically comparable blastocyst derived through fertilization of the eggs from a 40 year old, would be about half as likely to be euploid and/or propagate a healthy baby and by 45 years of age…less than 5%. .

While the effect of species on the potential of eggs to be euploid at ovulation is genetically preordained and nothing we do can alter this equation, there is unfortunately a lot we can (often unwittingly) do to worsen the situation by selecting a suboptimal protocol of controlled ovarian stimulation (COS). This, by creating an adverse intraovarian hormonal environment will often disrupt normal egg development and lead to a higher incidence of egg aneuploidy than otherwise might have occurred. Older women, women with diminished ovarian reserve (DOR) and those with polycystic ovarian syndrome are especially vulnerable in this regard.

During the normal, ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone), that are produced by the ovarian stroma (tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (that line the inner walls of follicles), and egg maturation. However, over-production of testosterone can adversely influence the same processes. It follows that COS protocols should be individualized and geared toward optimizing follicle growth and development time while avoiding excessive ovarian androgen (testosterone) production and that the hCG “trigger shot” should be carefully timed.

The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by those IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome in patients at risk – particularly those with diminished ovarian reserve (“poor responders”) and those who are “high responders” (women with PCOS , those with dysfunctional or absent ovulation, and young women under 25 years of age).

While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.
During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) that are produced by the ovarian stroma (the tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (cells that line the inner walls of follicles), and egg maturation.

However, over-production of testosterone can adversely influence the same processes. It follows that protocols for controlled ovarian stimulation (COS should be geared toward optimizing follicle growth and development (without placing the woman at risk from overstimulation), while at the same time avoiding excessive ovarian androgen production. Achievement of such objectives requires a very individualized approach to choosing the protocol for COS with fertility drugs as well as the precise timing of the “trigger shot” of hCG.

It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed towards the cells lining the inside of the follicle that are responsible for estrogen production. LH, on the other hand, acts primarily on the ovarian stroma to produce male hormones/ androgens (e.g. androstenedione and testosterone). A small amount of testosterone is necessary for optimal estrogen production. Over-production of such androgens can have a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality.

Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.

In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often a feature of this condition. The use of LH-containing preparations such as Menopur further aggravates this effect. Thus we recommend using FSH-dominant products such as Follistim, Puregon, and Gonal-F in such cases. While it would seem prudent to limit LH exposure in all cases of COS, this appears to be more vital in older women, who tend to be more sensitive to LH

It is common practice to administer gonadotropin releasing hormone agonists (GnRHa) agonists such as Lupron, and, GnRH-antagonists such as Ganirelix and Orgalutron to prevent the release of LH during COS. GnRH agonists exert their LH-lowering effect over a number of days. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in the LH level falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. GnRH Antagonists, on the other hand, act very rapidly (within a few hours) to block pituitary LH release, so as achieve the same effect.

Long Agonist (Lupron/Buserelin) Protocols: The most commonly prescribed protocol for Lupron/gonadotropin administration is the so-called “long protocol”. Here, Lupron is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to near zero. It is followed by uterine withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the long protocol which I prefer using in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a Lupron-induced bleed , this agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I supplement with human growth hormone (HGH) to try and further enhance response and egg development.

Lupron Flare/Micro-Flare Protocol: Another approach to COS is by way of so-called “(micro) flare protocols”. This involves initiating gonadotropin therapy simultaneous with the administration of GnRH agonist (e.g. Lupron/Buserelin). The intent here is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” represents “a double edged sword” because while it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal androgen production which could potentially compromise egg quality, especially in older women and women with PCOS, whose ovaries have increased sensitivity to LH. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe them at all.

Estrogen Priming – My approach for “Poor Responders” Our patients who have demonstrated reduced ovarian response to COS as well as those who by way of significantly raised FSH blood levels are likely to be “poor responders”, are treated using a “modified” long protocol. The approach involves the initial administration of GnRH agonist for a number of days to cause pituitary down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered and the woman is given twice-weekly injections of estradiol for a period of 8. COS is thereupon initiated using a relatively high dosage of FSH-(Follistim, Bravelle, Puregon or Gonal F) which is continued along with daily administration of GnRH agonist until the “hCG trigger.” By this approach we have been able to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients”.

The “Trigger”: hCG (Profasi/Pregnyl/Novarel) versus Lupron: With ovulation induction using fertility drugs, the administration of 10,000U hCGu (the hCG “trigger”) mimics the LH surge, sending the eggs (which up to that point are immature (M1) and have 46 chromosomes) into maturational division (meiosis) This process is designed to halve the chromosome number , resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes it had prior to the “trigger”. Such a chromosomally normal, M2 egg, upon being fertilized by mature sperm (that following maturational division also has 23 chromosomes) will hopefully propagate embryos that have 46 chromosomes and will be “competent” to propagate viable pregnancies. The key is to trigger with no less than 10,000U of hCGu (Profasi/Novarel/Pregnyl) and if hCGr (Ovidrel) is used, to make sure that 500mcg (rather than 250mcg) is administered. In my opinion, any lesser dosage will reduce the efficiency of meiosis, and increase the risk of the eggs being chromosomally abnormal. . I also do not use the agonist (Lupron) “trigger”. This approach which is often recommended for women at risk of overstimulation, is intended to reduce the risk of OHSS. The reason for using the Lupron trigger is that by inducing a surge in the release of LH by the pituitary gland it reduces the risk of OHSS. This is true, but this comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the percentage of chromosomally abnormal and of immature (M1) eggs. The use of “coasting” in such cases) can obviate this effect

I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.

Geoff Sher

ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.

For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Melissa 2506

Hi Dr Sher, my question relates to using frozen semen for IVF vs Fresh.
My husband has high sperm antibodies and poor morphology and motality. Will using frozen sperm to fertilise fresh eggs give me a good result or is fresh sperm deposit best ? Sperm has been given by ejaculation not testicular biopsy.
Thanks

reply
Dr. Geoffrey Sher

Generally speaking, good quality sperm freezes well, while poor quality sperm has poor viability. However, in your husband’s case, it could be that the antibodies that are compromising sperm morphology and motility. Thus I would suggest freezing sperm for a short period of time then thawing a straw of sperm and retesting it. This would give you an indication of how the freezing process impacts sperm viability!

Good luck!

Geoff Sher

reply
Julia

Hi
I have a question on the causes of low/inconsistent fertilization rates. I have done three egg collections over the last six months with pgs testing with very different fertilization results. We currently have unexplained fertility. In the first cycle, we collected 10 eggs of which 9 were mature and were fertilized using ICSI. 4 fertilized of which 3 were biopsied on day five and one was PGS normal. In our second cycle, we collected 8 eggs but half were not mature enough for ICSI so half were placed in a culture and fertilized using IVF and half were fertilized using ICSI, 3 from each group were fertilized and 4 were biopsied on day 5 and one was PGS normal. Our most recent cycle resulted in 15 eggs been collected. We only used IVF this cycle and were initally told that 3 eggs fertilized out of 13 mature eggs, 7 didn’t fertilize and 2 abnormally fertilized. Then today which is day threewe were told that two out of the three that they thought had fertilized had actually abnormally fertilized and two of the seven that they thought had not fertilized had fertilized late. I am just wondering is there any obvious tests that we should be doing , I am 39 and my AMH is 20 and my partners sperm is good. My protocol has not changed significantly especially with my last two cycles. I have been on gonal f and menopur and been triggered with Buserelin… any advice or guidance is appreciated

reply
Dr. Geoffrey Sher

One of the commonest questions asked by patients undergoing IVF relates to the likelihood of their eggs fertilizing and the likely “quality of their embryos. This is also one of the most difficult questions to answer. On the one hand many factors that profoundly influence egg quality; such as the genetic recruitment of eggs for use in an upcoming cycle, the woman’s age and her ovarian reserve, are our outside of our control. On the other hand the protocol for controlled ovarian stimulation (COS) can also profoundly influence egg/embryo development and this is indeed chosen by the treating physician.

First; it should be understood that the most important determinant of fertilization potential, embryo development and blastocyst generation, is the numerical chromosomal integrity of the egg (While sperm quality does play a role, in the absence of moderate to severe sperm dysfunction this is (moderate or severe male factor infertility a relatively small one). Human eggs have the highest rate of numerical chromosomal irregularities (aneuploidy) of all mammals. In fact only about half the eggs of women in their twenties or early thirties, have the required number of chromosomes (euploid), without which upon fertilization the cannot propagate a normal pregnancy. As the woman advances into and beyond her mid-thirties, the percentage of eggs euploid eggs declines progressively such that by the age of 40 years, only about one out of seven or eight are likely to be chromosomally normal and by the time she reaches her mid-forties less than one in ten of her eggs will be euploid.

Second; embryos that fail to develop into blastocysts are almost always aneuploid and not worthy of being transferred to the uterus because they will either not implant, will miscarry or could even result in a chromosomally abnormal baby (e.g. Down syndrome). However, it is incorrect to assume that all embryos reaching the blastocyst stage will be euploid (“competent”). ). It is true that since many aneuploid embryos are lost during development and that those failing to survive to the blastocyst stage are far more likely to be competent than are earlier (cleaved) embryos. What is also true is that the older the woman who produces the eggs, the less likely it is that a given blastocyst will be “competent”. As an example, a morphologically pristine blastocyst derived from the egg of a 30-year-old woman would have about a 50:50 chance of being euploid and a 30% chance of propagating a healthy, normal baby, while a microscopically comparable blastocyst-derived through fertilization of the eggs from a 40-year-old, would be about half as likely to be euploid and/or propagate a healthy baby.

While the effect of species on the potential of eggs to be euploid at ovulation is genetically preordained and nothing we do can alter this equation, there is, unfortunately, a lot we can (often unwittingly) do to worsen the situation by selecting a suboptimal protocol of controlled ovarian stimulation (COS). This, by creating an adverse intraovarian hormonal environment will often disrupt normal egg development and lead to a higher incidence of egg aneuploidy than otherwise might have occurred. Older women, women with diminished ovarian reserve (DOR) and those with polycystic ovarian syndrome are especially vulnerable in this regard.

During the normal, ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone), that are produced by the ovarian stroma (tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (that line the inner walls of follicles), and egg maturation. However, over-production of testosterone can adversely influence the same processes. It follows that COS protocols should be individualized and geared toward optimizing follicle growth and development time while avoiding excessive ovarian androgen (testosterone) production and that the hCG “trigger shot” should be carefully timed.

In summary, it is important to understand the influence species, age of the woman as well as the effect of the COS protocol can have on egg/embryo quality and thus on IVF outcome. The selection of an individualized protocol for ovarian stimulation is one of the most important decisions that the RE has to make and this becomes even more relevant when dealing with older women, those with DOR and women with PCOS. Such factors will in large part determine fertilization potential, the rate of blastocyst generation and indeed IVF outcome.
I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
• Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.

ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Kristy

Hi!
In our first year of trying to conceive we had a miscarriage and a chemical pregnancy. I have normal 28 day cycles but was diagnosed with DOR. We went through 3 egg retrieval’s and had 6 PGS embryos. I had an ovary removed due to a Cystadenoma that had taken over. 3 failed FET and every test comes back normal (hsg, hysteroscopy, ERA, uterine biopsy, sonohystogram, karyotyping, etc) with the addition of Lupron, doxycycline , medrol I am 6 weeks pregnant with slow rising beta and no yolk sac. They believe it is a missed miscarriage. Through a phone consult with Braverman, he believes I have silent endometriosis. However I have already had a laparoscopy and none was found. My husband and I are at a loss as to how to proceed next. Do we get a surrogate? Do we risk an unnecessary surgery? Do we switch clinics? Any advice would be appreciated as we have no idea where to go next.

reply
Dr. Geoffrey Sher

Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
a. A“ thin uterine lining”
b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c. Immunologic implantation dysfunction (IID)
d. Endocrine/molecular endometrial receptivity issues
e. Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF?
• The Role of Nutritional Supplements in Preparing for IVF

ADDENDUM:
Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.
Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.
I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.
It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.
I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Judie

Hi Dr. Sher.
Thank you for taking time to answer our questions! I am hoping you can shed some light or clarity on my situation. I am 42 and just underwent first IVF cycle which was cancelled at day 7 of stims. A little background: was pregnant from July to October with an early second trimester loss due to chromosomal abnormality. Following loss, i was lactating for about 5-6 weeks. Started on bcp’s around week 7 by RE and continued on active pills x 62 days. Three days off the pill prior to starting stims. On first day of my protocol I was told to take lupron 5 units. After that my regimen was as follows:
Lupron 5 units in the morning
Follistim 360 units in pm
Menopur 75 units in pm
On day 4 I was told there had been no progress and my estrogen was only 14 but instructed to continue same regimen for three more days and return for another ultrasound. At that point I was told that my ANC was zero and the cycle was cancelled. I was told there was no point in trying again unless I use donor eggs. Can I really be sterile just four short months after having been pregnant naturally (without even trying)? Is it possible that some other factor is at play? Could this be due to oversuppression? Other ideas? Can my antral follicle count really be zero and can it improve? I am beside myself. Anything you can tell me or any direction you can point me will be greatly appreciated!

reply
Dr. Geoffrey Sher

It is possible , although unlikely that you developed severe DOR after the pregnancy. However, this needs to be evaluated. You need a blood AMH to be done. Then we need to reconnect.

ADDENDUM:
Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.
Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.
I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.
It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.
I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Judie Kwolek

Thank you for your reply and suggestion. I will have the AMH done and reconnect. I was surprised to learn it had never been checked before i started ivf. When should I have it done, in your opinion?

reply
Amy

Hi Dr Sher

I am 35 years old, my husband is 34. We have recently experienced our second IVF failure and am trying to better understand what might have gone wrong.

We have two naturally conceived children aged 4 and 2. We have been trying to conceive a third baby for 15 months, and have spent the last 5 months investigating and undertaking IVF (with ICSI) after my husband was diagnosed with poor morphology and high viscosity last summer. Note though that his sperm quality seems to have improved though and his last sample was said to have 4% morphology and look good. I have (bar some distruption around Ivf cycles) regular 30 day cycles bleeding for 4-5 days. The only other thing I think to mention by way of context is that I have been experiencing quite severe night sweating for the past 8 months or so before and during my period. I have had my thyroid tested and asked my RE about perimenopause and he said he saw no issues on either front after bloodwork.

With our first cycle, we had 12 eggs retrieved, 6 mature, 2 fertilised and transferred at 3 days. My period started 4 days before test day. I then got a positive test result but within 48 hours was told HCG was dropping and it was a biochemical pregnancy. With the second cycle, we had 12 eggs retrieved, 8 mature, 5 fertilised but only 2 survived to blastocyst stage and they were both transferred. Again I started bleeding 4 days before my test day.

My feeling is that the timing of my cycles has been wrong relative to the receptivenesss of my endometrium. My progesterone levels have been noted as high around the time of egg retrieval and transfer (190 the day before transfer, I can’t recall the other reading), which I expressed concern about but nothing changed in my protocol. I asked for progesterone to be tested after transfer and it was low, I think, at 36 3 days after transfer and 33 5 days after transfer. My RE increased me from 2 400mg cyclogest a day to 3 after the 36 reading. But a few days later bleeding started. For both cycles my night sweating has begun a few days after egg transfer, making me feel that my period is coming and progesterone levels are falling. I don’t know if this is the right thing to be focussed on or not and would be so grateful for your thoughts and perspective. I want to make sure I am asking the right questions and encouraging focus in the right direction.

Many thanks,
Amy

Many thanks,
Amy

reply
Dr. Geoffrey Sher

Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
a. A“ thin uterine lining”
b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c. Immunologic implantation dysfunction (IID)
d. Endocrine/molecular endometrial receptivity issues
e. Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF?
• The Role of Nutritional Supplements in Preparing for IVF

ADDENDUM:
Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.
Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.
I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.
It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.
I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com

reply
Sowmya

Hello Dr. Sher
I am 25 yrs old with PCO and history of pelvic TB. Tubes are open but had no pregnancy in the past. I had FET on 02/05/2019 with two blastocysts. Beta hcg on 02/15/2019 is 43.4mIU/ml. Is this a good number? Does it look positive?

reply
Dr. Geoffrey Sher

Very encouraging!

Good luck!

Geoff Sher
_________________________________________________________________________________
ADDENDUM

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.
In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.
Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.
I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.
It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.
I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

.

reply
Dr. Geoffrey Sher

It would be worth a try!

Human embryo development occurs through a process that encompasses reprogramming, sequential cleavage divisions and mitotic chromosome segregation and embryonic genome activation. Chromosomal abnormalities may arise during germ cell and/or preimplantation embryo development and represents a major cause of early pregnancy loss. About a decade ago, I and my associate, Levent Keskintepe PhD were the first to introduce full embryo karyotyping (identification of all 46 chromosomes) through preimplantation genetic sampling (PGS) as a method by which to selectively transfer only euploid embryos (i.e. those that have a full component of chromosomes) to the uterus. We subsequently reported on a 2-3-fold improvement in implantation and birth rates as well as a significant reduction in early pregnancy loss, following IVF. Since then PGS has grown dramatically in popularity such that it is now widely used throughout the world.

Most IVF programs that offer PGS services, require that all participating patients consent to all their aneuploid embryos (i.e. those with an irregular quota of chromosomes) be disposed of. However, there is now growing evidence to suggest that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrection”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases occurring within our IVF network. So clearly, summarily discarding all aneuploid embryos as a matter of routine we are sometimes destroying some embryos that might otherwise have “autocorrected” and gone on to develop into normal offspring.

Thus, by discarding aneuploid embryos the possibility exists that we could be denying some women the opportunity of having a baby. This creates a major ethical and moral dilemma for those of us that provide the option of PGS to our patients. On the one hand, we strive “to avoid knowingly doing harm” (the Hippocratic Oath) and as such would prefer to avoid or minimize the risk of miscarriage and/or chromosomal birth defects and on the other hand we would not wish to deny patients with aneuploid embryos, the opportunity to have a baby.

The basis for such embryo “autocorrection” lies in the fact that some embryos found through PGS-karyotyping to harbor one or more aneuploid cells (blastomeres) will often also harbor chromosomally normal (euploid) cells (blastomeres). The coexistence of both aneuploid and euploid cells coexisting in the same embryo is referred to as “mosaicism.”

It is against this background, that an ever-increasing number of IVF practitioners, rather than summarily discard PGS-identified aneuploid embryos are now choosing to cryobanking (freeze-store) certain of them, to leave open the possibility of ultimately transferring them to the uterus. In order to best understand the complexity of the factors involved in such decision making, it is essential to understand the causes of embryo aneuploidy of which there are two varieties:
1. Meiotic aneuploidy” results from aberrations in chromosomal numerical configuration that originate in either the egg (most commonly) and/or in sperm, during preconceptual maturational division (meiosis). Since meiosis occurs in the pre-fertilized egg or in and sperm, it follows that when aneuploidy occurs due to defective meiosis, all subsequent cells in the developing embryo/blastocyst/conceptus inevitably will be aneuploid, precluding subsequent “autocorrection”. Meiotic aneuploidy will thus invariably be perpetuated in all the cells of the embryo as they replicate. It is a permanent phenomenon and is irreversible. All embryos so affected are thus fatally damaged. Most will fail to implant and those that do implant will either be lost in early pregnancy or develop into chromosomally defective offspring (e.g. Down syndrome, Edward syndrome, Turner syndrome).
2. “Mitotic aneuploidy” occurs when following fertilization and subsequent cell replication (cleavage), some cells (blastomeres) of a meiotically normal (euploid) early embryo mutate and become aneuploid. This is referred to as “mosaicism”. Thereupon, with continued subsequent cell replication (mitosis) the chromosomal make-up (karyotype) of the embryo might either comprise of predominantly aneuploid cells or euploid cells. The subsequent viability or competency of the conceptus will thereupon depend on whether euploid or aneuploid cells predominate. If in such mosaic embryos aneuploid cells predominate, the embryo will be “incompetent”). If (as is frequently the case) euploid cells prevail, the mosaic embryo will likely be “competent” and capable of propagating a normal conceptus.

Since some mitotically aneuploid (“mosaic”) embryos can, and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to reliably differentiate between these two varieties of aneuploidy would potentially be of considerable clinical value. The recent introduction of a variety of preimplantation genetic screening (PGS) known as next generation gene sequencing (NGS) has vastly improved the ability to reliably and accurately karyotype embryos and thus to diagnose embryo “mosaicism”.

The ability of mosaic embryos to autocorrect is influenced by the stage at which the condition is diagnosed as well as the percentage of mosaic cells. Many embryos diagnosed as being mosaic while in the earlier cleaved state of development, subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) during the process of undergoing subsequent mitotic cell to the blastocyst stage. Similarly, mosaic blastocysts can also undergo autocorrection after being transferred to the uterus. The lower the percentage of mosaic cells in the blastocyst the greater the propensity to autocorrect and propagate chromosomally normal (euploid) offspring. By comparison, a blastocyst with 10% mosaicism could yield a 30% healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

Aneuploidy involves the addition (trisomy) or subtraction (monosomy) of one or part of one chromosome in any given pair. As previously stated, some aneuploidies are meiotic in origin while others are mitotic “mosaics”. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve several pairs (i.e. complex aneuploidy). Aside from monosomy involving the absence of the y-sex chromosome (i.e. XO) which can result in a live birth (Turner syndrome) of a compromised baby, virtually all monosomies involving autosomes (non-sex chromosomes) are likely to be lethal and will rarely result in viable offspring. Some autosomal meiotic aneuploidies, especially trisomies 13, 18, 21, can propagate viable and severely chromosomally defective babies. Other meiotic autosomal trisomies will almost invariably, either not attach to the uterine lining or upon attachment, will soon be rejected. All forms of meiotic aneuploidy are irreversible while as stated, mitotic aneuploidy (“mosaicism) can autocorrect, yielding healthy offspring. Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies.

Since certain “mosaic” meiotic aneuploid trisomy embryos (e.g. trisomies 13, 18, & 21) can potentially result in aneuploid concepti. For this reason, it is my opinion that unless the woman/couple receiving such embryos is willing to commit to terminating a resulting pregnancy found through amniocentesis or chorionic villus sampling (CVS) to be so affected, she/they are probably best advised not to transfer have them transferred to the uterus. Embryos harboring other autosomal mosaic trisomic embryos, should they not autocorrect in-utero will hardly ever produce a baby and as such there is hardly any risk at all…in transferring such embryos. However, it is my opinion that in the event of an ongoing pregnancy, amniocentesis or CVS should be performed to make certain that the baby is euploid. Conversely, when it comes to mosaic autosomal monosomy, given that virtually no autosomal monosomy embryos are likely to propagate viable pregnancies, the transfer of such mosaic embryos is virtually risk free. Needless to say, in any such cases , it is absolutely essential to make full disclosure to the patient (s) , and to insure the completion of a detailed informed consent agreement which would include a commitment by the patient (s) to undergo prenatal genetic testing (amniocentesis/CVS) aimed at excluding a chromosomal defect in the developing baby and/or a willingness to terminate the pregnancy should a serious birth defect be diagnosed.

I strongly recommend that you visit http://www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
• A Fresh Look at the Indications for IVF
• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Hereditary Clotting Defects (Thrombophilia)
• Blastocyst Embryo Transfers done 5-6 Days Following Fertilization are Fast Replacing Earlier day 2-3 Transfers of Cleaved Embryos.
• Embryo Transfer Procedure: The “Holy Grail in IVF.
• Timing of ET: Transferring Blastocysts on Day 5-6 Post-Fertilization, Rather Than on Day 2-3 as Cleaved Embryos.
• IVF: Approach to Selecting the Best Embryos for Transfer to the Uterus.
• Fresh versus Frozen Embryo Transfers (FET) Enhance IVF Outcome
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.

Geoff Sher
_______________________________________________________
ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.

In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.

Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.

I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.

It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.

I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.

For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

reply
Jane

I have a question about your blog when you discuss Asherman’s syndrome. You say “The condition often results in fusion/adhesion of the opposing endometrial surfaces, but can also simply destroy the basal layer of endometrium without resulting in adhesions (non-adhesive Asherman’s).” I recently have a thinner lining after a surgery, but no scarring was detected on the hysteroscopy. Is this what you mean by non-adhesive? Thank you for your help. I am trying to find more information on this type of condition, “non-adhesive Asherman’s,” but can’t find any information.
In addition, I came across this article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582129/
“A possible explanation to this observation might be the existence of a spectrum of post curettage endometrial injuries ranging from a thin and unresponsive (but otherwise normal) endometrium at one end, to Asherman’s syndrome on the other. ” I was wondering if this is the type of non-adhesive Asherman’s you were describing. thanks again!

reply
Dr. Geoffrey Sher

It is uncommon, but possible that sharp curettage done over zealously, can cause permanent damage to the basal endometrium. But what I was referring to in my blog ids that post-pregnancy endometritis can permeate and damage the basal (germinal) endometrium without there necessarily being adhesions. A hysteroscopy might find no evidence of scarring in such cases which can equally damage endometrial response (proliferation) to estrogen.

Geoff Sher

reply
Jane

Thank you, my surgery was not related to a pregnancy. It was for a polyp removal, removal of some endometriosis, and removal of cervical stenosis. In your opinion, would this still allow the basal endometrium to be damaged? And if this is the case, would it not be detected in a hysteroscopy? I had almost no reaction to estrogen in my last attempt of frozen embryo transfer. Two previous cycles before the surgery my endometer was over 11 and it only reached 6.8 in the IVF following the surgery and my frozen embryo transfer was cancelled because it only reached 4.4. Would there be another explanation for this change in thickness other than the surgery? Thank you for all of your help!

reply
Dr. Geoffrey Sher

Unless there was an overzealous D&C done, it is unlikely that this was due to surgery. I would need much more information to be authoritative.

This having said, a trial of vaginal Viagra with parenteral or trans-dermal estrogen, should give an answer.

Geoff Sher

ADDENDUM:

Sher-Fertility Solutions (SFS) will be officially launched in April 2019. Through SFS I will provide fertility consultations (via SKYPE) to an ever-growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input and guidance.
In the past, I have limited my consultations with patients from afar to those who expressed a willingness to travel to Las Vegas for treatment by me. But now with the “birth” of SFS, all this is about to change. With one notable exception I will, as of April, 2019, no longer be conducting and performing hands-on IVF treatments. Rather, I will focus on providing SKYPE consultations and guidance to as many patients as possible. The one important exception will apply to approximately 1,000 existing patients who, following IVF previously performed by me, have remaining eggs or embryos stored (cryopreserved) at SIRM-LV and wish for me to perform their Frozen Embryo Transfers (FETs). I have agreed to accommodate such patients…..but only through August, 2019.
Patients will have ready access online, to SFS: by going to http://www.SherIVF.com; by phone (1-800-780-7437 or 702-533-2691) and via email (sher@sherivf.com or concierge@sherIVF.com). A onetime fee of $400.00, will provide enrollees with access to: a full review of all their medical records (+ assistance in requisitioning additional records, as needed); a comprehensive initial 1 hour, SKYPE consultation with me; additional SKYPE consultations (as might be required); a written medical report (which will include a recommended plan of action) that you can share with a Physician(s) of choice. I would, subject to your approval and a request by such Physician(s), also be willing to discuss your case with him/her/them. I will in due course post on my website, a list of Fertility Physicians in key locations all over the United States and abroad, whom I endorse and to whom I would be willing to direct SFS patients for subsequent treatment.
I have good news for those of you who are interested in traveling to Las Vegas for IVF. Dr Russel Foulk, Medical Director of SIRM-LV has expressed a willingness to be receptive to, treatment plans that I recommend for SFS patients Moreover, Dr Foulk has graciously agreed to interact with me during such treatments. I highly recommend Dr Foulk to those of you who, following consultation with me, wish to have me remain involved in the implementation of your treatment. This having been said, the final say in any management decision is always up to the treating physician.
It is both my objective and commitment to serve as a resource to SFS patients on complex RD issues such as: Unexplained IVF failure; Recurrent Pregnancy loss (RPL); Immunologic Implantation Dysfunction-IID; Genetic/chromosomal issues; effects of Diminished Ovarian Reserve (DOR) and advancing age on reproductive performance, etc.
I hope to ultimately expand the National and International reach of SFS, through my website (www.sherIVF.com) , through online webinars as well as Town hall- type consumer-based seminars, workshops and through social media. At the same time I will continue blogging on my website and doing bi-weekly Live-feed Facebook presentations (at “Dr Geoffrey Sher”) on a variety of subjects and topical issues.
For me this is a very exciting venture. Please become part of the SFS family and help spread the word!

I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .

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Jane

Thank you so much for all of your very helpful advice. The cervical stenosis removal I had was quite aggressive, and I had about a month of bleeding in the recovery. There was nothing detected in the hysteroscopy. Would possible damage to the cervix cause a thin lining and lack of response to estrogen? thanks again!

Dr. Geoffrey Sher

Thanks for the communication. No! Cervical damage would not affect the uterine lining1

Geoff Sher

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