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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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19,520 Comments

Dr. Geoffrey Sher

I doubt you have intrinsically abnormal eggs. I think your stimulation protocol needs to be reviewed and revised. Also, I think 250mcg of Ovidrel is too low a dosage for the “trigger”.

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 a “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
For women doing conventional IVF with a fresh embryo transfer, I usually add dexamethasone 0.75mg daily from the start of gonadotropin stimulation to the 8th week of pregnancy (and then is tailed of and stopped by the 10th week) and human growth hormone (HGH) daily from the 1st day of Lupron, up until the trigger with hCG. Women who test positive for Natural killer cell activation (Nka), receive an Intralipid (IL) infusion 10-14 days prior to the projected embryo transfer This is repeated with a +ve beta hCG pregnancy test result.
Those women, who for a variety of reasons do frozen embryo transfers (FET) and thus do not undergo embryo transfer in the same cycle as the egg retrieval, can omit taking the dexamethasone in the cycle of ER, deferring such to the subsequent FET cycle. They do however take HGH throughout the stimulation with gonadotropin and if they test positive for Nka, they will also receive dexamethasone during hormonal preparation for FET (continued until the 8th week of pregnancy when this is tailed off over 2 weeks and stopped by the 10th week.
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
Sneha

Hi Dr Sher,
I am 42 year old.I had PGS done for 4 embryos.All came abnormal
Is anyone of the following worth transferring?
+14,+15
-14,-18
+15,+18
+20,+22

reply
Dr. Geoffrey Sher

All are worthy of consideration for transfer.

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.

Many 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, growing evidence suggests that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrect”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases having occurred in my own practice. 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 (“Mosaicism”) 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”.

Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies. The ability of mosaic embryos to autocorrect is influenced by stage of embryo development in which the diagnosis is made, which chromosomes are affected, whether the aneuploidy involves a single chromosome (simple) or involves 3 or more chromosomes (complex), and the percentage of cells that are aneuploid. Many embryos diagnosed as being mosaic prior to their development into blastocysts (in the cleaved state), subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) as they develop to blastocysts in the Petri dish. This is one reason why “mosaicism” is more commonly detected in early embryos than in blastocysts. Embryos with segmental mosaic aneuploidies, i.e. the addition (duplication) or subtraction (deletion), are also more likely to autocorrect. Finally, the lower the percentage of mitotically aneuploid (mosaic) cells in the blastocyst the greater the propensity for autocorrection and propagation of chromosomally normal (euploid) offspring. A blastocyst with <30% mosaicism could yield a 30% likelihood of a healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

As stated, the transfer of embryos with autosomal meiotic trisomy, will invariably result in failed implantation, early miscarriage or the birth of a defective child. Those with autosomal mitotic (“mosaic”) trisomies, while having the ability to autocorrect in-utero and result in the birth of a healthy baby can, depending on the percentage of mosaic (mitotically aneuploid) cells present, the number of aneuploid chromosomes and the type of mosaicism (single or segmental) either autocorrect and propagate a normal baby, result in failed implantation, miscarry or cause a birth defect (especially with trisomies 13, 18 or 21). This is why when it comes to giving consideration to transferring trisomic embryos, suspected of being “mosaic”, I advise patients to undergo prenatal genetic testing once pregnant and to be willing to undergo termination of pregnancy in the event of the baby being affected. Conversely, when it comes to meiotic autosomal monosomy, there is almost no chance of a viable pregnancy. in most cases implantation will fail to occur and if it does, the pregnancy will with rare exceptions, miscarry. “Mosaic” (mitotically aneuploid) autosomally monosomic embryos where a chromosome is missing), can and often will “autocorrect” in-utero and propagate a viable pregnancy. It is for this reason that I readily recommend the transfer of such embryos, while still (for safety sake) advising prenatal genetic testing in the event that a pregnancy results.

Given our ability to recognize “mosaicism” through karyotyping of embryos, the question arrases as to which “mosaic” embryos are capable of auto-correcting in-utero and propagating viable pregnancies. Research suggests that that virtually no autosomal monosomy embryos will propagate viable pregnancies. Thus, the transfer of such mosaic embryos is virtually risk free. Needless to say however, in any such cases, it is 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.

___________________________________________________________
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
Sneha

Thanks Dr Sher.Which chromosome number do you absolutely decide against transfer?

reply
Judith

Dear Dr Sher,
Do you know what could cause all oocytes retrieved in IVF / ICSI to be all full of vacuoles?

Case: my husband and I (both 31 y/o, healthy, slighty irregular cycles) have been infertile for 4 years now. We have gone through the basic Dutch system of infertility, with ovulation induction, multiple IUI’s (using Gonal F), one IVF and one ICSI

The first IVF (short protocol – gonal f – 150 – fyremadel) yielded 6 oocytes, all full of vacuoles, and one bad embryo (no pregnancy). The second ICSI (short protocol – meriofert – 225 – fyremadel) yielded 11 oocytes, all full of vacuoles, and no embryo’s: total fertilization failure.

We had a second opinion with a Dutch doctor in another country who suggests that, after doing bloodwork, we could potentially try IVF with letrozole.
We are very, very curious if you ever had patients with the problem of vacualization and also, what your suggestion would be!

reply
Dr. Geoffrey Sher

Multiple vacuoles suggest an egg competency issue.
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
Alex

Dear Dr Sher,
Although my husband sperm is superb, we I had a split IVF/ICSI cycle, just to spread the risk. I had 9 eggs, 7 fertilized. In the IVF group, 2 out of 3 fertilized eggs made it to 3AA and 4BC blastocyst on day 5 (one egg arrested at day 3). In the ICSI group all 4 fertilized eggs arrested at morula or pre-blastocyst stage (stage 1 or 2) on day 5. The fertility clinic did not check at day 6. What could be the reason that all ICSI embryo’s did not develop properly, while IVF embryo’s did? Is this a known phenomenon?

reply
Dr. Geoffrey Sher

ICSI can in my opinion only improve matters. Perhaps the lab has not got the experience? Hard to say.

Intracytoplasmic Sperm Injection ICSI which began in 1992 as a treatment for severe male factor infertility, involves the direct injection of a single sperm into each egg under direct microscopic vision.
Soon after the turn of the 20th century it was reported that while the diagnosis of a male factor infertility had remained static, the use of ICSI had markedly increased and that indications for ICSI had expanded from solely male infertility (for which it had primarily been developed) to a wide variety of other indications such as “unexplained infertility, unexplained IVF failure, polycystic Ovarian Syndrome (PCOS) and cases where the woman’s eggs had become more resistant to conventional fertilization. ICSI was also being used in cases where sperm was absent (or virtually absent) from the ejaculate due to congenital or traumatic or medically acquired obstruction of the main collecting ducts (vasa deferentia), testicular failure and in cases where for traumatic, neurologic, or psychologi reasons (impotency) no semen/sperm was being ejaculated. In such cases, sperm obtained through Testicular Sperm Extraction (TESE), or aspiration (TESA) was being successfully used for ICSI. Today in the United states more than 70% of all IVF fertilizations are being conducted using ICSI with high fertilization and pregnancy rates being reported, regardless of sperm concentration, motility or morphology.
Clearly ICSI is increasingly replacing conventional insemination due to its many benefits and lack of definable drawbacks. In fact, pregnancy rates achieved by this method of fertilization are at least as high as those of conventional IVF performed in cases of non-male-factor infertility. Indeed, ICSI is associated with high fertilization and pregnancy rates regardless of sperm concentration, motility or morphology.
Notwithstanding, the above, the proposition that ICSI be preferentially used as the routine method for fertilizing eggs in IVF continues to meet with resistance. Die hards argue that about 1-3% of pregnancies resulting from ICS are associated with congenital developmental and genetic defects that affect the offspring. They cite conditions such as *Beckwith-Wiedemann syndrome, *Angelman syndrome, *hypospadias, sex chromosome abnormalities, a slightly increased miscarriage rate and the fact that male offspring resulting fom ICSI pregnancies are themselves at risk of subsequently developing male infertility in later life.

What you do not often hear from nay-sayers is that those studies that site the above mentioned risks do not distinguish between cases where ICSI is/was mandated for male infertility )and cases where ICSI is/was done for other (non-male infertility) reasons. If this was done, what in my opinion would emerge is that the above mentioned birth defects and developmental conditions are largely confined to the underlying male factor for which ICSI was indicated and are not due to the ICSI process itself. In fact a relatively recent study performed in Sweden demostrated this well. Here 542 children who were conceived naturally were compared with 941 children conceived through IVF (440 by conventional IVF & 541via ICSI) The babies/children were assessed at birth and during the first 5 years of life: The findings revealed that while the incidence of birth and developmental defects was indeed higher in ICSI babies, this only applied to cases where ICSI had been done for male infertility. It did not apply to cases where ICSI was done in the absence of male factor infertility.

Another very important consideration that supports the routine fertilization of eggs by ICSI is the fact that good quality IVF relies heavily on an ability to adequately assess egg maturation immediately following egg retrieval. To do this requires removal of layers of cumulus oophoris (CO) cells that cover the egg envelopment (zona pellucida). Only after the CO is stripped can the 1st polar body (PB-1) which is located immediately under the zona pellucida be identified and it is the presence of PB-1 signifies that indicates that the egg has gone through meiosis (reproductive division) and is thus mature (M2) and overwhelmingly, successful fertilzation and viable embryo development requires that the fertilized egg was mature (M2). This assessment for the presence of PB-1 cannot be reliably done without first removing the cumulus oophoris cells attached to the outer surface of the zona pellucida. The problem is that stripping the cumulus oophoris cells away, markedly reduces natural fertilization potential, leaving ICSI as the only alternative by which to subsequently achieve viable embryo propagation. The only way by which to avoid fertilization by ICSI would be to bypass the important step of assessing egg maturation and this in my opinion would compromize IVF outcome significantly. Thus optimization of the entire IVF process virtually mandates routine ICSI in IVF.
For the above reasons, I proudly count myself among a growing majority of IVF practitioners who support the routine use of ICSI for all IVF patients

*Angelman syndrome is a complex genetic disorder characterized by delayed development, intellectual disability, speech impairment, and problems with movement and balance (ataxia). Most cases are not inherited, particularly those caused by a deletion in the maternal chromosome 15 or by paternal uniparental disomy. These genetic changes are random events that take place during the formation of reproductive cells (eggs and sperm) or in early embryonic development.
*Beckwith-Wiedemann syndrome is a congenital growth disorder that causes large body size, large organs, and other symptoms. t results from a defect in the genes on chromosome 11. About 10% of cases can be passed down through families.
*Hypospadias: Hypospadias is a condition where the opening isn’t at the tip of the penis. Instead, it is located any place along the underside of the penis.

___________________________________________________________
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
Rose

Dr. Sher,
I am 43 years old. I had two IVF cycles done when I was 41, but got 4 abnormal embryos, which have been cryopreserved. Would you suggest transferring any of the following ? And in which order?
1. -18, -22
2. +15, -19, -22
3. -12
4. Del (8)(p11.2)

Thank you!

reply
Dr. Geoffrey Sher

I would transfer all except #2.

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.

Many 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, growing evidence suggests that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrect”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases having occurred in my own practice. 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 (“Mosaicism”) 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”.

Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies. The ability of mosaic embryos to autocorrect is influenced by stage of embryo development in which the diagnosis is made, which chromosomes are affected, whether the aneuploidy involves a single chromosome (simple) or involves 3 or more chromosomes (complex), and the percentage of cells that are aneuploid. Many embryos diagnosed as being mosaic prior to their development into blastocysts (in the cleaved state), subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) as they develop to blastocysts in the Petri dish. This is one reason why “mosaicism” is more commonly detected in early embryos than in blastocysts. Embryos with segmental mosaic aneuploidies, i.e. the addition (duplication) or subtraction (deletion), are also more likely to autocorrect. Finally, the lower the percentage of mitotically aneuploid (mosaic) cells in the blastocyst the greater the propensity for autocorrection and propagation of chromosomally normal (euploid) offspring. A blastocyst with <30% mosaicism could yield a 30% likelihood of a healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

As stated, the transfer of embryos with autosomal meiotic trisomy, will invariably result in failed implantation, early miscarriage or the birth of a defective child. Those with autosomal mitotic (“mosaic”) trisomies, while having the ability to autocorrect in-utero and result in the birth of a healthy baby can, depending on the percentage of mosaic (mitotically aneuploid) cells present, the number of aneuploid chromosomes and the type of mosaicism (single or segmental) either autocorrect and propagate a normal baby, result in failed implantation, miscarry or cause a birth defect (especially with trisomies 13, 18 or 21). This is why when it comes to giving consideration to transferring trisomic embryos, suspected of being “mosaic”, I advise patients to undergo prenatal genetic testing once pregnant and to be willing to undergo termination of pregnancy in the event of the baby being affected. Conversely, when it comes to meiotic autosomal monosomy, there is almost no chance of a viable pregnancy. in most cases implantation will fail to occur and if it does, the pregnancy will with rare exceptions, miscarry. “Mosaic” (mitotically aneuploid) autosomally monosomic embryos where a chromosome is missing), can and often will “autocorrect” in-utero and propagate a viable pregnancy. It is for this reason that I readily recommend the transfer of such embryos, while still (for safety sake) advising prenatal genetic testing in the event that a pregnancy results.

Given our ability to recognize “mosaicism” through karyotyping of embryos, the question arrases as to which “mosaic” embryos are capable of auto-correcting in-utero and propagating viable pregnancies. Research suggests that that virtually no autosomal monosomy embryos will propagate viable pregnancies. Thus, the transfer of such mosaic embryos is virtually risk free. Needless to say however, in any such cases, it is 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.

___________________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed IVF- treatment and related procedures on patients who, elected to travel to Las Vegas to be managed by me. However, with the launching of Sher-Fertility Solutions (SFS) in April 2019, I have taken on a new and expanded role. Now, rather than having hands-on involvement I confine my services to providing hour-long online Skype consultations to an ever-growing number of patients (emanating from >40 countries), with complex Reproductive problems, who seek access to my input, advice and guidance. All Skype consultations are followed by a detailed written report that meticulously describes and explains my recommendations for treatment. All patients are encouraged to share this report with their personal treating doctor(s), with whom [subject to consent and a request from their doctor] I will, gladly discuss their case with the “treating Physician”.
Through SFS I am now able to conveniently provide those who because of geography, convenience and cost, prefer to be treated at home or elsewhere by their chosen Infertility Physician.
“I wish to emphasize to all patients with whom I consult, that in the final analyses, when it comes to management, strategy, protocol and implementation of treatment, my advice and recommendations are always superseded by that of the hands-on treating Physician”.

Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 (in the U.S.A or Canada) or 702-533-2691, for an appointment. Patients can also enroll online on my website, http://www.SherIVF.com, or email Patti at concierge@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
Virali Shah

I just had IVF 4 days back. I was scheduled an hcg injection yesterday but I forgot. So I am planning to take it right now. But I would like to know if it will affect my chances of success if I missed the hcg injection yesterday and taking it 1 day late

reply
Dr. Geoffrey Sher

I am afraid that this could be quite problematic. Timing of the hCG trigger being critical.

Sorry!

Discuss with your RE.

Geoff Sher

reply
Alla Galanska

Hello Dr. Sher. I am 50 years old my husband is 52. I have transferred 2 embryos. Donor eggs, embryos tested for mutations. Endometrium 8 mm. 5 days before transfer. Embryos did not survive. Now I am preparing for a new protocol, they have appointed the same drugs in support, have not changed anything. advise what tests to do before the new protocol? Is it possible to push on changing the pattern? Alicia

reply
Dr. Geoffrey Sher

It could have to do with the protocol being used for ovarian stimulation in the donor.

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 a “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
For women doing conventional IVF with a fresh embryo transfer, I usually add dexamethasone 0.75mg daily from the start of gonadotropin stimulation to the 8th week of pregnancy (and then is tailed of and stopped by the 10th week) and human growth hormone (HGH) daily from the 1st day of Lupron, up until the trigger with hCG. Women who test positive for Natural killer cell activation (Nka), receive an Intralipid (IL) infusion 10-14 days prior to the projected embryo transfer This is repeated with a +ve beta hCG pregnancy test result.
Those women, who for a variety of reasons do frozen embryo transfers (FET) and thus do not undergo embryo transfer in the same cycle as the egg retrieval, can omit taking the dexamethasone in the cycle of ER, deferring such to the subsequent FET cycle. They do however take HGH throughout the stimulation with gonadotropin and if they test positive for Nka, they will also receive dexamethasone during hormonal preparation for FET (continued until the 8th week of pregnancy when this is tailed off over 2 weeks and stopped by the 10th week.
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
Danielle

Hello. I’m 32 years old and recently last year in October I donated eggs. I took the injections went to doctor visits every other day and I produced 32 eggs and 17 were healthy and the couple now has a healthy baby boy due in July 2019. I’ve gone to my fertility clinic, had blood tests done, everything looks great. I had a polyp removed surgically from my uterus and have been trying to conceive for 6 months now. I’m not sure what I’m doing wrong. I track my ovulation and assume because I have my period every month that I’m still producing eggs and my ovulation kit also said I was ovulating but it just seems like no matter what, every month I still get disappointed with not being pregnant. I had tried for 9 years and nothing happened but I also had a polyp in my uterus so I assume that was an issue like the fertility doctor told me. I’m at a loss and am ready to call it quits because I feel like no matter what I do or what vitamins I take that it’s just not meant to happen for me. It honestly hurts me to the point that sometimes I just go numb and dont even cry anymore over this. Is there any advice or suggestions that could possibly help my chances be higher? I’ve had a dye test done which we didnt even finish because it hurt so much that I couldnt sit through it. I just dont know what to do anymore…..

reply
Dr. Geoffrey Sher

Hi Danielle,

I sympathize. However, the fact that you produce good eggs does not rule out other causes of infertility such as an anatomical or immunologic implantation dysfunction or an overt/subtle male factor.

___________________________________________________________
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
Danielle

What exactly does that mean? I’m not sure what either of those mean that you stayed could be wrong?

reply
Dr. Geoffrey Sher

Please re-post your original question with my response and your new question. I have lost the thread!

Geoff Sher

reply
Danielle

Hello. I’m 32 years old and recently last year in October I donated eggs. I took the injections went to doctor visits every other day and I produced 32 eggs and 17 were healthy and the couple now has a healthy baby boy due in July 2019. I’ve gone to my fertility clinic, had blood tests done, everything looks great. I had a polyp removed surgically from my uterus and have been trying to conceive for 6 months now. I’m not sure what I’m doing wrong. I track my ovulation and assume because I have my period every month that I’m still producing eggs and my ovulation kit also said I was ovulating but it just seems like no matter what, every month I still get disappointed with not being pregnant. I had tried for 9 years and nothing happened but I also had a polyp in my uterus so I assume that was an issue like the fertility doctor told me. I’m at a loss and am ready to call it quits because I feel like no matter what I do or what vitamins I take that it’s just not meant to happen for me. It honestly hurts me to the point that sometimes I just go numb and dont even cry anymore over this. Is there any advice or suggestions that could possibly help my chances be higher? I’ve had a dye test done which we didnt even finish because it hurt so much that I couldnt sit through it. I just dont know what to do anymore…..

reply

Dr. Geoffrey SherApril 10th, 2019

Hi Danielle,

I sympathize. However, the fact that you produce good eggs does not rule out other causes of infertility such as an anatomical or immunologic implantation dysfunction or an overt/subtle male factor.

Dr. Geoffrey Sher

It is too soon to start being overly concerned. Yet, as I have pointed out, the fact that you produce good eggs does not exclude another underlying, unrelated factor such as an implantation dysfunction or male infertility.
___________________________________________________________
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

Brittany Carlson

Hello, I believe I have undiagnosed atypical PCOS. I have not ovulated since I came off of birth control in September 2018. My OB recently had me do a round of Provera and then Femera 2.5 mg and has not been monitoring me. I felt like I was about to ovulate and had all of the pre-ovulation signs and symptoms but the next day I did not have tender nipples which is always a sign I have after ovulation. All of my LH test strips were negative but they have remained fairly dark but never as dark as the control and have been this way for three weeks now. My basal body temp hasn’t risen either so I called my OB and she said to wait two weeks to see if I get my period. I do not believe I ovulated and I think the follicles that did develop turned into cysts because it feels like previous cysts that I have had. My OB also told me that BBT is not a reliable method to confirm ovulation and that I likely missed my LH surge. I’m wondering if I should just get back on birth control to resolve the cysts and then my first cycle off try another round of femara or what I should do? I have had one previous pregnancy five years ago that I had issues with but went to 37 weeks with a lot of medication and bedrest. I have luteal phase defect and low progesterone that I was taking progesterone supplements for when I was pregnant. I’m just not really sure if I am being managed properly or if I should go see a reproductive endocrinologist? I am sorry for the long message.

reply
Dr. Geoffrey Sher

I recommend we talk!

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
Paul

We have just had our first round of IVF. My wife has just turned 44. She had 13 eggs, 7 of which fertilized and 3 were sent for PGS (after ICSI). Sadly, none came back as normal. Is it worth our trying again – or has our time passed?

reply
Dr. Geoffrey Sher

It is really time to move to egg donor-IVF.

Egg donation is the process by which a woman donates eggs for purposes of assisted reproduction or biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro fertilization (IVF) technology, with the eggs being fertilized in the laboratory, unfertilized eggs may be frozen and stored for later use. Egg donation is a third party reproduction as part of assisted reproductive technology (ART).

For many women, disease and/or diminished ovarian reserve precludes achieving a pregnancy with their own eggs. Since the vast majority of such women are otherwise quite healthy and physically capable of bearing a child, egg donation (ED) provides them with a realistic opportunity of going from infertility to parenthood.

Egg donation is associated with definite benefits. Firstly, in many instances, more eggs are retrieved from a young donor than would ordinarily be needed to complete a single IVF cycle. As a result, there are often supernumerary (leftover) embryos for cryopreservation and storage. Secondly, since eggs derived from a young woman are less likely than their older counterparts to produce aneuploid (chromosomally abnormal) embryos, the risk of miscarriage and birth defects such as Down’s syndrome is considerably reduced.

Egg Donation-related, fresh and frozen embryo transfer cycles account for 10%-15% of IVF performed in the United States. The vast majority of egg donation procedures performed in the U.S involve women with declining ovarian reserve. While some of these are done for premature ovarian failure, the majority are undertaken in women over 40 years of age. Recurrent IVF failure due to “poor quality” eggs or embryos is also a relatively common indication for ED in the U.S. A growing indication for ED is in cases of same-sex relationships (predominantly female) where both partners wish to share in the parenting experience by one serving as egg provider and the other, as the recipient.

Ninety percent of egg donation in the U.S is done through the solicitation of anonymous donors who are recruited through a state-licensed egg donor agency. It is less common for recipients to solicit known donors through the services of a donor agency, although this does happen on occasion. It is also not easy to find donors who are willing to enter into such an open arrangement. Accordingly, in the vast majority of cases where the services of a known donor is solicited, it is by virtue of a private arrangement. While the services of non-family members are sometimes sought, it is much more common for recipients to approach close family members to serve as their egg donor.

Some recipients feel the compulsion to know or at least to have met their egg donor, so as to gain first hand familiarity with her physical characteristics, intellect, and character. This having been said, in the U.S. it is much more common to seek the services of anonymous donors. In terms of disclosure to their family, friends and child(ren), recipients using anonymous donors tend to be far more open than those of known donors about the nature of the child’s conception. Most, if not all, egg donor agencies provide a detailed profile, photos, medical and family history of each prospective donor for the benefit and information of the recipient. Agencies generally have a website through which recipients can access donor profiles in the privacy of their own homes in order to select the ideal donor.

Interaction between the recipient and the egg donor program may be conducted in-person, by telephone or online in the initial stages. Once the choice of a donor has been narrowed down to two or three, the recipient is asked to forward all relevant medical records to their chosen IVF physician. Upon receipt of her records, a detailed medical consultation will subsequently held and a physical examination by the treating physician or by a designated alternative qualified counterpart is scheduled. This entire process is usually overseen, facilitated and orchestrated by one of the donor program’s nurse coordinators who, in concert with the treating physician, will address all clinical, financial and logistical issues, as well as answering any questions. At the same time, the final process of donor selection and donor-recipient matching is completed.

Egg donor agencies usually limit the age of egg donors to women under 35 years with normal ovarian reserve in an attempt to minimize the risk of ovarian resistance and negate adverse influence of the “biological clock” (donor age) on egg quality.

No single factor instills more confidence regarding the reproductive potential of a prospective egg donor than a history of her having previously achieved a pregnancy on her own, or that one or more recipients of her eggs having achieved a live birth. Moreover, such a track record makes it far more likely that such an ED will have “good quality eggs”. Furthermore, the fact that an ED readily conceived on her own lessens the likelihood that she herself has tubal or organic infertility. This having been said, the current shortage in the supply of egg donors makes it both impractical and unfeasible, to confine donor recruitment to those women who could fulfill such stringent criteria for qualification.

It is not unheard of for a donor who, at some point after donating eggs, finds herself unable to conceive on her own due to pelvic adhesions or tubal disease, to blame her infertility on complications caused by the prior surgical egg retrieval process. She may even embark upon legal proceedings against the IVF physician and program. It should therefore come as no surprise that it provides a measurable degree of comfort to ED program when a prospective donor is able to provide evidence of having experienced a relatively recent, trouble free spontaneous pregnancy.

Screening of Donors
Genetic Screening: The vast majority of IVF programs in the U.S. follow the recommendations and guidelines of the American Society of Reproductive Medicine (ASRM) for selectively genetic screening of prospective egg donors for conditions such as sickle cell trait or disease, thalassemia, cystic fibrosis and Tay Sachs disease, when medically indicated. Consultation with a geneticist is available through about 90% of programs.

Most recipient couples place a great deal of importance on emotional, physical, ethnic, cultural and religious compatibility with their chosen egg donor. In fact they often will insist that the egg donor be heterosexual.

Psychological Screening: Americans tend to place great emphasis on psychological screening of egg donors. Since most donors are “anonymous,” it is incumbent upon the ED agency or the IVF program to determine the donor’s degree of commitment as well as her motivation for deciding to provide this service. I have on occasions encountered donors who have buckled under the stress and defaulted mid-stream during their cycle of stimulation with gonadotropins. In one case, a donor knowingly stopped administering gonadotropins without informing anyone. She simply awaited cancellation, which was effected when follicles stopped growing and her plasma E2 concentration failed to rise.

Such concerns mandate that assessment of donor motivation and commitment be given appropriate priority. Most recipients in the U.S. tend to be very much influenced by the “character” of the prospective egg donor, believing that a flawed character is likely to be carried over genetically to the offspring. In reality, unlike certain psychoses such as schizophrenia or bipolar disorders, character flaws are usually neuroses and are most likely to be determined by environmental factors associated with upbringing. They are unlikely to be genetically transmitted. Nevertheless, egg donors should be subjected to counseling and screening and should be selectively tested by a qualified psychologists. When in doubt, they should be referred to a psychiatrist for more definitive testing. Selective use of tests such as the MMPI, Meyers-Briggs and NEO-Personality Indicator are used to assess for personality disorders. Significant abnormalities, once detected, should lead to the automatic disqualification of such prospective donors.

When it comes to choosing a known egg donor, it is equally important to make sure that she was not coerced into participating. We try to caution recipients who are considering having a close friend or family member serve as their designated egg donor, that in doing so, the potential always exists that the donor might become a permanent and an unwanted participant in the lives of their new family.

Drug Screening: Because of the prevalence of substance abuse in our society, we selectively call for urine and/or serum drug testing of our egg donors.

Screening for STDs: FDA and ASRM guidelines recommend that all egg donors be tested for sexually transmittable diseases before entering into a cycle of IVF. While it is highly improbable that DNA and RNA viruses could be transmitted to an egg or an embryo through sexual intercourse or IVF, women infected with viruses such as hepatitis B, C, HTLV, HIV etc, must be disqualified from participating in IVF with egg donation due to the (albeit remote) possibility of transmission, as well as the potential legal consequences of the egg donation process being blamed for their occurrence.

In addition, evidence of prior or existing infection with Chlamydia or Gonococcus introduces the possibility that the egg donor might have pelvic adhesions or even irreparably damaged fallopian tubes that might have rendered her infertile. As previously stated, such infertility, subsequently detected might be blamed on infection that occurred during the process of egg retrieval, exposing the caregivers to litigation. Even if an egg donor or a recipient who carries a sexually transmittable viral or bacterial agent is willing to waive all rights of legal recourse, a potential risk still exists that a subsequently affected offspring might in later in life sue for wrongful birth.

Screening of the Recipient

Medical Evaluation: while advancing age, beyond 40 years, is indeed associated with an escalating incidence of pregnancy complications, such risks are largely predicable through careful medical assessment prior to pregnancy. The fundamental question namely: “is the woman capable of safely engaging a pregnancy that would culminate in the safe birth of a healthy baby” must be answered in the affirmative, before any infertility treatment is initiated. For this reason, a thorough cardiovascular, hepatorenal, metabolic and anatomical reproductive evaluation must be done prior to initiating IVF in all cases.

Infectious Screening: the need for careful infectious screening for embryo recipients cannot be overemphasized. Aside from tests for debilitating sexually transmittable diseases, there is the important requirement that cervical mucous and semen be free of infection with ureaplasma urealyticum. This organism which rarely causes symptoms frequents the cervical glands of 15-20% of women in the U.S. The introduction of an embryo transfer catheter via a so infected cervix might transmit the organism into an otherwise sterile uterine cavity leading to early implantation failure and/or first trimester miscarriage.

Immunologic Screening: Certain autoimmune and alloimmune disorders (see elsewhere) can be associated with immunologic implantation dysfunction (IID). In order to prevent otherwise avoidable treatment failure, it is advisable to evaluate the recipient for autoimmune IDD and also to test both the recipient and the sperm provider for alloimmune similarities that could compromise implantation.

Disclosure and Consent
Preparation for egg donation requires full disclosure to all participants regarding what each step of the process involves from start to finish, as well as potential medical and psychological risks. This necessitates that significant time be devoted to this task and that there be a willingness to painstakingly address all questions and concerns posed by all parties involved in the process. An important component of full disclosure involves clear interpretation of the medical and psychological components assessed during the evaluation process. All parties should be advised to seek independent legal counsel so as to avoid conflicts of interest that might arise from legal advice given by the same attorney. Appropriate consent forms are then reviewed and signed independently by the donor and the recipient couple.

Most embryo recipients fully expect their chosen donor to yield a large number of mature, good quality eggs, sufficient to provide enough embryos to afford a good chance of pregnancy as well as several for cryopreservation (freezing) and storage. While such expectations ore often met, this is not always the case. Accordingly, to minimize the trauma of unexpected and usually unavoidable disappointment, it is essential that in the process of counseling and of consummating agreements, the respective parties be fully informed that by making best efforts to provide the highest standards of care, the caregivers can only assure optimal intent and performance in keeping with accepted standards of care. No one can ever promise an optimal outcome. All parties should be made aware that no definitive representation can or will be made as to the number or quality of ova and embryos that will or are likely to become available, the number of supernumerary embryos that will be available for cryopreservation or the subsequent outcome of the IVF donor process.

TYPES OF EGG DONATION

Conventional Egg Donation: This is the basic format used for conducting the process of egg donor IVF. It involves synchronizing the menstrual cycles of both the recipient and the donor by placing the donor and the recipient on a birth control pill so that both parties start stimulation with fertility drugs simultaneously. This ultimately allows for precise timing of the fresh embryo transfer. Using this approach, the anticipated egg donation birth rate is >50% per cycle.

Preimplantation Genetic Sampling (PGS)-Egg Donation: The recent introduction of complete numerical chromosomal assessment (karyotyping) using metaphase Comparative Genomic Hybridization (mCGH) and Next Generation Gene sequencing (NGS) has the potential to change the manner in which egg donation will be performed in the future. CGH/NGS allows full egg/embryo chromosome analysis providing a 70- 80% assurance that the embryo(s) so selected for transfer are highly likely to be “competent” (i.e. capable of producing a healthy baby). Such PGS-egg selection provides about a 50% chance of a baby per transfer of an embryo derived through fertilization of a pre-vitrified euploid egg. This is at least double that reported when conventional egg donation is used. As a result, mCGH/NGS-Egg Donation allows for excellent results when one or two embryos are transferred, virtually eliminating the risk of “high order” multiple pregnancies (triplets or greater). Moreover, since numerical chromosomal irregularities (aneuploidy) are responsible for most miscarriages, the use of CGH also significantly reduces this dreaded complication.

PGS egg selection of necessity mandates the use of Staggered (ST)- IVF. Here the egg donor cycle is divided into two parts. The first involves the egg retrieval, fertilization, embryo biopsy for PGS analysis and embryo cryostorage. The second part involving warming or thawing of the frozen embryo(s) and the subsequent transfer of “competent” embryo(s) to the recipient’s uterus is conducted electively at least several weeks later once the results of PGS testing are available. Since, with St-IVF the egg retrieval and embryo transfer are separated in time, the retrieval can be performed without first having to synchronize the menstrual cycles of the recipient and the egg the donor. In fact, the recipient does not even have to be available when the egg donor is going through cycle. All that is needed is for designated sperm to be available (fresh or frozen) on the day of egg retrieval. This avoids unnecessary travel and inconvenience, and minimizes stress and cost.

Donor Egg Banking: Another imminent advance is the introduction of egg banking. Being able to freeze and bank donor eggs would solve most of these challenges. By using PGS in combination with a egg vitrification (ultra-rapid freezing), we are now capable of improving the birth rate per warmed/thawed egg by a factor of 3-4 fold (from a previous average of <8% per egg to about 27%). Through an electronic catalogue, recipients will be able to select and purchase 1-3 CGH-normal eggs from the comfort of their homes. Thereupon, the selective transfer of 1 or 2 embryos derived from such chromosomally normal eggs could achieve a 50-60% pregnancy rate without the risk of initiating high-order multiple pregnancies in the process. Through this process, the cost, inconvenience and risks associated with “conventional” fresh egg donor cycles would also be reduced significantly.

Financial Considerations
The fee paid to the egg donor agency per cycle usually ranges between $2,000 and $8,000. This does not include the cost associated with psychological and clinical pre-testing, fertility drugs, and donor insurance, which commonly range between $3,000 and $6,000. The medical service costs of the IVF treatment cycle ranges between $8,000 and $14,000. The donor stipend can range from $2,000 too as high $50,000 depending upon the exotic requirements of the recipient couple as well as supply and demand. Thus the total out of pocket expenses for an egg donor cycle in the United States range between $15,000 and $78,000, putting egg donation outside the financial capability of most couples needing this service.

The growing gap between need and affordability has spawned a number of creative ways to try and make IVF with egg donation more affordable. Here are a few examples:
• Egg banking (see above)
• Egg Donor Sharing, where one comprehensive fee is shared between two recipients and the eggs are then divided between them. The downside is that fewer eggs are available embryos for transfer and/or cryopreservation.
• Egg Bartering, where in the course of conventional IVF, a woman undergoing IVF remits some of her eggs to the clinic (who in turn provides it to a recipient patient) in exchange for a deferment of some or all of the IVF fee. In my opinion, such an arrangement can be fraught with problems. For example, in the event that the woman donating some of her eggs fails to conceive while the recipient of her eggs does, it is very possible that she might suffer emotional despair and even go so far as to seek out her genetic offspring. Such action could be very damaging to both her and the recipient, as well as the child.
• Financial Risk Sharing. Certain IVF programs offer financial risk sharing (FRS) which most recipient couples favor greatly. FRS offers qualifying candidates a refund of fees paid if egg donation is unsuccessful. FRS is designed to spread the risk between the providers, and the recipient couple.

Moral, Legal & Ethical Considerations: The “Uniform Parentage Act” which has been adopted by most states in the United States declares that the woman who gives birth to the child will be regarded as the rightful mother. Accordingly, there has to date not been any grounds for legal dispute when it comes to maternal custody of a child born through IVF with egg donation in the majority of states. In a few states such as Mississippi and Arizona the law is less clear but nevertheless, as yet, has not been contested.

The moral-ethical and religious implications of egg donation are diverse and have a profound effect on cultural acceptance of this process. The widely held view that everyone is entitled to their own opinion and has the right to have such opinions respected, governs much of the attitude towards this process in the U.S. The extreme views on each end of the spectrum hold the gentle central swing of the pendulum in place. This attitude is a reflection of the general acceptance in the united states of diverse views and opinions and the willingness to allow free expression of such views and beliefs provided that they don’t infringe on the rights of others.

So where do we go from here? Can and should we, cryopreserve and store eggs or ovarian tissue from a young woman wishing to defer procreation until it becomes convenient? And if we do this, would it be acceptable to eventually have a woman give birth to her own sister or aunt? Can or should we store viable ovarian tissue through generations. Should egg donation simply become a future source of embryos generated for the purpose of providing stem cells, to be used in the treatment of disease states or to “manufacture” fetuses as a source of spare body parts? If the answer to even some of these questions is yes…what about the checks and balances. Who will exercise control and where what form should such control take? Are we willing to engage this slippery slope where the disregard for the dignity of the human embryo leads us to the point where the rights of a human being are more readily ignored? …………………… Personally, I hope not.

___________________________________________________________
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
MB

Dear Dr. Sher,

I just turned 40 and my husband just turned 38. We have been trying to conceive for about 2 years. My husband has low morphology and motility with a diagnosis of male factor (MF) infertility but we are also dealing with my age and egg quality despite a high AMH for my age. My AMH is 2.8. I am heterozygous for the MTHFR mutation, and my husband is homozygous for the C677T MTHFR mutation. We both take methylated folate supplementation. In addition, I take a number of supplements, which I began after reading “It Starts with the Egg” and joining its Facebook forum and hearing account after account of how implementing the following supplements would make a huge difference in egg quality: CoQ10, melatonin, Vitex, NAC, Vit D, Vit E, alpha lipoic acid, and 75mg of DHEA daily. I had only started the supplements (having just read the book) a few weeks prior to my IVF cycle 2 (in October) and then gave myself the full suggested 3 months to prepare for cycle 3 last month (in March). My other medications include Adderall and occasional Ambien. My husband takes Fertile Aid and CoQ10; his medications include Paxil and Abilify for depression, as well as Arimidex and Clomid to try and boost testosterone (currently at level of 480).

Here are the results of our 3 IVF cycles. Cycle 1 (Microdose Lupron protocol with 150 Menopur, 300 Gonal-F) = 18 eggs retrieved, 14 mature, 13 fertilized with ICSI, 4 blastocysts sent out for PGS testing, 0 PGS normal. Cycle 2 (antagonist co-flare protocol, with Lupron first three days, then add in Cetrotide later, also still with 150 Menopur, 300 Gonal-F; added Omnitrope, human growth hormone (HGH) 42 units a day for 5 days before retrieval) =19 eggs retrieved, 13 mature, 8 fertilized with ICSI, 5 blastocysts sent for out for PGS testing, 1 PGS normal. Cycle 3 (antagonist co-flare protocol, same as cycle 2 but did 6 days of HGH prior to retrieval) = 18 retrieved, 12 mature, 11 fertilized with ICSI, 2 blastocysts send out for PGS testing, 0 normal embryos.

We have several questions numbered for your convenience:
(1) We were shocked that our cycle 3 was worse after implementing all the suggested supplements from the book and eliminating products with fragrance, phthalates, parabens, BPA, etc. I felt like this was going to be our best cycle ever and hopefully our last (our goal is to bank 2 more normal embryos giving us a total of 3 as we’d love to have at least 2 children). We’ve recently heard from one person that DHEA can “neutralize” the effects of HGH, and read everything on your blog about DHEA being potentially harmful in women age 40 and up doing IVF. Do you think that could’ve happened here? What do you know about effects of HGH taken with DHEA?
(2) Would it be beneficial to use HGH for longer than the 5-6 days before retrieval? I read in your blog that HGH needs to be given in a very specific time frame. It looks like this coincided with when my RE had us use it leading up to retrieval, but I’m not sure. We’ve heard mixed reviews, as someone used it for a full month prior to her retrieval and it seemed to make all the difference in doubling her PGS normal tested embryos and was her best cycle. Can using it for longer than a week ever be beneficial?
(3) What are your thoughts on using PICSI? Is that something that your clinic offers? (4) Does the MTHFR mutation play into any of this? Is there more you would suggest we could do for our MTHFR?
(5) We know we have MF and this looks like it could very well be an egg quality issue as well, but is it worth it to rule out sperm DNA fragmentation by doing testing?
(6) After reading all this, do you have any general suggestions of where we should go from here or next steps?
Thank you so much!

reply
Dr. Geoffrey Sher

Respectfully,

Quite honestly, this is not about PICSI, HGH usage or even the taking of DHEA (which I personally discourage). It is in my opinion about the protocol used for ovarian stimulation.I do not belive that the protocols used are optimal.

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
MB

Thank you Dr. Sher,

As a follow up, would you recommend transferring any of our following abnormals below? Especially curious on our Mosaic as even that has 2 complexities

C1 –
Abnormal Monosomy 21
Abnormal Monosomy 13, Monosomy 16
Abnormal Complex Aneuploidy
Abnormal Mosaic segmental loss on chr 7, Mosaic monosomy 22
—— Detailed results for complex aneuploid embryos and segmental copy number changes:
Trisomy 13
Monosomy 15
Trisomy 19
Mosaic 58.3 Mb deletion on 7q22.1-q36.3(100,545,461-158,810,314)

C2 –
Abnormal Complex Aneuploidy
Abnormal Trisomy 12, Monosomy 19
Abnormal Segmental loss on chr 8
Abnormal Segmental loss on chr 6
—–Detailed results for complex aneuploid embryos and segmental copy number changes:
6174-1
Trisomy 15
Monosomy 20
Trisomy 21

C3-
Abnormal Monosomy 19, Trisomy 20
Abnormal Trisomy 20, Monosomy 21

reply
Dr. Geoffrey Sher

Here are the ones I might consider transferring preferentially:
Abnormal Monosomy 21
Abnormal Monosomy 13, Monosomy 16
Trisomy 13
Monosomy 15
Trisomy 19
Mosaic 58.3 Mb deletion on 7q22.1-q36.3(100,545,461-158,810,314)

Abnormal Segmental loss on chr 8
Abnormal Segmental loss on chr 6

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

C3-
Abnormal Monosomy 19, Trisomy 20
Abnormal Trisomy 20, Monosomy 21

reply
Natashia

Hi Dr Sher,
I’m currently 7 weeks ‘pregnant’ from last FET and facing miscarriage. Our embryo today was measuring 1.6mm (some 5.5 week sized with a gestational sac a fair bit larger around – maybe 20mm) and no heart beat detected. Our embryo was genetically tested and competent Day 5 blastocyst. I have quite elevated NK cells (seen from uterine biopsy measuring high powered fields- I think at a rate of 30 cells per HPF) and have been on prednisolone since day 1, clexane since embryo transfer and intralipid 10 days before transfer and at week 5. Embryo glue was used also during u/s guided transfer.

Perhaps relevant to the story, I had my right tube out last year due to hydrosalpinx and have AMH level of 14pmol/L.

I’m due to return for pelvic u/s at week 8 to ‘call it’ and if there is no heart beat and growth, likely for a D&C.

In your experience, what do you think of this scenario and possibility of viability? Is a week enough to ‘call it’ if no heart beat on next scan?

What would you recommend as next steps if no heart beat? D&C?

Can I jump on the next stimulation cycle straight after D&C (no more embryos in storage).

Thank you kindly,

Natashia

reply
Dr. Geoffrey Sher

I would give it 1 more week to be certain. Thereupon if there is no viable pregnancy, I would indeed do a D&C.

Geoff Sher

reply
Natasha

Hi Dr Sher,

Tomorrow I am going for D&C for non viable IVF pregnancy (8 weeks). I plan to start my second round of IVF when I next get my period.

1st and only cycle so far, I did antagonist protocol and got 9 eggs (7 mature), 3 to blastocyst stage and 2 were genetically euplopid. We did a freeze all because I had a salphingectomy in between for hydrosalpinx. 1st FET was a chemical (HCG was 7), 2nd went really well (appropriately doubling HCG) until 7 week scan and found to be non viable (with repeat scan a week later).

I am 36 years old. My AHM IS 14pmol/L and have elevated NK cells on uterine biopsy (30 per high powered field) which saw me take intralipid, mini aspirin, clexane, and prednisone. I’ve long been on CoQ10, melatonin, antioxidants etc. We’ve just tested MTHFR genotype after miscarriage and I am heterozygous for MTHFRA1298C and my homocysteine levels are 4micromol/L. Most of the rest of my immunology work up is normal other than a slightly low Protein S free (45) tested during failing pregnancy. No male factor whatsoever.

Interestingly, I conceived my son (who just turned 4) the first month of trying naturally without any complication, other than being birthed quite a big boy (tall).

My RE wants to add hydroxychloroquinone next cycle as I have a family history of various autoimmune diseases and she is going to slightly bump up the dose of stimulants.

My question is;
1. What do you think of hydroxychloroquinine in this setting?
2. Would you do anything significantly different in the stimulation or immunotherapy regimes?
3. Could there be anything key ‘missing’ or perhaps I should just expect it is bad luck?

Thank you kindly for your time to reply

reply
Dr. Geoffrey Sher

First off, in my opinion, it is too soon to go directly into another cycle. Take one or two months off to allow your ovaries to recover before trying again. In my opinion, there is absolutely no evidence of a befit in using hydrochloroquine. You have an immunologic Implantation dysfunction: See below.

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

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
M

I’m trying to decide whether an IVF attempt is worth it with my own eggs or if I should just jump right to donor eggs. My doctor gave me a 10% chance of success with my own eggs. I’m 42, AFC – 8, AMH – 1.43. Any advice would be great. Thank you!

reply
Dr. Geoffrey Sher

Hi Amie…We absolutely need to tyalk (see below).

In my opinion, this has to do with selecting an optimal protocol for ovarian stimulation ASAP. Your age and diminishing ovarian reserve means that you are fast running out of time on the biological clock.

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
Jane

Dear Dr. Sher,
I am a 29-year old woman. Due to dysmenorhoea, my father (who is also a MD) suspected endometriosis already a year ago but this was contradicted by 2 gynaecologists. So we stopped with anticonception and started trying to conceive with high hopes. After 6 months of trying, I was pregnant but at 7 weeks, a blighted ovum was diagnosed. Misoprostol was subscribed to expel the foetus. After that, I had an MRI which did reveal deep endometriosis (sacro-uterine ligament, recto-sigmoid, rectovaginal). Luckily, there are no endometriomas on the ovaries and based on the hysteropscopy and MRI, the uterus looks fine without any adenomyosis. I was advised not to have surgery, but to start IVF, so we did. I had gonapeptyl and was stimulated with 150/187,5 dose Menopur for 12 days. In addition, I also tested slightly positive for APA (anticardiolipine IgG was 23 U/ml, cut off value is <20 U/ml). Homocystein was normal at 9 nmol/ml. For this, the fertility center prescribed low dose aspirin (80mg) and low dose steroids (prednisolone 10mg) that I take once a day starting from egg retrieval. My husband's sperm is superb. Result from IVF: I had 9 eggs, 7 fertilized (3/5 by IVF and 4/4 with ICSI). At day 5, I had only one 3AA embryo, which was transferred this morning, one 3CC embryo from the IVF group, the other embryo from the IVF group stopped developing at day 3. The 4 embryo's from the ICSI group, had not reached blastocyst stage this morning. We hope they would reach an AA stage by tomorrow. They were all behind, in the same stage. I am very worried about my embryo quality and terrified that if this one does not stick, I have no frozen embryo's, which I did not expect for my age. Is there anything else we can test or do?

reply
Dr. Geoffrey Sher

I fully comprehend your situation. I think I can be of substantive help here but we would need to talk (see below). Here is an explanation for how endometriosis impacts fertility and a broad outline of the approach needed.

Endometriosis is a condition that occurs when the uterine lining (endometrium) grows not only in the interior of the uterus but in other areas, such as the fallopian tubes, ovaries and the bowel. Endometriosis is a complex condition where, the lack or relative absence of an overt anatomical barrier to fertility often belies the true extent of reproductive problem(s).

All too often the view is expounded that the severity of endometriosis-related infertility is inevitably directly proportionate to the anatomical severity of the disease itself, thereby implying that endometriosis causes infertility primarily by virtue of creating anatomical barriers to fertilization. This over-simplistic and erroneous view is often used to support the performance of many unnecessary surgeries for the removal of small innocuous endometriotic lesions, on the basis of such “treatment” evoking an improvement in subsequent fertility.

It is indisputable that even the mildest form of endometriosis can compromise fertility. It is equally true that, mild to moderate endometriosis is by no means a cause of absolute “sterility”.

Rather, when compared with normally ovulating women of a similar age who do not have endometriosis, women with mild to moderate endometriosis are about four to six times less likely to have a successful pregnancy.

Endometriosis often goes unnoticed for many years. Such patients are frequently, erroneously labeled as having “unexplained infertility”, until the diagnosis is finally clinched through direct visualization of the lesions at the time of laparoscopy or laparoscopy. Not surprisingly, many patients with so called “unexplained” infertility, if followed for a number of years, will ultimately reveal endometriosis.

Women who have endometriosis are much more likely to be infertile. There are several reasons for this:

• First-Ovulation Dysfunction: In about 25 – 30% of cases, endometriosis is associated with ovulation dysfunction. Treatment requires controlled ovarian stimulation (COS). The problem is that the toxic pelvic environment markedly reduces the likelihood that anything other than IVF will enhance pregnancy potential.
• Second- Toxic Pelvic environment that compromises Fertilization Endometriosis is associated with the presence of toxins in peritoneal secretions while it is tempting to assert that normally ovulating women with mild to moderate endometriosis would have no difficulty in conceiving if their anatomical disease is addressed surgically or that endometriosis-related infertility is confined to cases with more severe anatomical disease…nothing could be further from the truth. The natural conception rate for healthy ovulating women in their early 30’s (who are free of endometriosis) is about 15% per month of trying and 70% per year of actively attempting to conceive. Conversely, the conception rate for women of a comparable age who have mild or moderate pelvic endometriosis (absent or limited anatomical disease) is about 5-6% per month and 40% after 3 years of trying. As sperm and egg(s) travel towards the fallopian tubes they are exposed to these toxins which compromise the fertilization process. In fact it has been estimated that there is a 5-6 fold reduction in fertilization potential because of these toxins which cannot be eradicated. Frankly, it really does not matter whether an attempt is made to remove endometriosis deposits surgically as this will not improve pregnancy potential. The reason is that for every deposit observed, there are numerous others that are in the process of developing and are not visible to the naked eye and whether visible or not, such translucent deposits still produce toxins. This also explains why surgery to remove visible endometriosis deposits, controlled ovarian stimulation with or without intrauterine insemination will usually not improve pregnancy potential. Only IVF, through removing eggs before they are exposed to the toxic pelvic environment, fertilizing them in-vitro and then transferring the embryos to the uterus represents the only way to enhance pregnancy potential.
• Third-Pelvic adhesions and Scarring: In its most severe form, endometriosis is associated with scarring and adhesions in the pelvis, resulting in damage to, obstruction or fixation of the fallopian tubes to surrounding structures, thereby preventing the union of sperm and eggs.
• Fourth-Ovarian Endometriomas, Advanced endometriosis is often associated with ovarian cysts (endometriomas/chocolate cysts) that are filled with altered blood and can be large and multiple. When these are sizable (>1cm) they can activate surrounding ovarian connective tissue causing production of excessive male hormones (androgens) such as testosterone and androstenedione. Excessive ovarian androgens can compromise egg development in the affected ovary (ies) resulting in an increased likelihood of numerical chromosomal abnormalities (aneuploidy) and reduced egg/embryo competency”. In my opinion large ovarian endometriomas need to be removed surgically or rough sclerotherapy before embarking on IVF.
• Fifth- Immunologic Implantation Dysfunction (IID). Endometriosis, regardless of its severity is associated with immunologic implantation dysfunction linked to activation of uterine natural killer cells (NKa) and cytotoxic uterine lymphocytes (CTL) in about 30 of cases. This is diagnosed by testing the woman’s blood for NKa using the K-562 target cell test or by endometrial biopsy for cytokine analysis, and, for CTL by doing a blood immunophenotype. These NKa attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in death of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or even an early miscarriage. . As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.

Advanced Endometriosis: In its most advanced stage, anatomical disfiguration is causally linked to the infertility. In such cases, inspection at laparoscopy or laparoscopy will usually reveal severe pelvic adhesions, scarring and “chocolate cysts”. However, the quality of life of patients with advanced endometriosis is usually so severely compromised by pain and discomfort, that having a baby is often low on the priority list. Accordingly, such patients are usually often more interested in relatively radical medical and surgical treatment options (might preclude a subsequent pregnancy), such as removal of ovaries, fallopian pubis and even the uterus, as a means of alleviating suffering.

Moderately Severe Endometriosis. These patients have a modest amount of scarring/ adhesions and endometriotic deposits which are usually detected on the ovaries, fallopian tubes, bladder surface and low in the pelvis, behind the uterus. In such cases, the fallopian tubes are usually opened and functional.

Mild Endometriosis: These patients who at laparoscopy or laparotomy are found to have no significant distortion of pelvic anatomy are often erroneously labeled as having “unexplained” infertility. To hold that the there can only infertility can only be attributed to endometriosis if significant anatomical disease can be identified, is to ignore the fact that, biochemical, hormonal and immunological factors profoundly impact fertility. Failure to recognize this salient fact continues to play havoc with the hopes and dreams of many infertile endometriosis patients.

TREATMENT:
The following basic concepts apply to management of endometriosis-related infertility:

1. Controlled Ovulation stimulation (COS) with/without intrauterine insemination (IUI): Toxins in the peritoneal secretions of women with endometriosis exert a negative effect on fertilization potential regardless of how sperm reaches the fallopian tubes. This helps explain why COS with or without IUI will usually not improve the chances of pregnancy (over no treatment at all) in women with endometriosis. IVF is the only way by which to bypass this problem.
2. Laparoscopy or Laparotomy Surgery aimed at restoring the anatomical integrity of the fallopian tubes does not counter the negative influence of toxic peritoneal factors that inherently reduce the chances of conception in women with endometriosis four to six fold. Nor does it address the immunologic implantation dysfunction (IID) commonly associated with this condition. Pelvic surgery is relatively contraindicated for the treatment of infertility associated with endometriosis, when the woman is more than 35 years of age. With the pre-menopause approaching, such women do not have the time to waste on such less efficacious alternatives. In contrast, younger women who have time on their side might consider surgery as a viable option. Approximately 30 -40 percent of women under 35 years of age with endometriosis will conceive with in two to three years following corrective pelvic surgery.
3. Sclerotherapy for ovarian endometriomas (“chocolate” cysts). About 15 years ago I introduced “sclerotherapy”, a relatively non-invasive, safe and effective outpatient method to permanently eliminate endometriomas without surgery being required. Sclerotherapy for ovarian endometriomas involves needle aspiration of the liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline into the cyst cavity. Treatment results in disappearance of the lesion within 6-8 weeks, in more than 75% of cases so treated. Ovarian sclerotherapy can be performed under local anesthesia or under general anesthesia. It has the advantage of being an ambulatory office- based procedure, at low cost, with a low incidence of significant post-procedural pain or complications and the avoidance of the need for laparoscopy or laparotomy
4. The role of selective immunotherapy More than half of women who have endometriosis harbor antiphospholipid antibodies (APA) that can compromise development of the embryo’s root system (trophoblast). In addition and far more serious, is the fact that in about one third of cases endometriosis, regardless of its severity is associated with NKa and cytotoxic uterine lymphocytes (CTL) which can seriously jeopardize implantation. This immunologic implantation dysfunction (IID) is diagnosed by testing the woman’s blood for APA, for NKa (using the K-562 target cell test or by endometrial biopsy for cytokine activity) and, for CTL (by a blood immunophenotype). Activated NK cells attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in rejection of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or an early miscarriage. . As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.

Women who harbor APA’s often experience improved IVF birth rates when heparinoids (Clexane/Lovenox) are administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy. NKa is treated with a combination of Intralipid (IL) and steroid therapy: Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating NKa.

The therapeutic effect of IL/steroid therapy is likely due to an ability to suppress pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. IL/steroids down-regulates NKa within 2-3 weeks of treatment the vast majority of women experiencing immunologic implantation dysfunction. In this regard IL is just as effective as Intravenous Gamma globulin (IVIg) but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.

5. The role of IVF: The toxic pelvic environment caused by endometriosis, profoundly reduces natural fertilization potential. As a result normally ovulating infertile women with endometriosis and patent Fallopian tubes are much less likely to conceive naturally, or by using fertility agents alone (with or without intrauterine (IUI) insemination. The only effective way to bypass this adverse pelvic environment is through IVF. I am not suggesting here that all women who have endometriosis require IVF! Rather, I am saying that in cases where the condition is further compromised by an IID associated with NKa and/or for older women(over 35y) who have diminished ovarian reserve (DOR) where time is of the essence, it is my opinion that IVF is the treatment of choice.

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:
• 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; hHow it Works; Administration; Side-effects; Reactions and Precautions
• 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
• How Many Embryos should be transferred: A Critical Decision in IVF.
• Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF
• Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice.
• Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options
• Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination-IUI) and Reproductive Surgery Versus IVF
• Treating Ovarian Endometriomas with Sclerotherapy.
• Effect of Advanced Endometriosis with Endometriotic cysts (Endometriomas) on IVF Outcome & Treatment Options.
• Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
• Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s &
• Induction of Ovulation with Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its use
• Clomiphene Induction of Ovulation: Its Use and Misuse!
___________________________________________________________
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
Katarina Gajić Holder

Greetings Dr. Sher,
I have a 4 year old son from IVF, where my problem was endometriosis, and my husband had very poor morphology. Fast forward to now, we ve been trying for a second child, both naturally and through 2 KET’s of the frozen embies we had from the first IVF, but no success. After doctors did their bloodwork and sperm check they claim my endometriosis is gone, and my husband morphology is good now, and he can even be a donor at this point.
So in these last 2 years we ve been trying to get pregnant again, its always the same thing. Every couple of months I get pregnant, start feeling symptoms (as I did very early on with my son too), one or two tests come out positive and then around my period the symptoms go away and period of course comes. Same pattern happened with the 2 KET’s we had. So even though Im seemingly healthier now than I was with my son, and so is my husband, now I keep having these chemicals.
Any advice on why this could be happening, or maybe which further testing to do would be much appreciated. If I couldnt get pregnant it would be somehow easier to make my peace with it, but this kind of “teasing” I get every few months is simply heartbreaking.
Thank You in advance for your thoughts and suggestions,

Katarina

reply
Dr. Geoffrey Sher

It seems to me that you have developed a probable endometriosis-related implantation dysfunction…probably immunologic in nature. I think you might benefit from a discussion with me (see below).

More than half of women who have endometriosis harbor antiphospholipid antibodies (APA) that can compromise development of the embryo’s root system (trophoblast). In addition and far more serious, is the fact that in about one third of cases endometriosis, regardless of its severity is associated with uterine natural killer cell activation (Nka) and cytotoxic uterine lymphocytes (CTL) which can seriously jeopardize implantation. This immunologic implantation dysfunction (IID) is diagnosed by testing blood for APA, for NKa (using the K-562 target cell test or by endometrial biopsy for cytokine activity) and, for CTL (by a blood immunophenotype). NKa cells attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in rejection of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or an early miscarriage. As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.

Women who harbor APA’s often experience improved IVF birth rates when heparinoids (Clexane/Lovenox) are administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy. NKa is treated with a combination of Intralipid (IL) and steroid therapy: Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating NKa.

The therapeutic effect of IL/steroid therapy is likely due to an ability to suppress pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. IL/steroids down-regulates NKa within 2-3 weeks of treatment the vast majority of women experiencing immunologic implantation dysfunction. In this regard IL is just as effective as Intravenous Gamma globulin (IVIg) but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.

The toxic pelvic environment caused by endometriosis, profoundly reduces natural fertilization potential. As a result normally ovulating infertile women with endometriosis and patent Fallopian tubes are much less likely to conceive naturally, or by using fertility agents alone (with or without intrauterine (IUI) insemination. The only effective way to bypass this adverse pelvic environment is through IVF. I am not suggesting here that all women who have endometriosis require IVF! Rather, I am saying that in cases where the condition is further compromised by an IID associated with NKa and/or for older women(over 35y) who have diminished ovarian reserve (DOR) where time is of the essence, it is my opinion that IVF is the treatment of choice.

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:
• 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!
• 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
• How Many Embryos should be transferred: A Critical Decision in IVF?
• Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF
• Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice.
• Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options
• Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination-IUI) and Reproductive Surgery Versus IVF
• Treating Ovarian Endometriomas with Sclerotherapy.
• Effect of Advanced Endometriosis with Endometriotic cysts (Endometriomas) on IVF Outcome & Treatment Options.
• Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
• Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s &
• Induction of Ovulation with Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its use
• Clomiphene Induction of Ovulation: Its Use and Misuse!

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
Amanda Chang

hi dr,

i have the only mosaic chromosome 21 loss embryo post pgs testing (25%). may i know your suggestion if i should transfer it?

reply
Dr. Geoffrey Sher

Yes! I would transfer it.

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.

Many 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, growing evidence suggests that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrect”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases having occurred in my own practice. 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 (“Mosaicism”) 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”.

Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies. The ability of mosaic embryos to autocorrect is influenced by stage of embryo development in which the diagnosis is made, which chromosomes are affected, whether the aneuploidy involves a single chromosome (simple) or involves 3 or more chromosomes (complex), and the percentage of cells that are aneuploid. Many embryos diagnosed as being mosaic prior to their development into blastocysts (in the cleaved state), subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) as they develop to blastocysts in the Petri dish. This is one reason why “mosaicism” is more commonly detected in early embryos than in blastocysts. Embryos with segmental mosaic aneuploidies, i.e. the addition (duplication) or subtraction (deletion), are also more likely to autocorrect. Finally, the lower the percentage of mitotically aneuploid (mosaic) cells in the blastocyst the greater the propensity for autocorrection and propagation of chromosomally normal (euploid) offspring. A blastocyst with <30% mosaicism could yield a 30% likelihood of a healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

As stated, the transfer of embryos with autosomal meiotic trisomy, will invariably result in failed implantation, early miscarriage or the birth of a defective child. Those with autosomal mitotic (“mosaic”) trisomies, while having the ability to autocorrect in-utero and result in the birth of a healthy baby can, depending on the percentage of mosaic (mitotically aneuploid) cells present, the number of aneuploid chromosomes and the type of mosaicism (single or segmental) either autocorrect and propagate a normal baby, result in failed implantation, miscarry or cause a birth defect (especially with trisomies 13, 18 or 21). This is why when it comes to giving consideration to transferring trisomic embryos, suspected of being “mosaic”, I advise patients to undergo prenatal genetic testing once pregnant and to be willing to undergo termination of pregnancy in the event of the baby being affected. Conversely, when it comes to meiotic autosomal monosomy, there is almost no chance of a viable pregnancy. in most cases implantation will fail to occur and if it does, the pregnancy will with rare exceptions, miscarry. “Mosaic” (mitotically aneuploid) autosomally monosomic embryos where a chromosome is missing), can and often will “autocorrect” in-utero and propagate a viable pregnancy. It is for this reason that I readily recommend the transfer of such embryos, while still (for safety sake) advising prenatal genetic testing in the event that a pregnancy results.

Given our ability to recognize “mosaicism” through karyotyping of embryos, the question arrases as to which “mosaic” embryos are capable of auto-correcting in-utero and propagating viable pregnancies. Research suggests that that virtually no autosomal monosomy embryos will propagate viable pregnancies. Thus, the transfer of such mosaic embryos is virtually risk free. Needless to say however, in any such cases, it is 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.

___________________________________________________________
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
Beth

Hi Dr. Sher,
I am currently pregnant from IVF. I am 26 weeks. I am writing to ask your opinion on 2 subjects. First, I have been having almost weekly sonograms since becoming pregnant due to being AMA and high risk. I am now reading that sonograms could be dangerous and cause autism potentially? I’m horrified to read this and wondering what damage I have done. Second, I have MFTHR and have been on Metanx since concieving. I recently had my folate level tested and it was off the charts high. I just read that high folate in pregnancy has been linked to a much higher rate of autism. I feel like I can’t win here. Why would my doctor be pushing things that are not safe for my baby? I’m so stressed out now thinking I have done wrong by my baby. I have been reading your blog for years and would love to hear your opinion on these controversial issues. Thanks

reply
Dr. Geoffrey Sher

To be very candid, I do not believe thee is any substantive evidence to support either of these concerns.

Congratulations and good luck!

Geoff Sher

reply
Dr. Geoffrey Sher

Yes I would! But discuss with your RE.

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.

Many 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, growing evidence suggests that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrect”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases having occurred in my own practice. 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 (“Mosaicism”) 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”.

Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies. The ability of mosaic embryos to autocorrect is influenced by stage of embryo development in which the diagnosis is made, which chromosomes are affected, whether the aneuploidy involves a single chromosome (simple) or involves 3 or more chromosomes (complex), and the percentage of cells that are aneuploid. Many embryos diagnosed as being mosaic prior to their development into blastocysts (in the cleaved state), subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) as they develop to blastocysts in the Petri dish. This is one reason why “mosaicism” is more commonly detected in early embryos than in blastocysts. Embryos with segmental mosaic aneuploidies, i.e. the addition (duplication) or subtraction (deletion), are also more likely to autocorrect. Finally, the lower the percentage of mitotically aneuploid (mosaic) cells in the blastocyst the greater the propensity for autocorrection and propagation of chromosomally normal (euploid) offspring. A blastocyst with <30% mosaicism could yield a 30% likelihood of a healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

As stated, the transfer of embryos with autosomal meiotic trisomy, will invariably result in failed implantation, early miscarriage or the birth of a defective child. Those with autosomal mitotic (“mosaic”) trisomies, while having the ability to autocorrect in-utero and result in the birth of a healthy baby can, depending on the percentage of mosaic (mitotically aneuploid) cells present, the number of aneuploid chromosomes and the type of mosaicism (single or segmental) either autocorrect and propagate a normal baby, result in failed implantation, miscarry or cause a birth defect (especially with trisomies 13, 18 or 21). This is why when it comes to giving consideration to transferring trisomic embryos, suspected of being “mosaic”, I advise patients to undergo prenatal genetic testing once pregnant and to be willing to undergo termination of pregnancy in the event of the baby being affected. Conversely, when it comes to meiotic autosomal monosomy, there is almost no chance of a viable pregnancy. in most cases implantation will fail to occur and if it does, the pregnancy will with rare exceptions, miscarry. “Mosaic” (mitotically aneuploid) autosomally monosomic embryos where a chromosome is missing), can and often will “autocorrect” in-utero and propagate a viable pregnancy. It is for this reason that I readily recommend the transfer of such embryos, while still (for safety sake) advising prenatal genetic testing in the event that a pregnancy results.

Given our ability to recognize “mosaicism” through karyotyping of embryos, the question arrases as to which “mosaic” embryos are capable of auto-correcting in-utero and propagating viable pregnancies. Research suggests that that virtually no autosomal monosomy embryos will propagate viable pregnancies. Thus, the transfer of such mosaic embryos is virtually risk free. Needless to say however, in any such cases, it is 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.

___________________________________________________________
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
Sonya

Hi Dr Sher,
Just wanted to share an update with you – following my sluggish second beta, my third rose nicely, and everything appears to be on track. I had my first ultrasound today (5 weeks, 4 days) and they can clearly see the gestational sac and yolk sac. But, no heartbeat. Do you think this sounds about normal? Thank you!

reply
Francesca Vicari

I am 44 years old and was diagnosed with PCOS at age 16. At age 42 I started ART and have had 7 IUIs. 1 natural cycle, 1 Clomid, 3 Letrozole, and the last 2 cycles were 200iu Gonal F daily for 10 days starting on cycle day 3 and 250mcg Orgalutran for 5 days starting on cycle day 8. Ovidrel 250mcg was administered on cycle day 13 and IUI was 36 hrs later. My last IUI resulted in pregnancy. Beta HCG 17 days post IUI was 21. 31 days post IUI beta HCG was 148. Pregnancy of unknown location was the diagnosis and I miscarried 1 week later.
My current Obgyn/RE told me 2.5 years ago that IVF was not an option because of my age. I’ve asked him if there was anything I could be doing to improve egg quality and he suggested CoQ10 supplements and low dose aspirin. I’ve read many articles on the use of low- dose naltrexone and HGH to improve egg quality and increase chances of conception. Are they suitable for IUI and someone in my case? What do you think of my current protocol? Should I be using a different ”trigger shot”?
I cannot express how grateful I am for any insight you can provide. I am so demoralized at this point.

reply
Dr. Geoffrey Sher

Respectfully, you needed IVF from the get go. At 44y, it is now highly unlikely that anything can improve your egg quality for iVF. You need IVF with an egg donor.

Egg donation is the process by which a woman donates eggs for purposes of assisted reproduction or biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro fertilization (IVF) technology, with the eggs being fertilized in the laboratory, unfertilized eggs may be frozen and stored for later use. Egg donation is a third party reproduction as part of assisted reproductive technology (ART).

For many women, disease and/or diminished ovarian reserve precludes achieving a pregnancy with their own eggs. Since the vast majority of such women are otherwise quite healthy and physically capable of bearing a child, egg donation (ED) provides them with a realistic opportunity of going from infertility to parenthood.

Egg donation is associated with definite benefits. Firstly, in many instances, more eggs are retrieved from a young donor than would ordinarily be needed to complete a single IVF cycle. As a result, there are often supernumerary (leftover) embryos for cryopreservation and storage. Secondly, since eggs derived from a young woman are less likely than their older counterparts to produce aneuploid (chromosomally abnormal) embryos, the risk of miscarriage and birth defects such as Down’s syndrome is considerably reduced.

Egg Donation-related, fresh and frozen embryo transfer cycles account for 10%-15% of IVF performed in the United States. The vast majority of egg donation procedures performed in the U.S involve women with declining ovarian reserve. While some of these are done for premature ovarian failure, the majority are undertaken in women over 40 years of age. Recurrent IVF failure due to “poor quality” eggs or embryos is also a relatively common indication for ED in the U.S. A growing indication for ED is in cases of same-sex relationships (predominantly female) where both partners wish to share in the parenting experience by one serving as egg provider and the other, as the recipient.

Ninety percent of egg donation in the U.S is done through the solicitation of anonymous donors who are recruited through a state-licensed egg donor agency. It is less common for recipients to solicit known donors through the services of a donor agency, although this does happen on occasion. It is also not easy to find donors who are willing to enter into such an open arrangement. Accordingly, in the vast majority of cases where the services of a known donor is solicited, it is by virtue of a private arrangement. While the services of non-family members are sometimes sought, it is much more common for recipients to approach close family members to serve as their egg donor.

Some recipients feel the compulsion to know or at least to have met their egg donor, so as to gain first hand familiarity with her physical characteristics, intellect, and character. This having been said, in the U.S. it is much more common to seek the services of anonymous donors. In terms of disclosure to their family, friends and child(ren), recipients using anonymous donors tend to be far more open than those of known donors about the nature of the child’s conception. Most, if not all, egg donor agencies provide a detailed profile, photos, medical and family history of each prospective donor for the benefit and information of the recipient. Agencies generally have a website through which recipients can access donor profiles in the privacy of their own homes in order to select the ideal donor.

Interaction between the recipient and the egg donor program may be conducted in-person, by telephone or online in the initial stages. Once the choice of a donor has been narrowed down to two or three, the recipient is asked to forward all relevant medical records to their chosen IVF physician. Upon receipt of her records, a detailed medical consultation will subsequently held and a physical examination by the treating physician or by a designated alternative qualified counterpart is scheduled. This entire process is usually overseen, facilitated and orchestrated by one of the donor program’s nurse coordinators who, in concert with the treating physician, will address all clinical, financial and logistical issues, as well as answering any questions. At the same time, the final process of donor selection and donor-recipient matching is completed.

Egg donor agencies usually limit the age of egg donors to women under 35 years with normal ovarian reserve in an attempt to minimize the risk of ovarian resistance and negate adverse influence of the “biological clock” (donor age) on egg quality.

No single factor instills more confidence regarding the reproductive potential of a prospective egg donor than a history of her having previously achieved a pregnancy on her own, or that one or more recipients of her eggs having achieved a live birth. Moreover, such a track record makes it far more likely that such an ED will have “good quality eggs”. Furthermore, the fact that an ED readily conceived on her own lessens the likelihood that she herself has tubal or organic infertility. This having been said, the current shortage in the supply of egg donors makes it both impractical and unfeasible, to confine donor recruitment to those women who could fulfill such stringent criteria for qualification.

It is not unheard of for a donor who, at some point after donating eggs, finds herself unable to conceive on her own due to pelvic adhesions or tubal disease, to blame her infertility on complications caused by the prior surgical egg retrieval process. She may even embark upon legal proceedings against the IVF physician and program. It should therefore come as no surprise that it provides a measurable degree of comfort to ED program when a prospective donor is able to provide evidence of having experienced a relatively recent, trouble free spontaneous pregnancy.

Screening of Donors
Genetic Screening: The vast majority of IVF programs in the U.S. follow the recommendations and guidelines of the American Society of Reproductive Medicine (ASRM) for selectively genetic screening of prospective egg donors for conditions such as sickle cell trait or disease, thalassemia, cystic fibrosis and Tay Sachs disease, when medically indicated. Consultation with a geneticist is available through about 90% of programs.

Most recipient couples place a great deal of importance on emotional, physical, ethnic, cultural and religious compatibility with their chosen egg donor. In fact they often will insist that the egg donor be heterosexual.

Psychological Screening: Americans tend to place great emphasis on psychological screening of egg donors. Since most donors are “anonymous,” it is incumbent upon the ED agency or the IVF program to determine the donor’s degree of commitment as well as her motivation for deciding to provide this service. I have on occasions encountered donors who have buckled under the stress and defaulted mid-stream during their cycle of stimulation with gonadotropins. In one case, a donor knowingly stopped administering gonadotropins without informing anyone. She simply awaited cancellation, which was effected when follicles stopped growing and her plasma E2 concentration failed to rise.

Such concerns mandate that assessment of donor motivation and commitment be given appropriate priority. Most recipients in the U.S. tend to be very much influenced by the “character” of the prospective egg donor, believing that a flawed character is likely to be carried over genetically to the offspring. In reality, unlike certain psychoses such as schizophrenia or bipolar disorders, character flaws are usually neuroses and are most likely to be determined by environmental factors associated with upbringing. They are unlikely to be genetically transmitted. Nevertheless, egg donors should be subjected to counseling and screening and should be selectively tested by a qualified psychologists. When in doubt, they should be referred to a psychiatrist for more definitive testing. Selective use of tests such as the MMPI, Meyers-Briggs and NEO-Personality Indicator are used to assess for personality disorders. Significant abnormalities, once detected, should lead to the automatic disqualification of such prospective donors.

When it comes to choosing a known egg donor, it is equally important to make sure that she was not coerced into participating. We try to caution recipients who are considering having a close friend or family member serve as their designated egg donor, that in doing so, the potential always exists that the donor might become a permanent and an unwanted participant in the lives of their new family.

Drug Screening: Because of the prevalence of substance abuse in our society, we selectively call for urine and/or serum drug testing of our egg donors.

Screening for STDs: FDA and ASRM guidelines recommend that all egg donors be tested for sexually transmittable diseases before entering into a cycle of IVF. While it is highly improbable that DNA and RNA viruses could be transmitted to an egg or an embryo through sexual intercourse or IVF, women infected with viruses such as hepatitis B, C, HTLV, HIV etc, must be disqualified from participating in IVF with egg donation due to the (albeit remote) possibility of transmission, as well as the potential legal consequences of the egg donation process being blamed for their occurrence.

In addition, evidence of prior or existing infection with Chlamydia or Gonococcus introduces the possibility that the egg donor might have pelvic adhesions or even irreparably damaged fallopian tubes that might have rendered her infertile. As previously stated, such infertility, subsequently detected might be blamed on infection that occurred during the process of egg retrieval, exposing the caregivers to litigation. Even if an egg donor or a recipient who carries a sexually transmittable viral or bacterial agent is willing to waive all rights of legal recourse, a potential risk still exists that a subsequently affected offspring might in later in life sue for wrongful birth.

Screening of the Recipient

Medical Evaluation: while advancing age, beyond 40 years, is indeed associated with an escalating incidence of pregnancy complications, such risks are largely predicable through careful medical assessment prior to pregnancy. The fundamental question namely: “is the woman capable of safely engaging a pregnancy that would culminate in the safe birth of a healthy baby” must be answered in the affirmative, before any infertility treatment is initiated. For this reason, a thorough cardiovascular, hepatorenal, metabolic and anatomical reproductive evaluation must be done prior to initiating IVF in all cases.

Infectious Screening: the need for careful infectious screening for embryo recipients cannot be overemphasized. Aside from tests for debilitating sexually transmittable diseases, there is the important requirement that cervical mucous and semen be free of infection with ureaplasma urealyticum. This organism which rarely causes symptoms frequents the cervical glands of 15-20% of women in the U.S. The introduction of an embryo transfer catheter via a so infected cervix might transmit the organism into an otherwise sterile uterine cavity leading to early implantation failure and/or first trimester miscarriage.

Immunologic Screening: Certain autoimmune and alloimmune disorders (see elsewhere) can be associated with immunologic implantation dysfunction (IID). In order to prevent otherwise avoidable treatment failure, it is advisable to evaluate the recipient for autoimmune IDD and also to test both the recipient and the sperm provider for alloimmune similarities that could compromise implantation.

Disclosure and Consent
Preparation for egg donation requires full disclosure to all participants regarding what each step of the process involves from start to finish, as well as potential medical and psychological risks. This necessitates that significant time be devoted to this task and that there be a willingness to painstakingly address all questions and concerns posed by all parties involved in the process. An important component of full disclosure involves clear interpretation of the medical and psychological components assessed during the evaluation process. All parties should be advised to seek independent legal counsel so as to avoid conflicts of interest that might arise from legal advice given by the same attorney. Appropriate consent forms are then reviewed and signed independently by the donor and the recipient couple.

Most embryo recipients fully expect their chosen donor to yield a large number of mature, good quality eggs, sufficient to provide enough embryos to afford a good chance of pregnancy as well as several for cryopreservation (freezing) and storage. While such expectations ore often met, this is not always the case. Accordingly, to minimize the trauma of unexpected and usually unavoidable disappointment, it is essential that in the process of counseling and of consummating agreements, the respective parties be fully informed that by making best efforts to provide the highest standards of care, the caregivers can only assure optimal intent and performance in keeping with accepted standards of care. No one can ever promise an optimal outcome. All parties should be made aware that no definitive representation can or will be made as to the number or quality of ova and embryos that will or are likely to become available, the number of supernumerary embryos that will be available for cryopreservation or the subsequent outcome of the IVF donor process.

TYPES OF EGG DONATION

Conventional Egg Donation: This is the basic format used for conducting the process of egg donor IVF. It involves synchronizing the menstrual cycles of both the recipient and the donor by placing the donor and the recipient on a birth control pill so that both parties start stimulation with fertility drugs simultaneously. This ultimately allows for precise timing of the fresh embryo transfer. Using this approach, the anticipated egg donation birth rate is >50% per cycle.

Preimplantation Genetic Sampling (PGS)-Egg Donation: The recent introduction of complete numerical chromosomal assessment (karyotyping) using metaphase Comparative Genomic Hybridization (mCGH) and Next Generation Gene sequencing (NGS) has the potential to change the manner in which egg donation will be performed in the future. CGH/NGS allows full egg/embryo chromosome analysis providing a 70- 80% assurance that the embryo(s) so selected for transfer are highly likely to be “competent” (i.e. capable of producing a healthy baby). Such PGS-egg selection provides about a 50% chance of a baby per transfer of an embryo derived through fertilization of a pre-vitrified euploid egg. This is at least double that reported when conventional egg donation is used. As a result, mCGH/NGS-Egg Donation allows for excellent results when one or two embryos are transferred, virtually eliminating the risk of “high order” multiple pregnancies (triplets or greater). Moreover, since numerical chromosomal irregularities (aneuploidy) are responsible for most miscarriages, the use of CGH also significantly reduces this dreaded complication.

PGS egg selection of necessity mandates the use of Staggered (ST)- IVF. Here the egg donor cycle is divided into two parts. The first involves the egg retrieval, fertilization, embryo biopsy for PGS analysis and embryo cryostorage. The second part involving warming or thawing of the frozen embryo(s) and the subsequent transfer of “competent” embryo(s) to the recipient’s uterus is conducted electively at least several weeks later once the results of PGS testing are available. Since, with St-IVF the egg retrieval and embryo transfer are separated in time, the retrieval can be performed without first having to synchronize the menstrual cycles of the recipient and the egg the donor. In fact, the recipient does not even have to be available when the egg donor is going through cycle. All that is needed is for designated sperm to be available (fresh or frozen) on the day of egg retrieval. This avoids unnecessary travel and inconvenience, and minimizes stress and cost.

Donor Egg Banking: Another imminent advance is the introduction of egg banking. Being able to freeze and bank donor eggs would solve most of these challenges. By using PGS in combination with a egg vitrification (ultra-rapid freezing), we are now capable of improving the birth rate per warmed/thawed egg by a factor of 3-4 fold (from a previous average of <8% per egg to about 27%). Through an electronic catalogue, recipients will be able to select and purchase 1-3 CGH-normal eggs from the comfort of their homes. Thereupon, the selective transfer of 1 or 2 embryos derived from such chromosomally normal eggs could achieve a 50-60% pregnancy rate without the risk of initiating high-order multiple pregnancies in the process. Through this process, the cost, inconvenience and risks associated with “conventional” fresh egg donor cycles would also be reduced significantly.

Financial Considerations
The fee paid to the egg donor agency per cycle usually ranges between $2,000 and $8,000. This does not include the cost associated with psychological and clinical pre-testing, fertility drugs, and donor insurance, which commonly range between $3,000 and $6,000. The medical service costs of the IVF treatment cycle ranges between $8,000 and $14,000. The donor stipend can range from $2,000 too as high $50,000 depending upon the exotic requirements of the recipient couple as well as supply and demand. Thus the total out of pocket expenses for an egg donor cycle in the United States range between $15,000 and $78,000, putting egg donation outside the financial capability of most couples needing this service.

The growing gap between need and affordability has spawned a number of creative ways to try and make IVF with egg donation more affordable. Here are a few examples:
• Egg banking (see above)
• Egg Donor Sharing, where one comprehensive fee is shared between two recipients and the eggs are then divided between them. The downside is that fewer eggs are available embryos for transfer and/or cryopreservation.
• Egg Bartering, where in the course of conventional IVF, a woman undergoing IVF remits some of her eggs to the clinic (who in turn provides it to a recipient patient) in exchange for a deferment of some or all of the IVF fee. In my opinion, such an arrangement can be fraught with problems. For example, in the event that the woman donating some of her eggs fails to conceive while the recipient of her eggs does, it is very possible that she might suffer emotional despair and even go so far as to seek out her genetic offspring. Such action could be very damaging to both her and the recipient, as well as the child.
• Financial Risk Sharing. Certain IVF programs offer financial risk sharing (FRS) which most recipient couples favor greatly. FRS offers qualifying candidates a refund of fees paid if egg donation is unsuccessful. FRS is designed to spread the risk between the providers, and the recipient couple.

Moral, Legal & Ethical Considerations: The “Uniform Parentage Act” which has been adopted by most states in the United States declares that the woman who gives birth to the child will be regarded as the rightful mother. Accordingly, there has to date not been any grounds for legal dispute when it comes to maternal custody of a child born through IVF with egg donation in the majority of states. In a few states such as Mississippi and Arizona the law is less clear but nevertheless, as yet, has not been contested.

The moral-ethical and religious implications of egg donation are diverse and have a profound effect on cultural acceptance of this process. The widely held view that everyone is entitled to their own opinion and has the right to have such opinions respected, governs much of the attitude towards this process in the U.S. The extreme views on each end of the spectrum hold the gentle central swing of the pendulum in place. This attitude is a reflection of the general acceptance in the united states of diverse views and opinions and the willingness to allow free expression of such views and beliefs provided that they don’t infringe on the rights of others.

So where do we go from here? Can and should we, cryopreserve and store eggs or ovarian tissue from a young woman wishing to defer procreation until it becomes convenient? And if we do this, would it be acceptable to eventually have a woman give birth to her own sister or aunt? Can or should we store viable ovarian tissue through generations. Should egg donation simply become a future source of embryos generated for the purpose of providing stem cells, to be used in the treatment of disease states or to “manufacture” fetuses as a source of spare body parts? If the answer to even some of these questions is yes…what about the checks and balances. Who will exercise control and where what form should such control take? Are we willing to engage this slippery slope where the disregard for the dignity of the human embryo leads us to the point where the rights of a human being are more readily ignored? …………………… Personally, I hope not.

___________________________________________________________
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
Sri Lakshmi

If a person does a 5 day frozen embryo donor transfer, and gets home pregnancy test and is negative at day 10 , has there ever been to your knowledge a late implantation done for the 14 today, to make blood work a postive ? Or is it physically impossible ???

reply
Mell

Hi Dr. Sher. I’m 39, my husband is 36. We live in different countries, IVF/IUI is not an option for us. I am the only one who can travel to see him where he lives and I don’t have healthcare coverage where he lives. I had one early miscarriage (5 weeks) September 2018, and I suspect some other chemical pregnancies. We’ve tried conceiving about 5-6 times in the past year. I have a very high AMH (9.3), but my other hormone levels all seem to be consistently within normal range (day 3: FSH 6.8, LH 6.3, Estradiol 93.3, Progesterone- 0.5; Prolactin 13.7, normal TSH). My vitamin D is low so I haven supplementing with that for a while. I’m guessing my high AMH might indicate some kind of PCOS, but I am fairly certain I ovulate every month. I’ve never missed a period and my cycles are 28-31 days long. I tried Clomid once unsuccessfully. I suspect my Progesterone levels are on the low side because it was low during my pregnancy; however I started miscarrying before we could do anything about it.. My RE thinks low progesterone is a strictly an egg quality issue. I suspect he would prescribe progesterone for me if I was pregnant and needed it. However, when I travel to see my husband, I usually stay there throughout my luteal phase, so I have no way of knowing what my progesterone levels are doing during the 2 week wait – and I am concerned that, if they are low, that could cause a chemical pregnancy? I am on Femara this cycle. I took DHEA / Ubiquinol for the past couple of months, but have stopped the DHEA now that I’m on Femara (I wasn’t sure how it might interact). This is more or less my situation . my questions to you: what would you recommend in my case? Would you guess that my issue is poor egg quality due to age? Are there any other tests you’d recommend in my case? Do you think long international flights could be making it more difficult for me to get / stay pregnant?

reply
Dr. Geoffrey Sher

Hi Mel,

Unfortunately I would need much more information, much of which would be derived from testing that likely has as yet not been done. So, I do not know where to start. This having been said, given your age and your history, IVF is definitely almost certainty needed and soon…before it is too late.

So sorry!

___________________________________________________________
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
Dan

Hi, I just found out I am pregnant naturally and I have started intralipids steroids clexane progesterone and aspirin however I have for the first time been diagnosed with a hypothyroid my tsh was 7.6 and my specialist prescribed 100 micrograms of levothyroxine I repeat bloods in 1 months time but I am worried of levels such as these will have adverse affects on the fetus I appreciate your opinion regards

reply
Dr. Geoffrey Sher

I doubt that there will be an adverse effect if your T3/T4 levels are regulated now.

Good luck!

Geoff Sher

reply
Pree

Hi Dr. I am 36, husband, 40. He had azoospermia. We did MicroTESE Icsi IVF. 2 rounds. 1st round failed, no embryos. 2nd round , 16 eggs, but only two fertilised. 2 embryos, PGS abnormal.
Results
1. XX Monosomy 7, Monosomy 15.
2. XY Monosomy 16
Q: Can these be transferred? Pls advice soon.

reply
Dr. Geoffrey Sher

Yes, but in the order of preference I would choose #2 over #1.

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.

Many 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, growing evidence suggests that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrect”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases having occurred in my own practice. 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 (“Mosaicism”) 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”.

Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies. The ability of mosaic embryos to autocorrect is influenced by stage of embryo development in which the diagnosis is made, which chromosomes are affected, whether the aneuploidy involves a single chromosome (simple) or involves 3 or more chromosomes (complex), and the percentage of cells that are aneuploid. Many embryos diagnosed as being mosaic prior to their development into blastocysts (in the cleaved state), subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) as they develop to blastocysts in the Petri dish. This is one reason why “mosaicism” is more commonly detected in early embryos than in blastocysts. Embryos with segmental mosaic aneuploidies, i.e. the addition (duplication) or subtraction (deletion), are also more likely to autocorrect. Finally, the lower the percentage of mitotically aneuploid (mosaic) cells in the blastocyst the greater the propensity for autocorrection and propagation of chromosomally normal (euploid) offspring. A blastocyst with <30% mosaicism could yield a 30% likelihood of a healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

As stated, the transfer of embryos with autosomal meiotic trisomy, will invariably result in failed implantation, early miscarriage or the birth of a defective child. Those with autosomal mitotic (“mosaic”) trisomies, while having the ability to autocorrect in-utero and result in the birth of a healthy baby can, depending on the percentage of mosaic (mitotically aneuploid) cells present, the number of aneuploid chromosomes and the type of mosaicism (single or segmental) either autocorrect and propagate a normal baby, result in failed implantation, miscarry or cause a birth defect (especially with trisomies 13, 18 or 21). This is why when it comes to giving consideration to transferring trisomic embryos, suspected of being “mosaic”, I advise patients to undergo prenatal genetic testing once pregnant and to be willing to undergo termination of pregnancy in the event of the baby being affected. Conversely, when it comes to meiotic autosomal monosomy, there is almost no chance of a viable pregnancy. in most cases implantation will fail to occur and if it does, the pregnancy will with rare exceptions, miscarry. “Mosaic” (mitotically aneuploid) autosomally monosomic embryos where a chromosome is missing), can and often will “autocorrect” in-utero and propagate a viable pregnancy. It is for this reason that I readily recommend the transfer of such embryos, while still (for safety sake) advising prenatal genetic testing in the event that a pregnancy results.

Given our ability to recognize “mosaicism” through karyotyping of embryos, the question arrases as to which “mosaic” embryos are capable of auto-correcting in-utero and propagating viable pregnancies. Research suggests that that virtually no autosomal monosomy embryos will propagate viable pregnancies. Thus, the transfer of such mosaic embryos is virtually risk free. Needless to say however, in any such cases, it is 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.

___________________________________________________________
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
Loli

Dr Sher , I had my 5day blastocyst transfer on March 18 and had my blood pregnancy test done on April 1st had an HCG of 1001, did a second testing 2 days later with an HCG of over 2000, is that an indication of twins?

reply
Dr. Geoffrey Sher

No! That is a normal rise with likely a singleton. I could be wrong though.

Geoff Sher

reply
Avinash

Sir
I have fet on 25 March then I check progesterone on day 7 on 31 March it was 145.50 ul .what a chance to get pregnancy

reply
Dr. Geoffrey Sher

That is a high progesterone but that alone is not sufficient to diagnose a pregnancy.

___________________________________________________________
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
Rose

Dr.Sher
I have a frozen embryo with the following pgs test result :
46,XX,del (8)(p11.2)
There is no indication on whether it’s mosaic or not. Would you recommend doing an FET ? Thanks.

reply
Dr. Geoffrey Sher

Personally, I would transfer the embryo and follow up with Prenatal Genetioc Testing (CVS or amniocentesis).

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.

Many 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, growing evidence suggests that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrect”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases having occurred in my own practice. 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 (“Mosaicism”) 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”.

Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies. The ability of mosaic embryos to autocorrect is influenced by stage of embryo development in which the diagnosis is made, which chromosomes are affected, whether the aneuploidy involves a single chromosome (simple) or involves 3 or more chromosomes (complex), and the percentage of cells that are aneuploid. Many embryos diagnosed as being mosaic prior to their development into blastocysts (in the cleaved state), subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) as they develop to blastocysts in the Petri dish. This is one reason why “mosaicism” is more commonly detected in early embryos than in blastocysts. Embryos with segmental mosaic aneuploidies, i.e. the addition (duplication) or subtraction (deletion), are also more likely to autocorrect. Finally, the lower the percentage of mitotically aneuploid (mosaic) cells in the blastocyst the greater the propensity for autocorrection and propagation of chromosomally normal (euploid) offspring. A blastocyst with <30% mosaicism could yield a 30% likelihood of a healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

As stated, the transfer of embryos with autosomal meiotic trisomy, will invariably result in failed implantation, early miscarriage or the birth of a defective child. Those with autosomal mitotic (“mosaic”) trisomies, while having the ability to autocorrect in-utero and result in the birth of a healthy baby can, depending on the percentage of mosaic (mitotically aneuploid) cells present, the number of aneuploid chromosomes and the type of mosaicism (single or segmental) either autocorrect and propagate a normal baby, result in failed implantation, miscarry or cause a birth defect (especially with trisomies 13, 18 or 21). This is why when it comes to giving consideration to transferring trisomic embryos, suspected of being “mosaic”, I advise patients to undergo prenatal genetic testing once pregnant and to be willing to undergo termination of pregnancy in the event of the baby being affected. Conversely, when it comes to meiotic autosomal monosomy, there is almost no chance of a viable pregnancy. in most cases implantation will fail to occur and if it does, the pregnancy will with rare exceptions, miscarry. “Mosaic” (mitotically aneuploid) autosomally monosomic embryos where a chromosome is missing), can and often will “autocorrect” in-utero and propagate a viable pregnancy. It is for this reason that I readily recommend the transfer of such embryos, while still (for safety sake) advising prenatal genetic testing in the event that a pregnancy results.

Given our ability to recognize “mosaicism” through karyotyping of embryos, the question arrases as to which “mosaic” embryos are capable of auto-correcting in-utero and propagating viable pregnancies. Research suggests that that virtually no autosomal monosomy embryos will propagate viable pregnancies. Thus, the transfer of such mosaic embryos is virtually risk free. Needless to say however, in any such cases, it is 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.

___________________________________________________________
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
Gia M.

Hello Dr. Sher,
Would you be able to tell me what mosaic monosomies are suitable for transfer?
Thank you,

reply
Dr. Geoffrey Sher

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.

Many 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, growing evidence suggests that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrect”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases having occurred in my own practice. 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 (“Mosaicism”) 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”.

Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies. The ability of mosaic embryos to autocorrect is influenced by stage of embryo development in which the diagnosis is made, which chromosomes are affected, whether the aneuploidy involves a single chromosome (simple) or involves 3 or more chromosomes (complex), and the percentage of cells that are aneuploid. Many embryos diagnosed as being mosaic prior to their development into blastocysts (in the cleaved state), subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) as they develop to blastocysts in the Petri dish. This is one reason why “mosaicism” is more commonly detected in early embryos than in blastocysts. Embryos with segmental mosaic aneuploidies, i.e. the addition (duplication) or subtraction (deletion), are also more likely to autocorrect. Finally, the lower the percentage of mitotically aneuploid (mosaic) cells in the blastocyst the greater the propensity for autocorrection and propagation of chromosomally normal (euploid) offspring. A blastocyst with <30% mosaicism could yield a 30% likelihood of a healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

As stated, the transfer of embryos with autosomal meiotic trisomy, will invariably result in failed implantation, early miscarriage or the birth of a defective child. Those with autosomal mitotic (“mosaic”) trisomies, while having the ability to autocorrect in-utero and result in the birth of a healthy baby can, depending on the percentage of mosaic (mitotically aneuploid) cells present, the number of aneuploid chromosomes and the type of mosaicism (single or segmental) either autocorrect and propagate a normal baby, result in failed implantation, miscarry or cause a birth defect (especially with trisomies 13, 18 or 21). This is why when it comes to giving consideration to transferring trisomic embryos, suspected of being “mosaic”, I advise patients to undergo prenatal genetic testing once pregnant and to be willing to undergo termination of pregnancy in the event of the baby being affected. Conversely, when it comes to meiotic autosomal monosomy, there is almost no chance of a viable pregnancy. in most cases implantation will fail to occur and if it does, the pregnancy will with rare exceptions, miscarry. “Mosaic” (mitotically aneuploid) autosomally monosomic embryos where a chromosome is missing), can and often will “autocorrect” in-utero and propagate a viable pregnancy. It is for this reason that I readily recommend the transfer of such embryos, while still (for safety sake) advising prenatal genetic testing in the event that a pregnancy results.

Given our ability to recognize “mosaicism” through karyotyping of embryos, the question arrases as to which “mosaic” embryos are capable of auto-correcting in-utero and propagating viable pregnancies. Research suggests that that virtually no autosomal monosomy embryos will propagate viable pregnancies. Thus, the transfer of such mosaic embryos is virtually risk free. Needless to say however, in any such cases, it is 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.

___________________________________________________________
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
melly

Dr. Sher,

Do women with endometriosis release ovums with hard shells making it more difficult for sperm to penetrate? Does this also contribute to the infertility in women with endo as well as the immune issues?

Thanks 🙂

reply
Dr. Geoffrey Sher

I do not believe this is the case.

Endometriosis is a condition that occurs when the uterine lining (endometrium) grows not only in the interior of the uterus but in other areas, such as the fallopian tubes, ovaries and the bowel. Endometriosis is a complex condition where, the lack or relative absence of an overt anatomical barrier to fertility often belies the true extent of reproductive problem(s).

All too often the view is expounded that the severity of endometriosis-related infertility is inevitably directly proportionate to the anatomical severity of the disease itself, thereby implying that endometriosis causes infertility primarily by virtue of creating anatomical barriers to fertilization. This over-simplistic and erroneous view is often used to support the performance of many unnecessary surgeries for the removal of small innocuous endometriotic lesions, on the basis of such “treatment” evoking an improvement in subsequent fertility.

It is indisputable that even the mildest form of endometriosis can compromise fertility. It is equally true that, mild to moderate endometriosis is by no means a cause of absolute “sterility”.

Rather, when compared with normally ovulating women of a similar age who do not have endometriosis, women with mild to moderate endometriosis are about four to six times less likely to have a successful pregnancy.

Endometriosis often goes unnoticed for many years. Such patients are frequently, erroneously labeled as having “unexplained infertility”, until the diagnosis is finally clinched through direct visualization of the lesions at the time of laparoscopy or laparoscopy. Not surprisingly, many patients with so called “unexplained” infertility, if followed for a number of years, will ultimately reveal endometriosis.

Women who have endometriosis are much more likely to be infertile. There are several reasons for this:

• First-Ovulation Dysfunction: In about 25 – 30% of cases, endometriosis is associated with ovulation dysfunction. Treatment requires controlled ovarian stimulation (COS). The problem is that the toxic pelvic environment markedly reduces the likelihood that anything other than IVF will enhance pregnancy potential.
• Second- Toxic Pelvic environment that compromises Fertilization Endometriosis is associated with the presence of toxins in peritoneal secretions while it is tempting to assert that normally ovulating women with mild to moderate endometriosis would have no difficulty in conceiving if their anatomical disease is addressed surgically or that endometriosis-related infertility is confined to cases with more severe anatomical disease…nothing could be further from the truth. The natural conception rate for healthy ovulating women in their early 30’s (who are free of endometriosis) is about 15% per month of trying and 70% per year of actively attempting to conceive. Conversely, the conception rate for women of a comparable age who have mild or moderate pelvic endometriosis (absent or limited anatomical disease) is about 5-6% per month and 40% after 3 years of trying. As sperm and egg(s) travel towards the fallopian tubes they are exposed to these toxins which compromise the fertilization process. In fact it has been estimated that there is a 5-6 fold reduction in fertilization potential because of these toxins which cannot be eradicated. Frankly, it really does not matter whether an attempt is made to remove endometriosis deposits surgically as this will not improve pregnancy potential. The reason is that for every deposit observed, there are numerous others that are in the process of developing and are not visible to the naked eye and whether visible or not, such translucent deposits still produce toxins. This also explains why surgery to remove visible endometriosis deposits, controlled ovarian stimulation with or without intrauterine insemination will usually not improve pregnancy potential. Only IVF, through removing eggs before they are exposed to the toxic pelvic environment, fertilizing them in-vitro and then transferring the embryos to the uterus represents the only way to enhance pregnancy potential.
• Third-Pelvic adhesions and Scarring: In its most severe form, endometriosis is associated with scarring and adhesions in the pelvis, resulting in damage to, obstruction or fixation of the fallopian tubes to surrounding structures, thereby preventing the union of sperm and eggs.
• Fourth-Ovarian Endometriomas, Advanced endometriosis is often associated with ovarian cysts (endometriomas/chocolate cysts) that are filled with altered blood and can be large and multiple. When these are sizable (>1cm) they can activate surrounding ovarian connective tissue causing production of excessive male hormones (androgens) such as testosterone and androstenedione. Excessive ovarian androgens can compromise egg development in the affected ovary (ies) resulting in an increased likelihood of numerical chromosomal abnormalities (aneuploidy) and reduced egg/embryo competency”. In my opinion large ovarian endometriomas need to be removed surgically or rough sclerotherapy before embarking on IVF.
• Fifth- Immunologic Implantation Dysfunction (IID). Endometriosis, regardless of its severity is associated with immunologic implantation dysfunction linked to activation of uterine natural killer cells (NKa) and cytotoxic uterine lymphocytes (CTL) in about 30 of cases. This is diagnosed by testing the woman’s blood for NKa using the K-562 target cell test or by endometrial biopsy for cytokine analysis, and, for CTL by doing a blood immunophenotype. These NKa attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in death of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or even an early miscarriage. . As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.

Advanced Endometriosis: In its most advanced stage, anatomical disfiguration is causally linked to the infertility. In such cases, inspection at laparoscopy or laparoscopy will usually reveal severe pelvic adhesions, scarring and “chocolate cysts”. However, the quality of life of patients with advanced endometriosis is usually so severely compromised by pain and discomfort, that having a baby is often low on the priority list. Accordingly, such patients are usually often more interested in relatively radical medical and surgical treatment options (might preclude a subsequent pregnancy), such as removal of ovaries, fallopian pubis and even the uterus, as a means of alleviating suffering.

Moderately Severe Endometriosis. These patients have a modest amount of scarring/ adhesions and endometriotic deposits which are usually detected on the ovaries, fallopian tubes, bladder surface and low in the pelvis, behind the uterus. In such cases, the fallopian tubes are usually opened and functional.

Mild Endometriosis: These patients who at laparoscopy or laparotomy are found to have no significant distortion of pelvic anatomy are often erroneously labeled as having “unexplained” infertility. To hold that the there can only infertility can only be attributed to endometriosis if significant anatomical disease can be identified, is to ignore the fact that, biochemical, hormonal and immunological factors profoundly impact fertility. Failure to recognize this salient fact continues to play havoc with the hopes and dreams of many infertile endometriosis patients.

TREATMENT:
The following basic concepts apply to management of endometriosis-related infertility:

1. Controlled Ovulation stimulation (COS) with/without intrauterine insemination (IUI): Toxins in the peritoneal secretions of women with endometriosis exert a negative effect on fertilization potential regardless of how sperm reaches the fallopian tubes. This helps explain why COS with or without IUI will usually not improve the chances of pregnancy (over no treatment at all) in women with endometriosis. IVF is the only way by which to bypass this problem.
2. Laparoscopy or Laparotomy Surgery aimed at restoring the anatomical integrity of the fallopian tubes does not counter the negative influence of toxic peritoneal factors that inherently reduce the chances of conception in women with endometriosis four to six fold. Nor does it address the immunologic implantation dysfunction (IID) commonly associated with this condition. Pelvic surgery is relatively contraindicated for the treatment of infertility associated with endometriosis, when the woman is more than 35 years of age. With the pre-menopause approaching, such women do not have the time to waste on such less efficacious alternatives. In contrast, younger women who have time on their side might consider surgery as a viable option. Approximately 30 -40 percent of women under 35 years of age with endometriosis will conceive with in two to three years following corrective pelvic surgery.
3. Sclerotherapy for ovarian endometriomas (“chocolate” cysts). About 15 years ago I introduced “sclerotherapy”, a relatively non-invasive, safe and effective outpatient method to permanently eliminate endometriomas without surgery being required. Sclerotherapy for ovarian endometriomas involves needle aspiration of the liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline into the cyst cavity. Treatment results in disappearance of the lesion within 6-8 weeks, in more than 75% of cases so treated. Ovarian sclerotherapy can be performed under local anesthesia or under general anesthesia. It has the advantage of being an ambulatory office- based procedure, at low cost, with a low incidence of significant post-procedural pain or complications and the avoidance of the need for laparoscopy or laparotomy
4. The role of selective immunotherapy More than half of women who have endometriosis harbor antiphospholipid antibodies (APA) that can compromise development of the embryo’s root system (trophoblast). In addition and far more serious, is the fact that in about one third of cases endometriosis, regardless of its severity is associated with NKa and cytotoxic uterine lymphocytes (CTL) which can seriously jeopardize implantation. This immunologic implantation dysfunction (IID) is diagnosed by testing the woman’s blood for APA, for NKa (using the K-562 target cell test or by endometrial biopsy for cytokine activity) and, for CTL (by a blood immunophenotype). Activated NK cells attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in rejection of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or an early miscarriage. . As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.

Women who harbor APA’s often experience improved IVF birth rates when heparinoids (Clexane/Lovenox) are administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy. NKa is treated with a combination of Intralipid (IL) and steroid therapy: Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating NKa.

The therapeutic effect of IL/steroid therapy is likely due to an ability to suppress pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. IL/steroids down-regulates NKa within 2-3 weeks of treatment the vast majority of women experiencing immunologic implantation dysfunction. In this regard IL is just as effective as Intravenous Gamma globulin (IVIg) but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.

5. The role of IVF: The toxic pelvic environment caused by endometriosis, profoundly reduces natural fertilization potential. As a result normally ovulating infertile women with endometriosis and patent Fallopian tubes are much less likely to conceive naturally, or by using fertility agents alone (with or without intrauterine (IUI) insemination. The only effective way to bypass this adverse pelvic environment is through IVF. I am not suggesting here that all women who have endometriosis require IVF! Rather, I am saying that in cases where the condition is further compromised by an IID associated with NKa and/or for older women(over 35y) who have diminished ovarian reserve (DOR) where time is of the essence, it is my opinion that IVF is the treatment of choice.

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:
• 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; hHow it Works; Administration; Side-effects; Reactions and Precautions
• 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
• How Many Embryos should be transferred: A Critical Decision in IVF.
• Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF
• Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice.
• Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options
• Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination-IUI) and Reproductive Surgery Versus IVF
• Treating Ovarian Endometriomas with Sclerotherapy.
• Effect of Advanced Endometriosis with Endometriotic cysts (Endometriomas) on IVF Outcome & Treatment Options.
• Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
• Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s &
• Induction of Ovulation with Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its use
• Clomiphene Induction of Ovulation: Its Use and Misuse!
___________________________________________________________
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
Kristin Cuthbert

Hi Dr. Sher,

I am a 35 year old woman with a history of PCOS. I have always had very high day 3 LH:FSH ratios and very long or absent cycles (35+ days). I conceived my daughter in 2015 with cycle monitoring with Letrozole and the shot of Ovidrel. We are trying to conceive baby #2 now. I started my period 6 days ago. My Day 3 LH was 5.3 IU/L and my FSH was 5.5 IU/L which I was happy about. However, I went today, Day 6, to get my blood drawn to see how my LH is looking (as I am using Ovulation Predictor Test strips but they are hard to read) and it is now 11.5 IU/L! The problem is the lab’s reference ranges for LH in the Follicular Phase is 2-12 IU/L and 8 -90 IU/L in the ovulatory phase. I looked online at some graphs and it appears that LH stays very low without rising until ovulation but here I am 6 days into my cycle with my LH increasing. Is this normal? Given the lab cut offs could this be a problem if we are trying to conceive whether naturally or with medications?

reply
Dr. Geoffrey Sher

It is possibly the effect of the inverted FSH: LH ratio…seen in PCOS.

Geoff Sher

reply
Kristin

Thank you Dr
Does this mean I could still possibly ovulate on cycle day (14 -17) or with an lh number this high on.day 6, is it more likely that my surge will happen in the next few days? Also I read your article on premature leutinization is this what I am experiencing? Are you accepting new patients? My family and I are moving to New York at the end of the year.

reply
Dr. Geoffrey Sher

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.

Patients 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 .

Geoff sher

reply
Kristin

Thank you doctor, this is very helpful! I will call tomorrow 🙂
Also referring back to my previous question what are your thoughts? Is it still possible to have an ovulatory cycle this month?

Penny

I did a day 5 blastocyst transfer on 22nd April 2019. On day 11 of transfer my hcg was 57. Is this a good reading. I am on duphoston.

reply
Dr. Geoffrey Sher

If you mean 6 days after the transfer…that is fine. If by Day-11 you mean 11 days after the transfer, that would be lowish. Repeat in 2 days to see if it doubles.

___________________________________________________________
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
Amy B.

I had a clot five years ago and the only “iffy” result was slightly elevated IGM beta glycoproteins, and phospholipids.
Fast forward – I have been trying to get pregnant for over two years. Numerous times I have “felt” pregnant, but have consistently gotten a negative pregnancy test. I have had 3 failed AIAs and now the next step is in In-Vitro. I am concerned about going on all these drugs – and feel that it might not even work because it seems there is something else impacting the process. Reading your website makes me question it even more. What would you recommend for someone with elevated phospholipid levels?

reply
Dr. Geoffrey Sher

You need a thorough evaluation of immunologic implantation dysfunction.

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
Katy

Hi Dr. Sher, I had egg retrieval which collected 24 eggs, I had 10 fertilised and frozen on day 1 due to OHSS, I’m currently starting a frozen cycle and have opted to have all 10 thawed out with the hope of getting them to day 5.. do you have any idea or a percentage on how many survive to blastocyst stage. Thank you.

reply
Dr. Geoffrey Sher

With frozen eggs, I would not expect more than 25% to make it to blastocyst.

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 .

Geoff Sher

reply
Parry

Hi Doctor Sher, ihope you are well, thank you for creating a very helpful blog!

I have low ovarian reserve/poor quality eggs. I had a IVF cycle in 2015 using long protocol, which failed and resulted in 1 very poor egg.

In 2016 I had another IVF cycle, using a different protocol & ICSI (clomid, short cycle). this time i also used both DHEA 75mg and Ubiquinol coenzyme Q 300mg per day for approx 12 weeks ahead of my cycle. This cycle thankfully resulted in 5 embryos, 3 of which made it to a 5day blastocyst (Grade A) resulting in a successful pregnancy in 2017. I froze the remaining 2 embryos.

I would like to try for my 2nd child and decided to do a frozen transfer in 2018, unfortunately this failed with a negative pregnancy result. there was no specific reason, during the treatment everything was ok. However i suffered the loss of my brother to cancer a couple of months before starting the process. i feel this difficult time had a part to play.

I now have 1 frozen embryo left, i am 36 years old, i recently visited my doctor and my AMH is similar to 2016, it is indicative of low ovarian reserve. my doctor suggested i use the same protocol as 2016 including the supplements to try and retrieve any possible eggs whilst i am still 36. if this fails we can then proceed to using the 1 frozen embryo.

Do you think this is a sensible approach, i am booked in for a June cycle, but have not started taking DHEA/Coenzyme yet, i am slightly worried about any negative effects the DHEA could have on my body. Do you think the DHEA will make the difference and how long should i take it for ?

I am still unsure whether to go for a fresh cycle Vs my Frozen egg.

Thank you in advance for any advice you may be able to give.

Parry

reply
Dr. Geoffrey Sher

Yes! That advice makes sense to me.

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:
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
Jaclyn

I have a healthy 3 year old who we got pregnant with on the first try. No complications. Since then I got pregnant again within 6 months of trying but resulted in a chemical pregnancy and a loss in the 5th week which was confirmed with two blood tests. Three months later I got pregnant again. At the 8 week mark we saw a healthy heartbeat but a baby that was measuring a week behind. Within two weeks I started spotting and it was determined by ultrasound the baby stopped growing and no heartbeat was found. My body miscarried naturally shortly after. I am nervous to try again without trying to find out more answers. what would be the next step? Is it likely I was just unlucky or there is some genetic chromosome problem that will cause this to happen again? I have very normal cycles and am healthy on paper. I was only taking a pre natal for these pregnancies. Could I need baby aspirin? Progesterone? Etc?

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
Joy Browne

I had 3 blastocyst transferred and I’m 4 weeks pregnant. Today I had a heavy bleeding with a large clot around 1:48am UK time. The heavy bleeding stopped during the night. I am bleeding now but not as heavy as before. I don’t know what must have happened.

reply
Dr. Geoffrey Sher

It is hard to say. However, I suggest having a quantitative blood pregnancy test done and repeated 2 days later to see if the levels are fising appropriately.If they are, wait 2 weeks or so and do an Ultrasound examination. That will be definitive.

___________________________________________________________
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
Tina W

Dear Dr. Sher,
We learned of my husband’s diagnosis of NOA when I was 34. He had repair of variocele followed 6 months later by successful microTESE. After 2 rounds of IVF (then second of which I began 1 month after turning 35) including 2 negative transfers of 2 three day embryos, I underwent natural cycle FET with the one remaining blastocyst from the second cycle (PGS untested) which resulted in the birth of my healthy son just after I turned 36. I started the process of IVF in an attempt to have a second baby immediately after I had weaned my son just after I turned 37. I had 2 IVF transfers with transfer of 2 three day embryos which were negative. I went through a 3rd IVF cycle which resulted in 1 blastocyst which I transferred in a subsequent natural cycle FET which resulted in an early miscarriage at 5 weeks. My husband had to undergo repeat microTESE which was again successful. I then proceeded to have 5 back to back egg retrievals in an attempt to bank embryos which resulted in 4 blastocysts. I transferred 2 of the higher grade ones in two subsequent natural cycle FET both of which were negative. Then I went through 6 cycles of back to back egg freezing followed by a third microTESE for my husband. Unfortunately only 12 of my 34 frozen eggs survived the thaw. From these retrievals, I ended up with 3 frozen blastocysts. I sent these 3 embryos in addition to the 2 previously frozen blastocysts for PGS testing and I got the results this week that there is only 1 PGS normal blastocyst, 1 mosaic (with some cells missing parts of chromosome 19) and 3 abnormals. I am preparing for the FET now. I am turning 39 in 1 week and wonder do I have any chance of success after such a long and difficult journey???

reply
Dr. Geoffrey Sher

I sympathize with you. Recurrent IVF failure (all be it secondary) takes a devastating emotional and financial toll.

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
John McGeown

Hi Dr,

Have just finished 2nd failed IVF/ICSI
(1st) IVF with Gonal- 18 eggs collected , 7 fertilised,3 at day 3 and 1 blastocyst which did not thaw (Dr said this would not survive anyway)
(2nd) ICSI with Menopure and calcium ionate-9 eggs collected, 4 fertilised, 2 at day 3 and no blastocysts

As you can imagine we are devastated and wondering if there is an inherant problem. We have done all tests (including DNA frag) but nothing to explain. We have not done genetic testing. Both young, I 33 and wife 36 with good AMH.

Just need some reassurance and advice as we have a full week wait to meet our consultant.

Is there any hope here or what could be the explanation?

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
o. sahin

is it okay we use man’s oral viagra pills as a vaginally
is it okay to use them just before frozen embryo transfer or shokud we use them quiet a time
how long should we use them to help getting thin uterin lining

reply
Dr. Geoffrey Sher

In my opinion that is not optimal. The absorbtion of the pills used vaginally is poor. It should be compounded.

The dosage is 25mg inserted four times per day starting after menstruation ceases and continued up to the day of progesterone (with frozen transfers) or the day of the hCG trigger (with conventional IVF and fresh transfers.

Geoff Sher

reply
Kelsi

I have frozen embryos but never a successful transfer. I have been through 5 cycles, but my lining has never gotten above 4.3 even with vaginal viagra and estrogen injections, patches, tablets, even a mini-stim cycle, Accupuncture, vitamin E, l-arginine, Heparin, Tamoxifen, neupogen infusions, etc. I’ve never been pregnant and have had no trauma to my uterus, so it is so bizarre that my lining will not respond to any of the protocols we have tried.
I read your article about using Terbutaline with viagra. How many days should I take terbutaline with viagra before trigger day?

Thank you!
Kelsi

reply
Dr. Geoffrey Sher

It was as far back as 1989, when I first published a study that examined the correlation between the thickness of a woman’s uterine lining (the endometrium), and the subsequent successful implantation of embryos in IVF patients. This study revealed that when the uterine lining measured <8mm in thickness by the day of the “hCG trigger” (in fresh IVF cycles), or at the time of initiating progesterone therapy (in embryo recipient cycles, e.g. frozen embryo transfers-FET, egg donation-IVF etc.) , pregnancy and birth rates were substantially improved. Currently, it is my opinion, that an ideal estrogen-promoted endometrial lining should ideally measure at least 9mm in thickness and that an endometrial lining measuring 8-9mm is “intermediate”. An estrogenic lining of <8mm is in most cases unlikely to yield a viable pregnancy.

A “poor” uterine lining is usually the result of the innermost layer of endometrium (the basal or germinal endometrium from which endometrium grows) ) not being able to respond to estrogen by propagating an outer, “functional” layer thick enough to support optimal embryo implantation and development of a healthy placenta (placentation). The “functional” layer ultimately comprises 2/3 of the full endometrial thickness and is the layer that sheds with menstruation in the event that no pregnancy occurs.

The main causes of a “poor” uterine lining are:

1. Damage to the basal endometrium as a result of:
a. Inflammation of the endometrium (endometritis) most commonly resulting from infected products left over following abortion, miscarriage or birth
b. Surgical trauma due to traumatic uterine scraping, (i.e. due to an over-aggressive D & C)
2. Insensitivity of the basal endometrium to estrogen due to:
a. Prolonged , over-use/misuse of clomiphene citrate
b. Prenatal exposure to diethylstilbestrol (DES). This is a drug that was given to pregnant women in the 1960’s to help prevent miscarriage
3. Over-exposure of the uterine lining to ovarian male hormones (mainly testosterone): Older women, women with diminished ovarian reserve (poor responders) and women with polycystic ovarian syndrome -PCOS tend to have raised LH biological activity.. This causes the connective tissue in the ovary (stroma/theca) to overproduce testosterone. The effect can be further exaggerated when certain methods for ovarian stimulation such as agonist (Lupron/Buserelin) “flare” protocols and high dosages of menotropins such as Menopur are used in such cases.
4. Reduced blood flow to the basal endometrium:
Examples include;
a. Multiple uterine fibroids - especially when these are present under the endometrium (submucosal)
b. Uterine adenomyosis (excessive, abnormal invasion of the uterine muscle by endometrial glands).

“The Viagra Connection”

Eighteen years ago years ago, after reporting on the benefit of vaginal Sildenafil (Viagra) for to women who had implantation dysfunction due to thin endometrial linings I was proud to announce the birth of the world’s first “Viagra baby.” Since the introduction of this form of treatment, thousands of women with thin uterine linings have been reported treated and many have gone on to have babies after repeated prior IVF failure.

For those of you who aren’t familiar with the use of Viagra in IVF, allow me to provide some context. It was in the 90’s that Sildenafil (brand named Viagra) started gaining popularity as a treatment for erectile dysfunction. The mechanism by which it acted was through increasing penile blood flow through increasing nitric oxide activity. This prompted me to investigate whether Viagra administered vaginally, might similarly improve uterine blood flow and in the process cause more estrogen to be delivered to the basal endometrium and thereby increase endometrial thickening. We found that when Viagra was administered vaginally it did just that! However oral administration was without any significant benefit in this regard. We enlisted the services of a compound pharmacy to produce vaginal Viagra suppositories. Initially, four (4) women with chronic histories of poor endometrial development and failure to conceive following several advanced fertility treatments were evaluated for a period of 4-6 weeks and then underwent IVF with concomitant Viagra therapy. Viagra suppositories were administered four times daily for 8-11 days and were discontinued 5-7 days prior to embryo transfer in all cases.

Our findings clearly demonstrated that vaginal Viagra produced a rapid and profound improvement in uterine blood flow and that was followed by enhanced endometrial development in all four cases. Three (3) of the four women subsequently conceived. I expanded the trial in 2002 and became the first to report on the administration of vaginal Viagra to 105 women with repeated IVF failure due to persistently thin endometrial linings. All of the women had experienced at least two (2) prior IVF failures attributed to intractably thin uterine linings. About 70% of these women responded to treatment with Viagra suppositories with a marked improvement in endometrial thickness. Forty five percent (45%) achieved live births following a single cycle of IVF treatment with Viagra The miscarriage rate was 9%. None of the women who had failed to show an improvement in endometrial thickness following Viagra treatment achieved viable pregnancies.

Following vaginal administration, Viagra is rapidly absorbed and quickly reaches the uterine blood system in high concentrations. Thereupon it dilutes out as it is absorbed into the systemic circulation. This probably explains why treatment is virtually devoid of systemic side effects

It is important to recognize that Viagra will NOT be effective in improving endometrial thickness in all cases. In fact, about 30%-40% of women treated fail to show any improvement. This is because in certain cases of thin uterine linings, the basal endometrium will have been permanently damaged and left unresponsive to estrogen. This happens in cases of severe endometrial damage due mainly to post-pregnancy endometritis (inflammation), chronic granulomatous inflammation due to uterine tuberculosis (hardly ever seen in the United States) and following extensive surgical injury to the basal endometrium (as sometimes occurs following over-zealous D&C’s).

Combining vaginal Viagra Therapy with oral Terbutaline;
In my practice I sometimes recommend combining Viagra administration with 5mg of oral terbutaline. The Viagra relaxes the muscle walls of uterine spiral arteries that feed the basal (germinal) layer of the endometrium while Terbutaline, relaxes the uterine muscle through which these spiral arteries pass. The combination of these two medications interacts synergistically to maximally enhance blood flow through the uterus, thereby improving estrogen delivery to the endometrial lining. The only drawback in using Terbutaline is that some women experience agitation, tremors and palpitations. In such cases the terbutaline should be discontinued. Terbutaline should also not be used women who have cardiac disease or in those who have an irregular heartbeat.

About 75% of women with thin uterine linings see a positive response to treatment within 2-3 days. The ones that do not respond well to this treatment are those who have severely damaged inner (basal/germinal) endometrial linings, such that no improvement in uterine blood flow can coax an improved response. Such cases are most commonly the result of prior pregnancy-related endometrial inflammation (endometritis) that sometimes occurs post abortally or following infected vaginal and/or cesarean delivery.

Viagra therapy has proven to be a god send to thousands of woman who because of a thin uterine lining would otherwise never have been able to successfully complete the journey “from infertility to family”.

___________________________________________________________
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
Nicole

Could injecting an inadequate dose of HCG trigger have caused embryo abnormalities? I believe I used all the diluent when mixing pregnyl instead of the 1 ml. I then injected what must have been 1000 units of HCG versus the required 10000 units. I had 8 blastocysts and zero successful pregnancies. My husband and I were both 29 years old at retrieval. Thanks for reading.

reply
Dr. Geoffrey Sher

Not likely to be the problem.

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
Nick

Dear Dr. Scher,
A few years ago my wife had a 7-week miscarriage followed by a chemical pregnancy on a fresh IVF transfer. She was 32 then, now is 35. No measurable fertility issues with her or me. We did PGS on the remaining frozen embryos, and got 2 normal out of 4. 1 resulted in our daughter in the first FET 3 years ago. We just transferred our one remaining PGS normal embryo, 5AB, which was hatching upon thaw, and my wife just got her first beta back as 32 at 9 days post FET (with our daughter it was 290 at 10 days post FET). We are thinking this will almost certainly be a chemical pregnancy, though I know we have to repeat the test. Do you know what could be going on? Her lining was a 9 and everything else looked great; she was on estrogen pills and patch and 1 mL progesterone shots nightly. We thought that we had figured out the miscarriage issue with PGS. We appreciate any info you might have. Thanks in advance for all you do.

reply
Dr. Geoffrey Sher

You need follow-up blood hCG tests to determine the viability of the pregnancy. Ultimately an ultrsound examiation done at 6-7 weqeks will be definitive.

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
o. sahin

dear dr sher
i need to get the vaginal viagra medicine for my thin uterus lining . i live another country. we dont have rvaginal viagra here. but my sister lives in canada. she tries to buy the medicine for me.. is the name is the medicine Viagra for Women or Vaginal Viagra or something else? can she buy it without prescription?

reply
Dr. Geoffrey Sher

I do not think vaginal compounded Viagra is available in Canada. Your sister needs to contact MDR Pharmacy in Encino, CA and talk to Robert Mhakane (the pharmacist).

Good luck!

Geoff Sher

reply
Sonya

Dr Sher,
I had a beta of 222 9dp5dt, and had a second beta of 347 at 11dp5dt. How do you interpret this sluggish growth? I’m a realist and am assuming it’s another chemical. For background, I’m 32, have thin PCOS, and have been doing IVF for 3 years (had 2 previous chemical pregnancies, one ectopic, 4 straight negatives). Thank you for your advice.

reply
Dr. Geoffrey Sher

Sonya,

I am afraid this does not look good. Repeat the beta hCG in a few days and let me know the result.

Goff Sher

reply
Sonya

Hi Dr Sher,

Following a disappointing second beta, which showed a 56% increase over 48hrs, I had a third beta, which came back at 784 – a 225% increase over the previous beta (in 48hrs). My nurse didn’t think it was worth doing more blood tests and was positive, and I’m scheduled for an ultrasound on Friday. Realistically, should I be expecting this to be a non-viable pregnancy?

reply
Dr. Geoffrey Sher

Not at all! I think you may have spontaneously reduced 1 pregnancy. Hopefully all will be fine. Wait for an ultrasound in about 2.5 weeks.

I know of no medical announcement associated with the degree of emotional anticipation and anguish as that associated with a pending diagnosis/confirmation of pregnancy following infertility treatment. In fact, hardly a day goes by where I am not confronted by a patient anxiously seeking interpretation of a pregnancy test result.
Testing urine or blood for the presence of human chorionic gonadotropin (hCG) is the most effective and reliable way to confirm conception. The former, is far less expensive than the latter and is the most common method used. It is also more convenient because it can be performed in the convenience of the home setting. However, urine hCG testing for pregnancy is not nearly as reliable or as sensitive e as is blood hCG testing. Blood testing can detect implantation several days earlier than can a urine test. Modern pregnancy urine test kits can detect hCG about 16-18 days following ovulation (or 2-3 days after having missed a menstrual period), while blood tests can detect hCG, 12-13 days post-ovulation (i.e. even prior to menstruation).
The ability to detect hCG in the blood as early as possible and thereupon to track its increase, is particularly valuable in women undergoing controlled ovarian stimulation (COS) with or without intrauterine insemination (IUI) or after IVF. The earlier hCG can be detected in the blood and its concentration measured, the sooner levels can be tracked serially over time and so provide valuable information about the effectiveness of implantation, and the potential viability of the developing conceptus.
There are a few important points that should be considered when it comes to measuring interpreting blood hCG levels. These include the following:
• All modern day blood (and urine) hCG tests are highly specific in that they measure exclusively for hCG. There is in fact no cross-reactivity with other hormones such as estrogen, progesterone or LH.
• Post conception hCG levels, measured 10 days post ovulation or egg retrieval can vary widely (ranging from 5mIU/ml to above 400mIU/ml. The level will double every 48–72 hours up to the 6th week of gestation whereupon the doubling rate starts to slow down to about 96 hours. An hCG level of 13,000-290, 0000 mIU/ml is reached by the end of the 1st trimester (12 weeks) whereupon it slowly declines to approximately 26,000– 300,000 mIU/ml by full term. Below are the average hCG levels during the first trimester:
o 3 weeks LMP: 5 – 50 mIU/ml
o 4 weeks LMP: 5 – 426 mIU/ml
o 5 weeks LMP: 18 – 7,340 mIU/ml
o 6 weeks LMP: 1,080 – 56,500 mIU/ml
o 7 – 8 weeks LMP: 7, 650 – 229,000 mIU/ml
o 9 – 12 weeks LMP: 25,700 – 288,000 mIU/ml
• A single hCG blood level is not sufficient to assess the viability of an implanting embryo. Caution should be used in making too much of an initial hCG level. This is because a normal pregnancy can start with relatively low hCG blood levels. It is the rate of the rise of the blood hCG level that is relevant.
• In some cases the initially hCG level is within the normal range, but then fails to double in the ensuing 48-72hours. In some cases it might even plateau or decline, only to start doubling appropriately thereafter. When this happens, it could be due to:
o A recovering implantation, destined to develop into a clinical gestation
o A failing implantation (a chemical pregnancy)
o A multiple pregnancy which is spontaneously reducing (i.e., one or more of the concepti is being lost) or,
o An ectopic pregnancy which will either absorb spontaneously (a chemical-tubal gestation), or evolve into a full blown tubal pregnancy continue and declare itself through characteristic symptoms and signs of an intraperitoneal bleed.
• The blood hCG test needs to be repeated at least once after 48h and in some cases it will need to be repeated one or more times (at 48h intervals) thereafter, to confirm that implantation is progressing normally.
• Ultimately the diagnosis of a viable pregnancy requires confirmation of the presence of an intrauterine gestational sac by ultrasound examination. The earliest that this can be achieved is when the beta hCG level exceeds 1,000mIU/ml (i.e., around 5-6 weeks).
• Most physicians prefer to defer the performance of a routine US diagnosis of pregnancy until closer to the 7th week. This is because by that time, cardiac activity should be clearly detectable, allowing for more reliable assessment of pregnancy viability.
• There are cases where the blood beta hCG level is extraordinarily high or the rate of rise is well above the normal doubling rate. The commonest explanation is that more than one pregnancy has implanted. However in some cases it can point to a molar pregnancy
• Finally, there on rare occasions, conditions unrelated to pregnancy can result in detectable hCG levels in blood and urine. They include ovarian tumors that produce hCG, such as certain types of cystic teratomas (dermoid cysts) and some ovarian cancers such as dysgerminomas.
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
• Genetically Testing Embryos for IVF
• IVF Failure and Implantation Dysfunction:
• Management of Immunologic Implantation Dysfunction (IID).
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• 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
• Ectopic Pregnancy
• Molar pregnancies

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 .

Geoff Sher

reply
Lily

Dear Dr Sheer
I’d like your opinion. I’m 41, i had a previous pregnancy (healthy boy) with my last embryos transfer 2 years ago. This was a donor egg Ivf, 2 embryos were place back ( 2 good quality blastocysts), 1 took, 1 amazing baby.
I’m going again for a second round, 2 embryos are currently left.
I really don’t know what to do. Should we transfer 1 or both? I’m in good heath, I don’t think a multiple pregnancy is that bad but I’ve read around and it’s scaring me. First idea was to go with the 2 like last time. Money wise and travel wise it will be more easy to only go once too.
What you would advice to your favorite patient 🙂 ?
What are the real odds of simple and multiple regarding my age with 2 blasts ?

reply
Dr. Geoffrey Sher

Lily,

No doubt, single embryo transfers are best! However, aside from age, if you are healthy with no predisposing factors leading to pregnancy induced complications, you might consider transferring both embryos.

___________________________________________________________
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

Geoff Sher

reply
Chelsea

Hello,
I am 29 with AMH of 3.3, day 3 Fsh of 8 and estrogen of 45. AFC is 13-15. Normal weight, no other health issues. Regular cycles and diagnosed with unexplained infertility. History of a miscarriage 2 years ago at 7 weeks with my current husband.

My husband is 37 with sperm counts ranging from 7-24 million with motility of 40-60%. Slow progressive grade. Morph is 3-5%.

We recently had a failed IVF cycle. 10 eggs retrieved, 8 mature, 5 fertilized. Day 3 all embryos were showing grade 3 fragmentation and none made it to blastocyst. I was on birth control for 4 weeks prior to stims. My ovaries were slow to wake up but I triggered on day 13 and my estrogen was 2000. My cycle was treated with follistim 375 and menopur 75mg. I kept questioning my doctor if I was on the right protocol as I was expecting more eggs collected and she told me I stimmed well and had a standard IVF cycle response. With our poor results, the doctor thought we would do better and thinks it could be egg or sperm quality and had nothing to do with the protocol. She even mentioned she wouldn’t recommend a different protocol. She just said we are not fertile but could still have a chance at pregnancy and denied that the birth control prior to stims had any affect. I would like your opinion. Could I have been born with defected eggs that cause fragmentation? Do you think sperm DNA fragmentation could be a factor? We thought it was a low numbers game with my husband and why we went to IVF but now it appears to be an inherent problem with our DNA?

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
Dr. Geoffrey Sher

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:

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
o. sahin

my lining was 7-8mm everymonth when my doctor checked but after medical abortion my line is very thin my new doctor says he will do PRP for uters when transfer time. is it enough to apply PRP one time and after that immediatly Fet is okay?

reply
Dr. Geoffrey Sher

Respectfully, in my opinion it is not going to help. Thlining needs to be >8mm and preferably >9mm.

It was as far back as 1989, when I first published a study that examined the correlation between the thickness of a woman’s uterine lining (the endometrium), and the subsequent successful implantation of embryos in IVF patients. This study revealed that when the uterine lining measured <8mm in thickness by the day of the “hCG trigger” (in fresh IVF cycles), or at the time of initiating progesterone therapy (in embryo recipient cycles, e.g. frozen embryo transfers-FET, egg donation-IVF etc.) , pregnancy and birth rates were substantially improved. Currently, it is my opinion, that an ideal estrogen-promoted endometrial lining should ideally measure at least 9mm in thickness and that an endometrial lining measuring 8-9mm is “intermediate”. An estrogenic lining of <8mm is in most cases unlikely to yield a viable pregnancy.

A “poor” uterine lining is usually the result of the innermost layer of endometrium (the basal or germinal endometrium from which endometrium grows) ) not being able to respond to estrogen by propagating an outer, “functional” layer thick enough to support optimal embryo implantation and development of a healthy placenta (placentation). The “functional” layer ultimately comprises 2/3 of the full endometrial thickness and is the layer that sheds with menstruation in the event that no pregnancy occurs.

The main causes of a “poor” uterine lining are:

1. Damage to the basal endometrium as a result of:
a. Inflammation of the endometrium (endometritis) most commonly resulting from infected products left over following abortion, miscarriage or birth
b. Surgical trauma due to traumatic uterine scraping, (i.e. due to an over-aggressive D & C)
2. Insensitivity of the basal endometrium to estrogen due to:
a. Prolonged , over-use/misuse of clomiphene citrate
b. Prenatal exposure to diethylstilbestrol (DES). This is a drug that was given to pregnant women in the 1960’s to help prevent miscarriage
3. Over-exposure of the uterine lining to ovarian male hormones (mainly testosterone): Older women, women with diminished ovarian reserve (poor responders) and women with polycystic ovarian syndrome -PCOS tend to have raised LH biological activity.. This causes the connective tissue in the ovary (stroma/theca) to overproduce testosterone. The effect can be further exaggerated when certain methods for ovarian stimulation such as agonist (Lupron/Buserelin) “flare” protocols and high dosages of menotropins such as Menopur are used in such cases.
4. Reduced blood flow to the basal endometrium:
Examples include;
a. Multiple uterine fibroids - especially when these are present under the endometrium (submucosal)
b. Uterine adenomyosis (excessive, abnormal invasion of the uterine muscle by endometrial glands).

“The Viagra Connection”

Eighteen years ago years ago, after reporting on the benefit of vaginal Sildenafil (Viagra) for to women who had implantation dysfunction due to thin endometrial linings I was proud to announce the birth of the world’s first “Viagra baby.” Since the introduction of this form of treatment, thousands of women with thin uterine linings have been reported treated and many have gone on to have babies after repeated prior IVF failure.

For those of you who aren’t familiar with the use of Viagra in IVF, allow me to provide some context. It was in the 90’s that Sildenafil (brand named Viagra) started gaining popularity as a treatment for erectile dysfunction. The mechanism by which it acted was through increasing penile blood flow through increasing nitric oxide activity. This prompted me to investigate whether Viagra administered vaginally, might similarly improve uterine blood flow and in the process cause more estrogen to be delivered to the basal endometrium and thereby increase endometrial thickening. We found that when Viagra was administered vaginally it did just that! However oral administration was without any significant benefit in this regard. We enlisted the services of a compound pharmacy to produce vaginal Viagra suppositories. Initially, four (4) women with chronic histories of poor endometrial development and failure to conceive following several advanced fertility treatments were evaluated for a period of 4-6 weeks and then underwent IVF with concomitant Viagra therapy. Viagra suppositories were administered four times daily for 8-11 days and were discontinued 5-7 days prior to embryo transfer in all cases.

Our findings clearly demonstrated that vaginal Viagra produced a rapid and profound improvement in uterine blood flow and that was followed by enhanced endometrial development in all four cases. Three (3) of the four women subsequently conceived. I expanded the trial in 2002 and became the first to report on the administration of vaginal Viagra to 105 women with repeated IVF failure due to persistently thin endometrial linings. All of the women had experienced at least two (2) prior IVF failures attributed to intractably thin uterine linings. About 70% of these women responded to treatment with Viagra suppositories with a marked improvement in endometrial thickness. Forty five percent (45%) achieved live births following a single cycle of IVF treatment with Viagra The miscarriage rate was 9%. None of the women who had failed to show an improvement in endometrial thickness following Viagra treatment achieved viable pregnancies.

Following vaginal administration, Viagra is rapidly absorbed and quickly reaches the uterine blood system in high concentrations. Thereupon it dilutes out as it is absorbed into the systemic circulation. This probably explains why treatment is virtually devoid of systemic side effects

It is important to recognize that Viagra will NOT be effective in improving endometrial thickness in all cases. In fact, about 30%-40% of women treated fail to show any improvement. This is because in certain cases of thin uterine linings, the basal endometrium will have been permanently damaged and left unresponsive to estrogen. This happens in cases of severe endometrial damage due mainly to post-pregnancy endometritis (inflammation), chronic granulomatous inflammation due to uterine tuberculosis (hardly ever seen in the United States) and following extensive surgical injury to the basal endometrium (as sometimes occurs following over-zealous D&C’s).

Combining vaginal Viagra Therapy with oral Terbutaline;
In my practice I sometimes recommend combining Viagra administration with 5mg of oral terbutaline. The Viagra relaxes the muscle walls of uterine spiral arteries that feed the basal (germinal) layer of the endometrium while Terbutaline, relaxes the uterine muscle through which these spiral arteries pass. The combination of these two medications interacts synergistically to maximally enhance blood flow through the uterus, thereby improving estrogen delivery to the endometrial lining. The only drawback in using Terbutaline is that some women experience agitation, tremors and palpitations. In such cases the terbutaline should be discontinued. Terbutaline should also not be used women who have cardiac disease or in those who have an irregular heartbeat.

About 75% of women with thin uterine linings see a positive response to treatment within 2-3 days. The ones that do not respond well to this treatment are those who have severely damaged inner (basal/germinal) endometrial linings, such that no improvement in uterine blood flow can coax an improved response. Such cases are most commonly the result of prior pregnancy-related endometrial inflammation (endometritis) that sometimes occurs post abortally or following infected vaginal and/or cesarean delivery.

Viagra therapy has proven to be a god send to thousands of woman who because of a thin uterine lining would otherwise never have been able to successfully complete the journey “from infertility to family”.

___________________________________________________________
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
o. sahin

dear dr sher. i know the best method is genetic test to understand the qualtiy of an embriyo.. which one is better 4ab or 2ab? actually if i write down my embrios, could you please number them from better than worse.. #1 is better #6 worse….
my blast embrios quality :
4aa
3bb
2bb
2ab
5bc
5cb

reply
Dr. Geoffrey Sher

Unfortunately morphologic embryo grading systems vary widely. I am not familiar with the one used here.

Sorry!

Geoff Sher

reply
Amandeep

Hello Dr. Sher. I am 32 years old pcos woman. I have normal bmi and no symptoms of pcos other than polycystic ovaries. I have done 3 ivf cycles. 2 with puregon and one with menupor. Both cycles I produced more than 18 eggs and around 13 fertilised each time without icsi. But we only get one average quality blastocyst hence unsuccessful cycle. What would you recommend in my case? I read your article on COS protocol. Should I try that? Thanks

reply
Dr. Geoffrey Sher

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
Kate

My husband and I are both 36 and had a failed first IVF cycle using a mid-luteal protocol. We were unexplained infertility and prior to our trigger, we had 15 follicles, measuring 13-21mm. We ended up retrieving 8, 7 mature, 4 fertilized. On Day 6, 3 arrested and 1 went to blast, which tested PGS abnormal. We were told we had an egg quality issue and that we’d trigger earlier this time. Would HGH help here? Or a different protocol? Is egg quality truly the only issue here?

reply
Dr. Geoffrey Sher

In my opinion, it is that likely this is a protocol-related egg/embryo issue.

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
Monica

Dr. Sher,
I am in my firs IVF cycle. We transferred a single day 5 blastocyst. Im currently 5 weeks 5 days and my beta today was 14,503. Does this number seem too high to you? My previous betas 9dp5dt was 125, 12dp5dt 575. I go for an US in 1 week. I would love to know your thoughts. Thank you.

reply
Dr. Geoffrey Sher

I would do the ultrasound ASAP

___________________________________________________________
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
Dr. Geoffrey Sher

Because with your hCG level being as high as it is you should be able to identify the presence of one or more gestational sacs now already and have a definitive answer.

Geoff Sher

Monica

Would you only concern with this level be possibly two gestational sacs? My RE’s office did not seem concerned and suggested waiting until 6 weeks before US. I have emailed my physician to speak to him directly. This was also an ICSI cycle I’m not sure if that makes any difference. Thanks for your time.

Dr. Geoffrey Sher

No! However, an US now would shed a great deal of light on the viability and predicament of this pregnancy. And why should you delay in anguish!

Geoff Sher

Andrea

Dr. Sher,
Have gone through 2 Retrieval’s and one transfer over the past year. Each procedure afterwards I get a stuffy nose for a few days then eventually flu like symptoms pop up 2 to 7 days afterwards. Always with a temp of 101.5 on average for at least 24 hours. Unfortunately my one transfer didn’t result in a pregnancy. Only one chromosome normal embryo from my first Retrieval out of 7 eggs. After my recent (2nd Retrieval (3 weeks ago, no chromosome normal embryos out of 5 eggs), same stuffy nose and flu like symptoms about a week after procedure. Met with my general OBGYN doctor and after explaining to her I keep getting sick after each IVF procedure, she ran some blood tests (I also had a severe allergic reaction to the antibiotics post Retrieval as well; hives, hot flashes,headaches,etc.. and it was discovered through one of the blood tests that my IgG4 was at a level 3. Doctor said she has never seen a level that low in an adult. Unsure what the IgG4 even is and if it’s related to infertility? I also have endometriosis, carrier of a genetic abnormality disorder (inversion classification), thyroid issues (currently on levothyroxine for the past year; 1.19 level according to recent blood test). My entire life I have suffered from horrific ovulation cramps, painful periods and in my personal opinion a “flamatory” issue. Love to know more about this IgG4 deficiency, what it even is and if this may be related to and possibly contributing to my infertility? To point out, have had miscarriages in the past prior to IVF 3 years ago (approx. 38 years old with my first miscarriage) All happened within weeks of finding out I was pregnant.

Thank you!

reply
Dr. Geoffrey Sher

I do not think your stuffy nose post ER or the IgG4 level has any prognostic significance as far as your IVF is concerned. However, I do suspect that your endometriosis and perhaps more specifically its relationship to immunologic implantation dysfunction could be a factor.

When women with infertility due to endometriosis seek treatment, they are all too often advised to first try ovarian stimulation (ovulation Induction) with intrauterine insemination (IUI) ………as if to say that this would be just as likely to result in a baby as would in vitro fertilization (IVF). Nothing could be further from reality It is time to set the record straight. And hence this communication!

Bear in mind that the cost of treatment comprises both financial and emotional components and that it is the cost of having a baby rather than cost of a procedure. Then consider the fact that regardless of her age or the severity of the condition, women with infertility due to endometriosis are several fold more likely to have a baby per treatment cycle of IVF than with IUI. It follows that there is a distinct advantage in doing IVF first, rather than as a last resort.

So then, why is it that ovulation induction with or without IUI is routinely offered proposed preferentially to women with mild to moderately severe endometriosis? Could it in part be due to the fact that most practicing doctors do not provide IVF services but are indeed remunerated for ovarian stimulation and IUI services and are thus economically incentivized to offer IUI as a first line approach? Or is because of the often erroneous belief that the use of fertility drugs will in all cases induce the release (ovulation) of multiple eggs at a time and thereby increase the chance of a pregnancy. The truth however is that while normally ovulating women (the majority of women who have mild to moderately severe endometriosis) respond to ovarian stimulation with fertility drugs by forming multiple follicles, they rarely ovulate > 1 (or at most 2) egg at a time. This is because such women usually only develop a single dominant follicle which upon ovulating leaves the others intact. This is the reason why normally ovulating women who undergo ovulation induction usually will not experience improved pregnancy potential, nor will they have a marked increase in multiple pregnancies. Conversely, non-ovulating women (as well as those with dysfunctional ovulation) who undergo ovulation induction, almost always develop multiple large follicles that tend to ovulate in unison. This increases the potential to conceive along with an increased risk multiple pregnancies.

So let me take a stab at explaining why IVF is more successful than IUI or surgical correction in the treatment of endometriosis-related infertility:
1. The toxic pelvic factor: Endometriosis is a condition where the lining of the uterus (the endometrium) grows outside the uterus. While this process begins early in the reproductive life of a woman, with notable exceptions, it only becomes manifest in the 2ndhalf of her reproductive life. After some time, these deposits bleed and when the blood absorbs it leaves a visible pigment that can be identified upon surgical exposure of the pelvis. Such endometriotic deposits invariably produce and release toxins” into the pelvic secretions that coat the surface of the membrane (the peritoneum) that envelops all abdominal and pelvic organs, including the uterus, tubes and ovaries. These toxins are referred to as “the peritoneal factor”. Following ovulation, the egg(s) must pass from the ovary (ies), through these toxic secretions to reach the sperm lying in wait in the outer part the fallopian tube (s) tube(s) where, the sperm lie in waiting. In the process of going from the ovary(ies) to the Fallopian tube(s) these eggs become exposed to the “peritoneal toxins” which alter s the envelopment of the egg (i.e. zona pellucida) making it much less receptive to being fertilized by sperm. As a consequence, if they are chromosomally normal such eggs are rendered much less likely to be successfully fertilized. Since almost all women with endometriosis have this problem, it is not difficult to understand why they are far less likely to conceive following ovulation (whether natural or induced through ovulation induction). This “toxic peritoneal factor impacts on eggs that are ovulated whether spontaneously (as in natural cycles) or following the use of fertility drugs and serves to explain why the chance of pregnancy is so significantly reduced in normally ovulating women with endometriosis.
2. The Immunologic Factor: About one third of women who have endometriosis will also have an immunologic implantation dysfunction (IID) linked to activation of uterine natural killer cells (NKa). This will require selective immunotherapy with Intralipid infusions, and/or heparinoids (e.g. Clexane/Lovenox) that is much more effectively implemented in combination with IVF.
3. Surgical treatment of mild to moderate endometriosis does not usually improve pregnancy potential:. The reason is that endometriosis can be considered to be a “work in progress”. New lesions are constantly developing. So it is that for every endometriotic seen there are usually many non-pigmented deposits that are in the process of evolving but are not yet visible to the naked eye and such evolving (non-visible) lesions can also release the same “toxins that compromise fertilization. Accordingly, even after surgical removal of all visible lesions the invisible ones continue to release “toxins” and retain the ability to compromise natural fertilization. It also explains why surgery to remove endometriotic deposits in women with mild to moderate endometriosis usually will fail to significantly improve pregnancy generating potential. In contrast, IVF, by removing eggs from the ovaries prior to ovulation, fertilizing these outside of the body and then transferring the resulting embryo(s) to the uterus, bypasses the toxic pelvic environment and is therefore is the treatment of choice in cases of endometriosis-related infertility.
4. Ovarian Endometriomas: Women, who have advanced endometriosis, often have endometriotic ovarian cysts, known as endometriomas. These cysts contain decomposed menstrual blood that looks like melted chocolate…hence the name “chocolate cysts”. These space occupying lesions can activate ovarian connective tissue (stroma or theca) resulting in an overproduction of male hormones (especially testosterone). An excess of ovarian testosterone can severely compromise follicle and egg development in the affected ovary. Thus there are two reasons for treating endometriomas. The first is to alleviate symptoms and the second is to optimize egg and embryo quality. Conventional treatment of endometriomas involves surgical drainage of the cyst contents with subsequent removal of the cyst wall (usually by laparoscopy), increasing the risk of surgical complications. We recently reported on a new, effective and safe outpatient approach to treating endometriomas in women planning to undergo IVF. We termed the treatment ovarian Sclerotherapy. The process involves; needle aspiration of the “chocolate colored liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline hydrochloride into the cyst cavity. Such treatment will, more than 75% of the time result in disappearance of the lesion within 6-8 weeks. Ovarian sclerotherapy can be performed under local anesthesia or under conscious sedation. It is a safe and effective alternative to surgery for definitive treatment of recurrent ovarian endometriomas in a select group of patients planning to undergo IVF

I am not suggesting that all women with infertility-related endometriosis should automatically resort to IVF. Quite to the contrary…. In spite of having reduced fertility potential, many women with mild to moderate endometriosis can and do go on to conceive on their own (without treatment). It is just that the chance of this happening is so is much lower than normal.

IN SUMMARY: For young ovulating women (< 35 years of age ) with endometriosis, who have normal reproductive anatomy and have fertile male partners, expectant treatment is often preferable to IUI or IVF. However, for older women, women who (regardless of their age) have any additional factor (e.g. pelvic adhesions, ovarian endometriomas, male infertility, IID or diminished ovarian reserve-DOR) IVF should be the primary treatment of choice. I strongly recommend that you visit 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: • 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! • 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 • How Many Embryos should be transferred: A Critical Decision in IVF? • Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF • Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice. • Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options • Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination) and Reproductive Surgery Versus IVF • Treating Ovarian Endometriomas with Sclerotherapy. • Effect of Advanced Endometriosis with Endometriotic cysts (Endometriomas) on IVF Outcome & Treatment Options. • Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF). • Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & • Induction of Ovulation with Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its use • Clomiphene Induction of Ovulation: Its Use and Misuse! ___________________________________________________________ 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

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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