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Dear Patients,

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

– Geoffrey Sher, MD

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19,522 Comments

Eleanore

Dear dr. Sher,
I’m a 31-year-old female. I’ve already had done 2 ICSI treatment because of azoospermia, with a disappointing result. For the first cycle I was 3 weeks on birthcontrol pill, after that for about 18 days I used Decapeptyl for the down-regulation, and 9 days of stimulation with Menopur 225 IU, the trigger was with Pregnyl 5000 IU. The result was 11 follicles, 7 eggs retrieved and only 2 eggs were mature for ICSI. For the 2nd cyclus I was on an antagonist protocol where I had to start with stimulation on the 3rd day of my menstruation with 150 IU Gonal-F in the morning and 150 IU Meriofert in the evening, I had to take Cetrotide on day 6 and triggerd with Pregnyl 5000 IU on day 9 (day 11 of my menstruation cycle). The result was 5 eggs retrieved of which only 1 was mature. It made it to day 5, where it was still a morula without fragmentation. So both protocols didn’t work for me. My AMH was at het first blood test 1.1. ug/L and 3.29 ng/ml by the 2nd test. Can you please advice me which protocol I should have? I’m afraid that this is about my egg quality. Is it? I’m looking forward to hearing from you. Kinds regards, Eleanore.

reply
Dr. Geoffrey Sher

Respectfully, aside from dealing with the azoospermia, in my opinion the low yield of mature eggs could have to do with the protocol used for ovarian stimulation in the 1st cycle and I would have triggered with 10,000U of hCG, not 5,000U. The azoospermia1, I would also not have used Decapeptyl for so long (in the 1st cycle).

Here is the protocol I advise for women, <40Y 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.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.
• 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:
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Eleanore

Dear dr. Sher,

Thank you for your response.
Can you please tell me for how long I should take the BCP in this protocol? And which dosage of an FSH-dominant gonadotropin would you advice me?
Thank you so much.

reply
Dr. Geoffrey Sher

The length of time on the BCP can vary , but it needs to be at least 10 days before overlapping with the agonist (Lupron/Buserelin/Superfact,etc.). The dosage would depend on information I presently do not have (e.g. recent AMH; prior response to previous stimulation, etc.).

Geoff Sher

reply
Eleanore

Thank you for replying dr. Sher. For the 1st cycle I used Menopur 225 IU en had 7 eggs of which just 1 was mature for ICSI. For the 2nd cycle I used in the morning Gonal-F 150 IU and in the evening Meriofert 150 IU, and had 5 eggs of which 1 was mature enough for ICSI. My recent AMH is 3.29 ng/ml,
FSH 4.7 mIU/ml,
Oestradiol 25,00 pg/ml,
LH 3.30 mU/ml
prolactine 202 mU/l
testosteron 0.18 ng/ml, All measured on the 3rd day of my menstruation cycle.
And what could be the cause of the fast grow of my follicles, cause on the sixt day of stimulation I have follicles round 18 or even 20 mm.
Thank you very much, doc!

Dr. Geoffrey Sher

Perhaps we should talk. Please call 800-780-7437 to set up a Skype consultation.

Geoff Sher

Nico

Dear Mr Geoffrey,
I would like to get some clearness in our situation. My wife (27) and I (36) are right in a ivf treatment. She got 2 (5 days grown) embryos inserted 10 days ago. On Monday she made a blood test and the hcg rate was 30. Two days later it was 45. Now she’s very concerned and worried.
Maybe you could give us your professional opinion about that situation/results.
Thank you very much,
Nico

reply
Dr. Geoffrey Sher

Hi Nico,

This is a slow rise. It should have doubled in 2 days. I suggest you repeat the beta hCG in 2 days from now. It should be around 100. If not, it could pose a problem.

Good luck!

Geoff Sher

reply
Dr. Geoffrey Sher

Yes it does, but that still does not mean everyone needs PGS.

About a decade ago, I, along with my associate, Levent Keskintepe PhD were the first to introduce full chromosome Preimplantation Genetic Sampling/Screening (PGS) into the IVF clinical realm to try and identify euploid embryos whose cells contained the required 46 chromosomes (23 pairs) necessary to render them potentially “competent” to propagate viable pregnancies. Aneuploid embryos (those that have more or less than a total of 46 chromosomes) are by and large considered to be “incompetent”, far less likely to propagate a viable pregnancy and thus largely unworthy of being transferred to the uterus.
Initially the primary method used for PGS was, comparative genomic hybridization (CGH). The methodology was not without certain problems. A few years ago, new and improved technology known as next generation gene sequencing (NGS) emerged. This has since all but replaced other methodologies. Gene sequencing determines the precise order of nucleotides within a DNA molecule. It includes any method or technology that is used to determine the order of the four bases—adenine, guanine, cytosine, and thymine—in a strand of DNA.
The widely held belief is that the ideal time to biopsy embryos for PGS is when they reach the most advanced stage of preimplantation development (the blastocyst stage) by 5-6 days post-fertilization. At this point several cells are microsurgically removed from the embryo’s outer cellular layer (trophectoderm-TE), processed and subjected to PGS analysis. The blastocysts are ultra-rapidly frozen (vitrified) and held for future dispensation in a subsequent frozen embryo transfer (FET) cycle, once test results are known.
Access to several cells through TE biopsy provides more DNA for reliable analysis that can be attained through the testing of a single cell removed from a day-2-3 cleaved embryo. It is this plus the belief that the hypercellular blastocyst is far less likely to be damaged through such microsurgical intervention that would be the case with a 4-10 cell, day-3 cleaved embryo that has led to the preferred timing for biopsy to be on day 5-6 blastocysts..
When PGS testing was first introduced, initial results were most-encouraging. Embryo implantation rates of >50% and birth rates of 50-60% when up to two euploid blastocysts were transferred, were being reported. In addition, the reported incidence of miscarriages and chromosomal birth defects was likewise greatly reduced. In fact, we were so encouraged that most of us predicted that a time would come where full embryo karyotyping through PGS would become a routine part of IVF. But alas…..we were soon to be disappointed when following the widespread introduction of PGS testing success rates started dropping. This was especially the case when PGS was performed on embryos derived from the eggs of older women and women with severely diminished ovarian reserve (DOR). With further investigation it began to dawn upon us that:
a) Chromosomal numerical integrity, while being the most important determinant of embryo “competency” was likely not the only factor that impacted embryo “competency”. Indeed advancing age was revealed to increase the incidence of embryo aneuploidy, independent of embryo karyotype and this is probably linked to non-chromosomal, genetic and metabolomic factors that might also be age-related.
b) Independent of embryo competency, there are many variables, that can and also do determine IVF outcome and these are often outside the control of the embryology/genetic laboratory. They include selection and implementation of individualized protocols for controlled ovarian stimulation (COS), endometrial factors that determine embryo implantation (e.g. anatomical an immunologic implantation dysfunction), technical skill of the physician performing embryo transfer etc.
c) Not all PGS-aneuploid embryos are “incompetent”. Some are mosaic (see elsewhere) and these are often capable of “autocorrecting” upon being transferred to the uterus, and propagating healthy babies.
Example A: Under optimal conditions embryo “competency” is determined by age and the protocol used for COS. In women <39Y of age roughly 1:2 blastocysts will likely be euploid “competent” and were such an embryo be gently and expertly transferred to a “receptive” uterine environment, the chance of a viable pregnancy should about 55-60%. This means that when ET is performed in such ideal IVF candidates, the chance of it resulting in a live birth should be about 27%-30% per embryo.
Example B: Conversely, when it comes to a woman in her mid-forties, the chance of an embryo being “competent” is probably < 1:8-10. And, the age-adjusted chance of such a Euploid embryo propagating a live birth is (for reasons cited above) theoretically well below 60% (perhaps around 40%-45%). This extrapolates to a baby rate of no more than 4%-5% per blastocyst transferred. Using the above examples: In Example A: Given that about 50% of the eggs (and thus resulting embryos) of young women are euploid and competent, the transfer up to 2 non-PGS tested blastocysts would likely yield the same results as would the transfer of a single PGS-tested euploid blastocyst. It follows that a patient/couple who are capable and willing to engage a twin pregnancy (which would occur in roughly 25% of such cases), might get as good a result by simply transferring two (2) untested blastocysts and in the process avoid the additional cost of PGS. In Example B: Conversely, the chance of a viable pregnancy in a woman in her mid-40’s would likely be 8-10 times greater when a “competent”, PGS-euploid blastocyst is selectively transferred as compared to when a non-PGS tested blastocyst is transferred to the uterus (4% versus 40%). Albeit that PGS-testing of blastocysts derived from fertilization of an older woman’s eggs is less reliable than for younger counterparts, there would be a distinct benefit/advantage in pre-selecting euploid, “competent” blastocysts for transfer in such cases. Since older women often also have DOR and thus produce fewer eggs/embryos, such women should benefit inordinately from the selective “stockpiling” (banking) of PGS-biopsied blastocysts (vitrification) over several cycles of IVF for collective PGS testing and the subsequent selective transfer of only the most “competent” ones to the uterus with FET. In conclusion, it is my considered opinion that PGS-embryo selection only be considered in the following circumstances: 1. Women over the age of 39Y and those who, regardless of age have significant DOR, are running out of eggs and time, and need to “make hay while the sun shines”! 2. Unexplained IVF failure. 3. Certain cases of recurrent pregnancy loss (RPL). 4. Family gender balancing cases 5. Women who have alloimmune implantation dysfunction (IID) with activation of uterine natural killer cells (NKa)…see elsewhere. 6. Where karyotyping reveals one or other partner to have a balanced chromosomal translocation 7. Known or anticipated specific genetic abnormalities When selectively used PGS is an excellent tool to improve implantation potential and IVF outcome (see above). While PGS provides a new and unique method for selecting the ideal embryos to be transferred, it is not a panacea when it comes to identifying “competent embryos”. There are factors other than numerical chromosomal integrity (karyotype) that can and do influence embryo “competency”, profoundly. PGS embryo selection is in my opinion currently over-used. This is especially the case when it comes to younger women with normal ovarian reserve. Unless the dust is allowed to settle such that this remarkable technology is properly applied, it is my belief that it stands the risk of progressively falling into disrepute. 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. • 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 • Why did my IVF Fail • Unexplained IVF Failure • Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF. • 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 • 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. • Avoiding High Order Multiple Pregnancies (Triplets or Greater) with IVF • The Role of Nutritional Supplements in Preparing for IVF ANNOUNCEMENTS: 1. About my Retirement After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Anna

Thank you for your thorough response!
We transferred two PGS normal and Mitograde normal embryos yesterday. A 6AA and 6BC. Our RE said not to focus on the grading so much because they are both PGS tested, and that would be more of trustworthy factor than the actual visual grading. Even those these two had normal mitograde numbers…He said he doesn’t believe in mitograde because plenty of babies have been more with elevated mitograde.

We would be thrilled to have twins (I’m 32, normal aMH, just Stage 3 endo) but I can’t help but focus on the 6BC being graded lower.

reply
Dr. Geoffrey Sher

I totally agree with your RE on both counts. In my opinion, Mitograde is superfluous and PGS trumps microscopic grading.

Good Luck!

Geoff Sher

reply
Kara

Hi Dr Sher. I had two IVF transfers with PGS tested chromosomes this year. Both resulted in a chemical pregnancy. From my 2 egg retrievals, they retrieved 27 eggs, but only 3 made it to testing. 2 were normal (and transferred) and 1 was abnormal. We don’t have any frozen embryos left, and are struggling with the decision to go to IVF #3 without any answers on why #1 and #2 didn’t work. Before IVF, we did 4 IUI’s that all failed. I am 31, with normal FSH and AMH levels. My husband and I did genetic testing prior to trying to conceive, and neither of us have a history of any medical or fertility issues in our families. We are both of healthy weight and live a fairly healthy lifestyle re: diet and exercise. I have been doing acupuncture and taking vitamins. We have now been trying for 2 years.

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

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
marwa

i had several failed ivf that ended with a bfn i found that i have high antithyroid antibodies with endo so my RE gives me prednisolone and lovenox during the preparation of my last two ivf which resulted in a chemical pregnancy twice i have normal cd56. what do you think i should take prednisolone for how long before ET and should i take intralipids also?

reply
Dr. Geoffrey Sher

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

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.
• 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
• 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!
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Lyn

Dear Dr. Sher,
Hello Dr. Sher,
I am a 42 y.o. who has had a long history of unexplained infertility. In my early 30’s my husband and I tried for more than one year with no success; which is what prompted us to see a specialist. It was determined that one of my tubes was blocked. The doctor successfully opened that tube and also removed two fibroids. Initially the thought was because my husband already had a child that he was fine. It was later determined he had low sperm count. The doctor then performed several unsuccessful IUI’s.
From there we went to another specialist. It was again confirmed that he had low sperm count. I was told all my levels were good; lining was good, everything was fine but we would need to do IVF. We did a fresh round where 3 fertilized high quality eggs were transferred and no pregnancy resulted. We did a frozen transfer where 3 eggs were transferred and no pregnancy resulted.
My husband and I divorced 7 years ago. I was asked by a friend if I would consider co-parenting. He did not have children and had not been tested but said that he had gotten someone pregnant before and she decided not to continue with the pregnancy. He has never had a semen analysis. We tried for three months and nothing happened. We were both frustrated so we decided to not continue on that path.
Now fast forward two years ago. I began dating a man who has two children but had a vasectomy years ago. We decided we want to try to have a child. January of this year we went to my previous specialist. I had all the testing done again and again they said everything was good. The doctor did note that I had two large fibroids but stated that he did not believe they were preventing me from getting pregnant. My significant other met with a specialist and decided to have aspiration procedure.
Last month I started the IVF protocol …menapur -300 gonal f -300, and eventually cetrotide then ovidril. I was told I had 6-8 follices on one ovary and 5-7 on the other. Everything was going well until the retrieval. When I woke up after the retrieval everyone was looking at me strangely. Later I was told that the doctor could not find one of my ovaries during the procedure and that only 3 follicles were retrieved and only two of those were mature. They were able to get sperm and they ICIS both follicles but only one fertilized. I had a day 3 transferred but I did become pregnant.
The doctors have said they are baffled. They have no idea why it has not worked. Do you have any thoughts or suggestions?

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

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
. Uterine fibroids
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Berry

Dear Dr Sher,

I just had my pretesting u/s and only had one single egg! :’-(((

Does it make any sense at all to go ahead and try IVF or is it pretty pointless and I’d better give up on my dream?

And if you think I should give it a try anyway, is there anything I can do to boost my numbers (and quality)?

THANK YOU for your help;
kind regards
Berry

reply
Dr. Geoffrey Sher

The antral follicle count can be very unreliable. I would more interested in your ovarian reserve (i.e. day 3 FSH/LH/E2 and your AMH). Ultimately it would be this, your age and finally your response to the appropriately selected protocol for ovarian stimulation that will be relevant.

In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
Older women as well as those who (regardless of age) have diminished ovarian reserve (DOR) tend to produce fewer and less “competent” eggs, the main reason for reduced IVF success in such cases. The compromised outcome is largely due to the fact that such women tend to have increased LH biological activity which often results in excessive LH-induced ovarian testosterone production which in turn can have a deleterious effect on egg/embryo “competency”.
Certain ovarian stimulation regimes either promote excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), augment LH/hCG delivered through additional administration (e.g. high dosage menotropins such as Menopur), or fail to protect against body’s own/self-produced LH (e.g. late antagonist protocols where drugs such as Ganirelix/Cetrotide/Orgalutron that are first administered 6-7 days after ovarian stimulation has commenced).
I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of a modified, long pituitary down-regulation protocol (the agonist/antagonist conversion protocol-A/ACP) augmented by adding supplementary human growth hormone (HGH). I further recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing/NGS)-normal blastocysts in such cases. This type of approach will in my opinion, optimize the chance of a viable pregnancy per embryo transfer procedure and provide an opportunity to capitalize on whatever residual ovarian reserve and egg quality still exists, allowing the chance to “make hay while the sun still shines”.
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.

• 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 Aproach
• 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.
• 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?
• 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
• Implications of “Empty Follicle Syndrome and “Premature Luteinization”
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Berry

Dear Dr Sher,

Thank you ever so much for taking your time to reply so quickly, and for giving me hope!!!

Sadly, I’m already 38.5 years old, so I am indeed one of the oldies…

I haven’t got my other values yet as I only got tested today, but I’ll happily forward them in about a week 🙂

Meanwhile, I’ll immerse myself in your articles! 🙂 Thank you so very much – also for helping and advising everyone here!!!

And, if we don’t read from you anymore before your retirement: Have a great time, enjoy it to the max – and know that you’ll be sorely missed :’-(

With grateful regards
Berry

reply
Dr. Geoffrey Sher

Thanks Berry, but my retirement is not due until late in next year and it might be postponed. I am getting a lot of pressure.

Geoff Sher

reply
Berry

Dear Dr Sher

Although probably sad for you, we are all extremely happy if you’re treating patients for a bit longer still!!! 🙂

With kind regards
Berry

Berry

Sorry, I meant AFC of 1, AMH is 0,78 µg/l.

It couldn’t get any worse, I guess :’-(

Dr. Geoffrey Sher

] 0.78 ug/L is the same as 0.78ng/ml…..same answer!

Geoff Sher

Julia

Hello Doctor Sher. I read your articles on OHSS, they are very detailed. thank you. But I have a question on what to do the day before and days after egg collection to help for a speedy recovery?

I triggered last night with 10,000 of HCG. I had my last scan and last blood test yesterday morning. the results were:
E2: 1,900 pg/ml
LH: 0.49
total follicle count: 30
follicles: LHS, mm (22,20,19,17,17,17,16,16,16,15,15,14,14,13,13,12)
follicles: RHS, mm (19,18,14,14,14,14,14,11,11,11,10,8,8,7)

I feel extremely full today, and my belly is very tight. I will have my egg collection tomorrow morning.

Is there anything I can do to make sure of a speedy recovery and reduce any risks of OHSS? And are there any warning signs I should watch for in case things are going bad?

Thank you!

reply
Dr. Geoffrey Sher

Unfortunately the dye was cast with the trigger shot. Now it will be a wait and see approach.

Good luck!

Geoff Sher

reply
Julia

Ok, thank you. I’ve read that some doctors recommend protein supplements (2x30g shakes), lots of Gatorade or electrolytes, and 75mg asprins each day. Would this be beneficial? Or should I have done this before the trigger shot?

Thank you!

reply
Berry

Dear Dr Sehr

Honor to whom honor is due! 🙂

Dr Sher, in the meantime, I’ve also got my day 2 blood test results (in addition to the devastating AMH of 1):
AMH 0,78 µg/l, FSH 13,0 U/l, LH 7, U/l, E2 30 µn/l, Prolaktin 17,1 µg/l, THS basal 1,11 mU/l, fT4 13,6 µg/l.

Obviously, I don’t even have to try PGD anymore because even if I was doing several banking cycles, the chances of getting enough eggs that a) fertilise, b) make it to day 5 and c) are normal (and d) implant) is next to nothing :’-(((

We are beyond shattered and are wondering if there is any treatment which might still make it possible for us to become parents (apart from using donor eggs)?

If we tried it naturally, would we stand a chance or rather not?
And is there anything we could do/take to increase chances?

Or will our dear baby never get a sibling? :’-(

With grateful but desperate regards
Berry

reply
Dr. Geoffrey Sher

An AMH of 0.78ng/ml while indicative of diminished ovarian reserve does NOT preclude the production of eggs for IV, provided a robust and optimal protocol for stimulation is used. However, this is age dependent and likely to worsen so time is of the essence.

In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
Women 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 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, 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

ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Berry

Dear Dr Sher

Thank you very, very much indeed for your wise words: they are hugely appreciated!!

Kindest regards
Berry

reply
Dr. Geoffrey Sher

You are very welcome Berry!

Good luck and G-d bless!

Geoff Sher

Lauren

I have recently undergone fertility treatment, Gonal f daily from cd 2-20 starting at 50iu dose, ending in 100iu. Triggering with ovitrelle and had a progesterone test cd28 which would be equivalent to day 21 in normal 28 day cycle. It showed a level of 42.6 and showed i ovulated. So got pregnant and currently 8 weeks pregnant on Wednesday. I am on off spotting brown blood and had a scan seven weeks which showed a heartbeat. I had intercourse and bled lightly red/pink again. I thought sex was safe during pregnancy. Is this indicative of impending miscarriage. Thank you.

reply
Dr. Geoffrey Sher

No it is not indicative of miscarriage, but I would advise against sexual penetration until all bleeding has ceased for about a week.

Good luck!

Geoff sher

reply
Lauren

Thank you for your reply. I Also forgot to say I am on aspirin 75mg daily as i took it throughout my previous pregnancy. Would this cause the bleeding this time round as I am approximately 30lbs lighter this pregnancy than carrying my daughter. Also experienced two previous miscarriages before my daughter. Should I stop taking it? Any advice would be helpful thank you.

reply
Alison

Hello Dr. Sher,
I would sincerely appreciate any information or help you could provide. I am 39 and have had two antagonist IVF cycles with Gonal-F/Menopur/Cetrotide and 250 mcg Ovitrelle. For the first (no OCP given / daily injections of 150 IU Gonal/150 IU Menopur, only 6 days of injections, follicles grew big too fast), 4 eggs were collected of 10 mature, only 1 fertilised with ICSI, quality grade D. In the second cycle I had the OCP (0.15/0030 mg desogestrel/ethinyl estradiol) for the previous month and Menopur was lowered to 75 IU. This time follicle growth rate was normal, injections lasted 8 days, of 8 mature eggs 5 were collected and 3 fertilised with ICSI. Two were transfered on Day 2 and 1 implanted but HCG was only 48 on Day 16. Although it rose well, both 6 and 7 week transvaginal scans showed a gestational sac of just 7mm, so abortion was induced.
For both cycles the endometrium was above 14mm on trigger.
For the next cycle I believe the doctors are planning to use a variation of the same treatment, and I am worried this may not be the correct protocol. However, they are unwilling to discuss this (it is public healthcare funded and they say they do what they believe is best).

In one private consultation I had the doctor said my hormone profile was a bit irregular (Day 3 LH 2 times higher than FSH) and they would need to take that into account, but did not specify how.

My question is, given your expertise, do you believe I am on the right protocol or are there any changes you could possibly suggest?

My hormone results on Day 3 of my cycle were:

AMH 3.17 ng/ml
Anterior follicle count: 5 right ovary 3 left ovary
FSH 7.41 mUI/mL
LH 13.07 mUI/mL
17-Beta Estradiol 65.63 pg/mL
Prolactin 19.75 ng/mL (4.79 – 23.3) MBA
TSH 1.54 μUI/mL
Testosterone 0.3 ng/mL

After the first poor IVF cycle the doctor also asked me to do a glucose challenge test with insulin determination, the results of which I believe were normal:

Baseline glucose 79,0 mg/dL
Glucose dose 75g
Glucose 60 min 131,0 mg/dL
Glucose 90 min mg/dL
Glucose 120 min 63,0 mg/dL
Baseline insuline 4.33 μUI/mL
Insuline 60 min 73.77 μU/mL JBP
Insuline 120 min 19.01 μU/mL

reply
Dr. Geoffrey Sher

Here is the protocol I advise for women, <40Y 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.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.
• 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:
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Alison

Thank you for your advice. In your opinion, then, it is not too much of an issue that my LH on Day 3 was 13.07 mUI/mL while my FSH was 7.41 mUI/mL?

reply
Alison

Given this, would you still recommend the A/ACP or would a conventional agonist protocol be a better way to go? Also, do you still recommend a small amount of menotropin? Thank you!

Sarah

Dr Sher,
Should I wait a number of cycles before starting IVF after stopping breastfeeding? If so, how many?

Thanks

reply
Dr. Geoffrey Sher

Two cycles of regular menstruation should suffice.

Good luck!~

Geoff Sher

reply
Yarmon

Hi Dr Sher,
I am nearly 41 with an AMH of 0.98, FSH 12.9 and 8 antral follicles. I had my 3 children quickly and easily (ages 5, 3.5, 17 months) and I am now in the process of beginning IVF with ACGH including checking gender. Could you please tell me your opinion about the protocol the clinic gave me?
Many, Many thanks
Day 1
Femara/Letrazole 2.5mg one Morning One Evening
Merional/Menopur 375
Day 2
Femara/Letrazole 2.5mg one Morning One Evening
Merional/Menopur375
Day 3
Femara/Letrazole 2.5mg one Morning One Evening
Merional/Menopur375q
Day 4
Femara/Letrazole 2.5mg one Morning One Evening
Merional/Menopur375
Day 5
Femara/Letrazole 2.5mg one Morning One Evening
Merional/Menopur375
Day 6
Orgalutran/Cetrotide 0,25mg
Scan to measure follicle development in Cyprus
Merioanl/menopur 375
Day 7
Orgalutron/Cetrotide 0.25mg
Merional/Menopur375
Day 8
Orgalutron/Cetrotide 0.25mg
Merional/Menopur
Day 9
Orgalutron/Cetrotide 0.25mg
Merional/Menopur
Day 10
Follicle scan and E2 + P4 blood test
Orgalutron/Cetrotide 0.25mg

Orally:
VITAMIN D 5 drops
PRE-NATAL VITAMIN
OMEGA 3 FİSH OIL
FOLIC ACID

reply
Dr. Geoffrey Sher

Respectfully, I do not espouse to the use of Femara for ovarian stimulation…especially not for older women or those with DOR..

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 Femara/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
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Kat

Dear Dr Sher,
Is it OK to combine the trigger shot using 1 x ovitrelle (250) and 2 x pregnyl (1,500 each)? I make this a total of 9,500 units.

I’ve always used 10,000 pregnyl in the past but in Europe there is a shortage of the 5,000 vials and I am unable to source them and ovitrelle is very very expensive. The alternative would be that I use the 1,500 pregnyl vials but I would need to inject 6 of them to get to 9,000 units!
Thanks
Kat

reply
Dr. Geoffrey Sher

I guess not…but frankly I have never tried this and thus cannot recommend it. Talk to your RE.

Geoff Sher

reply
Kat

Thank you Dr Sher. Will takin 2 x ovitrelle (500 total) give equal results to 10,000 pregnyl or is one or the other superior (in terms of egg maturation and euploidy)?

reply
Kat

Hi Dr Sher, thanks, assume it was a typo, did you mean 500 ovitrelle (rather than femara) as a trigger?

Dr. Geoffrey Sher

500mcg of Ovidrel. You cannot trigger with Femara.

Geoff Sher

Jojo

Do you recommend progesterone in oil over the crinone gel vaginally? I have been doing the PIO but it hurts so much and I can barely sit or walk up stairs. Just wondering if it’s ok to switch or if you prefer one over the other?

reply
Dr. Geoffrey Sher

Yes! I do recommend PIO preferentially but Crinone is probably OK too/.

Geoff Sher

reply
Alison

Dear Dr Sher, I have a DQ alpha question. My husband and I have a match. His profile is homozygous 1.2, 1.2 and mine is 1.2,3.1. Given this and other autoimmune factors on my side, we have decided to pursue gestational surrogacy as we have embryos frozen. We have found a wonderful surrogate (who has 2 children of her own). Before proceeding, I thought we should get her DQ alpha profile tested, especially given that my husband’s is homozygous. Her results have just come in and she is 5.1, 5.1. In your opinion, is this a match-free situation? I wasn’t sure whether the 1 element counts as a match or just the first number is relevant. I would be very grateful for your view on this. Many thanks in advance (and by the way I think it’s just fantastic that you welcome questions on your website – big thanks for that).

reply
Dr. Geoffrey Sher

There is no match here, so provided the GS does not have activation of NK cells by the K-562 test, she should be fine.

God luck and G-d bless!

Geoff Sher

reply
Alison

Thank you so much for your speedy reply – much appreciated. As the GS has been married for the last 10 years and has had 2 children of her own with her husband in that time without any issue (this would be her first surrogacy), can we assume she does not have NK cell activation or do you think the K-562 test is necessary to rule this out (hopefully)? Sorry for the additional question, that’s the last one I promise!

reply
Dr. Geoffrey Sher

Yes! That is ma reasonable assumption. Thus you could in my opinion safely forego the NKa testing.

Geoff Sher

reply
Ellen

Hi Dr Sher,
I am almost 38 years old, with low antral follicle count and FSH of 22.8. I tried IVF at your NYC clinic this past spring and it actually started out pretty well – 12 eggs retrieved, 8 embryos, 4 blastocysts frozen and sent out for testing. Unfortunately, all 4 of the blasts were abnormal 🙁 Is it worth another shot or with my age and FSH is there really no/low chances of ever getting a normal embryo? Is there anything I can take for egg quality at this point or is it too late? I was on a standard cycle last time, lupron start, 300 gonal f, 1 vial menopur, added in ganirelix toward the end. Thank you for your advice.

reply
Dr. Geoffrey Sher

In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
Women 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 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, 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

ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Annie

I need some help or advice, I have just had my 3rd round of Ivf. First round I had pgd testing, had 3 embryos tested 1 normal, put in as a FET and failed. My 2nd round I had 4 good quality blastocysts tested at day 5 with acgh testing, 1 normal. Me and my husband have worked hard over 3 and half months to change our diets, reduced parabens and bpa in our household/toiletries etc taken various supplements (Fairhaven ovaboost, vitamin b6,c,d&e, melatonin, ubiquinol, omega 3, pre conception multi vitamin, dhea) my 3rd collection was last week, our numbers were the best they have ever been from us, we had 21 fertilized and 14 at day 5 but then had the devastating news none of the 14 had developed anymore, they all got to compact morulas and just stopped. The lab left them an extra day or so to see if they would get to blastocyst but they didn’t. Can you give any advice as to why such a high number all just stopped. Thank you

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

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Mira

Hi Doctor, I have been advised to take my trigger injection tomorrow, I was prescribed 10,000 Pregnyl. But my pharmacy doesn’t have this, and so the doctor said to take 10,000 Gonasi instead. Is this the same thing? Will it work as effectively? Or should I keep trying to get the Pregnyl?

reply
ICSI

Hello Dr. Sher. My question – how long should a man (with no sperm issues) stay abstinent for ahead of the ICSI procedure? My clinic recommends 3-5 days, however I’ve also read that 1-2 days may actually produce better quality sperm, and given ICSI is less concerned by overall sperm numbers, a shorter period of abstinence may actually be a better way to go. I appreciate your thoughts on this.

reply
Dr. Geoffrey Sher

I concur with your Clinic’s advice.

Good luck!

Geoff Sher

reply
ICSI

Thank you Dr. very much for the fast reply! A related question to this – my semen cultures showed some growth of enterococcus faecalis (I think this is from my foreskin, which I’ve had before, as I have no other symptoms, and the last two semen tests last month were all clear). Could this possible infection stop the ICSI from going ahead?

reply
Mel

Hello. During our FET, we transferred 2 embryos, and recently found out we were pregnant. My first HCG beta was 304 at 13 days past ovulation, and my 2nd beta was 756 at 15 days past. Do you think these numbers indicate twins?

reply
Sarah

Hi Dr Sher,
I’m booked to go overseas to my chosen clinic for pretesting tomorrow but my period isn’t here, this will be my second period since I stopped breastfeeding so seems it is delayed as I am on cycle day 34 which is late for me.

My clinic says I can have pretesting done at ANY point in my cycle, albeit the first two weeks is preferable, but they have told me not to worry.

I have never heard of anyone having pretesting done on cycle day 35 so rightly or wrongly, I feel a bit nervous

Which tests would you delay until the first few days of my next cycle, if any?

They want me tested for:
Hormonal levels (FSH, LH, Oestradiol, Prolactin)
2) Thyroid results (TSH, fT4) and AMH hormone
3) Vaginal ultrasound scan of uterus and ovaries (antral follicle count)

Thanks
Sarah

reply
Dr. Geoffrey Sher

AMH and prolactin can be measured anytime. FSH/LH/E2 + AFC should be measured no later than day 4…in my opinion.

Geoff Sher

reply
Dhivya

Good morning Dr. Sher.
Can you pls clarify on the below.

My doctor is planning to give me intralipids directly- I.e she plans to give the entire bottle (250 ml) of 20% intralipids directly as IV without using saline.

However, I have seen the recommendation provided my many REs to be 100 ml of 20% intralipids with about 400 ml of saline.

What is the recommended approach in your opinion, kindly advise.

Regards
Divya

reply
Dr. Geoffrey Sher

Respectfully, I recommend 100cc of 20% IL diluted in 500cc saline, infused over a period of 3 hours.

Geoff Sher

reply
Marina

Hello doctor, I’m 41 y.o. with FSH=13 and AMH=0.27. After my recent failed IVF cycle (early ovulation), my current RE is pushing for a donor egg. Is there still hope for me? Husband’s sperm is normal. Recent IVF protocol was 450 Gonal F, 250 Menopur, Cetrotide. 5 follicles but 3 lost due to early ovulation; 2 collected, both fertilized & transferred day 2. BFN.
Currently I am doing acupuncture, taking DHEA 75, NeOQ10, Omega 3, Vitamin D, pre natal vitamins, probiotics. Is there still hope for my own eggs?

reply
Dr. Geoffrey Sher

In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
Older women as well as those who (regardless of age) have diminished ovarian reserve (DOR) tend to produce fewer and less “competent” eggs, the main reason for reduced IVF success in such cases. The compromised outcome is largely due to the fact that such women tend to have increased LH biological activity which often results in excessive LH-induced ovarian testosterone production which in turn can have a deleterious effect on egg/embryo “competency”.
Certain ovarian stimulation regimes either promote excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), augment LH/hCG delivered through additional administration (e.g. high dosage menotropins such as Menopur), or fail to protect against body’s own/self-produced LH (e.g. late antagonist protocols where drugs such as Ganirelix/Cetrotide/Orgalutron that are first administered 6-7 days after ovarian stimulation has commenced).
I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of a modified, long pituitary down-regulation protocol (the agonist/antagonist conversion protocol-A/ACP) augmented by adding supplementary human growth hormone (HGH). I further recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing/NGS)-normal blastocysts in such cases. This type of approach will in my opinion, optimize the chance of a viable pregnancy per embryo transfer procedure and provide an opportunity to capitalize on whatever residual ovarian reserve and egg quality still exists, allowing the chance to “make hay while the sun still shines”.
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.

• 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 Aproach
• 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.
• 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?
• 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
• Implications of “Empty Follicle Syndrome and “Premature Luteinization”
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Marina

Dear doctor,
Thank you very much for a prompt reply! I will certainly look at these articles. However, I am confused: should I still be taking DHEA 75 daily? And are you suggesting to add Seizan to the protocol? (My RE refusing as it is not FDA approved for fertility).

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Dr. Geoffrey Sher

I do not recommend DHEA, especially not for older women and those with DOR. As for Saizen, it could help egg development.

Geoff Sher

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Maria V

Hello Dr. Sher I recently saw a post about you on Facebook and that just made my day.
I have try to conceive for the past 5years after my husband had his vasectomy reversal but not luck
The last time we saw a Doctor was 3 years ago and he told us that we were never gonna have a baby my heart just broke I been so depressed all this past years we really want to have a baby can you please tell me what are my other options I would really appreciate it that thanks

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Dr. Geoffrey Sher

Men with no sperm in their ejaculates (azoospermia) whether due to non-obstructive or obstructive (usually post-vasectomy) causes, can have their sperm accessed surgically and still propagate pregnancies. There are 2 methods by which this can be achieved. : 1) TESE (testicular sperm extraction), where a biopsy of the testis is done or, 2) TESA (testicular sperm aspiration), which involves introducing a needle into the testis and aspirating fluid and tissue. Both methods can be conducted under local anesthesia and both will provide sperm-containing tissue and fluid for immediate processing and fertilization (using ICSI) or cryostorage for future use. However, the question is: Which method yields better results. An Israeli study performed on men with non-obstructive azoospermia, conducted about a decade ago, compared the results of TESE with those from TESA in the same patients and found TESE to be the preferred approach.
TSE/TESA is the preferred method for accessing sperm in men with azoospermia. By far the commonest indication for using this approach is post-vasectomy obstructive azoospermia where the use of TESE/TESA is far more successful and uncomplicated than is the alternative of having the man undergo surgical reversal. In fact, TESE/TESA yields a comparable IVF birth rate as for controls where normal sperm derived through masturbation is used. The approach is simple, relatively low-cost, and safe. In most cases, it is relatively painless and has a low complication rate. Moreover, in post-vasectomy men, it avoids the need for riskier and painful surgery designed to reconnect sperm ducts (vasa deferentia) while enabling the man to retain his chosen method of contraception after having propagated another pregnancy. In addition surgical vasectomy often fails to successfully reestablished duct patency and even when successful it often results in the subsequent reocclusion of the sperm ducts due to scar tissue formation. Moreover, in a large percentage of cases where vasectomy reversal was performed > 5 years after the vasectomy antisperm antibodies develop and this will almost always preclude subsequent natural conception even in cases where surgery had reestablished duct patency.

While in some cases of non-obstructive azoospermia, TESA/TESE will yield sperm capable of achieving fertilization through ICSI and also subsequent viable pregnancies, success rates are low. However, in such cases, this approach yields the only possibility of the male partner participating genetically in propagating pregnancy.

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.
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• 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.
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Jennifer

I recently read somewhere that some clinics require ICSI for PGS testing to ensure it’s accurate under the theory that if ICSI wasn’t done, there can be residue of other sperm hanging around and the genetic material may contain some of the sperm that didnt actually fertilize the egg and therefore ICSI is required for PGS. I am newly pregnant with a Next Generation Sequencing screened PGS normal embryo. We did not do ICSI. What do you make of this assertion?

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J

Dr. Sher,

I have gone through five cycles of IVF with PGS. Of the five FET transfers (1 blast each time), first two were negative, next two resulted in biochemical pregnancies, and one blighted ovum. Between transfers 3 and 4 we did an ERA Biopsy to confirm receptive lining. RPL bloodwork all came back normal with no issues. We have not been diagnosed with male or female issues. I am in my early 30s and have no health issues and no problem with stims or lining. For the 5th FET we added prednisone and blood thinners to the protocol – that was the cycle that resulted in the blighted ovum. The tissue from the D&C was tested normal (confirmed what we knew from PGS).

Is this a result of implantation dysfunction? How is implantation dysfunction treated? What are your thoughts on endometrial scratching? Should we transfer more than one blast? Anything else we should consider?

Thank you.

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Dr. Geoffrey Sher

I am not a believer in ERA and yes! this could well be an implantation dysfunction.

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

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Mariett

Dear Dr Sher . I’m 13 weeks pregnant with twins after ivf treatment. Although I haven’t had any specific blood tests done I was prescribed Tanziparin Sodium injections ( low molecular heparin ) starting on the first day of my tratment . For around 11 weeks of my pregnany I was taking also progesteron injections and estradiol tablets but I’m not taking them anymore. How long do you think I should keep having heparin injections ? Is there any blood test I could do to check if I still need to take it ? What is your opinion ? Thank you .

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Dr. Geoffrey Sher

If the indication is an hereditary clotting defect (thrombophilia) then it should continue throughout pregnancy. If it is for the detection of IgM or IgG-related antiphospholipid antibodies (APA), the heparinoid can be discontinued at around 10 weeks of pregnancy, in my opinion.

Geoff Sher

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amber

Dear Dr Sher

What are your thoughts on progesterone after FET? I’ve read that progesterone uterine versus blood do not correlate. I am week 7 and my weekly levels have been 10.8, 15.4 and today 13.5. I am now on 200mg suppositories QID. What should the levels be? I am worried and wanted your opinion for peace of mind. Do you suggest I increase to x5/day?

thank you for your advice!!!

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Dr. Geoffrey Sher

The level is probably OK f`or now, but at 20 weeks, it should be around 20ng/ml.

Geoff Sher

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OHSS

Hi Dr. Sher. I’m 7 days into my stimulation cycle now, and curious about OHSS risks after egg collection. I’m on 225 IU fostimon and 225 IU merional (is this considered high?) and will trigger with 10,000 HCG. No embryo transfer this time, we are freezing any to transfer later. Thoughts on OHSS and what I can do to avoid it? Or is it pretty low risk? Thanks!

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Dr. Geoffrey Sher

I cannot answer without knowing the # of follicles and the estradiol level.

Geoff Sher

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OHSS

Thanks Dr. Sher. The number of follicles yesterday was 23 (up from 8 on the day 1 AFC) and the estradoil was 2,012 pmol/l on day 6. I’m 29 years old and had AMH of 10 on day 1. Thank you 🙂

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Dr. Geoffrey Sher

That is quite high for day 6 and needless to say, your RE is probably aware of and trying to address the risk of OHSS.

Ovarian hyperstimulation syndrome (OHSS) is a life-endangering condition that occurs following ovarian stimulation for the treatment of infertility. It occurs due to overstimulation of the ovaries with the development of numerous follicles in susceptible women. Systemic effects can be very serious and can lead to life-endangering complications. Thus every effort must be made to avoid the condition and when it does threaten, to take the necessary steps to mitigate its effects, and at the same time attempt to protect egg quality which often is adversely affected as well. Prevention starts with recognizing those women who are at the greatest risk of developing OHSS. They include:
• Those with a history of having hyperstimulated on fertility drugs in the past.
• Younger women (<25y)
• Women who have biochemical indicators that suggest they are so at risk of developing OHSS (e.g. An AMH of >5ng/ml; basal FSH of <5MIU/ml; basal LH level being significantly higher than LH; Antral follicle count of >25)
• Women who have dysfunctional or absent ovulation.
• Women diagnosed with polycystic Ovarian Syndrome (PCOS)
In such cases, it is prudent to minimize the dosage of gonadotropins administered, but alas, this often will not eliminate risk of OHSS developing anyway. Aside from the risk that OHSS places the woman at, it can also have a devastating effect on egg quality/competency. Thus, all too often, the measures taken (see below) to reduce maternal risk come at a price.

PRESENTATION AND MANAGEMENT OF OHSS:
The onset of OHSS, heralded by the presence of large numbers (>25) of developing ovarian follicles and rapidly rising plasma estradiol levels, often exceeding 3000pg/ml within 7 or 9 days of stimulation, and rapidly peaking above 6,000 pg/ml prior to hCG administration. When this happens, the risk of OHSS developing is above 80%. The fear of this escalating often leads physicians to prematurely administer hCG in an attempt to abruptly arrest the process and prevent escalation of risk to the patient. However, the premature administration of the “trigger” shot arrests egg development and adds to the problem of poor egg/embryo quality in such cases.
Symptoms and signs of OHSS include: abdominal distention due to fluid collection (ascites), fluid in the chest cavity (hydrothorax), rapid weight gain (of a pound or more per day) due to tissue fluid retention, abdominal pain, lower back ache, nausea, diarrhea, vomiting, visual disturbances such as blurred vision and spots in front of the eyes (scotomata), a rapidly declining urine output, cardiovascular collapse and failure of blood to clot which sometimes results in severe bruising (ecchymosis) and frank bleeding. These symptoms and signs may appear before pregnancy can be diagnosed. If pregnancy occurs, the condition is likely to worsen progressively over a period of 3-5 weeks whereupon it rapidly resolves spontaneously over a few days. If no pregnancy occurs, the symptoms and signs all disappear spontaneously within 10-12 days of the hCG injection.
When increasing fluid collection in the abdominal cavity (ascites) starts to compromise breathing raising the head of the bed rose slightly by placing a 4-6 inch block at the base of each head post and using a few additional pillows, will sometimes help ameliorate the problem. In cases where this does not help or symptoms become severe, all or most of the fluid can readily and safely be drained through t transvaginal sterile needle aspiration (vaginal paracentesis-performed once or sometimes twice a week) can be performed once or twice weekly . The problem will usually self corrects within 10-12 days of the hCG shot if pregnancy does not occur or, by the 8th week of pregnancy.
Urine output should be monitored daily to see if it drops below about 500ml a day (about two cups and a half). A chest X-ray, to evaluate for fluid collection in the chest and around the heart should be done weekly along with blood tests for hematocrit, BUN, electrolytes, creatinine, platelet count and fibrin split products (FSP). If indicated on the basis of a deteriorating clinical situation, hospitalization might be needed for close observation and if necessary, to provide intensive care.
In all case of OHSS, the ovaries and contain numerous theca-lutein cysts and will invariably be considerably enlarged. This is irrelevant to the final outcome, unless ovarian torsion (twisting of the ovary on its axis), an extremely rare complication occurs. The latter would usually require surgical emergency surgical intervention.
Human chorionic gonadotropin (hCG) “Fans the flames “ of OHSS. That is why the occurrence of pregnancy worsens the condition. In women who do not conceive, the clinical severity of OHSS will usually peak 7-10 days after the hCG “trigger”, plateaus for another 3-4 days and thereupon rapidly improves within the ensuing week. Thus in the absence of hCG the condition is “self-limited”. Sometimes severe symptoms due ascites make it imperative to drain the fluid transvaginally (often repeatedly). This brings immediate relief but it can be short-lived requiring repeated drainage a few days later until the condition resolves. If the woman conceives following a fresh embryo transfer, the rising hCG blood levels can exacerbate the OHSS for several weeks, but either way, it usually disappears spontaneously by the 8th to 9th harrowing week of pregnancy. This is why there is a growing tendency to avoid fresh embryo transfers, preferring to do FET’s later once the woman is out of risk. It is also the reason for a move to avoid using 10,000U of hCG for the “trigger shot” or to avoid to supplant hCG with an “agonist” trigger. But this comes at a price…see below.

OHSS ANF POOR EGG/EMBRYO QUALITY/COMPETENCY:
OHSS is also associated with e poor egg/embryo quality. This is especially so in women with high ovarian LH-induced testosterone (e.g. those with PCOS). The often present with poorly developed (“dysmorphic”) eggs, with reduced fertilization potential and yielding “poor quality embryos”. However, in the author’s opinion (which admittedly runs contrary to popular opinion), this is unlikely to be due to an intrinsic deficit in egg quality. Rather, it more likely relates to intra-ovarian hormonal changes brought about by hyperstimulation and which compromise egg development. This effect, in my opinion, can often be significantly reduced through implementation of an individualized or customized ovarian stimulation protocols that minimize exposure of the developing follicles and eggs to excessive LH-induced ovarian androgens. This can be best achieved by limiting the use of LH-containing gonadotropins such as Menopur through selective institution of “prolonged coasting” (see below). Approaches to preventing OHSS include:
1. PROLONGED COASTING (My preferred approach) : My approach is to use a long pituitary DR protocol coming off up to 2 months on the BCP, overlapped in the last 3 days with the agonist, Lupron. The BCP is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling ovarian androgen (predominantly, testosterone) production and release. I then stimulate with low dosage FSHr (Follistim/Gonal-F/Puregon) to which I add a smidgeon of LH/hCG (Luveris/Menopur) from the 3rd day. Then, starting on day 7 of ovarian stimulation, I perform serial blood estradiol (E2) and ultrasound follicle assessments, watching for the # of follicles and [E2]. If there are > 25 follicles, 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 (without continuing US, follicle measurements) ) daily. The [E2] will almost invariably increase for a few days. I watch the E2 rise (regardless of how high a blood concentration it reaches) and then track it coming down again. As soon as the [E2] drops below 2500pg/ml (and not before then), I administer a “trigger” shot of 10,000U hCGu (Profasi/ Novarel/Pregnyl) or hCGr (Ovidrel/Ovitrel-500mcg) and perform an egg retrieval 36 hours later. ICSI is a MUST because “coasted” eggs usually have no cumulus oophoris envelopment 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 blastocyst (up to 6 days) and are then either vitrified and preserved for subsequent transfer in later hormone replacement cycles or up to two (2) fresh blastocysts are transferred transvaginal under US guidance.. The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If you start too early, follicle growth will stop and the cycle will be lost. If you start too late, you will encounter too many post-mature/cystic follicles (>22mm) that usually harbor abnormally developed eggs. Use of “Coasting” avoids unnecessary cycle cancellation, severe OHSS, and optimizes egg/embryo quality. The worst you will encounter is mild to moderate OHSS and this too is uncommon. The obvious remedy for these adverse effects on egg and endometrial development is to employ stimulation protocols that limit ovarian over-exposure to LH and allowing the time necessary for the follicles/eggs to develop optimally, prior to administering hCG through the judicious implementation of “Prolonged coasting” (PC).
2. MULTIPLE FOLLICLE ASPIRATION: In some cases, where because of mean follicle size exceeding 16mm or when “coasting” fails to effectively lower the [E2} below 2,500pg/ml within 3 days, the number of developing follicles can effectively and drastically reduced through target transvaginal aspiration, 1-3 PRIOR to planned the hCG trigger. This will almost invariably be accompanied by a rapid and significant drop in the plasma [E2] and in the process will drastically reduce reduce the risk of OHSS occurring without significantly compromising egg/embryo quality. The drawback of this effective approach is the fact that it interjects an additional surgical intervention into an already complex and stressful situation. i
3. TRIGGERING WITH LOW DOISAGE hCG; Because of the fact that hCG augments the development of OHSS (unless preceded by “coasting”), may RE’s prefer to use a lower dosage of hCG for the “trigger. This is either done by administering 5,000U (half the traditional dosage) or by administering, a 250mcg (rather than 500mcg) of DNA recombinant form of hCGr (Ovidrel/Ovitrel. Some clinicians, when faced with a risk of OHSS developing will deliberately elect to reduce the “trigger” dosage of hCG administered (from 10,000U to 5,000U or 250mcg of recombinant hCG-Ovidrel) in the hope that by doing so the risk of critical OHSS developing will be lowered. While this might indeed be true, it is my opinion, that such a reduced dosage is usually insufficient to optimize the efficiency of egg meiosis, e3specially when there are so many follicles present. While the use of a reduced “trigger” dosage of hCG does indeed reduce the risk and occurrence of OHSS-related life-endangering complications, the price to be paid is reduced egg quality/”competency”.
4. “TRIGGERING” WITH A GnRH AGONIST (E.G. “LUPRON/BUSERELIN): More recently, an increasing number of RE’s prefer to trigger meiosis by way of an agonist (Lupron/Buserelin/Superfact () “trigger” rather than through the use of hCG. The idea is to mimic what happens in natural cycles to promote egg maturation (meiosis) and ovulation, namely to have the agonist cause a “surge” in the release of body’s own pituitary LH to trigger egg meiosis (maturation) .But the amount of LH released in by the pituitary gland is often insufficient to optimize meiotic egg maturation and thus, while this approach also lowers the risk of OHSS it again comes at the expense of egg quality/competency.
A word of caution: I do not use long term administration of antagonists (Ganirelix/Cetrotide/Orgalutron), such as with the agonist/antagonist conversion protocol (A/ACP) in high responders whom are at risk of developing OHSS prolonged in-cycle administration of because it can interferes with the E2 assay (often causing the value to be understated), and serial measurement of E2 is a vital part of monitoring patients undergoing “coasting”

Good luck!

Geoff Sher

reply
Dr. Geoffrey Sher

Foer only 6 hrs, then just be a “couch potato”.

Geoff Sher

reply
Jules

Goodmorning doctor, please my husband finds it difficult to ejaculate. He ejaculates like once out of four trys and it’s frustrating cos we’ve been trying to have a baby for more than a year now. We’ve gone for a semen analysis and the result cane out fine. What could cause this and any solution for it?

reply
Dr. Geoffrey Sher

I suggest he undergoes a medical examination and if negative,,,then sex therapy!

Geoff Sher

reply
PSDS

Hello Dr. Sher,
I am a 36 year old female going thru unsuccessful IVF attempts for the last 3 years.
I have been pregnant 3 times naturally within first time of trying. I was diagnosed with hypothyroidism during my 1st pregnancy and have been taking medicines since then.
– I have one healthy 7 year old born in 2010, when I was 29 years.
– I got pregnant again naturally in 2013. But I was diagnosed with Fragile X permutation. I went thru Amniocentesis and found the baby had full mutation. So the pregnancy was terminated and I had a D&C
– We tried IVF with PGD/PGS testing. I had 2 frozen embryo cycles and both failed
– Then in 2016, I got pregnant again naturally but unfortunately had to terminate again due to Fragile X full mutation
– In mid-2016, I went to a different IVF clinic which used minimal stimulation. I ended up with 3 PGD/PGS tested embryos. Have tried 2 cycles of frozen embryo transfer both with one embryo each. I was able to get positive pregnancy test but both ended up being chemical pregnancies. One transfer included Prednisone.

Question: Why am able to get pregnant naturally but unable to with IVF even with PGD/PGS tested embryos?

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

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
amber

week 7 day 1 post FET. on estrogen 2mg TID, progesterone supp 200 mg QID. today, bHcg 9926 and estrogen 145. progesterone was 10.8 (June 21), so increased supp from TID to QID, then it was 15.4 (June 27). today down to 13.5 (still QID). Told prog levels should be 15-20. should the supp be increased to x5/day? thank you

reply
Amy

Hi Dr Sher,
I have a question about low LH levels. I’m 43, about to start down-regging. My cycle day 2 LH is 1.57, FSH is 5.17 and AMH is 0.9 ng/ml. I also have elevated prolactine levels at around 38 (lab range is up to 29).
I have read that such low LH levels can impair the quality of eggs. Is there anything that can be done during or before stimulation to treat that? Thank you.

reply
Dr. Geoffrey Sher

Indeed there is… The addition of a small amount of Menopur will counter that effect.

In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
I favor d the use of a modified, long pituitary down-regulation protocol (the agonist/antagonist conversion protocol-A/ACP) augmented by adding supplementary human growth hormone (HGH). I further recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing/NGS)-normal blastocysts in such cases. This type of approach will in my opinion, optimize the chance of a viable pregnancy per embryo transfer procedure and provide an opportunity to capitalize on whatever residual ovarian reserve and egg quality still exists, allowing the chance to “make hay while the sun still shines”.
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.

• 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 Aproach
• 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.
• 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?
• 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
• Implications of “Empty Follicle Syndrome and “Premature Luteinization”
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Rita

Hello Dr Sher, I’ve been trying to get pregnant for over 2y. I had an endometrial polyp which was removed last Oct and then we had 3 unsuccessful attempts for IUI. Finally went ahead w/IVF FET/ISCI. I had PGS 1 tested embryo transferred and I got pregnant. However around week 6 I had some bleeding w/clots and following week the embryo didn’t grow and neither had a heartbeat so the doctor concluded that it was unviable pregnancy. This followed w/D&C and a POC testing of fetal tissue which came back normal. Are there any known causes of such a miscarriage. I’m also on Thryoxine medication, though my TSH have been normal over 2 years, were higher than where my doc wanted to be but before transfer it was around 2. Would appreciate any further steps you can recommend

reply
Dr. Geoffrey Sher

The fact that you are on Thyroxine suggests an under-active thyroid which in women is often due to an autoimmune process (antithyroid antibodies). In 50% of autoimmune thyroid disease there is an immunologic implantation dysfunction which if present in your case, could explain your situation fully.

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

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.
• 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
• 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.
• Avoiding High Order Multiple Pregnancies (Triplets or Greater) with IVF
• The Role of Nutritional Supplements in Preparing for IVF
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
SalMol

Dear Dr

We have obstructive azzospermia(suspected ED blockage because the Vas Defrenc and Epidydimus are dilated.

Trans Resection of the ejaculatory duct done in 2010

Testi Biopsy show good sperm development.

We also have one blocked fallopian tube.

Cystopic Ovarian syndrome treated through a laparoscopy in 2011.

Two Fibrods remove in 2014.

Abortion in 2007

From 2013 to 2017 we have done 9 ET.

Three 3day ET and 6 5day ET.

Two pregnacies in 2017 after introduction of IL though loss occurred at early stage.

First pregnancy, HCG got up to 4000 at week 6 but lost it at week 7 after severe bleeding.

Second pregnacy, HCG started at 20 on day 8 after transfer and rose to 48 on day 10 and 66 on day 12. Low positive detected.

Saw blood glot on day 16 and going for ultrasound scan on day 20, Friday 07 July 2017. We are already suspecting loss as there are no pregnancy symptoms till today.

The DR is always happy with the lining and hormones.

We transferred a couple of Blastocysts, Expanded Blastocysts and Hatching embryos in vain.

Our questions is, what else can we ask our doctor to do in South Africa?

Immunologic Implantation Dysfunction?
DQ alpha genetic match?
Surrogacy?
Trans Resection of the ejaculatory duct repeat or any other means to remove obstruction?
Egg donor?
Sperm donor?
Embryo Donor?

We remain hopeful that we can have our own offspring if we get the right treatment and advice.

I read plenty of your advices/blog comments and strated reading your book now.

reply
Dr. Geoffrey Sher

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

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

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

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

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

I strongly recommend that you visit http://www.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
• 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

ANNOUNCEMENTS:
1. About my Retirement by mid-2018:
After > 30 years in the field of Assisted Reproduction (AR), the time is approaching for my retirement. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.
If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Paulina

Dr. Sher,
We are scheduling the transfer of a pgs normal frozen embryo. The FET protocol we are using does not include lupron or birth control pill. It is only estrace and minivelle patches beginning on day 3 of the cycle (prior to beginning progesterone). In order to extend the FET cycle to a specific date, we were told we can extend the time on estrogen. In this specific situation, we would be extending estrogen for an additional 9 days (23 days total estrogen). We have a history of linning being sufficient after 14 days of estrogen. Is it ok to extend estrogen that many days? In our case, how many days on estrogen do you think should be the max prior to starting progesterone?
Thank you!
Paulina

reply
Dr. Geoffrey Sher

H Paulina,

It could be OK, but if it were up go me, I would prefer to launch off a BCP and Lupron, and not to keep you on estrogen that long.

Good luck!

Geoff Sher

reply
Paulina

Dr. Sher,
Thank you for your response. We also have the option to do a FET cycle with a standard 14 days of estrogen (no BCP no Lupron). My question is, between the two below FET protocols, which do you prefer (assuming we do not care about controlling the transfer date).
1. BCP, Lupron, estrogen (until linning is sufficient), progesterone.
(Or)
2. Skip BCP and Lupron. Start with estrogen until linning is sufficient (NOT extending an extra 9 days as mentioned in my first post), then progesterone.
-Assuming we do not care to control the FET date, which protocol do you prefer and why?
Thanks again,
Paulina

reply
Paulina

Sorry, I don’t understand your response. No 1 or No 2?
Thanks again,
Paulina

Heidi

Hello Dr. Sher,
I conceived my little one using a 5 day FET transfer. Everything has been going very well, until we had an ultrasound to rule out any neural tube defects. At 14 weeks, a diagnosis of anencephaly was confirmed. My doctor suggested that I be induced and deliver the fetus as soon as possible, and avoid a dilation and evacuation procedure. My induction is scheduled for Sunday, I will be approx 15 1/2 weeks. My folic acid and B12 levels have been checked and they are off the charts good.

My question to you is, how long after the induction/delivery would you recommend we wait before transferring another embryo? We still have 2 left.
Also, aside from folic acid levels (as mine were normal), is there anything for the future we can either do or avoid to help this not occur again? I have been using metformin twice daily for over a year now, to help with my PCOS.

Thank you very much.

reply
Dr. Geoffrey Sher

I am so sad for you! I would wait until regular menstruation is reestablished for 2-3 months.

G-d bless and good luck!

Geoff Sher

reply
Heidi

So I have never been able to get regular menstruation on my own. Typically, we would use some sort of stimulation to begin a cycle – would you recommend a 2-3 month waiting period before starting on the hormones to begin a cycle again?

reply
Dr. Geoffrey Sher

It depends upon the cause of your amenorrhea. Call 800-780-7437 and we can talk.

Geoff Sher

reply
Life

Dear doctor,
I have a question about our 1 failed icsi.
After 4 months of trying naturly we visit a gynacologest she tried clomitab, ovafin, and 1 injection for 4 months with no good news.
Then she recommend a sperm anaylsys of my husband and the report was not good
The result shows oligotastozoospermia
And then dr told us that its not posible to get pregnant naturly so move to icsi
We go for icsi and its failed beacuse no embryo to blastosyst
They retrive 14 eggs
8 mature
4 fertilized
And at day 3 all stop growing
But on day 5 we trnsfr 3 of the eggs as doctor said their is 1% chance that they can grow inside the utrus i dont want to take that chance coz i know that was just a fake hope but my husband want to take that chance so we trnsfred
But its failed
And after that when we visit the doctor he said that the reason of that failer is your egg quality. but at the time of all that process they didnot inform me that their is any problm with me or my eggs quality
My FSH was 6.2
And AMH was 16.9
Now please help us what can we do further for having our own child as we both realy wanted
What can you suggest next treatment

reply
Dr. Geoffrey Sher

Your doctor was probably correct in stating that it was an egg quality issue rather than sperm….in spite of your husband’s oligoteratozoospermia. However this does not necessarily mean that the problem is intractable. It could , in my opinion , likely be due to the protocol used for ovarian stimulation. We should talk to see whether I can be of help.

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

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Jane

Hi Dr. Sher,
For estrogen priming:
– when do you like to start and stop estrogen (Day 20 through start of period?)
– patch or pill is best, and dosage?
– do you overlap the estrogen with an antagonist like ganirelix?
– do you like to start gonadotropins on Cycle Day 2 or Day 3 after priming?
Thanks for your expertise.

reply
Dr. Geoffrey Sher

In women who have severe DOR (AMH=<0.1 ng/ml) I modify the A/ACP The A/ACP through incorporation of “estrogen priming” with injections of estradiol valerate (Delestrogen), given twice weekly for about a week following the initiation of the A/ACP, and prior to commencing FSH-dominant gonadotropin stimulation. I then continue this through gonadotropin stimulation. Estrogen Priming appears to further enhance ovarian response….presumably by up-regulating ovarian FSH-receptors. ”.

Geoff Sher

reply
Denise

Hi Dr. Sher,
I’ve read that too much LH early in the cycle can damage egg quality, especially for older women who may start off with higher levels of LH in their bodies.
I am 40 years old, AMH 7, FSH 6, 8-12 antral follicles. I am doing IVF with PGS and have been prescribed 150gonal-f/150 Menopur.

1. Is 150 Menopur considered a high amount of LH for an older woman? Is it better to stay with 75iu?
2. Do you administer the Menopur at the start with gonal-f or wait until later in the cycle?
3. I’ve mostly seen the ratio of gonal-f to Menopur to be 2:1 or 3:1, when do you use this 1:1 ratio?
Many thanks!

reply
Dr. Geoffrey Sher

My personal preference is to use no more t5han 75U menopur in all cases. Menopur contains hCG/LH which both have a similar effect.

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
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Sarah

Hi Dr Sher, I’ve been in contact before and very much have appreciated and valued your advice. Just recap, my clinic have upped my dosage of thyroxine by 25ml as they weren’t happy with my TSH level being 3.39. Therefore I’m currently on 125ml now for my underactive thyroid. They are hoping 2 weeks will bring my TSH level down and then I will be receiving a prostap injection around day 21 of my cycle. My FSH stimulation will begin shortly after that for around 2 weeks (350 IU Menopur). I’ve also been given the dose of Prednisolone 20mg daily, starting on the first day of my FSH stimulation as my thyroid antibodies are high (352 IU/ml). I can get intralipid therapy at another clinic but I would like to know when you would recommend I get this done through my IVF cycle?

reply
Dr. Geoffrey Sher

Steroids with IL therapy need in my opinion to start no later than 10 days prior to projected ET.

Good luck!

Geoff Sher

reply
Sarah

Thanks very much. Would you recommend intralipid therapy after ET? If so, when?

reply
Alice Motshegare

Hi Doctor..I just had a failed IVF procedure and that’s very unfortunate in just did the pregnancy blood test today and and they called me that the where negative i had to cry till I have a headache am currently 30 years old it was my 1st Ivf and I have had infertility issues I also did a Laposcopic surgery before my IVf and my my doctor told me all my tubes were blocked and damaged and don’t know what may be the cause he ddnt explained to me that’s when he decided i should do Ivf that’s the only way for me to get pregnant i have been on medication i did ER the only
Got 6 eggs and out of 6 1 was fertilized and I did ET after 5days they told me the egg looks good until my pregnancy came Negative and I want to do another 1 on my next cycle I don’t if the problem could be my lining since well he did mentioned that my lining was too thin the 1st time I did insemination so during Ivf process he never said anything about my lining…

reply
Dr. Geoffrey Sher

So sorry for you!

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

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
Kitty

Dr Sher,
My only 5 day acgh tested top grade embryo isn’t not survive thawing. What are the reasons this may have happened? Should I try another clinic as I am worried they did something wrong?? Thanks

reply
Dr. Geoffrey Sher

Unfortunately, while chromosomal integrity is the most important consideration when it comes ro embryo “competency” it is not bthe only consideration.

Perhaps we should talk.

Please call 800-780-7437 and ask Julie to arrange a Skype consultation for you , with me.

Geoff Sher

reply
Adrian

Dear Dr. Geoff Sher,
Thank you reviewing my wife hcg number after Embryo Transfer and providing feedback. From our understanding, my wife , age 37 who has irregular menstrual cycle(sometime 2-4 months apart) had menstrutation on the day of 14-15 days after the Embryo Transfer. From our understanding some spotting and some bleeding like monthly period on this 15 days of ET lowered the hcg from 5200 to 3030 and kept lowering. We were little unlucky to have my wife’s period/bleeding after after ET and positive pregnancy Test result. Please kindly advise how, if any the bleeding/ministration can be avoided after Embryo Transfer and if there is way to not lower hcg and keep increasing the hcg also any advice that we can consider in future ET for a patient like my wife, who has a history of irregular ministration cycle. I also reading Dr Sher’s book “In Vitro Fertilization: The A.R.T. of making Babies”, IVF STEP 4: Embryo Transfer, I am getting a lot more information and insight from the book. Thank you for writing the in-depth, detail Book in IVF. Thanks -Adrian

reply
Dr. Geoffrey Sher

The bleeding does not “cause failing implantation” it is the result thereof. Thus unfortunately there is nothing that can be done. Treatment must be focussed on transferring “competent ” embryos to a “receptive” uterine environment.

Geoff Sher

reply
Adrian

Hi Dr. Geoffrey Sher, My wife had 2 Embryo Transfer. On day 10 after ET blood test was positive. On 14 days after ET level was 5200. On 17 days after ET hcg level was 3030. On 19 days after ET hcg level was 1100. On 21 days after ET level was 630 and suggested to stop progesterone medications. Please kindly suggest if the pregnancy is still positive or if there is no hope. Thank you-Adrian

reply
Dr. Geoffrey Sher

Sadly this does not bode well for the pregnancy.

Sorry!

Geoff Sher

reply
CR

Dear Dr. Sher,

My IVF protocol in the past were with Menopur 150IU & Follistim 150IU for two follicles at the beginning and continue the same for 10 stimulation days. Only one dominant follicle reached 20mm with estradiol at 302 pg/mL on the day of HCG injection.

Recently, a new doctor prescribed me with mini IVF protocol with Pergoveris 75IU for first four days of stimulation and the follicles grow to sizes 10mm & 11mm with estradiol at 104 pg/mL. Then he asked me to stop stimulation and continue with a natural IVF. On Cycle day 9, the follicles grow to sizes 14mm & 16mm with estradiol at 67.7 pg/mL. Then he instructed me to start injecting Pergoveris 75IU & Cetrotide and on cycle day 11, the follicles shrank to sizes 10mm & 11.5mm with estradiol at 20.4 pg/mL. He is then instructed me to stop injections and to switch to natural IVF. On cycle day 14, only one follicle left and size remain at 11mm with estradiol at 37 pg/mL. On cycle day 17, the follicle continue to shrink to size 7mm with estradiol at 31.5 pg/mL.

Questions:
1. Could you please explain why the follicle shrank?
2. Should we continue this IVF cycle or to cancel it?

Thanks for your advise.

Kind Regards, CR

reply
Dr. Geoffrey Sher

Respectfully, in my opinion, this protocol you recently were on leaves much to be desired. I think this (at least in part) would explain your response.

Here is the protocol I advise for women, <40Y 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.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.
• 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:
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

reply
CR

Thank you Dr. Sher for the advise. However, could you please explain why the follicle shrank during the IVF process?

Kind Regards, CR

reply
Dr. Geoffrey Sher

The stimulation was probably accompanied by premature luteinization.

Premature luteinization (“premature LH surge”) occurs when prior to the planned initiation of the hCG trigger, a progressive rise in LH, irreversibly compromises follicle and egg development and maturation. It is not a sporadic isolated event. It comes as a culmination of a series ovarian events, occurring mostly in susceptible women (i.e. usually older women and those with diminished ovarian reserve. It is more likely to occur when the protocol used for ovarian stimulation has failed to maintain LH activity at a low level prior to and throughout the ovarian stimulation process. Once it occurs in any given stimulation cycle it cannot be switched off by changing the stimulation in progress or by administering GnRH antagonists (e.g. Ganirelix/Cetrotide/Orgalutron) midway in the cycle in the hope that this could rescue the eggs under development. It is my opinion, once premature luteinization commences, the cycle is doomed and outcome is doomed to fail. The condition increases the likelihood of premature ovulation, failed release of eggs during needle-guided egg retrieval (so called “empty follicle syndrome” and the incidence of egg/embryo “incompetence” (chromosomal aneuploidy).
This situation is most commonly seen in older women and in women who have severely diminished ovarian reserve. In many cases its effect can be prevented through implementation of strategic and individualized protocols for controlled ovarian stimulation (COS) coupled with optimizing the type, timing and dosage of the “hCG trigger shot.”
Normally, following optimal ovarian stimulation, the “trigger shot” is given for the purpose of it initiating meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse, so that the egg can detach and readily be captured at egg retrieval (ER).
Older women, and women with diminished ovarian reserve, tend to have more biologically active LH in circulation. LH causes production of male hormone (androgens, predominantly testosterone), by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced ovogenesis (egg development). Too much LH activity compromises the latter, and eggs so affected are far more likely to be aneuploid following meiosis.
Women with the above mentioned conditions often have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the hCG trigger, leading to fruitless attempts at retrieval and the so called “empty follicle syndrome.”
The developing eggs of women who have increased LH activity (older women, and women with diminished ovarian reserve) are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Because of this, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole), drugs that contain LH or hCG (e.g., Menopur), or protocols of ovarian stimulation that provoke increased exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols”) and the use of “late pituitary blockade” (antagonist) protocols can be prejudicial.
The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used, and the timing of its administration in such cases cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG (hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG or Ovidrel can, by compromising meiosis, increase the risk of egg aneuploidy, and thus of IVF outcome.

Geoff Sher

reply
CR

Thank you Dr. Sher for your fruitful comments. It seems that this cycle there is still no ovulation. I usually ovulate on cycle day 15 naturally. However on cycle day 17, the estradiol was still low at 31.5 pg/ml, Progesterone 0.07 ng/ml, LH 12.2 IU/I and FSH 21.2 IU/I. I don’t think I ever will ovulate in this cycle. Will I get my menses next month if I do not ovulate this cycle?

Kind Regards, CR

Dr. Geoffrey Sher

hard to say because with that low an E2, there is not a likelihood that the endometrium will thicken sufficiently. You might have a bleed from erosion of a thin lining but that would not be a menstrual bleed.

Geoff Sher

Samantha

I mistakenly used to wrong needle for my HCG trigger injection tonight for my IVF cycle. I used the menopur needle, not the intramuscular injection needle. I’m supposed to have my egg retrieval on Sunday and am worried it will not work. Is it possible to still save this cycle?

reply
Verena

Dear Dr. Sher,

after a lot of ICSI- attempts (14 transfers after ICSI with very good embryos, minimum 30 embryos without nidation, part of them expanded blastocyst; only one pregnancy after the eleventh attempt that ended because of trisomy 22) I checked again our HLA- report. At first view there was no sharing at DQalpha for me (doctors in Germany pay no attention on it): 01:01 and 01:03 (female) and 01:03 (male). But now I read in the book of Alan Beer: “A 0102/0101 combination is virtually an identical match (breakdowns of the “1” numbers are essentially the same) so again there may be problems with inadequate blocking antibody production.”

What do you think about that? Is it then really similar to a 100% DQalpha Match in fact in our case? Is that the explanation, why there is no nidation since 4 years (only one, the trisomy 22)? We use Dexamethasone, Intralipid and G-CSF already in 8 ICSI- attempts! Single embryo transfer (SET) would be no solution neither if breakdowns of the “1” numbers are essentially the same? Is LIT a last possibillity for us or IVIG or should we give up now???? Should I prefer SET in case of trying again?

Thank you so much,
Verena

reply
Verena

Sorry, there was a mistake: in our case DQalpha is: female: 01:01 and 01:03 and my husband: 01:02

reply
Verena

Dear Dr. Sher,

I had a sleepless night – alloimmune influence because of similarity of DQalpha antigens!? I can try to organize a skype call, but understanding would be much easier per writing (e.g. email) for me to avoid loosing informations because of language and give comprehensible background.

Shortly to our ICSI- background:

– ICSI is necessary because of CBAVD- diagnosis of my husband (missing vas deferens), we have frozen TESE-sperms after his operation in 2013; gynecological everthing ok
– First ICSI in 2013 with age of 35
– After 6 ICSIs with good embryos and other good basic parameter without implantation: diagnosis of Hashimoto´s disease with TPO and TG-antibodies, high NKa (around 30 in my NK assay, now lower); Th1- dominance and DQalpha: 01:01 and 01:03 (me); 01:02 (husband).
– I thought that must be autoimmune ID so I took after that testings: Intralipid (two infusions before transfers), dexamethasone 1 mg with beginning of FSH, G-CSF (Granocyte) and heparine and ASS (because of hashimoto)
– Only one pregnancy last year after blastocyst transfer (DET) in the eleventh ICSI, ended because of trisomy 22 in the 8th week
– Best quality embryos (professor says development is “excellent”), perfect endometrium always, also other basic parameters good
– The last ICSI two months ago (meanwhile I am 39 after 14 ICSIs done) resulted in 9 mature eggs, 5 fertilized with TESE-sperms and 2 very good expanded Blastocysts transferred on day 5: no hCG again 🙁
– 14 transfers all in all, but “only” 8 with adequate immunologic medication (IL, Dexa etc.) with one short pregnancy in 2016.

LIT is already dated for august and second in octobre as “ultima ratio”, like the German professor says. We have no direct DQalpha Matching (only similarity because of “1” numbers according to Doc Beer), so NKa- rising like in real Matches should not be influenced? Only maybe inadequate blocking of antibody production, am I right?

Is there an alloimmune problem in this constellation at all in your opinion?
Could our planned LIT- strategy compensate that problem?
Can IVIG as an additional means induce adequate HLA-G signaling response or is that not necessary then (of course Intralipid an dexamethasone as always)?

My husband wants to give up – do you see a chance for us? Please give me a hint 🙂

Thanks for your great help always!
Thanks from (nearly) hopeless Verena

reply
Dr. Geoffrey Sher

It is likely , given the information you provided before that you and your husband have a partial DQa match and if your NK activity is indeed increased this, in my opinion indicates a significant alloimmune IID. I previously forwarded to you links (to my blog) on what the implications might be and how I address this problem with IL/prednisone therapy (I do NOT prescribe LIT as it adds nothing…in my opinion. I also point out in the articles that this problem is associated with a 50% reduction in the viable pregnancy rate per embryo transferred, that only a single embryo should be transferred at a time (and why), as well as the fact that embryo PGS is advisable with the selective transfer of karyotypically normal embryos so as to increase the take rate per single blastocyst transfer. This is my approach! Read the articles referenced and then consider setting up a Skype consultation with me , if you wish.

Good luck!

Geoff Sher

Verena

I am really confused because I read a lot in your books, papers and publications on the website(s) since years, especially about ID and I was happy when I saw our HLA- classification-result because we share completely NO HLA antigens (we have completely different HLA-A, B, C, DR, DQ antigens).
On the DQalpha loci we also differ with 01:01 and 01:03 (me) and 01:02 and 01:02 (husband). So the two possible combinations in the embryos are 01:01 and 01:02 OR 01:03 and 01:02. Why SET, which combination is better, which worse? Dr. Beer writes the “1” numbers are essentially the same – so isn´t the combination 01:01/01:02 as bad as the second possibility in our case 01:03/01:02? What would be the advantage of SET then? Is there any literature about different DQa combinations and their impact?

All the best from Germany! Sincerely,
Verena

reply
Dr. Geoffrey Sher

My error. I thought you shared 01. That changes a great deal, but as I also mentioned earlier, I do not hve confidence in the testing done in europe. I redally think you should go to Google, find Repr0source in Boston, MA and contact them by phone to arfrange to have your and your husband’s blood sent there for DQa and HLA matching. Also they should do the K-562 target cell test on your blood as well as APA/ATA/RIP. Mention my name and once these test results come back, call and set up a Skype consultation with me to discuss.

Geoff Sher

Geoff Sher

Dr. Geoffrey Sher

Respectfully,

I do not have confidence in the reproductive immunologic testing in Europe.

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

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers Should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
ANNOUNCEMENTS:
1. About my Retirement
After > 30 years in the field of Assisted Reproduction (AR), the time has finally come for me to contemplate retiring from full-time clinical medicine. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.

2. The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

Geoffrey Sher MD

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Chrissy

Hello Dr. Sher, I hope you can help me settle my expectations a bit. I had two donor frozen embryos transferred a week ago yesterday. I had a beta hcg test today that came back at 4.7. I have been told to retest on Monday. In the meantime, I am wondering what does it mean that the test is at 4.7. Most of what I’ve read so far says if the test is less than 5, it is negative. But wondering if, since these were donor embryos transferred that the same rule might not apply. I don’t want to get my hopes up, but I’ve had three prior cycles and never had any measurable hcg. Thanks!

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Dr. Geoffrey Sher

This hCG level indicates that a pregnancy was trying to get started. The level is low, and that unfortunately suggests that the pregnancy might not hold.

Geoff Sher

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Lauren Manning

Do you think NSAIDS specifically ibuprofen can impede implantation and decrease likelihood of achieving pregnancy? I understand acetaminophen is the safe choice throughout pregnancy for aches and pain.

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Dr. Geoffrey Sher

In general, I think NSAIDS are best avoided during a stimulation cycle.

Geoff Sher

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