Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
Dear Dr. Sher,
I am 38 years old with 5.35 ng/ml AMH and 8.8 mIU/ml FSH, AFC 12 to 14, immunological testing all normal, endometrial biopsy normal, double heterozyote for MTHFR 677CT AND 1298AC, laproscopy showed open tubes and no endometriosis. I ovulate regularly and have normal length cyles 28 to 34 days. I have no indications of PCOS. I have undergone 2 failed ivfs and just finished egg retieval for ivf #3. In all 3 ivf cycles I have had significant numbers of empty follicles. Here a summary of protocol:
Ivf #1
Agonist, 10 days 450 iu Menogon HP, DECAPEPTYL IVF 0,1 mg/1 ml, 5,000iu predalon for trigger,
with HCG and pregesterone luteal support
From 23 follicles only 5 eggs, 3 were M2 mature, 2 fertilized, worst quality embryos
Found out from acrid orange test husband had only 12% normal double strand DNA
IVF#2
Antagonist, 9 days 450 IU PERGOVERIS (450iu Fsh/225LH), orgalutran (ganirelix .25mg/0.5ml), trigger decapeptyl (2 shots), with HCG and pregesterone luteal support, 19 follicles, estrogen after 9 days stimming at 2770 wng/l but only four M2 eggs retrieved and with icsi fertilized, better quality than ivf#1 (less fragmentation) but slower growing 4 day morulas transfered, bfn
Ivf #3
Antagonist 8 days stimulation with 150 iu pergoveris, orgalutran(ganirelix .25mg/0.5ml), 250 mg ovidrel trigger, 10 follicles, 1 @20mm, 5 @17-20mm, 4 @ 14mm on morning of trigger day. Trigger 10pm, 36 hours later retrieval, from 10 follicles only 5 eggs. Still waiting for fertilization report.
My question is, if this time is another failed cycle, do you think I still have a chance of success and what would you recommend changing in my protocol for the best chance?
I truly appreciate all the ways you are helping women with fertility issues. I look forward to a response from you.
I forgot to mention, we seem to have overcome the sperm issue with supplements and regular “release” as the most recent test showed 75% good quality DNA double strand sperm.
In my opinion, the protocols used for ovarian stimulation need to be reviewed and adjusted.I do not agree with adding hCG to the stimulation and I definitely do not advocate <10,000U hCG or 500mcg Ovidrel for the trigger....to start with.
Frequently, when following vigorous and often repeated flushing of follicles at egg retrieval they fail to yield eggs, it is ascribed to “Empty Follicle Syndrome.” This is a gross misnomer, because all follicles contain eggs. So why were no eggs retrieved from the follicles? Most likely it was because they would/could not yield the eggs they harbored.
This situation is most commonly seen in older women, women who have severely diminished ovarian reserve, and in women with polycystic ovarian syndrome (PCOS). In my opinion it is often preventable when an optimal, individualized and strategic protocol for controlled ovarian stimulation (COS) is employed and the correct timing and dosage is applied to the “hCG trigger shot.”
Normally, following optimal ovarian stimulation, the hCG “trigger shot” is given for the purpose of it triggering meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse, so that the egg can detach and readily be captured at egg retrieval (ER).
Ordinarily, normal eggs (and even those with only one or two chromosomal irregularities) will readily detach and be captured with the very first attempt to empty a follicle. Eggs that have several chromosomal numerical abnormalities (i.e., are “complex aneuploid”) are often unable to facilitate this process. This explains why when the egg is complex aneuploid, its follicle will not yield an egg…and why, when it requires repeated flushing of a follicle to harvest an egg, it is highly suggestive of it being aneuploid and thus “incompetent” (i.e., incapable of subsequently propagating a normal embryo).
Older women, women with diminished ovarian reserve, and those with polycystic ovarian syndrome, tend to have more biologically active LH in circulation. LH 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 conditions 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, women with diminished ovarian reserve, and those with PCOS) 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 can, by compromising meiosis, increase the risk of egg aneuploidy, and thus of IVF outcome.
There is in my opinion no such condition as “Empty Follicle Syndrome.” All follicles contain eggs. Failure to access those eggs at ER can often be a result of the protocol used for controlled ovarian stimulation.
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
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•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.
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Unexplained IVF Failure
•Why did my IVF Fail
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoff Sher
Dr. Sher,
Currently, I’m doing a FET cycle and my transfer is with you next week (2/29). My TSH today is 2.62. Can I still do FET? Could I just recheck it if I get a positive beta and treat then? My primary doc has no idea.
Thanks!
The TSH is not relevant at all. There is nothing to treat if your thyroid hormone levels are normal.
Geoff Sher
Dear Dr Sher,
Thank you for your expertise.
I am missing the 3 KIR receptors although am hesitant to take GCSF injections. I do not have any lining issues so am wondering if I would benefit from the neupogen wash to improve uterine receptivity.
Are you able to clarify whether the neupogen wash is mainly indicated to improve uterine thickness or does it also help uterine receptivity for patients with implantation issues?
Thank you
Many thanks.
In my opinion the KIR receptor issue is of little practical relevance,. i also do NOT advocate the Neupogen wash.
Geoff Sher
Dr. Sher,
I’m nearly 40 years old but am a proud mommy to a beautiful 17 mo old boy through our first try at IVF (only had 2 good day 3 embyos). We previously tried for about 2 years previous with less invasive treatments. No known issues except possible thinner lining (always only got to about a 6 or 6.5 mm even with high e2 levels) and my age. We decided to try for another baby about 6 months ago, and already have three failed IVF attempts. First round the protocol wasn’t great and I only had 3 eggs retrieved with none that lasted fertilization to put back. Second round, my RE changed up the protocol (micro lupron) and it worked much better with 9 eggs, 8 mature, only 3 fertilized and we had 2, day 3 embryos to put back. Chemical pregnancy. Third attempt, slight tweak in that same protocol, I had the same # retrieved but 3 that made it! One good blast at day 5, one morula? at day 5 and we put both of those in. I ended up with one late bloomer to freeze (a slow growing day 6 blast is waiting for us). Same results last week, Beta of 5 on 9dp5dt. It’s hard to know why the last two cycles didn’t work with seemingly good quality embryos. My question is about hormones. The last two failed rounds I had night sweats for a night or two mid-way through the 2ww. This is a more recent development for me even during a non-medicated cycle – probably began in the past few years, and I always knew my period would show up within the week. Since I’m on such an increase in estrogen, I worry that I don’t have enough progesterone, even with endometrium (I also use the estrogen patches) to hold the embryos. This is just my best guess on what I believe is happening but could be way off. In your opinion, is it just bad eggs/old age, poor lining/uterus or could this be a hormonal issue? I don’t want to use our last frozen embryo without doing something different to try to help it stick. I’ve never done a FET so I don’t know how my body will react. I have a fabulous clinic and team I’m working with, but when I mention the night sweats and possible discord in hormones, nobody has an answer. Thank you kindly for any insight into all of this.
Whenever a patient fails to achieve a 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).
My answer to patients who ask me when is the time to stop undergoing IVF is ….Aside from the weight of the financial burden, the time to stop is when in spite of thorough and comprehensive evaluation, there is no remediable and treatable explanation for repeated failure.
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
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•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)
•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
•PGS-Biopsy for the Assessment of Embryo Numerical Chromosomal integrity (Ploidy): Should it be done on Day 3 or on Day 5-6 post fertilization?
•Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Secondary Infertility: Addressing the Root Causes
•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)
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•The Role of Nutritional Supplements in Preparing for IVF
I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoff Sher
Hi Dr, Sher, I have a 2 year old from an FET of a 6 day NON PGS tested blast. I did another cycle and opted for PGS day 5 testing. 2/3 blasts were normal (I am 34) and I transferred 1 and the cycle failed. It was recommended that I do NK testing. Is this what you recommend, or would you recommend a different course of action?