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.
Dr.Sher:
I am going to start my stimulation cycle very soon, but have a concern about my protocol. I am not sure if you can give me any comments.
I did total 7 IVF cycles. Got a lucky boy on the first conventional cycle. Four years later, the same doctor used the similar protocol with increased dosage of stimulation medicines (Follistim +Menupor) was failed. Then I did 5 more IVF cycles mostly using Follistim 225IU for 10-11 days for stimulation.
Now another doctor reviewed my previous medical records and wants me to use Menupur 375IU this time. I never use this kind of protocol before since I have PCOS problem. My usual baseline blood level are about FSH 2-4, LH 4-9, AFC 20-35. Although after taking two month Metformin my baseline LH decreased to 3-6(FSH increases to 7-8), I am still afraid all Menupor stimulation won’t have a good result.
Could you please give me any suggestions?
Thank you very much
I cannot interfere in treatment prescribed by another RE. However, I can point out how I decide on the choosing an ideal protocol for ovarian stimulation (see the list on my blog–below). Additionally let me say that whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET) whether she has conceived naturally from IVF or on her own before, 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).
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 promptl
•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)
•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?
•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)
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
I was wondering if these betas look okay 1st beta at 15dpo was 62.7, 2nd beta at 18dpo was 150, 3rd beta at 20dpo was 273, 4th beta at 22dpo 349. I did a day 5 fresh embryo transfer of 2 embryos. What do you think of all this I’m worried.
The rise is indeed slow…but I would not write it off yet. Do an US in 10 days from now.That will give the final answer.
Geoff Sher
Dear Dr Sher,
Unexplained infertility – multiple failures at our end – In your opinion wht are many RE’S – including all of our RE’s so far resistant to your ideas and methods?
I follow all your blogs and the information available has been very helpful with learning about this process. Just wondering what your thoughts are? Also, in cases of multiple failed IVF’s with a diagnosis of unexplained – do you think there is an underlying reason in most cases?
Thanks,
Catherine
Thanks,
I have responded to this post earlier.
Geoff Sher
Dear Dr. Sher,
4 questions
1)I have an extremely small follicle visible on day 8 of stims. I am a very poor responder. I did not have priming prior to starting stims and am on 75 menopur and 450 Gonal. When should Ganarelix be added to the cycle to prevent LH surge?
2) I tend to get falls surges during my cycles and I wondered if administering ganarelix early would prevent these and allow the follicle to grow without these LH surges?
3) Is there any harm in administering ganarelix when follicles are extremely small to have peace of mind and prevent unexpected ovulation?
4)When is the earliest in a cycle to administer ganarelix?
You are probably experiencing premature luteinization. This requires a very individualized approach to ovarian stimulation
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.
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 promptl
•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)
•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?
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
Dear Dr. Sher,
As I understand Estrogen priming protocol is done by administering Estrogen patches from the 7th or 9th day of LH surge day. Does it matter if the patch is put later such as the day before the period or day of the period and stims started soon after?
I use twice weekly Delestrogen (estradiol) injections starting after a Lupron-induced period ,at which point the Lupron is supplanted by daily Ganirelix/Cetrotide)….for about 1 week prior to begining FSH administration. I do not use oral estradiol or patches. The parenteral estradiol more evenly reaches the systemic circulation.
With regular long Lupron down regulation protocol where the initiation of a GnRH agonist (Lupron, Superfact, Buserelin) is initiated about 7-14 days prior to starting stimulation with gonadotropins and then continued throughout the COS cycle, the pituitary gland output of LH is largely exhausted and LH-induced testosterone is down-regulated. In this way, an adverse effect on follicle and egg development is minimized. The down side however, is the fact that prolonged administration of GnRH agonists could suppress subsequent ovarian response to ovarian stimulation with gonadotropins, by competitively binding with ovarian FSH receptors. It was against this background that I introduced an approach that combines the use of the GnRH agonist with a GnRH antagonist and termed this, the Agonist/Antagonist Conversion Protocol (A/ACP)
With the A/ACP, an antagonist (Ganirelix/Cetrotide/Orgalutron) is commenced at the onset of spontaneous menstruation, or following bleeding that follows initiation of GnRH agonist (e.g. Lupron/Superfact/Buserelin) therapy using a long-down-regulation protocol arrangement. The antagonist is then continued up until the day of the hCG “trigger”. I presently prescribe the A/ACP protocol for patients most of our IVF patients regardless of whether they are “normal responders” or “poor responders”. Preliminary results suggest a significant improvement in egg number, egg/embryo quality as well as in implantation and viable IVF pregnancy rates. The A/ACP has however, proven to be most advantageous in “poor responders” where additional enhancement of ovarian response to gonadotropins may be achieved through incorporation of “estrogen priming”. We have reported on the fact that the addition of estradiol valerate for about a week following the initiation of the A/ACP, prior to commencing FSH-dominant gonadotropin stimulation (and its continuation throughout COS) appears to further enhance ovarian response, presumably by up-regulating ovarian FSH-receptors. ”. We refer to this as the A/ACP+ E2V.
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 promptl
•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)
•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?
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