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.
My FS has only ever used short antagonist protocol on the 3 cycles I’ve done. First was using Puregon/Orgalutran for an egg freeze which got 16eggs. Next was embryo cycle with my ex partner which was Puregon/Orgalutran and got 6 eggs, 1 day 5 blastocyst. Next was egg freeze using Puregon/Orgalutran which got 10 eggs frozen. My dr has never suggested a different type of protocol. I stay with her because she is affordable & i can’t afford more expensive clinics. I am trying to bank my eggs as I have very low reserve. Is it ok to stay with this protocol? how do you tell your dr what to do, which protocol to use without insulting her? The dr is supposed to be the expert! What should I do? I want to bank as many eggs as I can get before they’re gone!
You seem tom be doing quite well in spite of lower ovarian reserve. While I would probably use a different approach to stimulation, you cannot argue with success, so I would stay the course. “If it ain’t broke…don’t try to fix it!”
Good luck!
Geoff Sher
Hi Dr Sher,
I am 37 year old, and I have begun banking my eggs for future use as I am single with no partner. Currently I have banked 15 eggs at age 35 and another 11 this year at age 37 (total now 26 eggs.) I plan to keep going with the aim to have around 40 and possibly even more if I am lucky enough to get them. I have very low AMH and am very scared I will lose my eggs if I don’t get them soon. Would 40 frozen eggs be likely to get me 1 baby? at this age I am not going to be greedy and wish for more than 1 child. I am suffering depression due to my situation and the race against time. You advice please. Thanks so much.
I would think 40 would be enough but it depends on the skill and expertise of the lab doing the freezing.
Geoff Sher
Hello Dr. Sher,
I am a 39 yr old about to turn 40 in November just starting to undergo IVF. I have had 2 prior miscarriages, one was tested to be trisomy. Last one was July 2014. Did one cycle of Clomid with natural intercourse. Then tried 2 natural IUIs in past year, then in July found out I have one hydrosalpinx and other tube damaged/blocked at beginning (not 100% sure). Don’t know how this happened. She had me tested for Chlamydia – came back negative. As far as I know I have never had any STDs. Any other reasons why I would have gotten the hydrosalpinx? I got pregnant twice naturally and even had a chemical pregnancy in the last 3 years.
Doc started me on estrogen/progesterone/low dose aspirin for 2 cycles, then to BCP. My last day 3 numbers were approximately FSH 4.9, estradiol 101, LH 2ish, progesterone 1.27. So estrogen a little high which worried me.
My cycles are rather short. 25 days is the norm. Not sure if it was always this way but I know it has been this way for at least 8-9 years. I usually only bleed about 2-3 days then it goes to sporadically light for a few days. I have been doing Chinese herbal medicine and acupuncture. My bleeding used to be much heavier. They seemed to get much lighter after that one cycle of Clomid.
Question 1: Does that level estrogen mean estrogen dominance or are those usually higher? Was concerned about that part and the fact that it is probably artificially suppressing my FSH level some.
I generally ovulate early – perhaps around day 10-11. When doc did a scan on me last time it was day 12 and she only saw 2-3 follicles on each side I think. However I remember when doing the IUI’s previously (just a few months ag0) she had counted more. maybe 6-9 in general.
I’m curious what your opinion is on the down regulation cycle she has me on. I’m thinking she thinks I have low ovarian reserve and that is why she prescribed it. I’m just unclear on what is best and also confused about the follicle count as they differed so much. I thought it was important what day to count the follicles.
Thank you so much.
I forgot to mention I’m taking the estrogen/progesterone/low dose aspirin combo from day 17 to day 3 of my cycle. To do this for 2 cycles, then on to BCP.
1: Does that level estrogen mean estrogen dominance or are those usually higher? Was concerned about that part and the fact that it is probably artificially suppressing my FSH level some.
A: It could be the result of the estrogen supplementation. However, a cyst needs to be excluded (US). And yes….a raised estrogen will falsely suppress basal FSH. You should have your blood AMH measured. It is a far better measure of ovarian reserve.
I generally ovulate early – perhaps around day 10-11. When doc did a scan on me last time it was day 12 and she only saw 2-3 follicles on each side I think. However I remember when doing the IUI’s previously (just a few months ag0) she had counted more. maybe 6-9 in general.
2: I’m curious what your opinion is on the down regulation cycle she has me on. I’m thinking she thinks I have low ovarian reserve and that is why she prescribed it. I’m just unclear on what is best and also confused about the follicle count as they differed so much. I thought it was important what day to count the follicles.
A: I would need much more information to be able to comment authoritatively on the selected protocol. However…see below.
Older women, and those who have diminished ovarian reserve (DOR) with resistance to ovarian stimulation (“poor responders” are often labeled as being producers of “poor quality eggs and embryos, and advised to seek IVF with egg donation. In fact, in my opinion such “recipe” or “one size fits all” attitude towards ovarian stimulation is not always justified. In my opinion it should be replaced by a customized approach that addresses specific individualized needs on a case by case basis. This article addresses my personal preference in selecting a stimulation protocol in such cases.
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).
•The Agonist/Antagonist Conversion Protocol Women who have a tendency to overproduce LH (i.e poor responders, older women) require a form of pituitary blockade (with GnRH agonist or an antagonist) throughout the stimulation period to prevent the progressive and excessive rise in LH –induced ovarian male hormones …(.mainly testosterone) can adversely influence egg development, resulting in compromised embryo quality. However, prolonged administration of GnRH agonists (e.g. Lupron/Lucrin/Buserelin/Superfact/Decapeptyl) starting several days prior to the initiation of gonadotropin therapy (the long protocol) and then continued through the gonadotropin stimulation phase (until the day of the hCG trigger) has one possible down side, namely that the agonist can compete for FSH binding sites on follicle cell FSH receptors and thereby blunt the response to gonadotropin stimulation. Obviously this is the last thing that women who have DOR (“poor responders”) need. It is for this reason that I, some time back developed the Agonist/Antagonist Conversion Protocol (A/ACP) With this protocol, the women starts by taking a combined BCP for 8 or more days, whereupon a GnRH agonist is overlapped with the pill for two days. The BCP is then stopped and daily agonist administration continues until the onset of menstruation (usually within 3-6 days). At this point the agonist is completely supplanted with daily injections of 125mcg, antagonist (Ganirelix/Cetrotide/Orgalutron). Commencing within a few days of initiating antagonist therapy, daily FSH-gonadotropins (usually Folistim) injections are commenced. A few days later daily injections of Menopur 75U daily is added. Gonadotropin and antagonist therapy are both discontinued on the day of the hCG trigger
•Agonist/antagonist conversion protocol combinred with Estrogen “priming”: The addition of parenteral estradiol valerate (E2V) for about a week following the initiation of the agonist/antagonist conversion protocol (A/ACP), prior to commencing FSH-dominant gonadotropin stimulation appears to further enhance ovarian response, presumably by up-regulating ovarian FSH-receptors. Accordingly, for women with severely diminished ovarian reserve (“very poor responders”) he adds “estrogen priming” by administering of estradiol valerate (Delestrogen) during the 1st week of antagonist therapy. This appears to enhance ovarian follicular response to gonadotropins. Following one week of “estrogen priming”, gonadotropin therapy is commenced and is this is continued along with antagonist therapy (as above) until the day of the hCG trigger. In my opinion, in cases of severe DOR with very poor response to stimulation, the use of A/ACP + “estrogen priming ” there is in my experience a relatively low (<15%) cycle cancellation rate. In fact , a significant number of patients who previously had been advised to give up and switch to egg donation subsequently achieved viable pregnancies using the A/ACP with “estrogen priming”.
•Augmentation of ovarian stimulation with Human Growth Hormone (HGH) Several researchers have shown that the administration of human growth hormone (HGH), as an adjunct to ovarian stimulation, enhances follicle response in older women and those with DOR and so can help optimize egg quality. It is thought that HGH hormone by increasing the production of insulin-like growth factor 1 (IGF-1), improves follicle development, estrogen hormone production and egg maturation. Two basic mechanisms have been proposed: 1) improving the response to gonadotropin therapy by up-regulating the FSH receptors on the granulosa cells that form the inner lining of follicles and, 2) through a direct enhancing effect of HGH on the egg’s mitochondrial activity. While human eggs do have HGH receptors, those retrieved from older women show decreased expression of such receptors (as well as a reduction in the number of functional mitochondria) as compared with those derived from younger women. In fact, it has recently been shown that older women treated with HGH showed a marked increase in functional mitochondria in their eggs along with improved egg quality. My personal experience in selectively prescribing HGH as an adjuvant to women with DOR, older women and those with unexplained egg quality deficits, is that if used in combination with the A/ACP it seems to indeed enhance egg quality and ovarian response, culminating in improved IVF outcome.
•Embryo Banking: 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
“When designing an individualized ovarian stimulation protocol woman with diminished ovarian reserve and/or older women the primary objective is to optimally regulate the intraovarian testosterone environment by: 1. avoiding protocols of stimulation that cause increased LH exposure, using predominantly FSH-dominant medications such as Follistim/Gonal-F and Puregon, limiting the administration of LH-containing gonadotropins, augmenting the protocol by adding HGH accurately timing the hCG trigger to coincide wit optimal follicle/egg development and offering such women access to “Embryo Banking with the selective transfer of PGS-selected embryos.
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
•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?
•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
Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
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.
Dr. Sher,
My wife and I are patients at Sher in NY and have recently underwent our 2nd embryo transfer with your facility. We came to Sher after my wife had a miscarriage at 10 weeks, following an unsuccessful first fresh transfer, and the misscarriage was after a FET consisting of 2 5day blasts. We were looking to do Chromosomal Analysis and additional testing to ensure we would never have to go through that heartache again. We are working with Dr. T.
Our Transfer was on 8/16 and we transferred a day 5 hatching blast that was PDG tested as “normal”. My wife has underdone Intralipid IVs, because we have been tested for Natural Killers and are positive for 1 (or 2) and begin taking prednisone ahead of any anticipated transfer. My wife’s lining at the time of transfer was a little more than 10mm and we implanted just the 1 embryo following an unsuccessful fresh transfer last month.
We were previously tested for blood clotting issues, semen analysis, all which came back to be fairly normal.
In reading through your case study, “Recurrent Unexplained IVF Failure with “Good Quality” Embryos”, i’m sure we did everything you explained and have still fallen short of our end goal, a healthy baby. Are there other tests, is there something else that we can look for to determine the issue?
We don’t currently have anything left in “the bank” and would need to begin from scratch. We have explored the option of donor eggs, but it seems that although my wife has a low reserve, the medication works; produces mature follicles, most of which fertilize and make it to day 5 and some test normal through PGD.
Hoping you can shed some light!
Thanks for your time,
EB
This sounds like an implatation dysfunction. It is possible that the type of defect is alloimmune rather than autoimmune and if so treatment would differ. Ask Dr T to also test both of you for DQ alpha/HLA matching and please read the articles listed below.
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).
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.
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
•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.
•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!
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
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.
Hello Dr. Sher,
I’m currently a patient at the SIRM office and just received my negative beta results after my 3rd FET. I would like your opinion on what I can perhaps do differently in my next cycle. Here is a little bit of information about me:
I am 34 years old and have done the following (all of these were done at SIRM):
– 3 IUI’s – all negative
– 1 fresh IVF – ectopic. I ended up with seven 5 day blasts and transferred 1 embryo.
– 1st FET – negative after transferring 2
– 2nd FET – chemical after transferring 2 (2nd beta didn’t double and dropped after)
-3rd FET – negative, transferred 1
My dr tested me for immune issues before I began my 3rd FET and found out I have elevated nka cells at 33% and also I’m a partial dq alpha match with my husband. For the past failed cycle, I was on prednisone and intralipids. I also only transferred 1 embryo due to the dq alpha issue. Other than the immune issues, I was told that everything else was fine…my lining always seems to be good and I respond well to the meds.
My dr recommended that I do CGH testing of my embryos for my next cycle so I will be doing that.
Before I start my next fresh IVF, I would like to know the following:
1. is there perhaps anything else that I should be tested for?
2. does this seem to be an issue with my embryos or an implantation issue? I find it hard to believe that its an embryo issue since I’m 34 (embryos were from when I was 33) and I ended up with seven 5 day blasts.
Thank you!
Hi Emma,
Unfortunately, without access to ALL your records, I cannot add much. I can tell you that you are in excellent hands at the NY office.
Good luck!
Geoff Sher