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.
Hello Dr. Sher
I am in search of answers or suggestions before I begin my next transfer. I am 36 and my husband is 49. 16 eggs were retrieved 15 of which were fertilized but only 8 made it to blast. I opted out on the genetic embryo testing because I didn’t understand it fully and I didn’t want additional probing done to my embryos. I had 2 embryos transferred fresh on day 5, which resulted in a positive pregnancy but my Hcg was 8 after the 2ww which I was told was not really viable. So I stopped all medications and my cycle came. I just tried a 2cd time. A frozen transfer where 2 more embryos were implanted, 1 of which was already hatching. I was worried because the US tech was pressing hard on my stomach to get a good view and as the doctor was entering with the embryos, almost to my uterus, the tech lifted the US probe and shoke everything in an attempt to readjust. I wanted to know if that could harm the process? Anyways after 2wks of being on twice a day vaginal progesterone and 1ml of oil based progesterone and 3 estrogen pills a day, my pregnancy test was negative. I just wanted to know if the situation with the tech affected the embryos chance. The nurse mentioned that I didn’t have the genetic screening test so they don’t know which ones are good. But what about before that test was available? I thought they froze the ones that survived to up to day 7. So are my embryos the problem or could it be inside my womb. I had an abortion at age 14, and 2 ectopic pregnancies, so no tubes left, could that be a factor as well? Thank you for any information you have to offer.
I strongly doubt that the failed outcomes had anything to do with technical factor. More important is to look into both the protocol used for ovarian stimulation and a thorough evaluation of implantation factors.
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
5.The cause of the infertility: 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)
Patients often ask me the question…”When should I stop doing IVF” or “when should I move on to egg donation and/or gestational surrogacy?”. The answer does not lie solely in the number of prior attempts made. Rather it is “when in spite of thorough evaluation” there is no “remediable/treatable cause” for failure that can be identified.
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
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•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
•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)
•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
First, please excuse my bad english, I’m not a native speaker. Could you please help me with an advice? I did IVF and my firs beta HCG result 10 days after ET was 120. 48 hours later, It was only 185. I was told it’s poor diagnostic sign. 48 days after that, I did beta HCG test in another lab and the result was 400. We were very happy, but than my friend inform me that the last test isn’t valid because we went in another lab… The unit was the same – miu/mL. Please, give me your opinion about that. Thank you so much in advance! Nina
Hi Nina,
I am afraid this does not look like a successful implantation. It is however important that you be followed by your RE to make sure that you dont have an ectopic (tubal) pregnancy. If you experience any sudden pain, go straight to your doctor or to the nearest emergency room.
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.
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 been reading a lot of your blog posts and am trying to learn 😉 I am 29 with PCO. We have been trying to conceive for years and have had two failed ICSI´s. My husband is 32 and had moderately low sperm quality. I am undergoing a new cycle in march/april, so I would very much appreciate your input. We are not americans and are getting treatment in Iceland, so things are done a little bit different there. My first treatment plan was: Suprefact for 2-3 weeks. Then started stimulation with 112,5 IE Gonal-F daily for 11 days. I was triggered with 250 mcg Ovitrelle. Had 25 follicles, the largest 24 mm, some 22 and 20 mm. At EC there were 16 eggs, 13 mature, but only 4 fertilized. Had two bad quality embryos transferred on day 2.
The second treatment was exactly the same but stimmed with Menopur instead. Had 4 follicles that were 17 mm, but EC only gave two eggs, one had no polar body and the other did not fertilize.
I have been reading about your coasting protocol for PCOS, but I don´t think I can get my doctor to change treatment that much. Could you make any other changes to my earlier protocols to better the egg quality? I am thinking about starting BCP and maybe ask for another HCG trigger. Do you think that would make any difference?
First, as you read me say before…and as again outlined below, you need a “coasting protocol in my opinion. Also, as I have previously indicated, in my opinion, 250mcg of Ovidrel is too low a dosage. You either need a 500mcg Ovidrel trigger or 10,000U hCGu.
My approach is consistently to use a long pituitary DR protocol with an agonist, coming off 1-2 months on the BCP. The latter is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling ovarian androgen release. I then stimulate with low dosage FSHr to which I add a smidgeon of LH/hCG (Luveris/Menopur) from the 3rd day and watch for the # of follicles and [E2] starting on the 7th day of COS. If there are > 25 follicles, I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. Then, provided the [E2] is >2500pg/ml, I stop the agonist and the gonadotropin stimulation and follow the E2 (only) daily, without doing further US examinations. The [E2] will almost invariably climb and I watch it go up (regardless of how high the concentration of E2reaches) and track it coming down again. As soon as the [E2] drops below 2500pg/ml (and not before then ever), I administer 10,000U hCGu or hCGf (Ovidrel/Ovitrel-500mcg) as the “trigger” and perform an egg retrieval 36h later. ICSI is a MUST because “coasted” eggs usually have no cumulus oophoris and eggs without a cumulus will not readily fertilize on their own. All fertilized eggs are cultured to blastocyst (up to 6 days). And up to two (2) are transferred transvaginally 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 the above approach 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.
I do not use antagonists in high responders (e.g., PCOS) because it interferes with the assay of E2 (often causing the value to be understated), a valuable index in assessing risk for the development of severe/critical OHSS. I also do not believe in the agonist trigger to prevent OHSS. The reason is that the magnitude of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the oocyte aneuploidy index.
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 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
•The Role of Nutritional Supplements in Preparing for IVF
•Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
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:
You asked me to send you the results of my NKa testing. They are as follows:
NK cell Activat: 3.4
NK IVI G Supress: 1.3
NK Intralip Sup: 2.9
The test was conducted at Fertility and Cryogenics Lab in Downers Grove Illinois.
Please let me know whether these results are normal and whether I need additional testing from another lab.
Additionally, you suggested that, in light of my PCOS, I take 2-3 months of pills “continuous” prior to doing a delestrogen cycle. I have switched my natural cycle to a delestrogen cycle in accordance with your recommendation. I have a few related questions.
1. When you say “continuous,” do you mean I should skip the fourth week of sugar pills and instead start a new pack so I am on continuous horomones?
2. Would I start Lupron during this period. E.g., after 2 pill packs?
3. I did take at least 2 weeks of pills prior to my first FET where my lining only got to 7mm. Will 2-3 months of pills potentially make a difference? I was not on injectable estrogen that time. By the way, it seems most doctors think all forms of estrogen are the same, and I don’t think that’s the case!
Thank you!
The lab that did your NK assay is not one I am familiar with or use. In my opinion there are only a handful of labs in the United states that can do this test reliably. I suggest that you repeat the NK assay at one of those. I recommend Reproductive Immunology Associates in Van Nuys, CA. Go to google to find their contact information.
Now to your questions:
1. When you say “continuous,” do you mean I should skip the fourth week of sugar pills and instead start a new pack so I am on continuous horomones?
A: I would take them as per usual and follow up with the sugar pills.
2. Would I start Lupron during this period. E.g., after 2 pill packs?
A: You would overlap the last few days of the BCP with Luprn, stop the pill, continue the lupron and when the period starts, then add the gonadotropins.
3. I did take at least 2 weeks of pills prior to my first FET where my lining only got to 7mm. Will 2-3 months of pills potentially make a difference? I was not on injectable estrogen that time. By the way, it seems most doctors think all forms of estrogen are the same, and I don’t think that’s the case!
A: Firstly, anything taken orally 1st has to be absorbed in the gastrointestinal tract. Then it pases through the liver where it is altered…before reaching the uterus in an altered state. Oral estrogen works, but in my opinion it is preferable to deliver the estrogen directly into the systemic circulation so it reaches the uterus unaltered. The best ways to achieve this are 1) by injection (I prefer this approach) or 2) by using skin patches.
Good luck!
Geoff Sher
Dr. Sher, I found your published paper on the agonist-antagonist conversion protocol with estrogen priming used in women with DOR. Do you have any published work on its use in women with PCOS or do you recommend the agonist protocol?
After 3 cycles with poor embryo quality, I’m looking for peer-reviewed literature to discuss with my doctor. We have tried the antagonist protocol and in my most recent cycle per my request we eliminated the use of Menopur in the early days of stimulation. This last cycle I had good even follicle growth of until the end when some stopped or barely grew and my E2 plateaued. While I produce many follicles (16-25) during my cycles, I’m a slow responder it seems as it takes 3 days or so for my body to get going. We haven’t moved on to a fourth cycle yet, but I’m sure we may be there soon, but only if I can find a protocol that will improve my chances.
The paper you found is the only published one!
Geoff Sher