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!
a)Can a single dose of ganirelix cause a huge drop in the LH level? Eg can it make it drop from 60 to 10-15? Or even one injection for 2 consecutive days? Can it cause such a huge drop?
b) Can ganirelix be administered when the lead follicle is just 11mm? If ganirelix is given at the same time as 150iu of Follistim will the 11mm follicle grow? Or will it stall?
Thank you so much!
Yes…it can cause a rapid drop in LH…but if given during the follicular phase it should not hamper follicle growth/development.
Good luck!
Geoff Sher
Hello Dr. Sher,
I’ve heard so much about you. Bless you for hosting and answering this forum! In short, I’m 41 with a 20 year old child. I finally met my husband in 2016, we married and immediately started trying to conceive. We got pregnant easily twice, and unfortunately miscarried twice. First was Turner’s, second was “not enough tissue to test” (at home mc w/ cytotec). I have an AMH if 3.38, AFC 20-22. We moved to IVF to try to avoid any more wasted time and loss with miscarriages, and so we could utilize PGS. I’ve just had egg retrieval two days ago. I was on 225 follistim and 75 menopur for eight days. The doctor insisted on reducing to 150 follistim on day 9 and 75 follistim on day 10. Ganirelix was added in day 5 and triggered with Ovidrel 250mcg. At each monitoring ultrasound I could see many follicles on each ovary that were not being recruited, presumably from lack of medication. I asked more than once about med levels and lack of recruited follicles and was brushed off. My doc was entirely focused on 8 follicles and only retrieved 8 eggs. Only 7 were mature. I believe it’s because they under-stimulated me. I was told I’d get the same amount of normal eggs with 8 or 30 collected. I didn’t buy it then and certainly don’t now. Now I only have 2 that have fertilized normally, which is also very curious because this clinic mandates that you use ICSI w/ PGS (which wasn’t necessary with my husband’s sperm quality and our history of natural pregnancy) Again, they only managed to fertilize 2. Shockingly disappointing. I also discovered that their success rate with the 41-42 age group is a dismal 4.8%. I have great stats to work with, and I feel they do not act aggressively enough. A nurse also informed me yesterday that this clinic “routinely goes for 8-12 eggs” which has never been mentioned to me previously and I find unacceptable as it seems they phone it in as a one size fits all protocol. I would love to hear your thoughts. Many thanks.
First: Based upon your AMH, you clearly still have remarkably good egg population (ovarian reserve). However, it is a fact that at 41y of age less than 15% of your eggs will have the potential to propagate chromosomally normal embryos. Second; If a less than ideal protocol is used for ovarian stimulation that percentage will drop further.Respectfully,, in my opinion, the better dosage of Ovidrel is 500mcg to promote more orderly meiosis and keep the percentage of “incompetent” (aneuploid) eggs generated at a minimum.
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. 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 in my opinion.
I try to avoid using such protocols/regimes in older women 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): 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
If you are interested in seeking my advice or services, 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 .
*FYI
The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Hello Dr. Sher,
1. what drives the decision regarding the day to transfer a frozen embie? Eg if lining is ready on day 10 can progesterone be started?
2. Is there a difference between the day to transfer a day 5 embryo and a day 6 embryo? Is day 5 embryo transferred after 5 days of progestrone and day 6 embryos after 6 days of progestrone? Or does it not matter?
1. what drives the decision regarding the day to transfer a frozen embie? Eg if lining is ready on day 10 can progesterone be started?
A: Yes it could be started in my opinion!
2. Is there a difference between the day to transfer a day 5 embryo and a day 6 embryo? Is day 5 embryo transferred after 5 days of progestrone and day 6 embryos after 6 days of progestrone? Or does it not matter?
A: In my opinion…day 6!
Geoff Sher
Hello Dr. Sher,
Thank you so very much for this opportunity to ask questions. After two miscarriages in a row, (at age 31/32, with PMH of severe Graves’ disease at age 15) my longtime endocrinologist (also well known RE) suggested testing for antithyroid antibodies. My results came back 3x upper limit of normal for antithyroid peroxidase, and we were advised regarding the likelihood of IID. We continued trying naturally for 18 months with no success. After seeing our local SIRM, I was tested for NK via a lab in California, which came back negative, to my extreme surprise! However, due to my own anatomy as well as male factor issues, we have now been recommended to initiate IVF. My question is: how accurate do you find this specific NK lab assessment to be? For such a long time, I have attributed my miscarriages to this cause. So for the NK CELL test to be negative, I was stunned. Are there any specific rules/specifications to the NK text for it to be accurate? Thank you so much.
Personally the lab you use makes a big difference. In CA, the only lab I feel confident in is Reproductive immunology associates (RIA) in Van Nuys.
I have been struck by the fact that patients suspected of having an immunologic implantation dysfunction, frequently are all too often recommended to undergo the wrong testing, often performed in the wrong laboratories and/ or that the results reported are misinterpreted. This cause a great deal of unnecessary confusion and leads to over-treatment of some and detrimental withholding of required treatment of others.
•Who Should Undergo IID testing:?
When it comes to who should be evaluated, the following conditions should in always raise a suspicion of an underlying IID, and trigger prompt testing:
•A diagnosis of endometriosis or the existence of symptoms suggestive of endometriosis (heavy/painful menstruation and pain with ovulation or with deep penetration during intercourse) I would however emphasize that a definitive diagnosis of endometriosis requires visualization of the lesions at laparoscopy or laparotomy )
•A personal or family history of autoimmune disease such as hyper/hypothyroidism (as those with elevated or depressed TSH blood levels, regardless of thyroid hormonal dysfunction), Lupus erythematosus, Rheumatoid arthritis, dermatomyositis, scleroderma etc.)
•“Unexplained” infertility
•Recurrent pregnancy loss
•A history of having miscarried a conceptus that, upon testing of products of conception, was found to be euploid (have a normal numerical chromosomal configuration.
•Unexplained IVF failure
• “Unexplained” intrauterine growth retardation due to placental insufficiency or late pregnancy loss of a chromosomally normal baby
•What Parameters should be tested?
In my opinion, too many Reproductive Immunologists unnecessarily unload a barrage of costly IID tests on unsuspecting patients. In most cases the initial test should be for NK cell activation, and only if this is positive, is it necessary to expand the testing.
The parameters that require measurement include:
oFor Autoimmune Implantation Dysfunction: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are: a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6, Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity (in my opinion).
oFor Alloimmune implantation Dysfunction: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in IID when there is concomitant NK/CTL activation (see elsewhere on this blog).
•How should results be interpreted?
Central to making a diagnosis of an immunologic implantation dysfunction is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. Then there is the interpretation of reported results. The most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In my opinion, trying to interpret the effect of adding IVIG or Intralipid to the sample in order assess whether and to what degree the use of these products would have a therapeutic benefit is seriously flawed and of little benefit. Clinically relevant NK cell deactivation can only be significantly effected in vivo and takes more than a week following infusion to occur. Thus what happens in the laboratory by adding these products to the sample prior to K-562 target cell testing is in my opinion likely irrelevant.
There exists a pervasive but blatant misconception on the part of many, that the addition of IL/IVIG can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL. However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells, which takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, in reality it would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory, by which time it would be far too late to be of practical advantage.
Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus, it should be infused 10-14 several prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later.
Geoff Sher
Dr Sher…im 41 just gave birth 6 months ago to my son….natural pregnancy..no ivf and/or medications to get pregnant. Period has been regular, every 25th day, until these past couple of months. One month i was 10 days late, neg pregnany test, after my period 12 days later my period started again, neg pregnany test, now this month im late again..are my hormones out of wack even tbough the past 4 months my periods were regular.
Could be out of wack…but check the blood hCG again.
Geoff Sher