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. – thank you for your detailed response. I’ve had all of the diagnostic tests you mention including two specialty implantation failurepanels done (with no abnormal findings – normal ANA, APA, etc) except I have not had the NK / other immunologic labs you mention. If the issue is autoimmune, what is the treatment and is that treatment evidence-based? I’ve had a child naturally – how likely is it that it could be alloimmune (it’s the same male partner)?
It is an indisputable fact that thousands of women with , “unexplained ” infertility/IVF and recurrent pregnancy loss (RPL) have, following selective immunotherapy with Intralipid (IL) or intravenous immunoglobulin (IVIG) in combination with corticosteroids, gone on to have healthy babies. So, why then is there such a “militant obsession” on the part of many, to denounce the entire concept of immunologic factors playing a role in implantation dysfunction? The most common reason cited is that there are no randomized controlled “gold standard” studies to support a causal relationship between immunologic implantation dysfunction (IID) and reproductive dysfunction (infertility/failed IVF and early miscarriage) or the efficacy of immunotherapy to treat the condition.
The double standard: But to single out IID for criticism is a clear example of a double standard since there are no reliable randomized controlled (“gold standard”) studies to validate virtually any IVF, outcome-based treatments currently in general use. It has not even been shown that outcome following IVF is superior to alternatives such as gamete intra-fallopian tube transfer (GIFT) or zygote intra-fallopian tube transfer (ZIFT). Yet, no one would dispute the fact that IVF is far more effective than either of the other alternatives, to the extent that both GIFT and ZIFT are rarely performed any longer and have largely been relegated to the pages of history. Similarly, there are no randomized studies that demonstrate a benefit in using commonly used adjunct procedures such as embryo assisted hatching (AH), embryo co-culturing, nuclear cytoplasmic transfer, uterine scratch, embryo vitrification, intracytoplasmic sperm injection (ICSI) etc. Yet, many highly ethical and competent IVF practitioners confidently tout some or all of these techniques as being efficacious and beneficial without turning a hair. The truth is that as is the case in many other medical specialties, progress has come has through experience gained by longitudinal studies ……..not through gold standard statistical testing.
Background: Ordinarily, upon reaching the uterus, the embryo makes itself invisible to uterine natural killer (NK) cells (the predominating immune lymphocytes in the uterine lining). There, provided that the NK cells do not become activated (NKa) and the embryo has a normal configuration of 46 chromosomes (euploid) and is thus “competent”, it will usually gain acceptance, implant and develop into a viable conceptus. However, in some women, the uterine NK cells become activated (NKa) and go “rogue”, confronting the embryo as a “foreign invader”. In response, they (and other uterine immune T-cells) release an excess of TH-1 cytokines (e.g. TNF-alpha and interferon-gamma) and attack the embryo’s “root system” (trophoblast) resulting in failed or dysfunctional implantation (i.e. Failure to conceive or early pregnancy loss).
Uterine NK cells were first identified and described in the mid-90’s and were soon touted as playing a vital role in regulating embryo implantation. This was soon followed by the determination that under certain conditions, NK cells became activated (NKa) leading to immunologic implantation dysfunction (IID) which could manifest as “unexplained” infertility, “unexplained” IVF failure and recurrent pregnancy loss (RPL). This spawned a lively debate on how to best assess, diagnose and treat the condition.
Why is it that until very recently, there has been a singular inability to reliably evaluate data derived from ART-related studies? To answer this question requires a realization that roughly 80% of ART failures are largely due to chromosomal numerical irregularities (embryo aneuploidy) which until the recent introduction of full embryo karyotyping (using techniques such as comparative genomic hybridization-CHG or next generation gene sequencing- NGS) was not possible to reliably assess. And, to reliably compare results between groups of IVF patients, it is essential that outcome per embryo transferred be computed. To achieve this requires that the “competency” of the embryos transferred be known prior to embryo transfer so that only chromosomally normal (euploid/”competent”) embryos can be transferred to patients of each group. Since virtually no previously reported clinical, outcome based IVF studies took this critical requirement into consideration virtually negates their validity, making them virtually meaningless.
How might we in the future, reliably establish value and efficacy of selective immunotherapy in IVF? In order to be reliable and representative, any study to assess a benefit of immunotherapy in women with IID would require that, demographically and clinically identical NKa positive patients, all of whom would be treated by the same physician using the same stimulation protocols, be randomly assigned to one of two groups. Group 1 would receive the designated immunotherapy regime and Group 2, would not. To be reliable, all variables that could affect outcome, would need to be kept constant. Only “competent” (euploid) blastocysts would be eligible for transfer and results would be reported as viable birth per embryo transferred.
Clinical Reproductive immunology is a very complex field which most IVF physicians do not take the time to try and understand. Most, simply follow the party line and dismissively reject the concept out of hand. So, when patients tell me that “My RE does not believe in immunologic factors causing infertility, IVF failure or Recurrent pregnancy loss”, I advise them, to go back and ask the doctor that gave this answer for a clear explanation as to what it is that he/she does not believe. …I submit to you, that in most cases a rational answer will not be forthcoming.
Geoff Sher
I have a history of recurrent miscarriage. 11 week missed miscarriage at 35 had D&C, 2 at 5-6 weeks age 36, live birth conceived naturally at 37, then 2 5-6 week miscarriages, one 8 week miscarriage (after normal HB on US) had D&C, 14 week miscarriage after normal HB at 9.5 weeks. No underlying uterine or other issues. Just Did first FET with one 5 day blast genetically tested normal. Got pos pregnancy test 8 days post ET, but at 18 days post HCG levels dropped. Dr. Now saying maybe I need an Immunology consult, but based on my review non of the ‘immunological’ treatments have been shown more effective than placebo in RCTs. I have one embryo left – what do you suggest? Why might it have been unsuccessful? I’m 42, husband 49.
Hello Dr!
My Dr has prescribed Dexamethasone for me (0.5mg). I see that in your protocol you use 0.75 mg. Is the 0.5 mg sufficient (the pills I was prescribed comes in 0.5mg tablets so I am supposed to take 1 per day)? Or is it better to take the 1 and half tablets to make 0.75 mg? Based on your recommendation i will speak to my Dr again about increasing the dosage. Thanks for always!
0.5mg daily is probably also adequate.
Geoff Sher
Dr.Sher
Is there any way to lower lh hormone since my is 20,01 (pcos) and which protocol should be used in ivf? Is it even possible to have mature eggs with such a high lh hormone?
I would suggest a few months on the BCP to try and lower LH and then go directly into a stimulation cycle using low dosage gonadotropins rather than clomiphene as the latter will further increase LH.
Geoff Sher
Dear Dr. Sher,
I had FET on 3/21 with donor embryo. I did not have Lupron prior to the FET. I had one shot of pregnyl on 3/21. Luckily, I have had 3 positive blood tests (including today) that show rising hcg levels. The progesterone level has gone down a bit instead of up. My question is- I have Pregnyl available from a previous FET- would it be beneficial for me to use it now as an extra support? Would it be at all harmful? If it is not harmful, I tend to think that I should use the Pregnyl. Please advise on that and any other suggestions that you might have. I am currently taking 1.1 ml of progesterone twice a day plus 4 inserts of 100mg progesterone twice a day. Thank you.
In my opinion there is absolutely no point/benefit in using the hCG supplementation with an FET.
Geoff Sher