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 have read blog for a long time now. Whenever I have a question or concern there is always an answer here. I greatly appreciate the wealth of information you provide. I was just wanting to know why you have chafed your stance on the dose of menopur you use in ivf. I know of many women who did IVF at SIRM and many of them only took half a vile of menopure during their cycles. I know of I think two SIRM doctors who have moved to other practices and they still only use “ just a splash” , so half a vile with their patients. There must be a reason why. I see that you now recommend 75 units of menopure. I understand that medicine is a practice that is always evolving, I just would like to know why you, the doctor who discovered that too much LH can be detrimental , have changed your mind. Last thing, why do you drop the dose of FSH after the first two days of a cycle? Thank you in advance.
I start with a half vial for 1st 2 days of stimulation and increase to 75U (1 vial) from day 3. I have found that patients do better with this very slight increase in the LH contained in Menopur.
Geoff Sher
Only 5 of our 21 embryos made it blast, I meant to say in that last line!
Hi!
I just had my egg rerival last week, two days before my 41st birthday. I got 33 eggs, 25 mature, and 21 fertilized. 3 made it to day 6 blast and two made it to day 7 blast. Doctor says all embryos are a solid B grade. We are now waiting for our PGS results on the 5. Doctor seemed a bit concerned more didn’t make it to blast and said the lab said a few eggs seemed to have quality issues, but Doctor said she thinks this might be due to the protocol she used and could tweak for a second round. She doesn’t believe I have egg quality issues (aside from age) as I have no other issues at all. My numbers are great (had amh taken less than a year ago and was 2.5). Also, when I was 37 I had my eggs frozen and got 24 eggs, 23 of which were mature.
Would you suggest doing another round with her tweaking the meds- maybe I was too stimulated and it messed with some of the egg quality? Or going to the frozen eggs? And do you think the fact that only 5 of our 21 embryos made it to blast a bad sign for their PGS results? Thank you!
Dear Dr Sher, we read your free book. Very helpful. Wondering if you recommend intralipids to a patient, do you typically repeat the intralipid after a positive pregnancy test. Thanks
yes a dosage is given after a +ve pregnancy test.
There is an ever growing realization, recognition, and acceptance of the fact that uterine immunologic dysfunction can lead to immunologic implantation dysfunction (IID) with “unexplained” infertility, IVF failure, and recurrent pregnancy loss (RPL). Although there are many factors that contribute to such implantation dysfunction, in the final analysis it is activated, “functional” uterine natural killer cells (NKa) in association with cytotoxic-T cells (CTL), which, through the production of cytotoxic cytokines (see below), damage the “root system” (trophoblast) of the embryo, causing the pregnancy either to be immediately rejected or so compromising placentation that early pregnancy loss occurs. Both immunoglobulin-G (IVIG) and intralipid (IL) therapy given in combination with corticosteroids (e.g. dexamethasone, prednisone, and prednisolone) are used to effectively reduce/down-regulate activated NK cells.
NK cells reach the uterus from the woman’s bone marrow, early in the menstrual cycle, as so called “parental” or “progenitor” cells. There, these early NK cells proliferate under the effect of estrogen. Only upon being exposed to progesterone do they begin to propagate “functional” NK cells that release cytokines and promote implantation. The concentration of functional NK cells in the endometrium is maximal about 7 days after exposure to natural(endogenous), or synthetic (exogenous) progesterone ….i.e. corresponding to the time the time when the embryo implants into the uterine lining (endometrium).
Functional uterine natural killer (NK) cells as well as T-helper cells are immune cells that frequent the uterine lining. They produce growth factors known as cytokines that regulate orderly implantation of the embryo and facilitate placentation (development of a functional placenta, the baby’s life line).There are two varieties of uterine cytokines: a) TH-2 (humoral) cytokines that promote permeation of the uterine wall by the embryo’s trophoblast (“root system and, b) TH-1 (cellular) cytokines that oppose trophoblastic proliferation and permeation of the uterine wall by culling interstitial trophoblastic cells. Orderly implantation and formation of a functional placenta (lifeline of the baby) requires that TH-1 and TH2 activity be in equilibrium
There are two categories of immunologic implantation dysfunction (IID) linked to NK cell activation (NKa).
•Autoimmune IID. Here, there is often a personal or family history of autoimmune conditions such as Rheumatoid arthritis, Lupus Erythematosus, and thyroid autoimmune activity (e.g. Hashimoto’s hypothyroidism) etc. Autoimmune IID also occurs in about one third of cases of endometriosis, regardless of severity.
•Alloimmune IID. Here uterine NK cell activation results from uterine exposure to an embryo derived through fertilization of an egg by a spermatozoon which shares certain genetic (HLA/DQ alpha)characteristics with that of the mother or embryo recipient.
In both autoimmune and alloimmune IID, the end point is an excessive NKa/CTL, TH-1 release that damages the embryos trophoblast, resulting in failed implantation or early pregnancy loss.
It is important to bear in mind that measurement of the concentration of blood NK cells has little or no relevance when it comes to assessing NK cell activation (NKa). Rather, it is the degree of NK cell activation (cytotoxicity) that matters. In fact, there are certain conditions (such as with endometriosis) in which the NK cell blood concentration is normal or well below normal and NK cell activation is markedly increased.
There are several methods by which NK cell activation (cytotoxicity) can be assessed in the laboratory. Methods such as immunohistochemical assessment of uterine NK cells and/or TH-1 and TH-2 cytokines have been used with some success. However, use of the K-562 target cell test remains the gold standard. With this test, NK cells are isolated from the woman’s blood using Flow Cytometry and are incubated in the presence of specific “target cells”. These are then incubated together. The percentage (%) of “target cells” killed through exposure to NKa/CTL-TH1 cytokines is then quantified.
Currently, there are less than a half dozen Reproductive Immunology Reference Laboratories in the U.S.A that are capable of performing the K-562 target cell test reliably. I have for 20 + years been working with Reproductive Immunology Associates (RIA) in Van Nuys, CA and preferentially recommend them to my patients.
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 several days 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.
It is very regrettable that so many patients are being denied the ability to go from “infertility to family” simply because (for whatever reason) so many reproductive specialists refuse to embrace the role of immunologic factors in the genesis of intractable reproductive dysfunction. Hopefully this will change, and the sooner the better.
Geoff Sher
PH: 702-533-2691
I had a 5 day Embryo transfer on 7/02. Today(7/06) , I went to the beach for two hours. It ended up being hotter than I thought. I drank plenty of water and stayed under an umbrella most of the time. I did sweat when I wasn’t under the umbrella. I felt okay, but I am worried that it was too hot out. What are your thoughts on being in the sun?
As long as you were not severely dehydrated, I would not be over-concerned~!
Geoff Sher
Hi Dr Sher, I had a 5 day transfer on Jun 27, beta is 238, E2 is 2128 and p4 is 11.5. Progesterone is supplemented by crinone AM and PM. Is the estrogen levels are too high? Is the progesterone too low?
No! I think it is OK!
Good luck!
Geoff Sher
Hi Dr. Sher
I am 31 year old with high FSH (ranging 15-19), low AMH of 1.5. My first IVF attempt failed due to no fertilization ( 3 eggs obtained). What would you recommend the best protocol for someone in my situation?Two different RE’s have recommended protocols with high doses of meds (Follistim and Menopur). Anything else you recommend to increase my chances. No male issues.
Thank you so much for your time.