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.
Dear Doctor
I am trying to understand your conversion protocol. Birth control is used first to quiet the pituitary gland production of FSH, and especially LH in women like me who are prone to premature lutenization right? The part I don’t understand is the lupron. When you start the lupron it expunges more LH and also FSH when done over several day’s right? Then how is it that a woman would not be over suppressed and still get a good ovarian response to the stims with the combination of birth control and lupron?
A friend of mine has used this protocol twice. She said she had a way better ovarian response when she used lupron vs synarel. She got 26 eggs when using lupron and 16 with synarel. Do you know why that could be?
We should talk this through.
Feel free to call my assistant Patti at 702-533-2691n and set up an online consultation.
Geoff Sher
Hi Dr. Sher,
I recently had a failed FET and decided to go back and bank a couple more embryos before my next transfer. My doctor just performed a saline sono to confirm my uterus looked “good”. He said it was beautiful. We will be switching from oral estrogen to patches this time around. I went on birth control at the start of the cycle with the intention of taking it 14 days to move toward transfer cycle. Im a little worried about going for a transfer cycle after a birth control pill initiated menses. What is your opinion on this? Would you wait for a regular period or confidently transfer after a bcp initiated period
Although my protocol for FET would differ somewhat, there is in my opinion, no problem with this approach!
Geoff Sher
Hello, I went for a ultrasound my provider said iam 6 weeks since we couldn’t hear a heart beat but we could see it during the US.
She did blood work for HVG quantitatives first draw was 56,000 48 hours it did not double it was 78,000. Are these ok number I asked if I could be miscarrying all she said was don’t worry just yet and that she wants me to repeat my blood work so now I’m of course worried since it’s my first pregnancy and my next US isn’t til September 4th. Any advice. I hear hcg doesn’t double after 6,000 and after 6 weeks it’s more about the ultrasounds
I think you have3 reason to feel guardedly optimistic. I agree with the strategy beingb implemented by your RE.
Good luck and G-d bless!
Geoff Sher
Hello, my husband and I have been trying for 4 years. Over this time we have tried:
– timed intercourse resulting in 2 chemical pregnancies
– 3 IUIs resulting in 1 chemical pregnancy
– 2 egg retrievals resulting in 5 genetically normal embryos
– 2 frozen embryo transfers resulting in 1 CP
I have completed a receptiva test and ERA which states that my timing for transfer was accurate and endometerin receptive. I tested positive for anti thyroid and am now taking a low dose of levothyroxine. My husband has an autoimmune disorder (psoriasis and psrioatic arthritis).
They want me to move onto intralipids my next frozen embryo cycle. This includes one infusion 40 days before and another a week before. They’ve said that I don’t need to get tested prior for Kn cells because most of the reports are inaccurate.
Do you agree not to get tested prior? Is there something the test will tell them regarding dosage of the intralipids that I should be asking about? Am I missing anything?
I respectfully do not agree. In my opinion, you need to be tested in advance. Treatment would be predicated upon the results.
A: Why did IVF fail:
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 15y 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
e.Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.
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).
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B: Autoimmune thyroid disease and IVF outcome:
Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.
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C: Managing IID:
Central to making a diagnosis of an immunologic implantation dysfunction (IID) is a need for the appropriate interpretation of Natural Killer Cell Activity (NKa). In this regard, one of the commonest and most serious errors, is interpret the blood concentration of natural killer cells as being relevant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. This activity can best be measured using the blood, K-562 target cell test (the gold standard). and/ or endometrial biopsy for cytokine activity.
With the K-562 test, 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 addition to reporting the result of the K-562 test, in the “native state” (without adding, Immunoglobulin-G (IVIG) or Intralipid (IL) which many Laboratories erroneously do to try and determine whether either or both of these immune therapies would have a therapeutic benefit or is/are unlikely to be of clinical value. The entire premise upon which this assertion is based, is in my opinion flawed. Clinically such NK cell deactivation can only be significantly affected in vivo as it takes more than a week following infusion to occur. Thus, what happens to the percentage of target cells killed with the K-562 test, by adding IVIG or IL is in my opinion irrelevant
Another way to assess endometrial NKa is by measuring TH-1 and TH-2 cytokines in endometrial tissue derived through biopsy.TH-1 cytokines kill the trophoblast (the root system of the embryo). Thus if is an excess of TH-1 cytokine activity is found with/without a disruption in the TH-1: TH-2 ratio, this points to NK cell activation.
There are basically two causes of immunologic implantation dysfunction (IID), a) Autoimmune (85%) & , b) Alloimmune (15%). The former occurs when the body reacts to its own tissue and the latter (far less common) when the male and female partners share certain genotypic similarities involving DQ alpha and HLA genes. In both cases IID results in rejection of the pregnancy due to uterine Natural Killer (NK) Cell and T-cell activation leading to the release of an excessive amount of TH-1 cytokines. These, “toxins” attack the embryo’s root system (trophoblast), killing the cells and causing implantation to fail.
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 endometrial cytokine activity tests.
It is important to recognize that currently there are only about 3 or 4 Reproductive Immunology Reference Laboratories in the U.S.A that, are capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity. I use a Reprosource, a laboratory located in Boston,MA.
Patients with Alloimmune implantation Dysfunction usually present with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive again or started having repeated early miscarriages. However, 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 an IID when there both a DQa/HLA match exists along with NK cell activation. With the exception of cases where both partners have a total (absolute DQa match and treatment requires the use of sperm from a non-matching sperm donor, about 90% of cases alloimmune implantation will have a partial match where 1: 2 embryos will match the woman’s DQa genotype and half will not. In cases of an alloimmune dysfunction (with associated NKa), treatment with IL or IVIG will in my opinion, will not protect against a matching embryo being rejected. It can only clear the NK environment for an embryo that does not match the woman’s DQa genotype. For this reason, it is my opinion that only 1 embryo should be transferred at a time because, given the fact that i:2 embryos will match, transferring >1 embryo at a time creates a risk that the matching embryo will evoke a local NKa/’cytokine response that will “muddy the water” for both. Thus, in cases of a “partial” DQa match I recommend against transferring more than a single embryo at a time.
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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.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•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
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•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) Why did my IVF Fail
•Recurrent Pregnancy Loss (RPL): Why do I keep losing my Pregnancies
•Genetically Testing Embryos for IVF
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
•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.
•IVF: Selecting the Best Quality Embryos to Transfer
•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?
•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!
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
•Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
•A personalized, stepwise approach to IVF
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ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher
Hi there. I am 4 weeks pregnant and HCG was 560. In 4 days, it was 3435. To be checked again in 5 days. Twins run in my husband’s side of the family….thoughts?
Could be a multiple. An US would mtell!
Geoff Sher