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 Doctor,
I had ivf cycle this year due to my partner has 0% poor morphology.During fresh cycle I was overstimulated and had OHSS so didn’t have embryo transfer.After 3 months I had frozen embryo transfer.Two embryos were transferred of grade 5BC and 3 BC.but none stick and it was negative.After that 3 months lafter again I had 2 embryos transferred with 2bc embryo using embryo glue but still result is negative.I am not sure why implantation has not happend.Please help me to find out what could be the reason.I have one frozen embryo left.But I want to do fresh cycle cgain is this a good idea?.What can I do for implantation?what all tests are required for implantation?Please advice?
Hi, is a blastocyst grade 3BC likely to achieve pregnancy?
It depends on the grading system your laboratory uses.
Geoff Sher
Hi Dr Sher, I am currently breastfeeding but would like a fet early next year. My periods have already returned regularly. My question is would I need to stop breastfeeding altogether before transfer or are there any hormone tests that I could have which would determine if levels were back to normal and suitable for transfer whilst breastfeeding?
While the hormonal fluctuations associated with BF would not completely preclude an FET pregnancy, it would in my opinion, adversely affect outcome. I would advise weaning off BF prior to doing an FET.
Geoff Sher
dr Sher
thank you for responding to my post, i have pcos tried laparascopy , and clomid but that never worked, later we found out that i had hydrosalphinx so ivf beacame my only option. i had bilateral tubal ligation in prep for ivf. 52 eggs were collected during my stimulation and i experienced ohss so froze all embryos, now i have 2 failed fet cycles, on every cycle i start swelling up on day 5 post transfer, i swell on my face ,lips and also experience a rash. my pregnancy test were all negative, i under went immmunological tests but all seems normal, the immunologist just prescribed prednisolone for just a month during my next fet. endometrial scratch became my only given option but since you do not agree with it, and i value your opinion i am feeling puzzzled
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 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
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).
Please know that all immunologic testing is not equivalent. Unless tests for immunologic implantation dysfunction (IID) are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful. . In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of reliable Reproductive Immunology Laboratories in the world and most are in the U.S.A. Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by suboptimal laboratories. Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID (autoimmune IID versus alloimmune) be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented.
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 (RPL)
•A history of having miscarried a conceptus that, upon testing of products of conception, was found to have a normal numerical chromosomal configuration (euploid).
•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 Intralipid (IL) /immunoglobulin-G 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. In addition, to be effective, IL/IVIG therapy needs to be combined with steroid (dexamethasone/prednisone/prednisolone) therapy to down-regulates (often) concomitantly activated T-cells.
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.
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•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
•IVF: How Many Attempts should be considered before Stopping?
•“Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
•IVF Failure and Implantation Dysfunction:
•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)
•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!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•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
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.
Geoffrey Sher MD
I just turned 41 4 weeks ago and am doing a second egg freezing with a different doc than my last. My first was at 39 years old (almost 40) and I only got 3 mature eggs. Think I yielded 10 follicles from stimulation with Estrace to start for 1 week and 320 Gonal and 75 menapur but then increased to 150 menapur half way through with Cetrotide trigger I believe. My fertility blood levels were great – FSH WAS 9.8 and AMH was 1.48. I remember the doc saying the follicles weren’t growing “together” in the beginning. They triggered me when I had 2 18’s, a 12, 2 11’s, a 14 and maybe 2 8’s. Believe they retrieved 8 and 3 ended up maturing. I am doing a 2nd round with a different doctor (Stanford Fertility) because I don’t feel comfortable just having 3 eggs in the bank and them being viable for one to two babies. Would you consider me DOR? or not respondent to fertility treatment? Did the doc trigger too soon?
My treatment plan I am starting in a few days is starting 10u of Lupron, 420 Follistum a few days later with 150 menopur and Novarel trigger. Should I ask the new doc to include a human growth hormone? I have a twin sister that was treated by the same doc at Stanford this last time and she did have a human growth hormone so not sure why he isn’t including since my lab numbers are little heightened from hers. Side note, she has 2 healthy embryos now and just delivered her first baby boy! She went through 3 IVF cycles with one cancelling in the middle due to no response with the same first doc that I mentioned but finally a successful one with the Stanford doc. My current labs changed a lot from last year….July ’17 my AMH was 0.29?! FSH was 16. I got them done again in September ’17 of this year and AMH is .99 and FSH is 12. I know labs can fluctuate with each period but why would my AMH be great last year and dip so low this year in July but then go up to .99 2 months later? I did have the September tests done through a lab at Stanford which was different than the lab in July of this year. Any insight on current upcoming treatment plan is greatly appreciated 🙂
In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
Older women as well as those who (regardless of age) have diminished ovarian reserve (DOR) tend to produce fewer and less “competent” eggs, the main reason for reduced IVF success in such cases. The compromised outcome is largely due to the fact that such women tend to have increased LH biological activity which often results in excessive LH-induced ovarian testosterone production which in turn can have a deleterious effect on egg/embryo “competency”.
Certain ovarian stimulation regimes either promote excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), augment LH/hCG delivered through additional administration (e.g. high dosage menotropins such as Menopur), or fail to protect against body’s own/self-produced LH (e.g. late antagonist protocols where drugs such as Ganirelix/Cetrotide/Orgalutron that are first administered 6-7 days after ovarian stimulation has commenced).
I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of a modified, long pituitary down-regulation protocol (the agonist/antagonist conversion protocol-A/ACP) augmented by adding supplementary human growth hormone (HGH).
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.
•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 Aproach
•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.
•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?
•Implications of “Empty Follicle Syndrome and “Premature Luteinization”
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
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 book,”In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD