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GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols

by Dr. Geoffrey Sher on January 25, 2017

Conventional GnRH Antagonist (GnRHa) Protocols:

GnRH antagonists (e.g. Ganirelix, Cetrotide, and Orgalutron) are currently used with many controlled ovarian stimulation (COS) protocols. The conventional approach is to administer 250mcg antagonist, daily starting from the 6th-8th day after commencing ovarian stimulation with gonadotropins. This traditional approach is in my opinion, best suited to younger patients who have normal ovarian reserve (AMH>2.0ng/ml or 15pmol/L) and are “good responders” to COS, provided that the stimulation cycle is launched with a spontaneous menstrual cycle and is not launched coming off a birth control pill (BCP) or following prolonged premenstrual hormonal suppression.  However, this approach can in my opinion be decidedly disadvantageous when used in older women (>39y), women with diminished ovarian reserve (DOR) or women with polycystic ovarian syndrome (PCOS) who all tend to have increased LH bioactivity.

Background information: An important role of LH is to promote male androgen hormone (testosterone, androstenedione and DHEA) production by ovarian connective tissue (stroma or theca) that surrounds follicles. While androgens (predominantly testosterone) represent the building blocks from which follicle granulosa cells manufacture estrogen and are thus essential for optimal follicular growth and egg development, too much LH activity can lead to over-production/exposure to ovarian androgens which might compromise follicular/egg development. Accordingly, when it comes to older women and those DOR and PCOS who tend to have excessive LH-induced ovarian testosterone, it is (in my opinion) essential to maintain LH activity at a subliminal level. Thus LH suppression needs to be in place from the very start of COS…not much later as when antagonist suppression is commenced 6-8 days into the COS process.  Accordingly, I believe that GnRH antagonist treatment should be commenced from the very initiation of ovarian stimulation…and that is the concept upon which the agonist/antagonist conversion protocol (A/ACP) is based….see below.

Bear in mind that the main reason for using antagonist suppression is to avoid the “Premature LH Surge”. This is a condition where high ovarian LH activity propagates androgen-induced “follicular exhaustion” and egg dysmaturity.  The term “premature LH surge” is a misnomer since it does not involve a sudden “surge” or sporadic rise in LH. In actuality it occurs as a steady rise in LH activity (a “staircase effect”) which elicits a progressive increase in ovarian stromal androgens that ultimately exhausts follicle development and compromises egg “competency”. A more accurate term might be “premature luteinization.” Such poorly developed eggs will often respond to the hCG trigger by becoming aneuploid (a numerical chromosomal abnormality

Thus, trying to avoid “premature luteinization” by administering GnRH antagonist 6-8 days into the COS cycle, is like” shutting the gate after the horse has already left the stable”.

The long pituitary down-regulation COS protocol:

Here, administration of a GnRH-agonist (Lupron, Superfact, and Buserelin) several days before COS is initiated, expunges all LH from the pituitary gland, exhausting it of reservoired LH. Thereupon, agonist administration is continued until the hCG “trigger”. In this way, developing follicles and eggs are protected throughout COS, from over-exposure to LH-induced androgens…thereby avoiding “premature luteinization”. In my opinion, this approach is ideally suited to younger women who have normal LH, normal or increased ovarian reserve (e.g. those with PCOS) and those who have DOR. The downside of this approach is that the GnRHa (Lupron/Buserelin) can competitively bind with ovarian follicle stimulating hormone (FSH) receptors and suppress ovarian response to gonadotropins, something that is more likely to occur with older women and those who have DOR. I introduced the Agonist/Antagonist Conversion Protocol (A/ACP) more than 15 years ago to try and counter this effect.

The agonist/antagonist conversion protocol (A/ACP):

With the A/ACP, GnRH antagonist (Ganirelix, Cetrotide, and Orgalutron) is administered by daily injection from the onset of COS.  The A/ACP COS-cycle is launched with the woman coming off a monophasic birth control pill that was administered starting in the 1st 5 days of the preceding cycle and continued for at least 10 days. The BCP is then overlapped with an agonist (e.g. Lupron/buserelin) for three days, whereupon the BCP is stopped and the agonist (Lupron/buserelin) is continued until the onset of menstruation. At or around this point, the agonist (Lupron/Buserelin) is supplanted by an antagonist (Cetrotide/Ganirelix/Orgalutron) and concurrently COS is initiated using an FSH-dominant bias (mainly Follistim/Gonal-F/ Puregon + a small dosage of a menotropins such as Menopur). The combined antagonist/gonadotropin therapy is continued until the hCG trigger.  For the reasons cited above, I prescribe some form of the A/ACP for my older IVF patients and those with DOR.

A/ACP with estrogen priming: The A/ACP can be modified for women with very severe DOR through incorporation of “estrogen priming”. We have reported on the fact that the administration of intramuscular estradiol starting about a week prior to commencement of COS. This often markedly enhances ovarian response (presumably by “estrogen priming” enhancing the sensitivity of ovarian FSH-receptors).

There is one draw-back to the use of the A/ACP. This is the fact that prolonged administration of GnRH antagonist throughout the stimulation phase of the COS cycle compromises the predictive use of serial plasma estradiol measurements as an indication of ovarian response to COH. The blood estradiol levels tend to be much lower in comparison with cases where GnRHa alone is used. The reason for the lower blood concentration of estradiol seen with prolonged exposure to GnRH-antagonist might be due to the result of subtle, antagonist-induced alterations in the configuration of the estradiol molecule, such that currently available commercial test used to measure estradiol levels are rendered less sensitive/specific. Accordingly, when the A/ACP protocols are employed, we rely much more heavily on the measurement of follicle growth by ultrasound than on the estradiol levels. Because of this downside, I refrain from using this approach in “high responders” who may be at risk of developing of severe ovarian hyperstimulation syndrome (OHSS) and in whom the accurate measurement of plasma estradiol plays a very important role in the safe management of their COS cycles.

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  • Sarah - November 29, 2017 reply

    Hello, I am in the middle of my second IVF and turned 39 in late September. My last AMH was measured this past summer at 1.94, but I currently have a low AFC of 6. My first IVF resulted in only retrieving 4 eggs out of 7 follicles, and only 2 were “mature.” I posted after my first IVF and you noted that my result could have been due to my protocol. The last day of stimming during my first IVF, I was on a high dose of 375 of Menopur, following a couple of days at 300. I have been on an antagonist protocol again this time at the max of 450 Follistim a day, however at only 75 Menopur. I specifically asked my doctor to limit Menopur due to the articles I’ve read of yours. I am currently on day 8 with 4 or 5 measurable follicles around 10-11 each and my estrogen is 410. I received instructions today to start taking Ganirelix tomorrow and to bump up my Menopur to 150. I am very cognizant of your opinion of limiting LH, so I am curious if you think 150 is too high a dose of Menopur.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 29, 2017 reply

    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”.
    Women who (regardless of age) have DOR have a reduced potential for IVF success. 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 effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, 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 and those who have DOR and should be limited.I try to avoid using such protocols/regimes (especially) in women with DOR, 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) versus “Fresh” ET: How to Make the Decision
    • 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.

    Geoffrey Sher MD

  • Lindsey - August 8, 2017 reply

    Hello Dr. Sher,

    I found your blog after doing some extensive research into IVF protocols. I also recently saw Vegas Baby. I’m doing my first IVF cycle this month and would love your insight on the antagonist protocol choice for me. It sounds like it’s a reasonable protocol for a young woman with normal ovarian reserve, but it seems you may prefer long lupron, especially with PCOS. Is my AMH high enough to be a concern with this protocol? Do you advise HCG to trigger? Half lupron, half hcg? I know there will likely be a concern with OHSS.

    The plan: antagonist without BCP suppression – 225 Gonal-F, 150 Menopur, add cetrotide.

    30 years old, no previous pregnancies
    AMH is 11.2 ng/mL (RE has never mentioned the possibility of PCOS – I don’t have any other signs that I am aware of)
    Day 3 FSH is 6.9 U/L
    Day 3 LH is 6.2 U/L
    Antral follicle count is 18 (10+8)

    Just wanting to arm myself with the most information possible before beginning this cycle. Thanks in advance for any insight,

    Lindsey

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - August 9, 2017 reply

    Here is the protocol I advise for women, <40Y who have adequate ovarian reserve.
    My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur---no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
    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.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • 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
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    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

  • David - March 8, 2017 reply

    Dr Sher,

    My wife is scheduled for her 3rd IVF after about 7 months on Lupron Depot and BCP. She had 2 laparoscopic surgeries for removing endometriosis. Her AMH prior to surgery was ~1.5 ng/ml but improved after surgeries to 2.5 and then most recently after 2nd surgery to 3.5 ng/ml. She is 36 years old and in her previous cycles produced 12 and 7 mature eggs. We tested 8 blastocysts from those cycles and found 6 to be chromosomally normal. Some resulted in chemical pregnancies but she has since been diagnosed with extensive diffuse adenomyosis. For this 3rd cycle the doctor wants to use antagonist protocol with 300IU FSH for the first 5 days and 300IU FSH + 150IU LH thereafter. We only used 75IU LH in her previous cycles that used agonist protocol (Lupron). Do you think 150IU LH is too much? Thank you.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 8, 2017 reply

    If an agonist protocol is used, my preference (by far) is to have it be a long pituitary down regulation protocol, rather than a “flare protocol”…see below.

    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).
    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

    Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
    Julie Dahan
    • Email: Julied@sherivf.com
    • Phone: 702-533-2691
     800-780-7437

    Geoff Sher

    I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

  • Ankita - March 1, 2017 reply

    I am a 32 y/o PCOS and Hashimotos patient who was on the GnRH antogonist protocol. My doctor had me on Gonal –F starting dose of 175 and lowered once to 150, Menopur 37.5, Cetrotide, and HCG trigger. From this we had 40 eggs retrieved, 32 fertilized naturally, 19 made it to blastocyst, 9 tested euploid, 3 no-result, and the remaining aneuploid. I miscarried at 6 weeks with a euploid embryo from this batch. We believe I am having autoimmune miscarriages, but should we be concerned with embryo quality given our stimulation protocol even though we have a good amount of euploid embryos? Any insight is appreciated!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 1, 2017 reply

    The # of embryos that made i to euploid blastocyst status is excellent and who can argue with such success. This is clearly not a stimulation or embryo issue.My concern is an autoimmune implantation dysfunction linked to your Hashimoto’s disease.

    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.

    Hope this helps!

    Geoff Sher
    PH: 800-780-7437

    Ankita - March 1, 2017 reply

    Thank you, Dr. Sher! This is helpful. Also, I urge you to open an Atlanta office! We are in need of this type of expertise in the south!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - March 1, 2017 reply

    Thank you Ankita!

    Geoff Sher

  • Jenny - February 28, 2017 reply

    Hi
    I’ve had 3 IVF rounds now. 1st round was under NHS and I ended up with 4 embryos. 1 transferred and 3 frozen. This round it was a chemical pregnancy lastest 1 day.
    Round 2 was private and I had immune treatment and had 2 frozen embryos transfered.. mad it 8 weeks but Miss carried. Had the EPRC but it was inconclusive because it was too small to test. Had mine and my husbands chromosomes tested and his sperm fragmentation this is all ok.
    I’m currently in the 2 week wait on round number 3. This time it was a fresh round and I was monitored very closely. There was a mix up for the first 3 days and I was supposed to be taking .5 superfact in the morning but I didn’t. They said not to worry and to carry on but then my LH levels kept increasing. Some days it would go up to 10 some days it would go up to 6. I was having 3 blood tests a day and taking Cetrotide a lot.. sometimes 10 in a day to lower my LH.
    I have polysistic ovaries.. more like tendencies because I don’t have some other symptoms like facial hair etc. The clinic told me this was not normal but they have seen a few times with people like me and not to worry. Egg collection had 21 eggs.. 16 mature and 14 fertilised.
    All carried on to day 5 and the clinic said they wanted to monitor until day 6 Because not quite blastocyst yet. Day 6 I had 2 embryos graded BB 3/4 transfered and then got a call later that day to say none of the remaining 12 we viable for freezing and they all stopped.
    Do you think if I had been on the suprfact from the beginning this could all have been avoided ?
    Should they at least have given me to option to cancel the cycle ?
    Am I just worrying over nothing and the fact the kept my LH under control was good ?
    I think it’s strange that my 1st round I had grade A embryos and 4 of them.. this time I’ve not got any to freeze and I did so much more this time.. like no drinking for 2 months, taking extra vitamins like COQ10 etc
    Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 28, 2017 reply

    It is hard to say for certain but one of the most important considerations is the selection and implementation of the ideal protocol for ovarian stimulation…especially in cases of PCOS.

    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.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
    • 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
    • Why did my IVF Fail?
    • 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
    • How Many Embryos should be transferred: A Critical Decision in IVF.
    • The Role of Nutritional Supplements in Preparing for IVF
    • Taking A Fresh Look at Ovarian Hyperstimulation Syndrome (OHSS), its Presentation, Prevention and Management
    • Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
    • Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    • The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?

    Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
    Julie Dahan
    • Email: Julied@sherivf.com
    • Phone: 702-533-2691
     800-780-7437

    Geoff Sher

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