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IVF and the Imperative to minimize the Incidence of Multiple Pregnancies

by Dr. Geoffrey Sher on August 13, 2017

All multiple pregnancies pose a risk to both mother and offspring. Pregnancy induced maternal complications such as miscarriage, pre-eclampsia, antepartum and post-partum hemorrhage become progressively more prevalent the higher the multiple gestation. For the babies, it is an escalating risk of premature birth and intrauterine growth retardation that places the offspring at risk.

While even twin pregnancies increase the risk to mother and babies, it is high-order multiples (triplets or greater) that prove to be most dangerous. In fact, in about 50% of such cases severely premature births that commonly occur in such cases, resulting in death or severe developmental complications such as cerebral palsy, psychomotor retardation, blindness and mental retardation; conditions which severely compromise the quality of life after birth and lead to devastating financial, social and societal hardship.

Most women going through IVF are desperate to have a baby and many are even willing to cast safety to the wind, abandon all cautions, and virtually do anything it takes to achieve success. Such women are highly vulnerable to the (fortunately) few reckless medical practitioners who might exploit such desperation.

IVF, because of an inclination on the part of many practitioners, to transfer multiple embryos at a time in the hope of improving success rates, has in the past contributed vastly in this regard. However, improving IVF technology and the ability to better identify “competent” embryos for transfer has in recent years resulted in a tendency to transfer only one or two embryos, leading to a significant decline in the incidence of high-order multiple IVF pregnancies.  Notwithstanding this, the transfer >2 embryos at a time still takes place far too often and with a few exceptions (e.g. in older women with poorer quality embryos) can no longer be justified in my opinion.

There is undoubtedly a need to better inform IVF consumers regarding the risks associated with the transfer of multiple embryos (especially >2) at a time. There is also an urgent need in the United States to introduce enforceable regulations to limit the number of embryos transferred, especially when it comes to embryos derived from the fertilization of young womens’ eggs, and when advanced embryos (blastocysts) are transferred.

The introduction of advanced preimplantation genetic screening to identify those embryos that are most likely to propagate a viable pregnancy can more than double the IVF baby rate per embryo transferred.  Yes, the time is fast approaching that the transfer of but one (1) embryo will result in one healthy baby more than 50% of the time. Indeed such genetic embryo testing can improve the efficiency of the IVF process reduce miscarriages and minimize the risk of chromosomal birth defects such as Downs Syndrome , thereby providing a “better way” to help patients safely build their families successfully.

The high rate of multiple gestations resulting from IVF is a complex problem that can no longer be justified as an acceptable side effect of treatment. The Hippocratic oath states the cardinal rule of medicine as “primum non nocere; foremost do no harm.”  It is imperative that this issue be addressed at multiple levels. This includes educating patients to the risks of high-order multiple gestations, as well as the steps practitioners can take to mitigate those risks, such as tailoring the treatment to the specific needs of each patient and limiting the number of embryos transferred. IVF Technology is one of the successes of modern medicine.  It would be unfortunate if this success were to be overshadowed by the creation of an even worse problem.  The challenge is ours.

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  • Nicole - August 14, 2017 reply

    Hi Dr.Sher,
    I have a 2 year old from my first FET. That was an elective single embryo transfer. Now I’m trying for baby #2 with my remaining day 5 blastocysts. 1. Single blast fet resulted in a miscarriage and the 2nd one didn’t work. My dr said he will now be willing to transfer 2 this coming cycle. What are your thoughts on this? I’m 31, my embryos are 29 years old all day 5. it will be my 3rd fet for baby #2. Do you agree that the chance of twins is 20% and the chance of overall success is 75% with the transfer of 2? I don’t know what to do!
    Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - August 15, 2017 reply

    Respectfully, I do not fully concur!

    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

    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

    Nicole - August 15, 2017 reply

    Wow, thank you for all of this information. I feel like I’m able to mark off a lot of the “boxes” so to speak- I’m under 35, I have 11 day 5 embryos frozen etc.

    Since I have a child from FET and my recent miscarriage was at 7 weeks and was just a sac, no baby developed- do you think I could rule out an immunologic issue?

    And if so, am I just having bad luck?

    Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - August 15, 2017 reply

    It is unlikely (but not impossible) to be an issue.

    Geoff Sher

    Nicole - August 15, 2017 reply

    Hi Dr. Sher- I tried to reply to your comment earlier and I’m not sure if it went thru.

    I’m young, I have good day 5 embryos, I have a child from this same “batch” of embryos. It seems that the only two unknowns are either that the 2 failed fet’s are either bad luck or an immunology related issue.
    Because I have a daughter from a prior FET and my miscarriage was at 7 weeks and just an empty sac can we assume it’s not immune related?

    Also, are you saying you think it’s a bad idea to transfer 2 day 5 blastocysts?

    Thanks

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - August 15, 2017 reply

    No! I do transfer up to 2 at a time.

    Geoff sher

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