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Why did my IVF fail?

by Dr. Geoffrey Sher on February 8, 2016

Whenever a patient fails to achieve a 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).

  1. 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.
  2. 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:
    1. A“ thin uterine lining”
    2. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
    3. Immunologic implantation dysfunction (IID)
    4. 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).

My answer to  patients who ask me when is the time to stop undergoing IVF is ….Aside from the weight of the financial burden, the time to stop is when in spite of thorough and comprehensive evaluation, there is no remediably and treatable explanation for repeated failure.

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  • Karissa - July 10, 2016 reply

    Hello,
    Your website and articles are fantastic. Reading and educating myself about the whole process helps me to deal with the time in between tests, scans and procedures so thank you.
    We are having to undergo ICSI due to my husbands low sperm count. I have one mildly poly-cystic ovary and hypothyroidism with a BMI > 35. It took us several years to find a fertility specialist who would help us. Now I’m 35 and my husband is 38. We have just completed our first round of IVF. Although we were prepared for the first cycle not to be unsuccessful (based on all the statistics I read), we were crushed when we discovered we only had one embryo for transfer and non available for freezing.
    I was on 250ug recombinant human follicle (Puregon) injections for 11 days, 250ug Ganirelix acetate (Orgalutran) for 7 days, and given 250ug Choriogonadotropin alfa (rch) (Ovidrel) as my trigger injection followed by 200mg progesterone pessaries BID. I had 13 eggs retrieved. Only 6 were mature. Only 1 made it to day 5 and was implanted and subsequently failed. Moving forward, we can only afford one more egg collection this year so obviously we need the next round to be more successful.
    One of my concerns is that all my drugs and the doses were given to me at the start of the cycle and despite blood tests and ultrasounds, nothing was amended based on my results. It doesn’t appear very individualized to me.
    We have an appointment to discuss the failed round and how to move forward with our specialist this week. I would appreciate any advice or questions you might suggest I ask.
    Warm regards,
    Karissa

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - July 10, 2016 reply

    Respectfully, I do not believe tghat a 250mcg dosage of Ovidrel is adequate. In my opinion if you buse recombinant hCG (Ovidrel), the ideal dosage is doublr that. I am personally convinced that the protocol used for ovarian stimulation is a pivotal consideration in determinism egg development and “competency”.

    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 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.
    • 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
    • Optimizing Response to Ovarian Stimulation in Women who Have Compromised Ovarian Response to Ovarian Stimulation in Women who Have Compromised Ovarian Reserve: 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:
    • 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
    I invite you to arrange to have a Skype or an in-person consultation with me to discuss your case in detail. If you are interested, please contact Julie Dahan, at:

    Email: Julied@sherivf.com

    OR

    Phone: 702-533-2691
    800-780-7437

    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.

    Geoff Sher

  • Mimi - April 20, 2016 reply

    Dear Doctor
    Thanks a million for this platform. I’m starting my treatment with frozen embryos tomorrow. My gynae says he’s gonna use intralipid because of implantation dysfunction and unexplained failed ivfs cycles. Please advice. I’m in south africa.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 20, 2016 reply

    Intralipid is only of value if you have activated uterine NK cells by bthe K-562 target cell testv and then to be effective it needs to be administered with corticosteroids.

    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
    • 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)
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Traveling for IVF from Out of State/Country–
    • A personalized, stepwise approach to 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

    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.

    Geoff Sher

    Mimi - April 23, 2016 reply

    Yes Sir it’s for NK cells in the uterine. He says he’s gonna use intralipid and neupogen. He didnt say anything abiut corticosteriod. Should I stop going to gym also?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - April 23, 2016 reply

    Copy!.

    Moderate exercise is in my opinion a good thing.

    Geoff Sher

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