IVF Case Study # 8: An Older Woman With Recurrent IVF Failure, Diminished Ovarian Reserve and Immunologic Implantation Dysfunction

13 Dec
Recurrent Pregnancy Loss
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This continues our series of IVF case studies. Here in our 8th case we discuss a couple who had experienced 22 previously unexplained IVF failures who had diminished ovarian reserve (DOR) plus immunologic implantation dysfunction (IID) and subsequently conceived when treated with an agonist/antagonist conversion protocolwith estrogen priming and selective immunotherapy to down-regulate activated natural killer cells (NKa).

Christine, a 42 year old physician from Australia had endured 23 prior unsuccessful fresh embryo transfers over a period of more than a decade. By the time I got to know her she had severelydiminished ovarian reserve (her day-3 FSH was 26MIU/ml).

After a lengthy telephone consultation with her, I urged her to send a blood sample from Melbourne, Australia to a reputable Reproductive Immunology Reference Laboratory in Southern California for testing to screen for immunologic implantation dysfunction (IID). It soon became apparent that she had an autoimmune thyroid condition (antithyroglobulin and antimicrosomal antibodies) along with activation of uterine Natural Killer Cells (NKa+). After controlled ovarian stimulation(COS) using an aggressive agonist/antagonist conversion protocol with estrogen priming, and pre-treating her immunologic implantation dysfunction (IID) with selective immunotherapy, I harvested just three eggs. We subsequently transferred two embryos to her uterus. She conceived in this cycle and gave birth to a healthy baby boy nine months later.

This case shows that there is no merit in doing IVF over and over again in the face of repeated prior failures, without making a strong effort to determine the reason for such failures. In Christine’s case, by the time I saw her for the first time, she already had severely diminished ovarian reserve (DOR) as well as an immunologic implantation dysfunction (IID) linked to Natural Killer cell activation (NKa). We addressed the severe DOR by stimulating her with an agonist/antagonist conversion protocol plus estrogen priming and harvested 3 mature eggs (MII’s) and transferred 2 good quality embryos. We addressed the IID through selective immunotherapy by down-regulated her NK cell activity and corticosteroid therapy to establish a favorable uterine environment. She duly conceived.

This case also demonstrates that in women with severe DOR, diminished egg/embryo quality can in part be effectively by using an individualized approach to ovarian stimulation such as the agonist-antagonist conversion protocol with estrogen priming; LA10-E2V.

Addendum: It is important to understand that IVF is an ART-Science blend and not all practitioners agree on the same strategies. Thus, in the final analysis, it is important, after discussion with your personal doctor, to follow his/her advice to the letter.


  • Elisabeth says:

    Will definitely follow up with my RE. Thanks for your input!

  • Elisabeth says:

    Hi Dr Sher,
    Thank you for your very informative blog!

    I am 37 and have severe DOR with an AMH of <0.16 and I am a poor responder to stimulation (last time I only got 2 follicles with FSH 350)

    I want to do a more aggressive A/ACP (start with FSH 600).

    Question #1) For how many days should I do FSH 600 before reducing the dosage? For 2,3,4 or 5 days?

    Question #2) When I reduce the FSH dosage, would you recommend that I reduce it to 375?

    Many thanks for your input!

    • Geoffrey Sher says:

      Yes we reduce after 2 days on 600U and then add 37.5U Menopur daily.

      But much more important in my opinion is that you seriously consider “Staggered IVF” with “embryo Banking” and “CGH embryo selection” before your biological clock runs out of time altogether (see below”).

      Please go to the home page of this blog, http://www.IVFauthority.com . When you get there look for a “search bar” in the upper right hand column. Then type in the following subjects into the bar, click and this will take you to all the relevant articles I posted there.
      1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)

      2. Ovarian Stimulation for IVF: The most important determinant of IVF Outcome” (Nov. 2103)

      3. “Agonist/Antagonist Conversion Protocol”

      4. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)

      5.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)

      6. “IVF success: Factors that influence outcome”

      7. “Use of the Birth Control Pill in IVF”

      9.”Staggered IVF”

      9.“Embryo Banking”

      10.“Array CGH versus metaphase CGH in IVF patients….’

      11.“Egg Donation”

      Consider calling 800-780-7437 or 702-699-7437 to arrange a Skype with me so we can discuss your case in detail.

      Finally, perhaps you would be interested in accessing my new book (recently released). It is the 4th edition (and a re-write) of “In Vitro Fertilization, the ART of Making Babies”. The book is available through “Amazon.com” as a down-load or in book form. It can also be obtained from most bookstores.

      Geoff Sher

      P.S: Please go to http://www.youtube.com/watch?v=Vp3GYuqn2eM&feature=youtu.be
      To view a video-tutorial by Linda Vignapiano RN, Clinical Manager at SIRM-Las Vegas.

    • Elisabeth says:

      Will look at Staggered IVF, Embryo Banking and CGH embryo selection!!

      Just to clarify:
      When I reduce the Gonal-f after 2 days, do I add 37.5 of Menopur OR did you mean 37.5 of Luveris??


      • Geoffrey Sher says:

        Either….but do not do implement without first discussing with your personal RE and obtaining his/her approval.

        Geoff Sher

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