IVF and Immunology: The Role of Immunologic Factors and Selective Immunotherapy

15 Dec
Ask Dr. Sher A Question

Few innovations in IVF have evoked the degree of controversy and bad press as has the thesis that reproductive immunologic factors play a role in unexplained IVF failure and recurrent pregnancy loss (RPL), and that immunotherapy presents a valid treatment of these problems. This despite the fact that thousands of women with repeated and unexplained IVF failure, and/or RPL have following diagnosis and selective immunotherapy, gone on to have healthy babies. The question then, is why is there a compulsion on the part of many to selectively criticize the role of an immunologic component in reproductive failure? Is it due to arogance, ignorance, politics or all three?

The most comon criticism is to claim that the whole concept of immunologic implantation dysfunction (IID) requies proof through randomized statistical trials and that without such proof there is no basis for teating such disorders. I would submit that this position is hypocritical and represents a “double standard”. Consider the fact that were all procedures and therapies provided in the AR arena to be subjected to the same degree of scrutiny, there would virtually be no clinical AR service that could justifiably be offered and the entire discipline would fall apart. It is a fact that if the same criteria were required fo an AR procedure or treatment to be elligible for inclusion in a compedium of AR, the book would be less than a single page in length.

The truth is that given the multitude of variables that influence IVF outcome it would be impossible to control all variables other than the one being evaluated. That is why to todate, virtually all clinical treatments/processes currently in use in the AR arena have gained acceptance through a process of longitudinal efficacy testing (by trial and error), rather than through “gold standard”, randomized and controlled statistical testing.

Consider the following: Embryo abnormalities account for 70%-80% of IVF failure, while implantation problems (including immunologic factors), only account for 20%-30%. One of the important reasons why in the past it has not been possible to reliably conduct randomized statistical trials in IVF is that to do so it would be necessary at the very least to confidently assess ” embryo competency” (i.e. the ability of an embryo, upon reaching a receptive uterine environment to proagate a healthy pregnancy). Obviously to study the effect of variables such as immunologic implantation on IVF, it is essential that “embryo competency” first be known, otherwise how would one assess the impact of variations in the “lesser” variable (IID) on outcome. Alas, hitherto the use of Microscopic embryo grading and even preimplantation genetic diagnosis genetic diagnosis (PGD) using fluorescence in-situ hybridization (FISH) to accurately determining embryo “competency”, has been poor.

An important recent innovation introduced in 2006 by SIRM could change all this and open the door to evidence based statistical testing of the variables that affect IVF outcome. This breakthrough came with the recent introduction of a new genetic process known as comparative genomic hybridization (CGH) that through assessing all the embryos chromosomes can relatively reliably differentiate between chromosomally normal (“competent”) and abnormal (“incompetent”) embryos. me.

And so perhaps at last we will be able to better evaluate the role of immunologic factors in the genesis of implantation dysfunction as well as the benefit of selective immunotherapy, and thereby put this controversy to rest. Such a study is currently underway at SIRM , and while complete interpretation must await its completion and full statistical analysis, preliminary findings suggest that there indeed is likely to be a distinct benefit in selectively treating women with immunologic implantation dysfunction (IID)with Intralipid (IL) steroids (e.g. dexamethasone and prednisone) and/or heparin therapy.


  • Dr Sher, sorry to message you again, cant find the K-562 cell tests in my results unless its called something else so here are my results below, do you think we have a chance is the steriod treatment of having a baby despite the DQ Aloha result?
    Thank you so much for your time.
    NK Assay Full Panel
    test in range out of range
    50:1 14.1
    25:1 7.9
    12.5:1 4.5
    IVIG 12.5 mg/ml 50:1** 6.6
    IVIG 12.5 mg/ml 25:1** 3.8
    IVIG 6.25 mg/ml 50:1** 9.5
    IVIG 6.25 mg/ml 25:1** 6.5
    %CD3 74.8
    %CD19 12.8(H)
    %CD56 11.6
    %CD19+cells, CD5+ 9.3
    ** > 10% reduction in killining at each effe tor/target ratio

    TH1/TH2 Intacellular Cytokine Ratios
    TNF-a:IL-10 (CD3+CD4+) 50.0(H)
    IFN g:IL – 10 (CD3+CD4+) 26.2(H)

    Leukocyte Antibody Dectection Panel
    Flowcytometry Negative
    (T-Cells) IgM+ 12.2
    (T-Cells) IgG+ 2.7
    (B-Cells) IgM+ 5.4
    (B-Cells) IgG+ 5.5

    DQ Alpha
    Me 0101, 0102
    Husband 0102, 0103

    PAI-I 4G/5G Mutation detected
    MTHFR mutation c.C665T (Heterozygous)

    • Geoffrey Sher says:

      Your NK cells are activated based on these results and you and your partner share a partial DQ alpha match….see below regarding alloimmune implantation dysfunction. You also have an hereditary clotting disorder or thrombophilia (not likely serious) , which will require treatment once you are pregnant.

      Please go to the home page of 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. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.

      5. “Thyroid Autoimmune Disease and IVF”

      6. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)

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

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

      9. “IVF success: Factors that influence outcome”

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

      11.”Staggered IVF”

      12.“Embryo Banking”

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

      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.

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