DQ alpha/HLA Sharing: Does It Always Lead To Reproductive Failure?

23 Oct
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It is not unusual for couples who share DQ alpha/HLA similarities to first give birth to a healthy baby only to subsequently develop infertility, recurrent IVF failure or recurrent pregnancy loss. Such couples find it hard to comprehend how after having experienced an often uncomplicated pregnancy and birth they could then go on to develop immunologic implantation dysfunction. Hopefully, this brief article will serve to explain how and why DQ alpha/HLA sharing between the embryo recipient (female partner) and the sperm provider (male partner) does not inevitably lead to implantation dysfunction and reproductive loss.

When DQ alpha and/or HLA sharing exists between a female and male it will usually require repeated embryo exposures for the host’s uterine natural killer cells to become sufficiently activated to cause damage to the embryo’s root system (trophoblast). Once natural killer cells become activated, they begin to over-produce substances known as TH-1 cytokines which attack the trophoblast and so damage it that the embryo is promptly rejected. Sometimes, the effect is not immediately lethal and the pregnancy “limps along,” only to miscarry, usually in the first trimester. If, in spite of there being DQ-alpha/HLA sharing between the male and female partners, a “competent” embryo reaches the uterus prior to the advent of NK-cell activation (NKa+) it would escape severe damage to its root system and, provided that NKa+ does not subsequently ensue the pregnancy will usually go on to full term. On the other hand, should NKa+ occur, such a pregnancy would likely miscarry. Thus, outcome very much depends on the level and timing of NK cell activation.

The bottom line: In cases of alloimmune implantation dysfunction, it is the frequency and number of embryo-NK cell exposures over time that will determine the absence, presence and degree of NKa+ and so determine the fate of the pregnancy. This serves to explain why successful pregnancies are usually the ones that occur early in the male-female relationship and why subsequently with a progressive build up of NKa+ a successful pregnancy will often be followed by a series of miscarriages and eventually by a complete failure to conceive (i.e. “perceived infertility”).


  • Alison says:

    Dear Dr Sher,

    I note you describe the case above (mother 0102, 0105 and father 0102, 0102) as a partial match. On another page on your website (http://haveababy.com/fertility-information/ivf-authority/dq-alpha-matching-in-ivf-controversy), you say: “if both the husband’s DQa’ genes are the same as any one of the mother’s two DQa’s, (or if the mother and father both identical DQa’s genotypes), then 100% of the embryos will “match”” (i.e. a complete match). We have just got our DQa results (me: 0102, 0301) and my husband (0102, 0102) and therefore this is very relevant to us. Also I note you say that those who have two identical DQas like my husband would usually have been conceived early on in a relationship. Interestingly, his parents (strict Catholics so contraception wasn’t involved) were married for 15 years before he came along…I look forward to your response. Many thanks in advance.

    • Alison says:

      Sorry – in case my main question below was not clear: if I am 0102, 0301 and my husband is 0102, 0102 – is this a partial or a complete match? Thanks.

    • Geoffrey Sher says:


      I apologize if I was in error. This is indeed a “complete match” Now it all hinges on whether you test positive for NKa by the-562 target cell test. If not, you are OK but if so then there really is likely to be a serious issue.

      Again…so sorry for my oversight!

      Geoff Sher

  • Gadeer says:

    Hi, My DQ Alpha is as follows:


    My husband’s is

    0102, 0102

    Can we still have a baby? I miscarried 7 times, and I also happen to have elevated levels of NK cells and TH1, please help me.

    • Geoffrey Sher says:

      This is a partial DQ alpha match but it would only represent aproblem if in addition you have activated uterine naturalkiller cells by the K-562 target cell test….see below.

      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.”Recurrent Pregnancy Loss (RPL)”

      2. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.

      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.

      Important Announcement:

      Dr Al Peters (Medical Director at SIRM-New Jersey), and I ,recently established the “SIRM Reproductive Immunology Forum(SRIF) which will provide a venue where you can address and hopefully find solutions to problems relating to Immunologic Implantation dysfunction (IID) that often manifest with “Unexplained” infertility, IVF Failure and Recurrent Pregnancy Loss (RPL..

      To this end we established http://www.InfertilityImmunology.com , a dedicated website where you can:
      • Register with SIRF
      • Request and receive (free of charge) a PDF copy of our book: “Unexplained” Infertility and Miscarriage : The Immunologic Link”
      • Be kept abreast of what is current in the IID arena
      • Post questions for Dr Peters and I to respond to and,
      • Interact with other patients on a separate discussion board dedicated to this.

      We look forward to hearing from you!

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