Infertility, Our Infertility story

The plot thickens…my phone consult with Dr. S

March 3, 2011

I had a phone consultation today with Dr. S.  This doctor treats all of the hard cases like me and most of his patients are from out-of-state and abroad.

He feels absolutely confident that I have an immune problem.  He is ordering the proper tests for Erick and I both to confirm his suspicions.  Those tests will include antiphospholipid antibodies (anticardiolipins, APA, etc.), NK activation with IVIg, HLA and DQa, reproductive immunophenotype, thyroperoxidase and thryoglobulin.

There are two types of Immunologic Implantation Dysfunction:

  1. Autoimmune – This is where your body produces an immunologic response to your body.  Easy to treat.  Accounts for 90% of problems.
  2. Alloimmune – This is where your body has an immunologic response to cell components from someone else, as in the male contribution to the embryo.  This one is more tricky to treat and possibly not treatable.  Accounts for 10% of problems.

Anyone want to guess which he thinks is our problem?  Yes, that’s right – alloimmune.  He says this is rare.  Well, I suspected immune issues could be my problem, but I didn’t exactly expect this. If he’s right, at least we’ll finally know what we’re dealing with.


I should also point out that many doctors do not believe in this, including my current RE.  Camp #1 says there’s not enough research.  Camp #2 says it’s very complicated and many doctors do not understand it.  Also, it’s been hard to prove with so many variables, but now with embryo chromosomal testing, conclusive research will be possible.

I’m having zero luck with the non-believers at this point, so I choose to believe in this.  This is on the forefront of this field. Just think about how many people were thought to be crazy with their ground-breaking ideas at first.  Also, there are tons of people for whom this has worked.

He thinks I have this for the following reasons:

  1. He thinks I have immune problems because I have had 11 mostly good embryos transferred over the last several years.  None have resulted in a baby.  He says that typically 1 out of every 2 blastocysts is normal, so there should have been five good ones.
  2. Repeat miscarriages – I can get pregnant, I just can’t stay that way.
  3. Most (if not all) immune problems result in first trimester losses.
  4. He specifically thinks allo-immune because my ability to hang on to an embryo or fetus keeps getting shorter.  First miscarriage at 10 weeks, then 7 weeks and now 4 weeks.

What happens with alloimmune

This is all very complicated stuff and I’m trying to learn as much as I can.  But basically your body attacks the embryos.  In normal pregnancy, it’s paradoxical that a mother’s body allows something foreign (an embryo) in her body, but that’s how it works.  A pregnancy must be recognized by the mother’s body as a foreign object to trigger the appropriate immunologic mechanisms which allow the embryo to implant and grow. But in this case, when the man transmits via his sperm certain genes that are too similar to the mother’s genetic make-up, the immune system rejects the embryo.

From Dr. S’s blog:

So it is that in less than 10% of IVF cases that are associated with ID the embryo (through the contribution made by the sperm) shares too many genetically similar characteristics with the host (the mother). When this happens, repeated exposures to such an embryo will over time evoke an imbalance in the cytokines released by the uterine immune cells. This is characterized by activation of uterine NK cells (Nka). In such cases the “root system” of the embryo” can be compromised and the the embryo may be destroyed immediately but most often will instead “limp” along only to miscarry when its supply of nutrients and oxygen is outstripped by demand.

Thus alloimmune ID usually does not destroy the embryo immediately. Rather, after sustained erosion of its reserve, the conceptus will miscarry.

We diagnose alloimmune ID by testing the male and female partners for shared of genetic markers known as of as DQa and HLA. A sufficient degree of matching clinches the diagnosis.

Subsequently over time, with repeated exposures of matching embryos to the mother’s uterus, NK cells will become activated and the couple will find themselves miscarrying. Eventually the NKa will become permanently established and the couple will fail to conceive.

Other comments:

  • Dr. S said it was a real shame that NONE of our products of conception have ever been tested.  In number one, the hospital could have but didn’t and we didn’t know any better at the time.  It was not necessary for the second one because it was genetic (blighted ovum).  And, for the third, by the time I got to the hospital there was nothing left to test and I was so distraught that I didn’t collect anything at home.  And, the fourth, too early.  So, girls, if you miscarry, please try to save what you can and get it tested.
  • Another interesting thing he said is that he doesn’t think I should have had the uterine septum removed.  He said it will not cause implantation failure and only could pose a risk for a late miscarriage.  But, without justification, says it should not be performed because it can leave scar tissue, which in turn could be a real problem and absolutely cause implantation issues.  Hmm…great.

So, he said if we have alloimmune, he does think we still have good chances.  But whereas autoimmune problems are 100% reversible, this is not and is harder.  It all depends on how much the male and female partners DQa genes “match”, whether the male’s DQa genes are identical and the severity of uterine NK cell activation.  In these scenarios, it would not be treatable.

So, now we get the blood tests and go from there.  I really hope he’s wrong and even if it is immune issues, I hope it’s auto-immune, which can absolutely be treated.  But, regardless, at least we’ll know for sure.  Information is good.

Do any of you have this problem or know someone who does?  Thoughts? Comments?

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  • Glad you’re talking with Dr. Sher — seems like he knows his stuff, and with the immunology issues it’s important to have someone who’s a believer (since so many REs are skeptical).

    As you say, more information is good. Hope the blood tests bring back useful information and it sets you on the path to success!

  • Lex

    I hope that your doctor can figure out exactly what to do. But I find it odd that he’d rather you risk a 2d trimester loss by not removing the septum.
    Did he say that autoimmune was 100% reversable? My doctor thinks that’s what’s wrong with me and even with treatment, sure I made it to 9 weeks, but I didn’t get further. Even the treatment she wants me on next time is still a shot in the dark.

  • Whitney Anderson

    Lex, I already had the septum removed by another doctor. I think he was saying while a 2t loss *could* happen, it would be very unlikely. Anyway, yes, I think he said autoimmune is reversible. What treatment does she want you on next time? When you say, your dr thinks that is what you have, were you tested?

    • Maria Debono

      Hi…. I know this post is a bit old but just came across it while searching about alloimmune testing. I have been diagnosed with autoimmune issues and did 2 ivfs with appropriate treatment. But still I didn’t get pregnant. I heard about alloimmune tests and decided to test. I believe the test is called HLA DQ ALPHA right? I had already done it when I checked for autoimmune issues but my husband didn’t. Do I need to repeat it? Is it enough if he does it now and then we check for compatibility with my earlier results later?

      • Whitney Anderson

        Maria, yes one test for one partner alone means nothing. It’s all about what they mean together, so yea, your husband would have to have the same test. Good luck!

  • Jay

    Its very good advice to make sure you test the products of miscarriage. I am so very glad I insisted on testing both my losses, it gave me so much information going forward.

    The good thing (if you can say that) is in an alloimmune situation, you can know for sure, through a relatively simple test, that this is indeed your situation.

    Autoimmune can be treated, but its tricky, with ab inherently greater risk of later complications. Also sometimes, if its not manifested in clearly elevated levels of autoantibodies or molecules like C reactive protein etc, it is very hard to pin down a diagnosis unlike an alloimmune situation.

    Hope you get some answers, and hope you can find a clear path forward soon.

  • Jay

    I should add that alloimmune rejection is complicated mechanism to understand even for an immunologist (like me), and I’m in a department that studies this stuff on a full time basis.

    But basically this concept of a genetic mismatch between 2 individuals that hinders the progress of a pregnancy is such an old one. The most classic and easily solved case is that of Rh negativity.

    Now you have the HLA situation coming to light. Somebody presented this fascinating paper about about a mismatch between 2 individuals (and its the father’s fault here) creating an high risk scenario for pre-eclampsia. Again, NK cells and HLA involvement.

    Its really not easy in these cases, and you ultimately have to end up going either for sperm or egg donation to have a low risk pregnancy. But someone who has lived through the hell of RPL, you just want to have this torture end.

  • Jess


    a) I am SO Glad you went to share. more information is good.

    b) while I think some people go overboard with immune stuff unnecessarily, I do think there are cases such as yours, where clearly something isn’t going right. Sher is less a stab in the dark than going to a standard RE. I’ve seen many RPL people never be able to have a child, or keep trying and maybe the 10th IVF can work.

    c) Re’s don’t like to admit it, but there is still so much they don’t know. And true, a lot of this can’t be proven. But people with recurrent loss without a clear reason are actually such a small subgroup, it’s hard to conduct such a study and hard to prove it’s not other factors. So yes, while there is no research to base it on yet… there’s good reasons for that being the case.
    When it comes to egg and embryo quality, and their interactions with the uterus- these things are pretty much in their infancy of understanding. And it’s beyond the scope of knowledge of a regular RE and an immunologist- I can see the need for reproductive immunology- it’s complicated. I have seen way too many women try things like blood thinners to no avail. I think there are some of us which science can’t help… yet. And I think alloimmune might be the subgroup. The science hasn’t caught up to the technology yet.

    d) The problem here is deciding when it’s enough for you, or when it’s time to change course. I hope that meeting with him and CCRM will give you enough information so that you can make a well informed decision of what road to take. I think you are being smart here to weigh all of the options. In the long run, for me, adoption made the most sense for my set of circumstances. I couldn’t deal with more IVFs or more testing for a mere chance, but I think we all must come to our own conclusions. I am so glad you are moving in this direction. Best wishes to you.

  • Dr. Sher rocks! We cycled at SIRM LV and absolutely loved him. He really is a scientific genius and has done so much research in this area. I found my local REs didn’t do *any* research, but just followed “tried and true” older protocols.

    While we ultimately weren’t successful there, I have no regrets about cycling there. When we started ART I wanted to be able to say we did the very best we could.

    Best wishes. I hope this provides some answers.

  • Jenna

    Hello Whitney,

    I just wanted to say you are very smart for talking with Dr Sher! I am 8 weeks pregnant with his help! I live in Vegas so thank goodness we dont have to travel. We had one other IVF last year that ended in m/c so when we first came to SIRM they tested me for the NK cells. I hear that it is very common in women and in many cases it is the reason for m/c. I was positive and had 2 infusions for it last month. I really like Dr. Sher and I was so very confident that he would know how to get us pregnant. I only know of the NK cells, not all the other test you mentioned so I cant give advice on those.

    I hope this cycle with Sher works for you! Belive and think happy thoguhts!!

  • AP

    Wow. I don’t know about any of this, but you must feel a little better with a possible problem identified. My doctor just told my my thyroid is low and I jumped for joy. Give me something to solve and I can deal with it, give me a vague, “let’s see what happens,” and I want to punch someone.

    I hope you feel the same way and I’m thinking of you as you start this journey.

  • I’m so glad the consult with Sher went well – he’s awesome, isn’t he? All this stuff is super complicated, but I’m glad he’s testing you for stuff. If you do have an alloimmune issue, check out some historical posts of Kristi She just had a baby after many losses and IVF failures, and she attributes it to intralipids, IVIG and other immune treatments.

    Hope you find some answers that result in a baby!!!

  • Rachel

    We are consulting with Sher also. Had 2 previous IVF failures. A friend who had 2 babies through SIRM referred us and we had first phone consult March 2011. First blood tests showed activated NK cells. Sher has now ordered blood tests to determine autoimmune vs alloimmune. Waiting on those results. So pretty much in the same place as you are Whitney. Currently planning to sign up for May IVF cycle. Have also heard about Dr. Braverman in NY, who is also a reproductive immunologist. Not sure if any of you have heard anything about his practice

  • Jeff

    Hi Whitney and everyone, this is incredibly helpful and inspiring – thank you. Found it doing some searches on IVF. Wonderful site and blog. Are there any updates that can be shared on this particular post? Last one was Spring 2011. We are facing a very similar situation. My wife and I are wondering if she might have immunologic implantation dysfunction – but when we asked our doctor after a second failed IVF attempt, he shrugged it off as an absolute non-factor. Should we ask to pursue tests regardless? Thank you!

    • Jeff

      Bueller? 🙂

  • Polly

    Hi Whitney – Have just found you blog and am finding it incredibly insightful. Congratulations on your beautiful twins! For those readers with RPL that is linked to NK and/or T cell issues, it might be interesting to check out this British article about a recent success story using a malaria medication to suppress these cells: I don’t know whether this treatment is available in the States or if it is what Dr Sher is using; however it looks like a promising development.

  • Jaclyn Kratohvil

    Hi Whitney,

    I came across your blog and I have been running into many issues ttc. We tried IVF and miscarried the first cycle, then had a failed frozen cycle. Since we were out of embryos and money we decided to try IUI and went to a different clinic. The reason we tried IVF first is my husband had vasectomy in his first marriage. Anyway, we tried the first IUI and it failed. But the problem is that about 4-5 days before my expected period I have a rush of blood, then goes back and forth between spotting brown, to a couple drops of red but no full period… until my 28th day… I’m pretty regular. I knew something was wrong bc as I already am a spotter, I do not spot red until I am ready to have a full flowing period. I do not have PCOS, they did find a uterine polyp before doing IVF that they removed. So I demanded to be tested for all the RPL test. Needless to say we found out that I have Factor 2 clotting disorder. So I started taking baby aspirin, waited a cycle and then tried another cycle. On day 10piui I started with the bright red bleed… and then on and off spotting as I currently am and will expect my period. I forgot to mention each IUI I saw implantation bleeding. Light pink mucus with 1 wipe. I know thats what it was because my body does not have that discharge ever. So we are heartbroken because I feel like no one can tell us what is wrong…. but I feel like there is a disconnect somewhere after the sperm and egg meet and then it really does seem like it tries to implant and fails. I’m surprised my doctor has not tested me for this NK cells…. I plan on calling tomorrow and asking him. Do you have any other recommendations that I should be tested for based on what I told you? I know you aren’t a doctor so I don’t mean to put that pressure on you but it sounds like you have been through so many test as well. Its so hard going through this and feeling like something is wrong and doctors aren’t figuring it out 🙁