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Thread: Endometriosis and implantation failure

  1. #1
    Join Date
    Feb 2009
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    Default Endometriosis and implantation failure

    Dr. Saleh,

    Eighteen months ago, I was diagnosed with endometriosis when my doctor found 2 chocolate cysts on ultrasound. At the time, he recommended against surgery given my age (I'm now 39) my lack of pain, and his concern that it could reduce my ovarian reserve.

    Since then I have had what I believe to be multiple implantation failures but no successful pregnancies (all natural cycles). I have read that implantation failure is more common in women with endometriosis, but I am unclear on why this would be so. Do you know what it is about endometriosis that tends to cause implantation problems? What course of treatment do you generally recommend in women with this issue? At this point I am considering surgery again, as I feel like I have nothing to lose.

    Thanks

  2. #2
    Join Date
    Oct 2008
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    387

    Default

    Surgery would not help with the immune part as endo is a persistent microscopic disease. Please see below:



    Endometriosis is a complex condition where, the lack or relative absence of an overt anatomical barrier to fertility often belies the true extent of reproductive problem(s).
    All too often the view is expounded that the severity of endometriosis-related infertility is inevitably directly proportionate to the anatomical severity of the disease itself, thereby implying that endometriosis causes infertility primarily by virtue of creating anatomical barriers to fertilization. This over-simplistic and erroneous view is often used to support the performance of many unnecessary surgeries for the removal of small innocuous endometriotic lesions, on the basis of such "treatment" evoking an improvement in subsequent fertility.
    It is indeed indisputable that even the mildest form of endometriosis can compromise fertility. It is equally true that, mild to moderate endometriosis is by no means a cause of absolute "sterility".
    Rather, when compared with normally ovulating women of a similar age who do not have endometriosis, women with mild to moderate endometriosis are about three to four times less likely to have a successful pregnancy. Two important reasons for such reduction in fertility potential are:
    a) Endometriosis is associated with the presence of local pelvic toxins that significantly reduces the fertilization potential of eggs as they pass from the ovary to the fallopian tube via the pelvic cavity and,
    b) Given that the pathogenesis of endometriosis almost certainly involves an abnormal immune response, many such women tend to reject the embryo (fertilized egg) as it attempts to gain attachment to the uterine lining (endometrium).
    The reported annual birth rate for normally ovulating women under 35 yrs who are free of endometriosis or any other pelvic disease, is about 80% .For women 35-40yrs of age, the comparable annual rate is about 50-60% and for women in their early 40’s, it is approximately 20-25% In contrast women in similar age categories who have even the mildest degree of endometriosis can expect a 3-4 fold reduction in annual birth rate.
    Since, the reason for women with mild to moderate endometriosis having a much poorer reproductive performance has little to do with ovulation dysfunction or anatomical disease, it is should come as no surprise that the use of fertility drugs, surgery to ablate small endometriotic deposits and minor adhesions, and/or intrauterine insemination is unlikely to any improvement in pregnancy rate over no treatment at all. Women under 35 years who fit this profile, and who conceive following fertility hormone therapy, intrauterine insemination (IUI) or surgery, should consider that they probably became pregnant in spite of, rather than due to, such treatment. Failure to recognize this reality carries with it the risk that when it comes to planning for another baby, the woman will erroneously belief that having conceived before means that their should be no difficulty in doing so again and be lulled into a false sense of complacency. In reality, the achievement of a viable pregnancy by a woman with mild/moderate endometriosis, whether it occurred spontaneously or following such treatment does not improve her subsequent ability to conceive.
    Younger women (under 30 yrs) with mild/moderate pelvic endometriosis (who have patent fallopian tubes, are ovulating normally and have fertile male partners), have about a 30-40% chance of having a baby within 3 years. Accordingly they have a justifiable choice between taking a “wait and see “approach, (avoiding surgery, fertility drugs and intrauterine insemination which in my opinion is unlikely to improve the chance of a successful pregnancy over no treatment at all) and In Vitro Fertilization which by involving the direct extraction of eggs from the ovaries and initiating the fertilization process in the Petri dish/incubator, the IVF procedure facilitates fertilization, is much likely to be successful, but might have been avoided by a "wait and see approach".
    Finally, I wish to point out that in addition to the toxic "peritoneal factor" present in all women with endometriosis, our research has shown that up to 1/3 of women with endometriosis (regardless of severity), in addition have an immunologic barrier to implantation. This population of women will not conceive until the immunologic problem has been diagnosed and suppressed through selective immunotherapy. It therefore behooves all women with endometriosis who are planning to have a family to be thoroughly tested for antiphospholipid antibodies (APA), Natural Killer cell activation (NKa) and reproductive immunophenotype. These tests should only be done in a reproductive immunology reference lab of which to my knowledge no more than a half dozen , capable of performing these tests with the required sensitivity currently exist in the U.S.A.
    Given the effect of the biological clock, women over 35yrs who have endometriosis-related infertility,do not have time to waste and should, in my opinion do IVF as a first line approach, regardless of their immunologic status.
    In the absence of clear evidence of increased NK cell activity, I recommend a conservative approach in women under 35years ( who potentially have some time)....and, regardless of age women who have increased NK cell activity , should in my opinion undergo selective immunotherapy with immunoglobulin G (IVIG) because we have found that without such treatment they are not likely to conceive regardless of the approach to treatment) undergo IVF.

    Hope that helps. Please do not hesitate to contact me for any additional questions.

  3. #3
    Join Date
    Feb 2009
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    6

    Default

    Thank you, Dr. Saleh--this is very helpful. I believe too that immune issues are an important piece of the puzzle. I've had an NK assay through Rosalind Franklin's lab, which showed significant elevations (50:1 killing activity = 31%). In addition, I tested borderline for APA, positive for anti-ovarian antibodies, heterozygous for MTHFR, and homozygous for PAI-1. Over the last several months I have had Lymphocyte Immunization Therapy and monthly infusions of IVIG, which lowered my 50:1 NK killing power to <15%. I've also tried Lovenox, dexamethasone, Prometrium and baby aspirin with every cycle. Unfortunately, even on this aggressive protocol, I've had 3 more consecutive failed cycles (one +hpt that faded out within 2 days and 2 more implantation failures). I'm now wondering if my immune issues are just too complex and severe to be treatable or if there could be some other issue causing my implantation problems (a missing beta integrin? the pelvic toxins you referenced? egg quality? the PAI-1?).

    At this point, I feel like my options are as follows:

    1) IVF (expensive and how would it help if I can't implant?)
    2) surgery (could hurt more than help?)
    3) Humira (but my TH1:TH2 cytokine ratios tested normal)
    4) ???

    Do you have any additional thoughts or suggestions? I am slowly starting to lose hope.

    Thanks so much for your help.

  4. #4
    Join Date
    Oct 2008
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    387

    Default

    IVF is way cheaper than monthly IVIG infusions. I now use intralipids which is much safer and as effective. Surgery not a good idea. You may have an egg quality issue and IVF should help.

    Please see below:

    INTRALIPID INFUSION: A SAFE AND INEXPENSIVE ALTERNATIVE TO IVIG FOR IMPLANTATION DYSFUNCTION:


    Intralipid (IL), is a synthetic product composed of 10% soybean oil, 1,2% egg yolk phospholipids, 2.25% glycerin and water. Based on research performed at SIRM and elsewhere, infusion of IL lowers Natural Killer cell activation (Nka) as effectively as does, intravenous gammaglobulin (IVIG.) When indicated IL (as with IVIG) is infused 7-10 days prior to ET and one more time again after a positive pregnancy in women whose Nka is due to an autoimmune causes (antiphospholipid antibodies and/or antithyroid antibodies). In cases of alloimmune implantation dysfunction (DQa and/ HLA matching between the embryo recipient and the male partner) the same applies but in this situation the infusion is repeated at 2-4 week intervals until the 24th week of pregnancy.
    We have supplanted IVIG with IL therapy in a significant number of women undergoing IVF , and who had immunologic embryo implantation dysfunction. The results thus far have been excellent, way beyond our initial expectations.
    At last we now have a safe and inexpensive alternative to IVIG therapy…Intralipid! What is more, IL costs about 10 times less than IVIG, is not a blood product and is without significant side effects.

  5. #5
    Join Date
    Oct 2015
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    11

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    I was diagnosed with endometriosis when I was 34 yo, during a laparoscopic tubal surgery. Since then I've had many IVF implantations failures with my own eggs. Now I'm trying fertility treatment with donoregg and I've had to implantations failures: one kemical prægnante and one negativ. It looks like the results of the treatments are the same: with own eggs or with donor eggs. Maybe I have some immune problems? What do you you think I should do?

  6. #6
    Join Date
    Oct 2015
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    Dr. Saleh,
    Now I am 42 Y.o. and have been in treatment with donor egg twice: first with to fresh blastocysts and secondat with frossen to blastocysts. Both implantation failures.

  7. #7
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    Oct 2008
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    I would have to review your records to determine if the issue was really immune implantation failure or egg quality. If you can have a NK activity assay, that would determine if your NK are hyperactive. Is that something you can do locally?

  8. #8
    Join Date
    Oct 2015
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    11

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    Dear Saleh,
    I have asked the clinic today and they say that is not possible to perform NKa in Denmark. My gynecologist in Dk days that I can try prednisolon 10 mg from the mens day. I live in Dk and I perform a fertility treatment with donor egg in Spain.

  9. #9
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    Oct 2008
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    The problem is that Prednisone is not enough. I advise intralipids as well but make sure there is no other factor at the uterine level as well. Best of luck

  10. #10
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    Oct 2015
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    Do you mean both prednisolon and intralipids? Or Intralipids instead of prednisolon? And how much Intralipids do I have to take? Next month I am going to proceed a hysteroscopy at the clinic in Spain, where I'll get my uterine tubes closed from the uterine side and afterwords I will proceed ERA biopsy/test too.
    What do you think about it? Do you have any good advice regarding these procedures? Do you recommend anything else to be done?
    I have three frosen blastocysts left and my gynecolog in Spain and the gynecolog in Dk adviced me to use one at the time. What do you think about it?

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