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Immune issues and recurrent ICSI failure

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  • Immune issues and recurrent ICSI failure

    Dear Dr Sher,

    I am 39 and have been trying for the past 6 years. In the past 5 years, I have had about 5-6 ICSIs (have lost count) and 4 frozen cycles. I always produce a good number of eggs (10-12) and have gone to the balstocyst stage several times but they never implant. I was considered normal but my partner's sperm was not the best (not great quality). In December 2008, it was discovered that my TH1:Th2 Cytokine ratio TNF -a@ IL10 (CD3+CD4+) was 40.1 and IFN -g:IL10 (CD3+CD4+) were 24.4. I was put on humira for 1 month and the levels went down to 33.1 and 12.0. I was on humira for another month and my levels were considered normal.
    50: 1 11.3
    25:1 7.4
    12:5:1 5.2
    IgG conc 12.5 50:1 5.7
    IgG conc 12.5 25:1 3.1
    IgG conc 6.25 50:1 6.5
    IgG conc 6.25 25:1 4.1
    % CD3 80.2
    % CD 19 3.6
    % CD56 11.7
    % CD19+cells, CD5+ 5.6
    I then had an ICSI with 13 embryos, 2 balstocysts were transferred and 4 were frozen. They then put me on baby aspirin, an injection to thin my blood twice a day and a drug to stop spasms until the result. The result was negative. I am 39 and don't know what to do next. I am wondering whether they should have put me on steroids and IVIg as well. Should I do a frozen transfer even though the success rates are quite low?
    Thanks.

  • #2
    The biggest issue I see is your age. At 39 there is a higher risk of making an abnormal embryo. Remember that up to 40% of good appearing blastocysts are still genetically abnormal. Some can still make babies, ie. Down's syndrome, although, most end in early miscarriage or failure to implant. Your NK cell activity seems high. Now a days we are treating this with Intralipid instead of IVIG. It is cheaper, safer and seems to work just as well to suppress NK cell activity. Immune treatment will not improve egg quality. This can be done by carefully manipulating the stimulation protocol. We evaluated TFN alpha blockers like Enbrel and Humira several years ago and rejected them for IVF use.

    If you contact me directly, I would be happy to review your case with you in more detail. Then I can make specific recommendations.

    Jeffrey Fisch
    jfisch@sherinstitute.com

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