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Scientific BackgroundPremature Ovarian Failure (POF)This disorder relates to the loss of reproductive function before the age of 40 due to loss of ovarian function. It may by caused by chrom osom al abnorm alities, chemotherapy, or radiotherapy, yet there have been many “unexplained” cases. Earlier studies have shown that organs specific auto antibodies are commonly found in most patients with autoimmune diseases. POF is associated with unrelated autoimmune disorders of endocrine and other tissues (e.g., myasthenia gravis, autoimmune thyroiditis, juvenile rheumatoid arthritis and others) raised the hypothesis that in some of the patients the cause for disease is autoimmune in nature. Indeed, autoantibodies to ovarian tissue were shown both on sections from such patients ovaries (1-3). And in serum (4) In this study, sera in 69% of POF patients were found positive for ovary or egg specific antibodies. These sera were much less reactive to liver, placenta or thyroid tissues (4%, 22%, and 1% respectively within the same study In-Vitro Fertilization/Embryo TransferOvarian stimulation protocols are routinely employed in order to induce superovulation and maximize the recruitment of preovulatory oocytes which, in turn, would increase the number of embryos produced and improve the success rates. In another study on ovarian autoimmunity (5), research focused on 51 patients admitted to the IVF/ET program due to tubal or male factor infertility. Serum estradiol (E2) levels were analyzed within this group in response to hMG, and patients were divided to “low responders” (<300 ng E2/ml) and “good responders” (>400 ng E2/ml). The AOA test was run in parallel on both subgroups. The study revealed that 77% of the “low responders” had elevated or positive anti-ovarian antibodies whereas none of the “good responders” showed any detectable levels. Unexplained Infertility: In addition, two other recent studies showed AOA levels to have an impact on IVF failure. In the first study (7) it has been shown that women with failed pregnancies had higher frequency of AOA 58%, compared to that in women who were pregnant (25%). In the other study (8), 12.5% of 50 patients with >5 failed IVF cycles and 0% of 50 patients who did conceive within the first 3 cycles had AOA. This study suggested AOA is a possible marker for sub clinical autoimmune disease that cause repeated IFV failure. One recent study (6) showed that AOA as a marker for infertility, is independent from Inhibin B and FSH levels. This suggested that AOA should be tested in addition to these markers, and its levels can not be inferred based on levels of these hormones. Clinical SignificanceThe anti-ovarian antibody test provides a quick and easy way to evaluate the causes for POF, or the causes for failures or decreased performance in the IVF procedures, it provides a tool for early assessment for whether large enough number of eggs could be retrieved for subsequent IVF/ET in patients admitted to IVF cycles, without actually starting the cycle. The numbers of retrieved eggs in “low responders” was close to threefold lower than that in “good responders”. The test outcome may be coupled to specific treatments. This disorder may be partially or fully alleviated for the critical period of time, by immunosuppressive treatment (see above). Treatment may be employed prior to ovarian stimulation. The test may also be used to monitor the effect of the treatment(s). |
Case Reports/TreatmentsTwo POF patients were positive for both the ovarian and the egg antigens, had high gonadotropin (LH and FSH > 50 IU/ml), E2 <110.13 pmol/L, normal karyotype, age<40y, and experienced ovarian failure for at least 1 year before the treatment (4). The patients were treated with Medrol (Methylprednisolone) 96 mg/day for 10 days, followed by 48 mg/day, 16 mg/day, and 8 mg/day (2 days each). Both showed a statistically significant reduction in the AOA level within 1 week after the treatment, lasting at least 5 months. One patient resumed spontaneous menstrual cycles after 3 months and became pregnant after 2 cycles, the other resumed menstruation after 1 month and became pregnant after 1 cycle. Both pregnancies reached full term. POF resumed after each birth. In another study(8), ten AOA-positive patients who had >5 failed IVF cycles were treated with Prednisone, 10 mg/day, beginning 4 wks before ovulation induction and lasting through the first trimester. Of these patients, 33% conceived following treatment, with a take-home baby rate of 22%. Test MethodologyThe test is performed on diluted serum in a standard autoimmune ELISA format, utilizing ovulation induced ovarian membrane fraction as capture antigen and a second antibody conjugated to Alkaline Phosphatase as the quantitative signal. Positives are assessed statistically as having >3 SD above the mean of normal sera values. Sample RequirementsSerum (red or tiger top test tube, spun and separated) shipped at room temperature. The patient should not be taking hMG or GNRH fertility drugs or any immunosuppressive drugs. References
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