REVIEW – February 2009

Autoimmunity in female infertility II. Antiovarian autoimmunity-associated antibodies to follicle stimulating stimulating


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Reproductive autoimmune failure can be associated with overall activation of the immune system or with immune system reactions specifically directed against ovarian antigens. Antiovarian autoantibodies can be directed to different antigens including gonadotropins and their receptors, for example, antibodies against the β-subunit of follicle stimulating hormone (anti-FSH). These antibodies recognize epitopes all over the β-subunit molecule, but a region determining the specificity of receptor binding is predominantly recognized. The function of FSH is essential for folliculogenesis in the spontaneous menstrual cycle and is widely used in stimulation of poly-folliculogenesis during in vitro fertilization (IVF).

The current review focuses on antiovarian antibodies, specifically, on anti-FSH. Anti-FSH can primarily be natural antibodies. Anti-FSH IgA detected in female circulation could be part of the mucosal response involved in inducing immunotolerance to seminal consti­tuents. Anti-FSH IgM associates with the peripheral level of FSH hormone and contributes, along with mucosal-associated induction of IgA, to the produc­tion of circulating anti-FSH IgG. Higher production of anti-FSH antibodies could contribute to female infertility. Induced production of anti-FSH IgM and IgG antibodies could be related to a general propensity to autoimmunity or to previous IVF treatments. Elevated values of anti-FSH IgA in IVF patients suggest a genetically determined failure of mucosal tolerance in the genital tract. In addition to sera, anti-FSH IgG and IgA antibodies are present in the follicular fluid with anti-FSH IgG accumulating in the preovulatory follicle. In the context of infertility treatment, high levels of serum anti-FSH IgG and IgA antibodies impair the outcome of ovarian FSH stimulation in IVF.

Detection of anti-FSH antibodies is now available in Tartu, Estonia. This review provides information concerning the technical issues of blood sampling, indications for anti-FSH detection and interpretation of results.