Antibodies to sperm membrane antigens

The occurrence of sperm-specific antibodies in 60-70% of vasectomized men shows that occlusion of the efferent ducts can induce autoimmunity, and infections may also stimulate immune responses, possibly through an adjuvant effect. However in most cases no explanation for the immune response can be found.

Male laboratory animals immunized with homologous sperm in complete Freund's adjuvant develop orchitis with destruction of the germinal tissue, but in men the autoimmunity apparently does not affect spermatogenesis. Apart from modest deposits of immunoglobulin around seminiferous tubules, testicular histology has been normal in most men with sperm-specific antibodies who (for other reasons) have had testis biopsies performed, and semen samples often show normal sperm counts and normal motility. However, the presence of antibodies on motile sperm can be demonstrated by simple techniques such as the immunobead-binding test, in which particles covered with anti-immunoglobulin attach to the sperm, or the rather similar mixed antiglobulin reaction (MAR). The use of class-specific anti-immunoglobulins in these tests has ied to the observation that IgA antibodies (but not IgG antibodies) impair or inhibit the migration of sperm through cervical mucus. Sperm covered with IgA are seen to shake vigorously in the mucus without forward progression. This explains the strong fertility reducing effect of locally produced IgA antibodies in semen or cervical mucus.

The significance of IgG antibodies, which predominate in serum and are transudated to semen (1% of serum concentration), is less clear, because in men from infertile couples IgG antibodies are rarely found without IgA antibodies also being present. The percentage of eggs being fertilized by in vitro fertilization (IVF) is usually reduced when the sperm reveal strong immunobead or MAR reactivity, but also here IgA may be playing the major role. In vitro experiments with human IgG antibodies have indicated that in certain cases they could block fertilization, but on the other hand vasovasostomized men with only IgG anti-sperm responses have been found to have the same high fertility rate as vasovasostomized men without sperm-specific antibodies. The explanation why responses with only IgG antibodies are rarely seen among men from infertile couples might therefore be that such men usually do not end up in infertility clinics!

Evidence of immunological subfertility or infertility, i.e. strong IgG and IgA reactivity in immunobead test or MAR combined with detection of free antibodies in seminal plasma or high titers in serum, is found in approximately 10% of the men from couples with unexplained infertility.

In women, most laboratories have found sperm-specific antibodies in serum to be rare and generally present only in low titers. The explanation seems to be that women are exposed only to sperm mixed up with seminal plasma, which contains potent immunosuppressive factors, some of which adhere to the sperm membrane as sperm-coating substances. A multilaboratory study revealed significant immune responses in only 2% of women from couples with unexplained infertility. Detection of antibodies in liquefied cervical mucus (e.g. by indirect immunobead test) seems more informative, particularly since antibodies can apparently occur in cervical mucus without being detectable in serum.

High-dose corticosteroid therapy - with a 30-40% success rate - is now rarely used due to occasional severe side-effects (aseptic necrosis of femoral head). To overcome the impaired migration of IgA-covered sperm through cervical mucus, intrauterine insemination has been used with some success. In cases with strong immunization, IVF may offer the best choice. Although the fertilization rate is usually-reduced, once fertilization has occurred the pregnancy rate seems to be the same as for patients without sperm-specific antibodies.

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