Historical Background of Immune Infertility Associated with Anti-sperm Antibody (ASA) in Women

Abstract

The sperm was the first target for immunocontraception. The production of sterility in the female by immunizing her to sperm of the same species is a possible solution to excessive fertility. Since Landsteiner and Metchnikoff documented antibody production against sperm in animals in 1899, a number of experiments had been carried out on the relationship between sperm immunity and infertility. Most of the experimental data arose from the immunization of male and female rodents against testicular, epididymal, and seminal antigens. However, the results obtained were inconclusive, with some showing positive relationship, while others arrived at the opposite conclusions.

In human, Rosenfeld was the first to suggest that a woman repeatedly injected with human semen became infertile in 1926. However, it seems to be a harmful and dangerous clinical trial as there might be common antigens against other organs except for reproduction in semen.

In 1964, Franklin and Dukes reported their clinical observations on anti-sperm antibodies (ASAs) in women. Surprisingly, they found 72.1% of women with unexplained infertility had a much higher incidence of sperm-agglutinating activity. There was a supportive appreciation for their clinical findings that they stimulated significant interest in the hypothesis that female immunological reactions to sperm could be involved in the etiology of otherwise unexplained infertility and in the concept of an anti-sperm contraceptive vaccine. However, there was a serious problem for their studies that the phenomenon of sperm-agglutination is not always a specific event by ASA. It has been well known that sperm-agglutination frequently occurs naturally, not related with the existence of ASA.

Because of the nonspecificity of the sperm-agglutination test for detecting ASA, a sperm-immobilization test (SIT), that utilized the function of sperm-immobilization in the presence of complement, was developed by Isojima et al. Other studies also confirmed the reliability of SIT as an assay for detecting ASA closely related to female infertility. In the previous review by Koyama, the incidences of sperm-immobilizing antibodies in the sera of unexplained and organic infertile women were found to be 13.2% and 1.4%, respectively, while the incidences of sperm-immobilizing antibodies in the controls, such as children, unmarried women, and pregnant women, were 0%, 0%, and 0.5%, respectively. In conclusion, the SIT proved to be one of the most reliable methods to detect ASA relevant to infertility in women.