Immune Infertility

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Infertility is defined as the inability to conceive after a year of unprotected intercourse, and its prevalence is rising globally, with various causes in both male and female partners. Immune reactions to sperm can account for 2–30% of infertility cases. Sperm possesses both autoantigenic and isoantigenic properties, leading to the production of antisperm antibodies (ASAs) and sperm-reactive T cells in infertile individuals. Notably, over 75% of men who have undergone vasectomy produce autoantibodies to sperm, complicating the restoration of fertility even after successful vasovasostomy. Initial claims regarding the role of ASAs in human infertility may have been overstated due to unreliable methodologies and a limited understanding of the immune response and sperm cell antigenicity. This confusion, combined with a lack of well-designed studies and effective treatments, led to the dismissal of ASA evaluation in infertile couples as insignificant. However, advancements in assay accuracy and the recognition of mucosal immunity that operates independently of systemic immunity have prompted a reevaluation of the role of sperm cells and genital tract secretions in ASA analysis.