The obstruction/leakage/infection/inflammation of the testis, and especially the epididymis and vas deferens, frequently induces high titers of ASAs [13–17]. Between 50 and 100 % of men that undergo vasectomies subsequently develop ASAs in serum and semen [17]. Following vasectomy, sperm granuloma frequently develops in epididymal distension results due to increased intraluminal pressure. The sperm granuloma is a dynamic structure where active phagocytosis occurs by macrophages. It is plausible that the immune process inducing ASAs production initiates here, since T cells have also been observed.

ASAs can penetrate from circulation into the male genital tract via rete testis, epididymis, vas deferens, and accessory glands. They can attach to sperm at any of these regions after transudation. In spermatozoa retrieved directly from the distal end of the vas deferens in patients undergoing vasectomy reversal (vasovasostomy), ASAs, both IgG and IgA, were present in 78.6 and 32.1 % of the patients, respectively [18].

The infection and/or inflammation of the male genital tract can cause ASAs formation; however, the data are inconsistent. Jarow et al. [19] described a positive association between prostatitis and ASAs using the gel agglutination assay in serum. In a series of 365 patients with documented inflammation/infection of the male genital tract, suffering from—in accordance to the American Urological Association definition—chronic bacterial prostatitis, inflammatory chronic prostatitis/chronic pelvic pain syndrome, noninflammatory chronic pelvic pain syndrome, chronic urethritis, and chronic epididymitis, no association between ASAs formation/titers and the intensity of these diseases was demonstrable [20].

Immunological cross-reactivity between antigens of the sperm membrane and Chlamydia trachomatis may occur and explain some cases of an association between infections and ASAs formation [20]. Epitopes of chlamydial HSP60 protein cross-react with those of human HSP60. However, clinical data fail to detect an association between chlamydial infections and the presence of ASAs in seminal plasma [21].

It is unclear whether varicocele, testicular trauma, surgery, or testicular torsion can induce ASAs formation. Also, the association between cryptorchidism and ASAs remains controversial [17].

Although suggested by epidemiologic studies, the direct proof of ASAs as a cause of infertility is difficult to obtain, since prospective studies comparing pregnancies in patients with and without ASAs are limited [22–24]. In the retrospective studies, the degree of sperm autoimmunization showed a significant inverse correlation with the incidence of spontaneous pregnancies. In the first report by Rumke et al. [25] using a 10-year follow-up of 254 infertile men with serum sperm-agglutinating activity, the ASAs titers were found to be inversely correlated with the occurrence of spontaneous pregnancies. If only normozoospermic men were included, no pregnancy was observed with very high ASAs titers. In a cohort of 108 infertile couples, the pregnancy rates were significantly higher when males had low antibody titers than in those with high titers [6]. In another set of 157 infertile couples, the cumulative spontaneous pregnancy rates over 6 years were higher (~ 50 %) when the IBT results were < 0.50 %; lower (~ 30 %) when test results were 50–90 %; and very low (~ 15 %) when the test showed > 90 % ASAs binding in IBT [26]. A significant inverse correlation between the degree of sperm autoimmunization and pregnancy rates after vasovasostomy was observed in a follow-up study of 216 men [27]. However, this observation was not confirmed by others [28].