Antisperm Immunity and Infertility

Jin-Chun Lu; Yu-Feng Huang; Nian-Qing Lu

Disclosures

Expert Rev Clin Immunol. 2008;4(1):113-126. 

In This Article

To What Extent Did ASAs Affect Fertility?

It was reported that the fertilization rate in the antisperm group (61.3%) was significantly lower than that in the control group (76.8%). However, the implantation rate per embryo transferred (23.5%) and, consequently, the modified pregnancy rate per oocyte recovery procedure (34.4%) in immunologically infertile women were significantly higher than those in the control group (7.9 and 17.8%, respectively). Although sperm-immobilizing antibodies prevent sperm-egg interactions, they do not seem to have any adverse effects on the likelihood of pregnancy. Moreover, the occurrence of a cellular or humoral immune response against sperm seems to augment the uterine receptivity for the implantation of fertilized ova or blastocyst, and to be favorable for successful pregnancy by the IVF-embryo transfer (ET) procedure.[62]

Similarly, antibodies to several sperm molecules inhibit sperm-oocyte interaction/fertilization in vitro. Interestingly, active immunization with many of these molecules does not inhibit fertility in vivo. In addition, gene knockout animals of many of these molecules do not inhibit fertility. For example, although antibodies to fertilin/PH-30 inhibit fertilization in vitro,[63] active immunization with fertilin/PH-30 does not affect fertility in vivo; although antibodies to sperm integrins α6 and β1 inhibit sperm-oocyte fusion in vitro, gene knockouts of these molecules do not affect the fertility in vivo.[64]

In spite of the difficulty to explain these contradictory results, it was generally accepted that most autoantibodies occurring in biological fluids do not cause autoimmune diseases. For ASAs, if the cognate antigen is not involved in the process of fertilization or the antibodies do not bind to the functional domain of the antigen, these sperm autoantibodies will not alter sperm function. Therefore, different effects between in vitro and in vivo may be a result of ASA-sperm antigen binding in vitro and ASAs untouchable to sperm antigens in vivo. Moreover, the antibody-binding region of the antigen may be different from the region being active in metabolic processes.[4] Several authors reported that there was no statistically significant difference in the pregnancy rate between those women with and without ASAs.[65] Of cause, conflicting opinions about the effects of ASAs on fertilization could be due to inadequate experimental approaches in evaluating antisperm immunity.[66]

Another challenge is to establish an appropriate animal model to investigate the efficacy of a sperm antigen. The commonly used animal model is the mouse. However, until now, no one has reported a 100% block in fertility after immunization with any single antigen in a murine model. Even immunization with the whole sperm or their solubilized preparations does not cause a total block in fertility of male or female mice. The maximum reduction in fertility after immunization with any antigen/sperm preparation is up to 70-75%. Very few, if any, knockouts of a single gene have made mice totally infertile. The recently reported Izumo gene knockout and the double knock out of oocyte proteins CD9 and CD81 that could interact with sperm Izumo did make the male mice almost totally infertile.[67,68] It remains to be seen whether the 70-75% reduction in fertility in a mouse model could be translated to a 100% reduction in humans. Promisingly, after active immunization or deleting a single gene, a few mice were found totally infertile.

In conclusion, sperm antigens and ASAs appear to have both adverse and favorable effects, with some even having no effect on fertility. But when do they act on fertility, and to what extent do they affect fertility? All these questions are yet to be answered.

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