ASA Effects on Fertility
The potential detrimental effect of ASA on male and female fertility was brought to the attention of reproductive biologists back in the 1950s. The studies conducted on rodents described the deleterious consequences of autoimmune responses to sperm and testis antigens, by producing orchitis and aspermatogenesis.52 Their clinical relevance was provided first by a study describing spontaneous sperm agglutination of ejaculated spermatozoa in association to the detection of serum ASA in infertile men.53 A few years later, a report described the presence of ASA in sera of women with unexplained infertility.54
Since then, numerous reports have related the detection of ASA in whole spermatozoa and in biological fluids with alterations in gametes and embryos and a consequent decreased conception rate in men and women. Figure 12.1 briefly summarizes some of the fertilization-related events in which ASA interference has been reported.55 There is evidence indicating that agglutinating ASA reduce sperm
FIGURE 12.1 Steps of the fertilization process that can be affected by the presence of antisperm antibodies (ASA). ASA can affect (a) sperm passage through the cervical mucus, (b) sperm transport through the uterus, (c) sperm-oocyte interaction, (d, e) early embryo development, and (f) embryo implantation.
forward progressive motility and affect sperm penetration through cervical mucus56 and transport to the Fallopian tubes.57 In addition, there are reports describing ASA impairment of sperm capacitation,58-59 as well as sperm interaction with oocyte vestments, in particular the zona pellucida 60 and the oolemma.61 With regard to the ASA effect on acrosomal exocytosis, our group previously reported the presence of antibodies toward spermatozoa in follicular fluid with the ability to modulate the release of acrosomal contents, affecting sperm-zona pellucida interaction.62
The use of assisted reproductive technologies for infertility treatment led investigators to further assess the effect of male and female ASA on in vitro fertilization (IVF), early embryonic development, and pregnancy outcome. Our team previously reported the presence of ASA in sera from women undergoing IVF embryo transfer and their deleterious effect on IVF.63 Moreover, sperm surface ASA were found to impair IVF, early embryonic development, embryo implantation, and fetal development.64 Several other studies addressed this question, although results are still inconclusive. In this regard, a systematic metaanalysis study involving more than 4000 reproductive cycles (both IVF and intracytoplasmic sperm injection [ICSI]) revealed no relationship between semen ASA levels and pregnancy rates.65 The discrepancies found may be attributed, at least in part, to patient heterogeneity in the study groups, as well as the methods and thresholds used for ASA assessment.