The impact of antisperm antibodies on human male reproductive function: an update

Abstract

Immune infertility occurs due to the presence of antisperm antibodies (ASA). This type of infertility has a relatively low prevalence (2.6-6.6% in infertile men), and its etiology, risk factors, targets and consequences for male fertility are not completely understood. While it is largely accepted that abnormalities in the blood-testis barrier and/or blood-epididymal barrier are the main factors behind its etiology, and that sperm motility is the most frequently reported altered parameter, few are the well-defined risk factors and ASA targets only now started to be disclosed, with proteins involved in sperm-oocyte interaction rising as the most significant. The development of potential treatments is also limited, being the corticosteroids the more promising. Overall, there are still many knowledge gaps related to immune infertility. With this review we aimed to gather all the information collected from studies developed in humans in the last decade. Despite the controversial results/inconsistencies, that are not only a result from the complexity of mechanisms/variables involved in ASA infertility, but also from the technical approaches to assess ASA and the lack of a consensus regarding the thresholds to be used, this manuscript aims to bring a fresh update on the field. It has become clear that, to obtain more/reliable data, there is a need to assess ASA in all the routine seminal analysis, following WHO recommendations. In this way it will be possible to obtain consistent and comparable information, that can add to current knowledge. Additionally, multicentric studies with large cohorts are also missing, and future research should take this into consideration.

Detection of Sperm DNA Integrity and Some Immunological Aspects in Infertile Males

“…According to the age category, the studied cases demonstrated lower records of sperm morphology in the age group 40-49 and ≥50 years. These outcomes were in agreement with several investigation studies of aging effect on fertility (Ahmed, et al, 2019;Silva, Ramalho-Santos and Amaral, 2021). In addition, the progressive sperm motility for the age category ≥50 years was below the reference value of the WHO (Björndahl and Brown, 2022) that was in agreement with similar studies (Stewart and Kim, 2011).…”

“…The findings showed no significant difference between the direct and indirect techniques for detecting both classes of IgA according to their distributions on sperm parts in all subjects, including the primary and secondary types of infertility, which have been confirmed by previous studies. ASAs affect virtually all components of sperm, diminished sperm-oocyte binding, faulty zona pellucida penetration cervical mucus penetration, and sperm survival (Silva, Ramalho-Santos and Amaral, 2021). Furthermore, the ASAs linked to abnormal embryo development by retarding the cleavage process, blocking the initiation of the embryo, and most significantly affecting fertilization rates when localized both at the head and the tail tip levels of sperm.…”

Pathogenesis of Autoimmune Male Infertility: Juxtacrine, Paracrine, and Endocrine Dysregulation

“…In spite of all data cited above, the link between the presence of ASAs in men and infertility continues to be disputed, and it is unclear whether ASAs adversely affect the outcome of in vitro fertilization (IVF) or results of intracytoplasmic sperm injection (ICSI) [ 88 ].…”

“…Studies on ASAs and post-ICSI pregnancy rates have generally shown that ASAs do not affect post-ICSI pregnancy rates [ 59 , 88 , 89 , 90 , 91 ].…”

Sperm Physiological Response to Female Serum—Potential New Insights into the Reproductive Incompatibility Diagnostics

“…Thus, serum and follicular fluid share similar IgG and IgA content. Interestingly, among all immunological factors that may affect fertilization and reproductive success, little attention has been paid to antibodies (but see, e.g., antisperm antibodies studies; [ 41 ]), especially to anti-HLA antibodies [ 42 ]. Anti-HLA antibodies are formed in response to contact with non-self HLA antigens after blood transfusion, organ or tissue transplantation, and pregnancy.…”