Sexual intercourse is associated with recognition of partner-derived major histocompatibility complex (MHC) and minor histocompatibility alloantigens (MiHAs) by females. Male sperm-associated MHC antigens, expressed on spermatozoa and leukocytes, as well as MiHAs including sperm-specific antigens (SPAGs), are recognized by female T lymphocytes infiltrating the cervicovaginal region. This can occur via direct presentation of male MHC molecules on male antigen presenting cells and indirect presentation of male antigen peptides (MHC and MiHAs) bound to female MHC molecules on female antigen presenting cells. This process along with the presence of anti-inflammatory chemokines and cytokines and sHLA-G present in seminal fluid leads to activation of male antigen-specific FOXP3+ Treg locally and in regional lymph nodes. This regulatory response has been shown to promote survival and progression of spermatozoa within the cervical mucus as well as implantation of the embryo. Most important, it is believed to set the stage for fetal-maternal tolerance during pregnancy. Conversely, under certain circumstances, alloresponses to male antigens can lead to the production of anti-MHC and anti-sperm-specific antigens antibodies resulting in infertility. Altogether, these observations show that alloimmunity induced after sexual intercourse plays an essential role in reproduction. In addition, while the influence of pregnancy in transplantation is well established, some studies suggest that repeated sexual exposure to male antigens can increase the risk of solid organ transplant rejection.

The effectiveness of presumed consent policies in increasing donation and transplantation rates remains a matter of debate within the transplant community. The rationale for their implementation was derived from a limited body of experimental evidence and has largely relied on cross-country panel analyses reporting higher donation rates in opt-out systems. However, no previous study has systematically examined the risk of bias inherent in these analyses using a structured methodological framework. To address this gap, an operative framework of the deceased donation process was developed through the systematization of its phases and conditioning factors. This framework was subsequently used to perform a systematic review of cross-country panel data studies, applying the Risk Of Bias In Nonrandomized Studies of Interventions tool to assess risk of bias. Eighteen studies were identified. Although most (n = 12) reported higher donation and/or transplantation rates in countries with presumed consent, risk of bias assessment identified serious limitations in 16 studies and critical limitations in 2. The principal concerns were inadequate control of confounding factors and misclassification bias resulting from imprecise definitions of how consent policies are implemented in practice, beyond the legal distinction between opt-in and opt-out systems. These findings suggest that, despite their apparent consistency, cross-country panel studies do not provide sufficiently robust evidence to support presumed consent as an effective strategy for increasing donation and transplantation rates. Greater emphasis should therefore be placed on the development of evidence-based donation policies that incorporate all validated determinants of effective deceased donation systems worldwide. Recommendations for improving research design in this field are also proposed.