Partner-specific biological interactions in human reproduction

The World Health Organization estimates that 17.5% of adults’ worldwide experience infertility during their lifetime, while approximately 15%–30% of couples undergoing infertility evaluation receive a diagnosis of unexplained infertility. Current diagnostic approaches predominantly assess female and male reproductive factors separately, although successful conception, implantation, and placentation depend on continuous biological interactions between the partners. This review aims to critically evaluate the concept of couple biocompatibility as a pair-dependent component of human reproduction and explore its potential as a framework for future precision reproductive medicine. We distinguish individual reproductive factors and interaction modifiers from genuine partner-specific effects, including differential sperm responses to female reproductive tract secretions, maternal immune adaptation to paternal antigens, and maternal KIR–paternal/fetal HLA-C interactions. We further classify candidate biomarkers as partner-specific, partner-interaction, or downstream reproductive outcome biomarkers and evaluate their current clinical maturity. No core partner-specific or partner-interaction assay currently qualifies as a validated, guideline-supported test of general couple biocompatibility. However, integration of defined-pair functional assays with multi-omics, extracellular-vesicle profiling, advanced reproductive models, and computational approaches may provide a foundation for future couple-specific diagnostic platforms. Rather than replacing established infertility assessment, couple biocompatibility could extend it toward precision reproductive medicine in which reproductive potential is evaluated not only at the level of each individual, but also at the level of the biological pair.