Unraveling the Molecular Events of Human Fertilization: A Systematic Review of Human Gamete Studies

The interaction between molecules of gametes is intricate, as fertilization is a highly regulated process in humans. With recent breakthroughs in molecular biology, it has become possible to investigate these events in unprecedented detail, though some mechanistic steps remain unclear. This systematic review followed PRISMA rules. Peer-reviewed literature was searched through major scientific databases between 2015 and 2025, limited to human studies. The initial search yielded 89 records. After removing duplicates and applying inclusion/exclusion criteria, 53 full-text articles were assessed, with 35 deemed eligible. Molecular mechanisms, experimental methods, and translational implications were highlighted in data extraction and synthesis. The included studies shed light on sperm–oocyte recognition, interaction with the zona pellucida, signaling pathways in the acrosome reaction, and cortical reaction dynamics after fertilization. New methods, including CRISPR/Cas9 genome editing, transcriptomic screening, and human embryoid models, have enhanced the understanding of gamete processes. However, unanswered questions remain on the role of sperm protein SPACA6, heterogeneity of species in zona pellucida binding, and ethical restrictions in human fertilization studies. Implementation of advanced molecular techniques has significantly increased understanding of human fertilization, but essential information is still lacking. Addressing these gaps will require ethically sound advances to translate fundamental research into clinical applications.

Key Words: Human fertilization, PRISMA, CRISPR/Cas9, transcriptomics, zona pellucida, SPACA6, embryoid models, cortical reaction.