BACKGROUND: Male factor infertility accounts for up to 50% of couples' inability to conceive. Despite this significant burden, perspectives on male fertility have evolved over millennia, shaped by cultural, medical, and scientific frameworks. Tracing this trajectory illuminates how historical observations laid the foundations for modern andrological science.
OBJECTIVES: This scoping review maps the evolution of male fertility research from ancient civilizations through contemporary precision medicine approaches, identifying key paradigm shifts, persistent knowledge gaps, and emerging frontiers in the field.
METHODS: Following Arksey and O'Malley's framework, we systematically searched historical medical texts, archaeological records, and biomedical databases (PubMed, Embase, Web of Science) from inception to 2025. Sources encompassing ancient fertility practices, medieval to early modern medical writings, the microscopy revolution, the endocrinology era, and contemporary molecular approaches were included. Data were extracted and synthesized thematically across temporal epochs.
RESULTS: Our review reveals five major paradigm shifts: (i) ancient empiricism (3000 bce to 500 ce) emphasizing humoral balance and dietary interventions; (ii) medieval stagnation with persistence of Galenic theories; (iii) the microscopic revolution (1677-1900) establishing cellular foundations; (iv) the endocrine era (1900-1990) elucidating hormonal regulation; and (v) the molecular age (1990 to present) introducing genetic, epigenetic, and systems biology approaches. Key milestones include the discovery of spermatozoa, the development of semen analysis, the identification of the hypothalamic-pituitary-gonadal axis, assisted reproductive technologies, and contemporary omics-based diagnostics. Persistent challenges include an incomplete understanding of idiopathic infertility and limited treatment options for specific conditions.
CONCLUSIONS: Male fertility research demonstrates remarkable continuity alongside revolutionary breakthroughs. While ancient practitioners recognized lifestyle and environmental factors now validated by modern science, contemporary precision medicine approaches promise personalized diagnostics and targeted interventions. Future directions include integration of multi-omics data, artificial intelligence-assisted diagnosis, and regenerative medicine strategies for previously untreatable conditions.
