Cracking the fertility code: a comprehensive review of biomarkers and functional measures.

Abstract

Human fertility is regulated by a complex, integrated network of biological systems that collectively determine reproductive competence in males and females. Conventional fertility assessment relies on established clinical biomarkers, including reproductive hormone profiles, gamete-based functional assessments and imaging indicators of gonadal structure and function. While clinically informative, these measures capture only partial views of molecular and cellular processes underlying gametogenesis and reproductive capacity. Recent advances in reproductive medicine have expanded the biomarker landscape through genetic and epigenetic profiling, enabling identification of pathogenic variants, chromosomal abnormalities and regulatory modifications associated with infertility syndromes. In parallel, multi-omics approaches are increasingly being used to characterize molecular networks governing gamete development, meiotic integrity, DNA repair and cellular differentiation. This review presents a comprehensive synthesis of fertility biomarkers, spanning endocrine, genetic, epigenetic, structural, metabolic and inflammatory systems. Current evidence is examined on endocrine and reproductive hormone biomarkers, followed by an investigation of genetic and epigenetic markers of reproductive dysfunction, as well as structural and imaging-based biomarkers and inflammatory and metabolic indicators. Finally, emerging biomarker platforms are highlighted as key advances towards precision reproductive medicine. Collectively, these developments support a shift towards a more comprehensive, biomarker-driven framework for the evaluation and management of infertility.