Homocysteine and female reproductive health: a narrative review

Research on the role of homocysteine (Hcy) in female reproductive disorders has provided new insights for enhancing female fertility and improving clinical pregnancy outcomes. However, further studies are needed to fully elucidate the complex mechanisms involved and optimize therapeutic strategies, to develop more effective interventions for women with reproductive health conditions. This narrative review systematically synthesizes evidence from clinical and mechanistic studies published over the past 15 years. We critically appraise study limitations, distinguish between observational associations and causal evidence, and contextualize heterogeneity in study populations and diagnostic thresholds. Numerous epidemiological and clinical studies have reported a consistent association between Hcy dysregulation and adverse reproductive outcomes across the female lifespan. Elevated Hcy is implicated in the pathophysiology of polycystic ovary syndrome (PCOS), diminished ovarian reserve (DOR), reproductive aging, unexplained infertility (UI), endometriosis, and adverse pregnancy outcomes, and is linked to poor outcomes in assisted reproductive technology (ART). A growing body of evidence indicates that optimizing Hcy levels via dietary, lifestyle, and targeted nutritional interventions may improve reproductive outcomes. Close clinical monitoring is essential for any pharmacological intervention to ensure safety and efficacy. This review provides a comprehensive synthesis of the role of Hcy in female reproductive disorders and the therapeutic potential of Hcy-targeted interventions, serving as a reference for improving female fertility and clinical pregnancy outcomes. Large-scale, multicenter randomized controlled trials are required to further validate the efficacy of Hcy-lowering therapies in improving live birth and long-term maternal and neonatal outcomes. Continued research in this field will enable the development of targeted, personalized prevention and treatment strategies for women with reproductive disorders.