Macrophage migration inhibitory factor in human fertility: A systematic review of clinical and reproductive implications, 2015–2025

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine involved in inflammatory and immune regulation. This systematic review evaluated current evidence on the association between MIF and human reproductive function in male and female populations. PubMed, Scopus, Embase, and Google Scholar were systematically searched for studies published from 2015 to 2025. After duplicate removal and eligibility screening, 12 studies were included. Data on study design, population characteristics, reproductive conditions, and MIF expression were extracted and synthesized qualitatively. The included studies reported associations between altered or elevated MIF levels and several reproductive and pregnancy-related conditions, including endometriosis, polycystic ovary syndrome, recurrent pregnancy loss, endometrioma, and hypertensive disorders of pregnancy. MIF was frequently implicated in inflammatory pathways and hormonal regulation within reproductive tissues. The available evidence suggests that MIF may be involved in disease pathophysiology and may have potential as a biomarker in selected reproductive disorders. Overall, current evidence indicates that MIF is associated with multiple reproductive pathologies and may contribute to inflammatory and endocrine regulation in fertility-related conditions. However, further well-designed studies are needed to clarify its diagnostic and clinical utility in reproductive medicine.