The role of melatonin deficiency in the pathogenesis of idiopathic infertility in women of advanced maternal age: A prospective cohort study

The low efficacy of assisted reproductive technology programs in women aged 35–45 with idiopathic infertility necessitates the search for pathogenetic factors that remain undetected during standard ovarian reserve assessment. Objective. The aim of the study if to comprehensively characterize the clinical, laboratory, endometrial, molecular-genetic, and metabolic profiles of advanced maternal age women with idiopathic infertility associated with melatonin deficiency. Materials and Methods. The authors conducted a prospective comparative cohort study, including 239 patients aged 35–45 with idiopathic infertility and one or more failed IVF cycles. The main group (n=115) comprised women with nocturnal salivary melatonin levels <40 pg/mL, while the comparison group (n=124) consisted of patients with melatonin levels ≥40 pg/mL. Hormonal profiles, aromatase activity ratios, endometrial immunohistochemical markers (ERα, PR-A, CD56, CD138), the MTNR1B rs1387153 polymorphism, HOMA-IR, IGF-1/IGFBP-3, and 25(OH)D were evaluated. Non-parametric tests and regression analysis were used. Results. Melatonin deficiency was associated with a higher incidence of cervical diseases (OR=3.51), nonalcoholic fatty liver disease, and chronic dermatoses (OR=7.09). It was also linked to a 25.0 % reduction in AMH, a 23.2 % increase in FSH, a 28.5 % decrease in the follicular aromatase activity ratio, decreased PR-A expression, an ERα/PR-A imbalance, increased CD56+ cell counts, and a higher frequency of the MTNR1B T allele (67.0 %; OR=1.85). Conclusion. Nocturnal salivary melatonin levels may be considered an informative biomarker for an unfavorable pathogenetic variant of idiopathic infertility in advanced maternal age women.