THE ASSOCIATION BETWEEN MELATONIN DEFICIENCY AND MTNR1B GENE POLYMORPHISM WITH IVF OUTCOMES IN WOMEN WITH IDIOPATHIC INFERTILITY

Ichmelyan Albert Misakovich, Bogdasarov Azat Yuryevich, Davidyan Liana Yuryevna, Bogdasarova Regina Azatovna

The aim of the study was to evaluate the significance of melatonin deficiency and MTNR1B gene polymorphism for the outcomes of assisted reproductive technologies (ART) in women aged 35-45 with idiopathic infertility. A prospective comparative study (2019–2024, n=239) was conducted. The main group (n=115) comprised patients with melatonin deficiency (nighttime saliva <40 pg/ml), the comparison group (n=124) had normal levels. A comprehensive analysis was performed: melatonin diurnal profile (HPLC-MS), its level in follicular fluid, MTNR1B polymorphism (rs1387153), hormonal profile, aromatase activity, IGF-1/IGFBP-3 levels, endometrial immunohistochemistry. Statistics: Mann-Whitney U test, χ², Spearman correlation. The study showed that melatonin deficiency was detected in 48.1% of patients. Its nighttime level was 3.4 times lower than in the control group (14 [11-17] vs 47 [43-51] pg/ml, p<0.0001), and in follicular fluid it was 41.5% lower (2.67 [2.24-3.09] vs 4.55 [3.81-5.26] pg/ml, p<0.0001). The main group had a higher basal estradiol level (62.8 [57.5-67.3] vs 58.9 [55.4-61.4] pg/ml, p=0.0002). Melatonin deficiency correlated with insulin resistance (r=-0.254) and inflammatory gynecological pathology (r=-0.246). MTNR1B polymorphism was detected in 25.2% of patients with deficiency and was associated with more frequent insulin resistance (χ²=8.3, p=0.004). Thus, the study showed that melatonin deficiency is a common condition associated with metabolic and inflammatory disorders in women with idiopathic infertility. Its combination with MTNR1B polymorphism forms an unfavorable phenotype. Assessment of melatonin status and genetic testing are promising for personalizing preparation for repeated IVF attempts.

Keywords:melatonin, melatonin deficiency, MTNR1B, polymorphism rs1387153, idiopathic infertility, IVF, insulin resistance