Introduction. Normal ovarian reserve (OR) determining the ovarian response to follicle development containing fully-featured oocytes is an important factor in pregnancy, including assisted reproductive technology (ART) programs. The causes of premature OR decrease are multifactorial. The study of gene polymorphism as a cause of the premature OR decrease deserves attention.Aim: to determine genetic predisposition to premature OR decrease and create a prognostic model based on study results.Materials and Methods. A retrospective comparative cohort study was conducted. A total of 200 reproductively active patients with infertility underwent ART were examined. The patients were divided into 2 groups: Group 1 included 100 patients with a premature OR decrease; Group 2 consisted of 100 patients with a normal OR. All patients underwent molecular genetic study. Genetic polymorphisms of the genes ESR1, ESR2, FSHR, CYP19A were studied.Results. The final clinical phenotype is shaped by multiple factors – genetic and environmental. Several genetic variants contribute to the formation of premature decrease in ovarian reserve. Gene combination of CYP19A1 and FSHR displayed the greatest synergistic effect, potentiating each other and predisposing to a poor ovarian response as part of stimulated superovulation.Conclusion. Identifying genetic markers is a promising method for individual OR evaluation, including its premature decline. Multilocus analysis and a prognostic model based on combining several polymorphic gene variants will allow to assess risks of premature OR decrease and individualize ART programs.