The goal of our study was a comprehensive assessment of obstetric, gynecological, somatic and genetic factors, contributing to high risk of insufficient luteal phase (ILP) and relating gestational disorders to the latter in relevant patients for further optimization of therapeutic and preventive measures. Material and Methods — A cohort study with a mixed cohort was carried out. The clinical material of the retrospective study was presented based on the results of analyzing 300 cases of patients with verified diagnoses of the threat of spontaneous abortion, miscarriage, and complete spontaneous abortion, who were hospitalized in the period of 2018-2020. As part of a prospective study, we analyzed 66 blood samples of women treated at the State Budgetary Healthcare Institution Simferopol Clinical Maternity Hospital No.2 in Crimea in 2020. The polymerase chain reaction method in real time mode, with the use of the developed kits, was used for CYP3A5 6986A> G polymorphism. Results — A comprehensive assessment of obstetric, gynecological, somatic and genetic factors allowed identifying the most informative prognostic markers for the risk of developing luteal phase insufficiency and related gestational disorders, including irregular menstrual cycle, cases of drug-induced abortion, preceding specific infectious diseases (chlamydia, Ureaplasma urealyticum infection), gynecological pathology (polycystic ovary syndrome), surgical interventions performed for gynecological pathology (ovarian resection and ovariectomy), as well as single nucleotide polymorphism rs776746 in the CYP3A5 gene. Conclusion — The identified prognostic criteria make it possible to identify a group of patients with a high risk of miscarriage even before the conception; such patients need more careful and systematic medical monitoring for the timely diagnosis of possible pregnancy complications. Early diagnosing of potential issues would allow clinicians to take preventive measures, along with initiating timely treatment. As a result, the percentage of reproductive losses would go down.