Oligomenorrhea is a polyetiological disease, and in the adolescent population is most often considered as a physiological condition, due to the lack of a clear relationship with any particular somatic or gynecological pathology. Hormonal research, in most cases, is not informative. In this regard, it is relevant to search for molecular biological markers that allow diagnosing the disease in the early stages of its development. Modern studies have revealed the possibility of participation of the phragil X chromosome gene (FMR1), located on the long arm of the X chromosome in the Hq27.8 locus, in the pathology of folliculogenesis. The role of premutation – an increase in the number of CGG repeats ranging from 50 to 200 – in the genesis of PNA and infertility is represented by few scientific reports [1]. The least studied is the relationship of reducing the number of CGG repeats of less than 26 with the risk of ovarian dysfunction [2]. To date, there are no studies conducted in the adolescent population regarding the relationship of the abnormal number of CGG repeats in the FMR1 gene with ovarian dysfunction, manifested by various menstrual disorders. Studies of the FMR1 gene product, the FMR1 protein (FMR1P), have also not been conducted in adolescents.

The purpose of the study is to improve the differential diagnosis of oligomenorrhea in adolescents based on the investigation of molecular genetic markers as predictive factors of ovarian dysfunction.

Study Design: The study included 80 adolescent girls diagnosed primary and secondary oligomenorrhea. One of the objects of the study was the fragile X mental retardation-1 (FMR1) gene on the X chromosome and protein FMR1 (FMR1P). The determination of allele variants of FMR1 genes was carried out by PCR. In addition to the studies included in the standard of patient management with oligomenorrhea, the ELISA method defined the serum content of anti-ovarian antibodies, AMH, Inhibin-B.

In retrospect, patients with oligomenorrhea were divided into 3 groups depending on the various heterozygous subgenotypes of the FMR1 gene: I group – heterozygous individuals with «het-norm / low» subgenotype - the number of CGG repeats of one allele within the normal range (26-34), and in the second allele - less than the lower limit of the norm (26); II group - heterozygous individuals with het-norm / high, whose number of CGG repeats of one allele - within the normal range, and in the second allele - exceeds the upper limit of standards (34); III group - unaffected individuals, the FMR1 gene contains 29 or 30 repeats of the sequence CGG.

Results and Conclusion: Based on the results of our study [3], we have identified the clinical heterogeneity of the cohort of patients with oligomenorrhea, caused by various heterozygous subgenotypes of the FMR1 gene, formulated the clinical-laboratory characteristic of each subgenotype and developed a personalized algorithm for examination and therapy of adolescents with oligomenorrhea. 1. Heterozygous low - characterized by an increased titer of autoantibodies to TPO and ovarian antigens, increased production of AMH, FMR1P, hyperandrogenism and small cystic ovarian transformation and can be considered as an autoimmune phenotype of polycystic ovary syndrome. The incidence according to our study was 25%; 2. Heterozygous high - characterized by an decreased level of FMR1P, inhibin B, AMH relative to age-related standards, with moderately elevated gonadotropins, which can be considered as the initial signs of POI. The incidence was 13.75%.