RU-2861359-C1 - METHOD FOR PREDICTING RISK OF DEVELOPING PREMATURE OVARIAN INSUFFICIENCY

Abstract

FIELD: medicine; obstetrics; gynaecology. SUBSTANCE: invention can be used for predicting the risk of developing premature ovarian insufficiency. With the number of CGG repeats in the promoter region of the FMR1 gene less than 35, a follicle-stimulating hormone level of less than 10 mIU/ml, an anti-Müllerian hormone level of more than 1.5 ng/ml and, according to ultrasound examination, with an antral follicle count of at least 12, a low risk of premature ovarian insufficiency is predicted. With the number of CGG repeats of 35-54, a follicle-stimulating hormone level of 10-12 mIU/ml, an anti-Müllerian hormone level of 1.0-1.5 ng/ml and an antral follicle count of 8-11, a moderate risk of premature ovarian insufficiency is predicted. With the number of CGG repeats of 55-200, a follicle-stimulating hormone level of more than 12 mIU/ml, an anti-Müllerian hormone level of less than 1.0 ng/ml and an antral follicle count of less than 8, a high risk of developing premature ovarian insufficiency is predicted. EFFECT: high information content, reproducibility and clinical significance in identifying risk groups for reduced ovarian reserve at early stages by analysing the number of CGG repeats of the FMR1 gene in combination with hormonal assessment. 1 cl, 1 tbl, 3 ex

Inventors

• Abusueva Zukhra Abusuevna
• Alieva Nuriyana Abdusamadovna

Dates

Publication Date

20260505

Application Date

20251029

Claims (1)

1. A method for predicting the risk of developing premature ovarian failure, including conducting a hormonal examination, characterized in that a molecular genetic study of the FMR1 gene, located on the long arm of the X chromosome Xq27.3, is additionally carried out, with the number of CGG repeats in its promoter region determined, while the obtained data are evaluated in conjunction with hormonal indicators, and the results are interpreted as follows: if the number of CGG repeats is less than 35, the level of follicle-stimulating hormone is less than 10 mIU/ml, if the level of anti-Müllerian hormone is more than 1.5 ng/ml and, according to ultrasound data, with the number of antral follicles of at least 12, a low risk of premature ovarian failure is predicted; With a CGG repeat count of 35-54, a follicle-stimulating hormone level of 10-12 mIU/ml, an anti-Müllerian hormone level of 1.0-1.5 ng/ml, and an antral follicle count of 8-11, a moderate risk of premature ovarian failure is predicted; with a CGG repeat count of 55-200, a follicle-stimulating hormone level greater than 12 mIU/ml, an anti-Müllerian hormone level less than 1.0 ng/ml, and an antral follicle count of less than 8, a high risk of developing premature ovarian failure is predicted.

Description

The invention relates to the field of medicine, namely to obstetrics and gynecology, and can be used to predict the risk of premature depletion of the ovarian reserve, menstrual irregularities and infertility in women of reproductive age. Analogues of the invention There are various methods for diagnosing and correcting premature ovarian failure, aimed primarily at restoring ovarian function, including: Patent No. 2750159 “Method for diagnosing premature ovarian failure”, Patent No. 27482461 “Method for laboratory diagnosis of premature ovarian failure by determining autoantibodies to steroidogenic enzymes cytochrome P450 in blood serum (plasma) using enzyme immunoassay”. Criticism of analogs Patent No. 2750159, "Method for Diagnosing Premature Ovarian Failure," has the following shortcomings: the diagnostic accuracy of the analogous method is limited. It detects pathological changes primarily at the stage of severely declining ovarian function, which reduces its value for early prognosis. Furthermore, the method does not account for the genetic development of premature ovarian failure (POF). The assessment is based solely on functional and morphological parameters, without considering the individual characteristics of the patient, making it uninformative. Patent No. 27482461, "A Method for the Laboratory Diagnosis of Premature Ovarian Failure by Determining Autoantibodies to the Steroidogenic Enzyme Cytochrome P450 in Blood Serum (Plasma) Using an Enzyme-Linked Immunosorbent Assay," has the following drawbacks. A known, similar method is aimed at identifying autoimmune forms of POF by detecting autoantibodies to the cytochrome P450 enzymes involved in steroidogenesis. Its application is limited: autoantibody detection reflects only one possible mechanism of ovarian damage and does not account for genetic predisposition. Furthermore, the method's sensitivity is low in early or subclinical forms of the disease, and interpretation of the results requires a high level of laboratory standardization. Prototype As a prototype, we have taken patent No. 2815539 "Method for predicting premature ovarian failure in women of reproductive age with oligomenorrhea". The prototype method includes echographic determination of ovarian volume and the number of antral ovaries, characterized in that the presence of one of the alleles DRB1 * 01, DRB * 04, DRB1 * 03, DQB1 * 302, DQB1 * 501 HLA class II, a fluctuating level of follicle-stimulating hormone against the background of still preserved menstrual rhythm or the first delays of menstruation, and with an ovarian volume of less than 5 cm, a number of antral follicles less than 10, an increase in the pulsation index of more than 1.1 and a resistance index of 0.71 in the hilum and parenchyma of more than 0.9 and 0.55, respectively, vascular blood flow of the ovaries, they predict premature ovarian failure. Criticism of the prototype The prototype method is based on assessing ovarian reserve based on follicle-stimulating hormone and anti-Müllerian hormone levels, as well as the number of antral follicles. However, this approach has several significant limitations. The prototype does not take into account molecular genetic factors, particularly the number of CGG repeats in the FMR1 gene, making it impossible to identify women with a genetic predisposition to decreased ovarian reserve at the preclinical stage. Furthermore, hormonal and ultrasound parameters are influenced by age, stress, and other factors, reducing the accuracy of the prognosis. The method does not fully provide clear stratification of patients by risk. Purpose of the invention The aim of the invention is to increase the accuracy and early prognostic value of diagnosing the risk of premature ovarian failure by using indicators reflecting genetic predisposition, in particular determining the number of CGG repeats of the FMR1 gene in combination with hormonal parameters. The essence of the invention The method predicts the risk of developing premature ovarian failure (POF) using a genetic marker—the number of CGG repeats in the FMR1 gene—in combination with an assessment of hormonal parameters. This allows for the identification of a predisposition to decreased ovarian reserve. - The woman being examined undergoes a molecular genetic study using standard amplification and sequencing methods, determining the levels of follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) and the number of antral follicles (AF). - The woman being examined undergoes hormonal testing, and the results of these tests are evaluated together with the data from the molecular genetic analysis of the FMR1 gene: - if the number of CGG repeats is less than 35 and the hormonal parameters are: FSH - <10 mIU/ml, AMH -> 1.5 ng/ml and the number of antral follicles is at least 12, a low risk of premature ovarian failure is predicted; - with 35-54 repetitions in combination with a moderate increase in FSH 10-12 mIU/ml, a decrease in AMH 1.