ВЗАИМОСВЯЗЬ ГЕНА РЕЦЕПТОРА ЛЕПТИНА (LEPR ) И РЕЗУЛЬТАТОВ ЭКО У ЖЕНЩИН С НАРУШЕНИЕМ ОВУЛЯЦИИ

Abstract

The relevance of the problem is associated with the increasing prevalence of anovulatory infertility against the background of increased body weight in women, which reduces the effectiveness of IVF.
Objective – to study the genetic determination of leptin levels in women with anovulatory infertility and its relationship with the effectiveness of IVF.
Materials and methods. The study involved 109 women with confirmed anovulatory infertility, menstrual dysfunction, increased body weight and a negative IVF result (mean age 29.6 ± 3.6 years). The control group included 73 women with a history of 1 or more normal births with a healthy child aged 30.2 ± 1.6 years and a BMI that did not exceed age norms. All women had levels of luteinizing hormone, follicle-stimulating hormone, and anti-Müllerian hormone. Serum leptin levels were determined by enzyme immunoassay using Penisula laboratories and ELISA test systems. To study single nucleotide polymorphisms of the leptin receptor gene (LEPR), genomic DNA was isolated from peripheral blood leukocytes using the Puregene Blood Kit. Polymorphism was determined by sequencing after polymerase chain reaction using forward and reverse primers. Nucleotide sequencing was performed using the ABI Big Dye Terminator protocol on an ABI 3100 Avant genetic analyzer. Additionally, the following were performed: ultrasound examination of the pelvic organs.
Results. For patients with anovulatory infertility and increased body weight, the most typical is the minor LEPR-GG genotype, which was detected in 67.9% and associated with an increased leptin level (χ2 = 24.8), another 32.1% of them had the LEPR-AA genotype associated with a low leptin level. In the control group, 97.3% had the LEPR-GA genotype, which corresponded to normal values of the leptin level in the blood serum (χ2 = 35.9). The most common causes of unsatisfactory IVF results in women with the LEPR-GG genotype were the presence of a thin endometrium (48.6%), poor ovarian response (54.1%), decreased oocyte quality against the background of superovulation stimulation (71.6%), no pregnancy (45.9%) or biochemical pregnancy (31.1%). In the presence of the LEPR-AA genotype, the most common causes of failure were early termination of pregnancy (62.9%) and biochemical pregnancy (22.8%).
Conclusion. In patients with an increase in BMI, leptin levels can be both higher and lower than normal. Low leptin levels are associated with the LEPR-AA genotype, and high levels are associated with the LEPR-GG genotype. The presence of minor LEPR-AA and LEPR-GG genotypes increases the risks of unfavorable IVF outcomes in patients with anovulatory infertility.