ESR1 GENE RELATED RISK IN THE DEVELOPMENT OF IDIOPATHIC INFERTILITY AND EARLY PREGNANCY LOSS IN MARRIED COUPLES.

The aim of the work was to assess genetic risk of reproductive disorders in married couples, conditioned by polymorphic variants A-351G and T-397C of ESR1gene. The study involved 412 persons - 206 married couples: 69 married couples with idiopathic infertility, lasting over 5 years, and 137 married couples with early reproductive losses in their past medical history. The data of population frequencies for the European population, obtained from the open database of 1000 Genomes project, were used as a comparison group. The polymorphic variants A-351G and T-397C of ESR1 gene were investigated using the method of polymerase chain reaction with subsequent analysis of the restriction fragment length polymorphisms. It was determined that the presence of genetic variant -351GG (log-additive model of inheritance) and the combination of genotypes -351GG/-397CC of ESR1 gene was associated with the increasing risk of developing male idiopathic infertility. The association of the polymorphic variant A-351G of ESR1 gene with the increasing risk of developing idiopathic infertility (log-additive model of inheritance) and early reproductive losses (over-dominant model of inheritance) was revealed in women from the examined married couples. Significant protective effects in terms of reproductive disorders in men were found for the combinations of genotypes -351AA/-397TT and -351AA/-397TC of ESR1 gene. The obtained results demonstrated new view about the ESR1 identical genetic mechanisms of developing idiopathic infertility and early pregnancy loss in couples. These determined specificities highlight the need of conducting genetic investigations of both ESR1 polymorphic variants in couples and the significance of searching for phenotypic manifestations of investigated reproductive disorders which occurred due to genetic variants.

POSITIVE EFFECT OF BETAINE-ARGININE SUPPLEMENT ON IMPROVED HYPERHOMOCYSTEINEMIA TREATMENT IN MARRIED COUPLES WITH REPRODUCTIVE DISORDERS.

Treatment of hereditary hyperhomocysteinemia and the achievement of optimal folate status is necessary for persons of reproductive age in order to increase live birth rate. Patients are usually advised to take folic acid, a key nutrient in homocysteine remethylation. The results of study showed risk factors for hyperhomocysteinemia development in investigated married couples: male gender, MTHFR, MTR1 genes variants, lower vitamin B12 blood serum and no additional intake of vitamin B12. Since MTHFR, MTR1 genes variants affect to decrease the efficiency of homocysteine metabolic transformations, to contribute also to endothelial dysfunction in one of patients group we used betargine combined with folic acids and vitamin B12 administration. Patients group with combined administration including betargine within 2 weeks, in comparison with the group without its supplement, had significantly decreased level of homocysteine in plasma, less than 12 µmol/l (81.03% and 50% of cases, respectively). Folic acid and vitamin B12 mean values in blood serum was significantly increased in patients after two week vitamins administration including betargin. Further research is needed to establish the duration of betaine-arginine intake until the target homocysteine level will be reached, as well as to estimate the durability of clinical effect achieved after consumption.