Kryvopustov O. Prognosis and treatment optimization of threatened abortion in women based on the progesterone receptor gene allele polymorphism

The scientific thesis is devoted to increase the treatment efficacy of women with threatened abortion by means of natural micronized progesterone therapy considering the clinical data and progesterone receptor gene allele polymorphism. In general, 212 women were enrolled into the study. Among them, there were 117 women without any obstetric, gynecological, and severe extragenital pathology at the moment of their enrollment (study group 1) and 95 patients with a diagnosis of threatened abortion (study group 2). Among the study group 2 patients, 67 women were getting treatment not taking into account allele single nucleotide polymorphism (SNP) in PGR (study subgroup 2a) and 28 women were getting treatment based on SNP in PGR (study subgroup 2b). The risk of threatened abortion development based on SNP in PGR by comparison of the two study groups was determined. It was found out that high stress level by PSS and homozygous carrier of the G allele of SNP in PGR rs590688 contributed to the higher risk of pathology development. The homozygous carrier of the G allele of rs590688 demonstrated 2.5 times higher risk than other genotypes of that polymorphism. The initial dose of natural micronized progesterone for women with threatened abortion depending on prognostic response to the mentioned therapy has been substantiated. The group of women with threatened abortion having high response to the therapy with natural micronized progesterone included those who had pain syndrome approaching or equal to 4 by NRS, no or very moderate bloody vaginal discharge, and heterozygote CG or minor homozygote GG of rs590688 (C/G) polymorphism. Their dose of treatment with natural micronized progesterone had to include 300 mg a day, i.e., 100 mg per 3 times daily. The group of women with threatened abortion demonstrating low response to the therapy with natural micronized progesterone included patients with pain syndrome exceeding 4 by NRS and/or with severe bloody vaginal discharge, and/or those having major homozygote CC of rs590688 polymorphism (C/G). The dose of natural micronized progesterone for such women had to be 600 mg a day, i.e., 200 mg per 3 times orally daily. In the study subgroup 2a the statistically significant differences in distributing genotypes of SNP in PGR rs590688 between patients taking increased dose of therapy and those continuing taking the initial dose were disclosed. It was recognized that major homozygote CC was seen 3.3 times more frequently in women with threatened abortion requiring increased dose of therapy in comparison to those having positive effect by taking natural micronized progesterone in its initial dose of 300 mg a day. Women having major homozygote CC of rs590688 demonstrated low efficacy of treatment with natural micronized progesterone compared to women with other genotypes. Analyzing obtained data of the study subgroup 2b we found out the efficacy of pain relief achievement within seven days of progesterone therapy to be 1.7 times higher (p < 0.001) and efficacy of bloody discharge subsidence achievement within seven days to be 1.9 times higher (p < 0.05) in case of using differential therapy based on clinical genetic approach. Besides, the duration of progesterone treatment in case of using individualized therapy was 1.4 times shorter (p < 0.001). Patients of the subgroup 2b demonstrated the statistically significant increase of progesterone level in blood (p < 0.001) and PIBF in urine (p < 0.001) during the treatment. Consequently, we can state about the increased efficacy of treating women with threatened abortion by means of natural micronized progesterone therapy elaborated on the basis of clinical genetic approach considering clinical course peculiarities and SNP in PGR rs590688.