Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study.

We assessed the predictive ability of a combined genetic variant panel for the risk of recurrent pregnancy loss (RPL) through a case-control study. Our study sample was from Ukraine and included 114 cases with idiopathic RPL and 106 controls without any pregnancy losses/complications and with at least one healthy child. We genotyped variants within 12 genetic loci reflecting the main biological pathways involved in pregnancy maintenance: blood coagulation (F2, F5, F7, GP1A), hormonal regulation (ESR1, ADRB2), endometrium and placental function (ENOS, ACE), folate metabolism (MTHFR) and inflammatory response (IL6, IL8, IL10). We showed that a genetic risk score (GRS) calculated from the 12 variants was associated with an increased risk of RPL (odds ratio 1.56, 95% CI: 1.21, 2.04, p = 8.7 × 10-4). The receiver operator characteristic (ROC) analysis resulted in an area under the curve (AUC) of 0.64 (95% CI: 0.57, 0.72), indicating an improved ability of the GRS to classify women with and without RPL. Ιmplementation of the GRS approach can help define women at higher risk of complex multifactorial conditions such as RPL. Future well-powered genome-wide association studies will help in dissecting biological pathways previously unknown for RPL and further improve the identification of women with RPL susceptibility.

Novel missense mutation in ligand binding domain of AR gene identified in patient with androgen insensitivity syndrome from Ukraine.

To improve diagnostic informativity of AR gene mutation analysis in patients with AIS, we recommend to include novel identified missense mutation c.2507T>G in the list of AIS-causing mutations.

Association of PvuII polymorphism in ESR1 gene with impaired ovarian reserve in patients from Ukraine.

The association of ESR1 PvuII polymorphism (rs2334693) with impaired ovarian reserve was studied by genotyping this polymorphism using PCR-RFLP in patients and two control groups from Ukraine. Statistically significant differences in the prevalence of p-allele frequency (-397T) was seen in the group of patients with impaired ovarian reserve (0.597) compared to control groups I under 35years (0.480) and II over 35years (0.453), both p<0.05. The data suggest that PvuII polymorphism of ESR1 is associated with diminished ovarian reserve.

A distribution of two SNPs in exon 10 of the FSHR gene among the women with a diminished ovarian reserve in Ukraine.

PURPOSE: To evaluate the association between phenotype and follicle stimulating hormone receptor (FSHR) genotype in women with ovarian dysfunction and patients with "poor response" to gonadotropin stimulation of ovulation. METHODS: FSHR gene SNPs were analyzed by PCR and RFLP. "Poor responders" (ovarian dysfunction) group and "good responders" group constituted the study group. Normo-ovulatory women who gave birth to naturally conceived children formed control groups: under 35 years of age (control I) and over 35 years of age (control II). RESULTS: The frequency of Ala307-Ser680/Ala307-Ser680 genotype was significantly more prevalent in the ovarian dysfunction group (26%) compared to the control I (7.7%) (P < 0.001) and a "good responders" group (12.5%) (P < 0.05); and in a "poor responders" group (33.3%) compared to a "good responders" group (P < 0.05), control I (P < 0.001) and control II (17.5%) (P < 0.05). CONCLUSIONS: Our data shows the prevalence of the Ala307-Ser680/ Ala307-Ser680 genotype in the both groups of patients. The finding should have impact on the delineation of stimulation protocols.