Background. Miscarriage is a common complication in early pregnancy. Current studies have shown a higher prevalence of miscarriage, ranging from 10 to 20%. The review is devoted to modern concepts of etiology and pathogenesis of early pregnancy losses. Aim. Assess the role of epigenetic factors and molecular-genetic markers in the pathogenesis and prediction of early pregnancy losses Materials and methods. In order to write this review domestic and foreign publications were searched in Russian and international search systems (PubMed, eLibrary, etc.) for the last 10-15 years. Relevant articles from the peer-reviewed literature and clinical practice guidelines were included. Results. Many recent studies have proved the contribution of various epigenetic factors to the pathogenesis of spontaneous miscarriages, and the molecular-genetic determination such kinds of pregnancy complication has been confirmed. Conclusion. The miscarriage in early gestation is driven by combined impact of epigenetic and molecular-genetic factors, as well as the presence of intergenic interactions. It is may lead to deterioration of physiological functions, and maternal pathologenic pathways could be changed as during her periconceptional period as so during the pregnancy.

Aim. To assess the association between polymorphisms of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G and their combinations in patients with recurrent early pregnancy losses (RPL). Materials and methods. This study included two groups of women (age range 20-35 years): 50 currently non-pregnant women with a history of 2-5 unexplained recurrent early spontaneous abortion and unknown causes of miscarriages (RPL group), and 50 currently non-pregnant women with a history of having given birth to at least one live baby and without a history of spontaneous abortion, preterm labor, stillbirth, preeclampsia and other pregnancy complications (control group). Gene polymorphisms were detected by the technique of polymerase chain reaction-real time. We have analyzed the frequencies, Hardy-Weinberg equilibrium, V-Kramer test, χ2 test, odds ratio (OR) and its 95% confidence interval (95% CI). General (χ2 test, df=2) and multiplicative (χ2 test, df=1) models of inheritance have been used to assess the presence of gene polymorphisms. Results. Significant association between heterozygotes genotype PAI-1-5G4G (72% vs 32%, p=0.000; OR 5.46; 95% CI 2.32-12.87) and RPL was found. Heterozygous genotype FII-20210GA was detected only in RPL group (4% vs 0%). Combinations of genetic polymorphisms of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G increase the risk of RPL by 2.4 times (56% vs 20%; χ2=29.20, р=0.000; OR 3.69, 95% CI 1.52-8.97; strong V-Kramer association). The combination of two heterozygotes variants of minor alleles was found to be a risk factor for RPL (34% vs 10%; χ2=8.73, р=0.004; OR 4.64, 95% CI 1.55-3.84). Combined PAI-1-5G4G + FVL-1691GA genotypes was detected only in RPL group of women (2% vs 0%). No significant association between the combination of three heterozygotes variants of minor alleles and RPL. Conclusion. Our data suggest significant gene-gene interaction of the heterozygotes variants of minor alleles of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G polymorphisms in patients with recurrent miscarriage. Combined genotypes FVL-1691GA/PAI-1-5G4G can be considered as a genetic molecular predictor of recurrent early pregnancy losses.

Aim.To develop the prognostic model to calculate the probability of severe preeclampsia in healthy young reproductive age woman. Materials and methods.This study included two groups of healthy women aged 1835 years with spontaneous singleton pregnancy: 100 patients with severe preeclampsia (patient group), and 100 women with non-complicated pregnancy (control group). All women had not a risk factors of preeclampsia such as history of hypertension, autoimmune, metabolic, renal, or cardiac diseases, and family or individual history preeclampsia or thromboembolism before this pregnancy. Their body mass index in the 1-st trimester of gestation was 35 kg/sq. m. Gene polymorphisms were detected using the polymerase chain reaction-real time technique. The data were analyzed with methods of binary and multifactorial mathematical statistics. Our analysis of the predictive models was performed by using logistic regression. To determine the diagnostic value of the predictive models used the ROC-curve is followed by determining the area under it (AUC). Results.Some prognostic models to calculate the probability of severe preeclampsia were build using an anamnestic, clinical and genotypic characteristics and multifactorial analysis. Combination of genotypesAGTR2-1675АA/eNOS3-786СC; tobacco smoking; bacteriuria; acute respiratory infections and/or acute vulvovaginitis during 23 trimester of gestation were determinate as most informative predictors of severe preeclampsia. Logistic model included three predictors: bacteriuria; acute respiratory infections and/or acute vulvovaginitis during 23 trimester of gestation had higher prognostic value. ROC analysis identified a high specificity (89.58%) and sensitivity (76.47%) of the model, and the integral index of the effectiveness of predictive markers (AUC=0.885), according to the expert scale of values which is indicative of a very high quality model. Conclusion.It is recommended to use this elaborated predictive model for the purpose of individual risk assessment of severe preeclampsia in healthy young reproductive age woman.