Spontaneous abortion is a complex, multifactorial pathology, where various genetic, neural, endocrine, and immunological factors are involved. Cytokines, Toll-like receptors, and progesterone receptors play critical roles in embryonic implantation and development. A delicate, stage-specific equilibrium of these proteins is required for successful pregnancy outcome. However, genetic variation from one individual to another results in variation in levels of Th1/Th2 cytokines, strength of identification of infectious agents by Toll-like receptors, and quality of progesterone recognition. Thus, a complex study encompassing effects of major SNPs of cytokine, TLR, and PGR genes on the risk of miscarriage is needed. In this study, we investigated SNPs of 9 genes (TLR2 G753A, TLR4 C399T, TLR9 G2848A, TGF-β1 C509T, PGR PROGINS, IL-6 G174C, IL-8 C781T, IL-10 C592A, and TNFα G308A) in 106 women, whose pregnancy ended in miscarriage, and 74 women, who delivered in term without any pregnancy complication. All participants are from Ukrainian population. As a result, TLR9 and IL-10 SNPs have been found to play critical roles in the development of spontaneous abortion. TLR2, TLR4, IL-6, IL-8, and PGR SNPs were identified as secondary factors that can also affect the risk of miscarriage. There was no association found between TGF-β1 and TNFα polymorphisms and miscarriage.

Objective: to investigate the morphological and immunohistochemical features of placental damage due to the incorporation of 137Cs depending on the scenario of pregnancy completion. Materials and methods. The study material consisted of placentas from 60 women with reproductive losses in anamnesis and signs of termination of the current pregnancy (first group) and placental samples from 30 women with an uncomplicated gestation and an unencumbered anamnesis (control group). The detailed study required the distribution of placental samples from the first group into subgroups. Subgroup 1a included 38 placentas from women who gave birth at 37–40 weeks, despite signs of termination of the current pregnancy. Subgroup 1b – placentas of 13 women who gave birth at a gestation period of 28–36 weeks + 6 days. Subgroup 1c – 9 placental samples from women who gave birth at a gestation period of 22–27 weeks + 6 days. The volumetric activity of the 137Cs in the placentas was measured using β-spectrometer. The histology of the placenta was studied using a standard technique. The following expressions were studied in placenta: CD31 / PECAM-1, CD45 / T200 / LCA, CD56 / NCAM-1, CEA / CD66e Ab-2, Vimentin, using indirect streptavidin peroxidase detection method. Results. Placentas accumulate 137Cs. The different volumetric activity of the isotope correlates with scenarios of pregnancy. Due to the action of incorporated 137Cs with a specific mass of more than 1.1 Bq/kg, placental dysfunction develops. The consequences of placental dysfunction depend on the volumetric activity of the 137Cs and the preservation of adaptive and compensatory reactions in the placenta. Morphological and immunohistochemical features of placental damage to incorporated 137Cs were established, depending on the scenario of completion of pregnancy. A marker of unfavorable completion of pregnancy is the expression of a carcinoembryonic antigen (CEA) in the placenta. Conclusions. Premature termination of pregnancy (PTP) is a multifactorial pathology associated with pathological changes in immune and neuroendocrine regulation and hereditary, infectious, and environmental factors that disrupt the adaptation mechanisms in the mother-placenta-fetus system. Intraplacental irradiation of 137Cs is one of the factors in the multifactorial nature of reproductive losses. As a result of intraplacental irradiation of 137Cs, the architecture of the placenta is disturbed, the activity of pro-inflammatory cytokines CD45 and CD56 increases, and the coagulation cascade is activated. Extreme effects depend on the volumetric activity of the isotope incorporated in the placenta and the organ’s compensatory capacity. Accumulation of up to 1.0 Bq/kg 137Cs does not affect the course of gestation. Internal irradiation with an activity of 4.5–10.4 Bq/kg 137Cs triggers late preterm labor. The nature of the damages corresponds to the category of «lesion of the maternal stroma» of the placenta. The volumetric activity of 137Cs over 10.4 Bq/kg is a probable cause of early preterm labor and antenatal fetal death. At the same time, the maternal and fetal structures of the placenta suffer damage. Expression of vimentin is a marker of placental destruction due to internal irradiation of 137Cs with a specific gravity of more than 4.5 Bq/kg. Expression of CEA in the structures of the placenta of women with PTP is a unique find and marker of premature birth and antenatal fetal death with intraplacental irradiation of 137Cs with an activity of more than 4.5 Bq/kg. Key words: pregnancy, placenta, reproductive losses, 137Cs, CD45 / T200 / LCA, CD56 / NCAM-1, CD31 / PECAM-1, Vimentin, CEA / CD66e Ab-2.

Aim. The study is aimed at the evaluation of the association of IL6 gene -174G/C polymorphism and ESR1 gene -397C/T polymorphism with recurrent pregnancy loss (RPL) pathogenesis and at the investigation of the ESR1 gene -397C/T variant regulatory significance for the IL6 gene function. Methods. A case group of 75 women with RPL history and a control group of 106 unrelated healthy women, who have given birth to at least one child conceived in natural way, were genotyped by a PCR based restriction fragment length polymorphism assay. Results. There was no significant difference in IL6 -174G/C or ESR1 -397C/T genotype and allele frequencies between the case and control groups. Combined genotype distribution analysis showed significantly (p < 0.05) lower frequency of individuals homozygous for both IL6 -174G and ESR1 -397C alleles in case group (0.026) comparing to control (0.094). Conclusions. Genotype comprising IL6 -174G and ESR1 -397C alleles in homozygous state may be considered as a genetic marker of successful pregnancy maintenance during gestation early stages

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.

Habitual miscarriage is a stressful condition and a significant factor of frustration for married couples. The psycho-emotional state of the pregnant woman affects the course of the subsequent pregnancy and its outcome. Correction of the psychological component of habitual miscarriage is a promising direction for preventing reproductive losses. The aim of the work is to study the psychological components of miscarriage and determine the ways of their correction. Materials and methods. The level of chronic stress was studied in pregnant women with symptoms of miscarriage and a history of habitual reproductive losses (main group) based on indicators of psychoemotional state, the condition of the autonomic nervous system, and the degree of activation of stress-implementing systems. The results were evaluated with the scale PSS, PSM-25 as adapted by N. Ye. Vodopianova, Spielberger–Khanin inventory and the scale by L. D. Malkova, Baevsky index, cortisol content in the blood and urine. The pregnant women with a physiological course of pregnancy and uncomplicated history were included in the control group. Based on the fact that the etiology of habitual miscarriage is multifactorial, and the psychological component is amenable to correction, stress-protective therapy was included in the treatment complex of habitual miscarriage. To assess the effectiveness of treatment, the main group was divided into subgroups: 1 – with psychotherapy, 2 – without psychotherapy. Results. A high level of personal perception of stress, anxiety and asthenia determine the psycho-emotional state of the main group pregnant women, among whom two dominant psycho types were identified: A – a high level of anxiety and low neuropsychic resistance; B – poise and good adaptive ability against the background of stress. Non-drug stress-protective therapy in the complex of miscarriage treatment contributes to: a decrease in psycho-emotional stress in pregnant women with psycho type A – 2.6 times, anxiety level – 1.7 times, asthenia level – 2.3 times; and also: a decrease in similar indicators in pregnant women with psycho type B – 1.6 times, 3.9 times and 2.5 times, respectively (P < 0.05); a decrease in the frequency of premature termination of pregnancy by more than 11 %. Conclusions. The psychological component of miscarriage is a high level of personal perception of stress, anxiety and asthenia. Stress-protective therapy in combination with pathogenetic therapy of miscarriage improves pregnancy outcomes for the mother and the fetus. It is advisable to conduct pregravid training with the participation of a psychologist in women with a history of reproductive losses in order to overcome the psychological component of stress perception, expand adaptive potential, increase neuropsychic stability, and form a positive orientation toward pregnancy and motherhood.