No 12 (2019)

MicroRNA is a class of short non-coding RNAs that carry out epigenetic regulation of many biological processes, including the course of pregnancy. More than 500 microRNAs associated with the formation and functioning of the placenta are presently known. The expression level of these microRNAs may be an indicator of placental changes during pregnancy. A number of placenta-specific microRNAs detected in maternal plasma can be regarded as potential non-invasive markers of maternal and fetal health. The data available in the modern scientific literature on changes in the expression of placenta-specific microRNAs circulating in the plasma of a pregnant woman with fetal growth restriction are analyzed. MicroRNAs can play an important, but currently not fully investigated role in the initiation of gestational complications. The use of microRNAs in the prediction and treatment of diseases and pregnancy complications is a promising area that requires further investigation.

The paper reviews the literature on clinical cases of parasitic uterine myoma (PUM). The incidence of PUM is steadily increasing after endoscopic surgery. A rare pathology of ectopic (wandering, parasitic) uterine myoma is more and more common due to the use of a morcellator during organ-sparing surgery. The presence of PUM that is predominantly iatrogenic has been proven and histologically verified in all the described clinical cases. But, taking into account the low incidence rate of this pathology, it requires further investigation and development of clinical recommendations for the management of patients with PUM.

Objective. To evaluate the efficiency of DNA-based noninvasive prenatal test (NIPT) in identifying major aneuploidies in Russia. Subjects and methods. The investigation enrolled 27,845patients who had undergone NIPT in 2013-2018. The patients’ mean age was 34.2±3.63 years; the mean gestational age at which the women underwent NIPT was 15 weeks and 2 days’ gestation. Results and discussion. Various NIPTs in Russia in 2013-2018 revealed a high risk of fetal chromosomal anomalies in 739 (2.6%) cases, 733 (99.18%) of them underwent invasive prenatal diagnosis, the presence of fetal chromosomal abnormalities was not confirmed in 12 (1.63%) cases. False negative results were 0.014%. The initial study could not yield a NIPT result in 1322 (4.7%) patients because of a low fetal fraction; however, the repeat study was effective in 80.1% of them. Conclusion. NIPT is a more accurate study than standard combined prenatal screening and has high sensitivity and specificity for trisomies 13, 18, and 21.

Objective. To elaborate an analytical approach to predicting fetal macrosomia (FM) on the basis of maternal serum lipidome analysis. Subjects and methods. A prospective cohort study enrolled 120pregnant women with FM and gestational diabetes mellitus (GDM). Serum lipid levels were analyzed by mass spectrometry. Results. The best prognostic models were obtained at 11-14 and 24-28 weeks’ gestation in women with GDM (the sensitivity and specificity were 0.91/0.96 and 0.93/0.96, respectively), at 11-14 weeks in the entire group and in patients without GDM (0.85/0.91 and 0.93/0.92). The findings make it possible to predict FM according to the presence or absence of GDM. Conclusion. The introduction of the developed models into obstetric practice will become a new tool for assessing the risk for FM, which will be able to reduce its rate and to improve maternal and perinatal outcomes.

Objective. To search for biomarkers of fetal growth restriction (FGR) based on a study of the metabolic profile of pregnant women. Subjects and methods. Plasma samples from 38 pregnant women were investigated during the study. The pregnant women were divided into two groups: 1) 17 pregnant women with FGR; 2) 21 women with physiological pregnancy. The samples were analyzed using liquid chromatography with mass spectrometric detection. Control of the analysis of experimental results and their processing were done applying Agilent MassHunter software. Results. The investigators identified 18 metabolites min with statistically significantly different levels. Correlation analysis established a signif icant relationship between the identif ied metabolites and clinical and anamnestic data. There was a moderate correlation of FGR with 3 amino acids: beta-alanine (rs = 0.413, p = 0.003), cysteine (rs = 0.588, p <0.001), and ornithine (rs = 0.427, p = 0.002). Conclusion. The findings substantiate the prospects of investigating beta-alanine, cysteine, and ornithine as diagnostic markers of FGR. The high correlation of these metabolites with Doppler readings determines the possibility of their inclusion in the integrated diagnosis of FGR.

Aim. To identify anamnestic, clinical, and morphological differences between patients who had preterm births at different gestational ages. Material and methods. The study represents a retrospective analysis of medical records of 356 women with preterm births who were managed at the Rostov Regional Perinatal Center in 2011. The participants were divided into four groups categorized by gestational age at delivery. Results. A history of recurrent pregnancy loss and missed miscarriage is associated with extremely preterm birth. The fundamental distinctive feature of extremely preterm birth is the presence of inflammatory changes in the umbilical cord. Cervical insufficiency is also a risk factor for early and extremely preterm birth. There were statistically significant differences in the levels of placental adaptive-compensatory reactions, specifically in detection rates of villous maturation disorders and placental circulatory disorders. Conclusion. The duration of pregnancy depends on the condition of the placenta. With the depletion of adaptive-compensatory reactions, the risk of preterm birth increases.

Objective. To determine the prevalence of low body mass index (BMI) for pregnant women, the characteristics of their medical history, and unfavorable pregnancy outcomes and to assess the risk of unfavorable outcomes in women with low BMI. Subjects and methods. A retrospective cohort study was conducted using data on 57,226 births registered in the Arkhangelsk Regional Birth Registry for 2012-2015. The prevalence of sociodemographic and medical factors was investigated in singleton pregnant women with low and normal BMI. Stillbirth rates, preterm labor, a baby’s low or very low weight, five-minute Apgar scores, the need for neonatal transfer, and early neonatal death were studied as outcomes. Differences between the groups of women with low and normal BMI were determined using the Pearson’s chi-square test. Unadjusted and adjusted odds ratios with 95% confidence intervals were determined by multivariate logistic regression analysis. Results. Compared with women with normal BMI, in the group of mothers with a low BMI (n = 3401, 7.0% of the total number of births) there was a large proportion of primiparous, young, unemployed, smoking women, and those with a lower maternal educational level. The women with low BMI were found to have an increased risk of giving birth to a low birth weight baby. Conclusion. Low BMI of a woman increases the risk of having a low birth weight baby.

Aim. To investigate the association between the 657T>C polymorphism of the synaptonemal complex SYCP3 gene (rs769825641) and the development of idiopathic recurrent pregnancy loss (iRPL) in ethnically homogeneous Kazakh population. Material and methods. Three thousand two patients with iRPL and 300 women with normal reproductive function underwent independent replicative TagMan genotyping. Results. The study findings support the association between the studied polymorphism and the development of iRPL in the Kazakh population. The frequency of carrying the unfavorable C allele in the study group (3,97%) was significantly higher than in women with normal reproduction function (2,0%) (x2 = 4, 04; p < 0.05). Conclusions. Synaptonemal complex proteins play an important role in regulating meiosis in iRPL, suggesting the possibility of considering the studied polymorphism as a possible genetic risk factor for iRPL of unknown cause.

Objective. To evaluate the impact of controlled mechanical microvibration of human embryos during the first five days of development on pregnancy rates in assisted reproductive technology (ART) programs. Subjects and methods. The investigation enrolled 75 (a microvibration group) and 300 (a control group) married couples without contraindications or complications developed during ART programs. During cultivation under mechanical microvibration, the incubator was placed on an ArisTT180-s platform (K&S Advanced Systems Ltd, Israel) in the active vibration mode with a frequency of 40 Hz for 30 seconds at a rest interval of 30 minutes. Results. The pregnancy rate per ovarian stimulation cycle was 42.7% (n = 32) in the microvibration group versus 33.7% (n = 101) in the control group (p = 0.09). The pregnancy rate per embryo transfer was 50.8 and 40%, respectively (p = 0.097). Conclusion. The use of controlled mechanical microvibration to grow embryos can significantly increase pregnancy rates in ART programs.

Objective. To assess the time course of perioperative changes in the blood coagulation system during uterine artery embolization (EMA) based on monitoring the indicators of the hemostatic system, including thromboelastography (TEG), and to identify a thrombogenic propensity (or absence. Subjects and methods. The investigation enrolled 37 female patients with EMA, in whom the risk factors predisposing to thromboembolic events were excluded during preoperative examination. Dynamic monitoring of coagulography and TEG measures was performed in the perioperative period. Results. A day after EMA, the patients tended to have hypercoagulation, as evidenced by TEG (decreases in R time and K time and increases in a-angle and maximum amplitude), as well as activation of fibrinolysis (an increase in LY 30 levels). At the same time, a study of coagulogram indices revealed increases in the level of hypercoagulability markers (fibrinogen, D-dimer, soluble fibrin-monomer complexes) and in prothrombin index and a decrease in activated partial thromboplastin time. The findings generally suggest that there is an increased risk for venous thromboembolic events (VTEE) in the postoperative period after EMA. Conclusion. The revealed features of hemostasiological changes in patients after EMA suggest that there is a need for the continuous monitoring of the hemostatic system and the development of effective preventive measures for VTEE.

Objective. To investigate the polymorphism of the CYP11A1, CYP17A1, and CYP19A1 genes in reproductive-aged women with polycystic ovary syndrome (PCOS) versus those without the latter. Subjects and methods. The investigation enrolled 188 reproductive-aged women. Group 1 consisted of 94 women with PCOS; Group 2 included 94 women without PCOS. All the patients underwent molecular genetic analysis of SNP polymorphisms of the VNTR genes of the pentanucleotide ((tttta)n) polymorphism at position -528 of the CYP11A and CYP17A1 gene promoter region (-34T > C (MspA1), rs743572) and CYP19A1 (c.-39+15658 C>T, C40824T, rs2470152) using the test system made by the OOO SibDNA (Novosibirsk). The amplification reaction was carried out using a CFX96 real-time PCR detection system (Bio-Rad, USA), followed by statistical data processing. Results. The frequency distribution of CYP11A1 (tttta)n genotypes, CYP17A1 rs743572 and CYP19A1 rs2470152 genes did not statistically significantly differ in PCOS and healthy women (p > 0.05). However, the CYP11A1 (tttta)n polymorphism tended to accumulate alleles with a larger number of (tttta)n repeats in PCOS women than in healthy ones. The VNTR genotypes with 6/6, 6/8, and 8/8pentanucleotide repeats were typical. Conclusion. The genetic factor did not seem to play a key role in the development of PCOS in the examined women. This study may be useful for subsequent meta-analyses that can reveal insights into the pathogenesis of the disease.

Objective. To evaluate the microcirculation of the fetoplacental complex in smoking pregnant women by laser Doppler flowmetry. Subjects and methods. The investigation included 105 pregnant women who were divided into 3 groups: 1) 35 patients with physiological pregnancy without extragenital pathology (a control group); 2) 35 with gestational hypertension (a comparison group); 3) 35 smoking patients (a study group). The above groups underwent laser Doppler flowmetry evaluation of microcirculation in each trimester of pregnancy. Results. Laser Doppler flowmetry recorded significant changes in the fetoplacental complex in smoking pregnant women who developed a spastic hemodynamic type of microcirculatory disorders. Conclusion. The use of laser Doppler flowmetry along with existing techniques (ultrasonography, cardiotocography, dopplerometry) will be able to diagnose microcirculatory disorders in the fetoplacental complex in the first trimester of pregnancy.

A change in the socialization of society, a tendency toward late pregnancy planning, and an increase in the incidence of uterine fibroids among reproductive-aged women determine the relevance of treatment for this disease and take on social significance. Objective. To evaluate the comparative efficacy of mifepristone (Ginestril), a selective progesterone receptor modulator (SPRM) (Esmya), and a gonadotropin-releasing hormone GnRH agonist (Buserelin Depot) in the treatment of women with uterine fibroids and internal endometriosis. Subjects and methods. A total of 150 women diagnosed with uterine fibroids and internal endometriosis of the corpus uteri were selected. The inclusion criteria were the presence of symptoms of uterine fibroids, refusal of surgical treatment, a desire to maintain reproductive function, and preparation for planned pregnancy. All the patients were randomly divided into three groups of 50 people each according to a prescribed drug (mifepristone, ulipristal acetate, GnRH agonist) and for the convenience of statistical analysis. Therapy was prescribed for 3 months. All the examinees were reproductive-aged. Results. When mifepristone and ulipristal were used, there was the highest frequency of devascularization of myomatous nodules, as evidenced by Doppler study. Twenty-nine of 36patients receiving mifepristone had myomas transformed from proliferating to simple. The ulipristal and GnRH-agonist groups had similar data (28/35 and 26/36, respectively). After 3 months of treatment, the largest number of cases without active peri- and intranodular blood flow in the area of a myomatous nodule were recorded in the mifepristone group (62%; n = 31). Six months after the start of the study (3 months after completion of therapy), the uterine volume was re-estimated. At this stage, 6 (4%) women who became pregnant were excluded from the study. The adverse reactions of Ginestril use included weight gain (by less than 3% of the baseline weight in one (2%) patient), headache, and weakness (in two (4%) patients). Patients with liver and kidney dysfunction were excluded before ulipristal acetate was administered. The use of Esmya was accompanied by reversible endometrial thickening by more than 16 mm (12%) after its treatment cessation, hot flashes (6%), psychoemotional disorders (12%), headache (12%), and acne (12%). The administration of Buserelin Depot resulted in headache, psychoemotional disorders (14%), decreased libido (12%), and insomnia (12%). Conclusion. Drug therapy aimed at eliminating the symptoms of uterine fibroids is an effective tool for organ sparing, preparation for pregnancy, and surgical treatment. Mifepristone most actively converts the clinical variant of proliferating fibroids into a simple one. The highest safety profile and the possibility of dose adjustment is an important aspect of choosing mifepristone. The prescription of ulipristal requires mandatory additional examination. This drug is comparable to mifepristone in the degree and rate of a decrease in the size of myomatous nodules. The GnRH agonist more markedly reduces the size of the uterus in fibroids concurrent with internal endometriosis of the corpus uteri. The use of the GnRH agonist is associated with the higher incidence of side effects compared with ulipristal and mifepristone.

Rehabilitation of vulvar cancer patients is a continuous process that starts at diagnosis and continues throughout life. A multidisciplinary rehabilitation care approach involves the participation of a whole health team of physicians and nurses in various areas. For the early detection of relapses, diagnostic monitoring (tumor markers, ultrasonography, magnetic resonance imaging, positron emission tomography/computed tomography) is indicated for all patients. Particular attention should be paid to the quality of life in women, by restoring the physiological functions impaired due to the illness and/or treatment, by correcting the mental status and sexual dysfunction.

Background. Obstetric thrombotic microangiopathies (TMA) in pregnancy develop in 8-18% of all TMA cases and are one of the causes of maternal and perinatal deaths. The diagnosis in the shortest possible time and the speed of pathogenetic therapy initiation are the basic factors that influence disease outcomes and further prognosis in a woman. Description. The paper presents a rare clinical case of a 33-year-old female patient with the malignant course of atypical hemolytic uremic syndrome (aHUS) in the presence of HELLP syndrome. It describes the clinical, anamnestic, laboratory, and instrumental data of the patient, and the features of her management and treatment. Conclusion. Early diagnosis, timely initiation of plasmotherapy, pathogenetic treatment on 4 days after the onset of aHUS in the malignant course of aHUS with severe multiple organ dysfunction could quickly achieve not only a hematologic response, but also completely restore the function of the kidneys and other affected organs.

Background. Radiation-induced breast angiosarcomas are an extremely rare disease characterized by a low response to available treatment options and by an unfavorable prognosis. The diagnosis is complex and requires histological and immunohistochemical verification. Description. This paper describes three clinical cases of patients treated for radiation-induced angiosarcomas in the N.N. Blokhin National Research Center of Oncology. Conclusion. The diagnosis and treatment of radiation-induced sarcomas remains a complex issue in modern oncology. The inclusion of these patients in clinical trials and even in the descriptions of individual clinical cases seems to be important steps towards finding an effective treatment for this pathology.