A steady increase in average maternity age at the time of first childbirth lead to a higher risk of fetal chromosomal abnormalities. The Order No. 1130n of the Ministry of Health of the Russian Federation establish the screening protocol at 11–14 weeks of gestation with assessing the followed criteria of fetal chromosomal pathology: the nuchal translucency thickness, nasal bone measurement, ductus venosus pulsatility index, tricuspid regurgitation, and heart rate. The value of non-invasive prenatal testing (NIPT) in the early prenatal diagnosis of the most common chromosomal abnormalities, as the trisomies 21, 18, 13, and monosomy X is also increasing. Additionally, numerous other fetal karyotype abnormalities can also be suspected at 11–14 weeks of gestation by revealing a number of other ultrasound signs. The article presents the literature review on additional ultrasound signs of various, both more and less common, chromosomal abnormalities. Pathological signs, abnormalities of fetal anatomy and extrafetal structures in the first trimester, which could be used as additional ultrasound signs of chromosomal pathology of various organs and systems (central nervous system and head, heart and blood vessels, urinary system, abdominal organs, fetal skeleton, as well as the placenta, umbilical cord, amniotic membranes) are described in the article. Despite the use of NIPT, including its extended panels, there remains a need to use ultrasound to detect the signs of rarer, but no less significant chromosomal pathologies, such as triploidies, mosaic trisomies, rare autosomal trisomies, duplications, and deletions.

BACKGROUND: The efficiency of existing methods of predicting preeclampsia is far from 100%, which dictates the need to search for new additional markers. Retroplacental blood is a unique and practically unstudied biological substrate, and its composition probably influences the course of pregnancy. This study aimed to investigate the biochemical parameters of retroplacental blood in preeclampsia. MATERIALS AND METHODS: The study included 53 pregnant women who were divided into two groups: the first group had normal pregnancy (n=28), and the second group had severe preeclampsia (n=25). All pregnant women underwent cesarean section at delivery. Peripheral and retroplacental blood sera were examined. Sampling was performed immediately after mechanical separation of the placenta and separation of the afterbirth. Levels of alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total protein, albumin, urea, creatinine, total and direct bilirubin, glucose, and uric acid were determined on a Beckman Coulter AU480 biochemical analyzer (Germany). RESULTS: The biochemical composition of retroplacental and peripheral blood showed significant differences (p 0.05). In physiologic pregnancy, the levels of ALT, AST, LDH, urea, creatinine, direct bilirubin, and uric acid were significantly (p 0.05) higher by 1.9, 20.1, 11.4, 1.14, 1.19, 2.0, and 1.15 times, respectively, whereas glucose levels were 1.5 times lower in the retroplacental blood. In patients with severe preeclampsia, the levels of AST, LDH, creatinine, total and direct bilirubin, and uric acid were significantly (p 0.05) increased in retroplacental blood by 11.7, 11.5, 1.3, 1.2, 2.2, and 1.11 times, respectively, and glucose levels decreased 1.57 times. When comparing the biochemical composition of the peripheral blood of the first and second groups, reliable differences (p 0.05) were noted only in ALT, AST, total protein, albumin, urea, and creatinine. However, in the retroplacental blood under physiologic pregnancy and preeclampsia, significant differences (p 0.05) were found only for urea, creatinine, and uric acid levels. CONCLUSION: The study of the biochemical composition of the retroplacental blood can provide a more complete picture of the pathogenesis of preeclampsia.

Currently, recurrent miscarriage is considered a polygenic multifactorial disease, that is, a condition in which the predisposition to miscarriage is related to various genetic factors. The realization of these factors depends largely on the environment. This paper analyzes the current world literature on the effect of single-nucleotide polymorphisms of genes associated with recurrent miscarriage. The literature review summarized data from recent meta-analyses regarding the association between recurrent miscarriage and genetic polymorphisms leading to endothelial dysfunction (vascular endothelial growth factor A gene and endothelial NO synthase genes), hereditary thrombophilia (Leiden mutation and polymorphisms in the methylene tetrahydrofolate reductase gene), immunological disorders (cytokine genes, including interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha), altered receptor interactions in the endometrium (progesterone receptor and ESR1 and ESR2 estrogen receptor genes), and imbalance between lipoproteins of different densities (apolipoprotein E gene). The study of genetic predisposition to miscarriage is necessary to identify high-risk cases, initiate timely and careful monitoring, and develop personalized preventive techniques.

В данном учебно-методическом пособии представлена схема практического занятия по акушерству для студентов медицинских вузов, обучающихся по специальности «Лечебное дело». Во втором издании учебного пособия дополнен и обновлен раздел о возможностях применения симуляционных методик обучения дисциплине «Акушерство и гинекология», актуализированы подходы к ведению беременности, родов и послеродового периода. Учебно-методическое пособие издано для подготовки к практическим занятиям по дисциплине «Акушерство и гинекология», рекомендовано преподавателям медицинских вузов, студентам медицинского факультета и клиническим ординаторам.

В данном учебно-методическом пособии представлена схема практического занятия по гинекологии для студентов медицинских вузов, обучающихся по специальности «Лечебное дело». Во втором издании учебного пособия дополнен и обновлен раздел о возможностях применения симуляционных методик обучения дисциплине «Акушерство и гинекология», актуализированы подходы к ведению пациенток с гинекологической патологией. Учебно-методическое пособие издано для подготовки к практическим занятиям по дисциплине «Акушерство и гинекология», рекомендовано преподавателям медицинских вузов, студентам медицинского факультета и клиническим ординаторам.

Objective. To examine the association between the carriage of endothelial dysfunction-related gene polymorphisms and recurrent pregnancy loss (RPL). Patients and methods. This case-control study included 87 patients who were divided into two groups. The study group consisted of 65 patients with a history of two or more consecutive pregnancy losses (2 to 11 losses). Primary RPL was detected in 20 patients, secondary in 26, and tertiary in 19. The control group consisted of 22 women with a history of three or more full-term births without episodes of miscarriage. The frequency of polymorphisms of the VEGFA -634G>C and IL6 -174G>C genes was determined by a ready-to-use real-time polymerase chain reaction (RT-PCR) test kits. Results. Carrying the VEGFA -634G>C GC genotype increases the risk of RPL 4-fold (p = 0.0072) and the IL6 -174G>C GC genotype – 3-fold (p = 0.028). Analysis of the impact of combinations of unfavorable genotypes showed that 65.0% of patients with primary RPL, 61.5% with secondary RPL, 63.2% with tertiary RPL, and 9% of healthy controls had a combination of GC VEGFA -634G>C and CC IL6 -174G>C. One of the key environmental factors determining the realization of susceptibility genes is age: the maximum age at the time of the first intended pregnancy was observed in patients with primary RPL (32.6 years vs. 25.5 years in the control group; p < 0.05), with 9% of healthy controls having a combination of two genotypes associated with pregnancy loss. That is, successful pregnancy at a younger age is possible even when carrying multiple risk alleles. The birth interval length is also important for successful pregnancy: a short inter-pregnancy interval allows to carry out the reproductive function during the most favorable period of the reproductive system before the influence of genotypes predisposing to RPL begins. Other environmental factors leading to the realization of carriage of RPL risk alleles include a history of intrauterine interventions and sexually transmitted infections. Conclusion. Study of the VEGFA -634G>C and IL6 -174G>C gene polymorphisms may serve as an effective method to predict RPL. For patients carrying these unfavorable gene polymorphisms, it is especially important to perform the reproductive function in time, i.e., before the realization of environmental factors. Key words: recurrent pregnancy loss, VEGF, endothelial dysfunction, susceptibility genes

Operative vaginal delivery with obstetric forceps is associated with a high risk of maternal and fetal injury. The lack of reliable and up-to-date knowledge about forceps manipulation and its safety creates a fear of using forceps and leads to a gradual loss of skill in the use of the instrument. This article covers the indications for forceps application according to relevant clinical guidelines, systematizes the results of current national and international studies on the benefits and risks of using obstetric forceps for the mother and fetus. Special attention is paid to the comparison of outcomes of operative vaginal deliveries using different instruments and comparison with operative abdominal deliveries with the same indications for surgery. In the conclusion of the analysis, the evidence for the appropriateness of using obstetric forceps to achieve a better perinatal outcome and avoid unwarranted cesarean section and related complications was formulated. Key words: obstetric forceps, vacuum extraction, cesarean section, maternal morbidity, maternal mortality, operative vaginal delivery, perinatal morbidity, perinatal mortality

Objective. To study the role of fibulin-5 (FBLN5) gene polymorphisms in the genesis of cervical insufficiency (CI). Patients and methods. This observational retrospective study included 49 patients with clinical manifestations of CI and 31 patients without history of CI. Four most studied single-nucleotide polymorphisms (SNPs) in the FBLN5 gene were selected: rs2284337, rs2018736, rs2474028, rs12589592. DNA was extracted from whole venous blood, and genotyping was performed by polymerase chain reaction (PCR). STATISTICA 12.0 and SNPstats software packages were used for statistical data processing. Results. It was found that the rs2474028(T) allele of the FBLN5 gene is associated with a risk of developing CI (p = 0.0019). In addition, a comparison of a high-risk CI subgroup and a control group revealed that carriage of the heterozygous rs2018736(A/C) or the heterozygous rs12589592(A/G) genotypes of the FBLN5 gene is protective and reduces the risk of developing CI (p = 0.019 and p = 0.0021, respectively). Conclusion. The presence of single-nucleotide polymorphisms in the FBLN5 gene is associated with the development of CI. Key words: cervical insufficiency, pathogenesis, fibulin-5, FBLN5, SNP

The number of births among patients with uterine scar defect after cesarean section is increasing worldwide. To reduce complications during pregnancy, these patients undergo surgical correction of uterine scar defect – metroplasty, which is performed in the preconception period by laparotomy, laparoscopy, and the vaginal route. Objective. To analyze the literature on the effectiveness of metroplasty for uterine scar defect after cesarean section. Conclusion. It is necessary to search for new cellular products that can initiate and sustain differentiation of myofibroblasts, block the processes of their apoptosis, which will contribute to uterine wound healing without scar formation. Key words: cesarean section, laparoscopy, metroplasty, uterine scar defect, uterine scar

The pathogenesis of pre-eclampsia (PE) is based on the disorders of placental circulation, which develop due to the impaired migration of extravillous trophoblast. Local processes at the maternal-fetal interface can be assessed through the retroplacental blood (RB) which flows during placental separation. Objective. To study the parameters of antioxidant status of RB in uncomplicated pregnancy and PE. Patients and methods. The study included 50 pregnant women: 36 women with uncomplicated pregnancy and 14 women with PE. Total antioxidant capacity (TAC) of plasma was measured by the luminol chemiluminescence method. Results. In uncomplicated pregnancy, total antioxidant capacity of RB was increased compared to peripheral blood (PB) (1236 ± 344 sec vs. 852 ± 246 sec; p < 0.0001), which indicates that RB provides a balance of pro-oxidants and antioxidants at the maternal-placental-fetal interface. The increase in total antioxidant capacity of RB plasma in PE compared to uncomplicated pregnancy (1716 ± 922 sec vs. 1236 ± 344 sec; p = 0.007) may be both compensatory and pathogenetic mechanisms of the disease. Thus, the prevention and treatment of PE with antioxidants should be discussed. The increase in total antioxidant capacity of RB plasma was observed in severe PE (2304 ± 948 sec vs. 1236 ± 344 sec, p < 0.0001), which is associated with an unfavorable prognosis. Conclusion. Our pilot study of the antioxidant defense status of retroplacental blood shows that pre-eclampsia leads to a significant imbalance between pro-oxidants and antioxidants at the maternal-placental-fetal interface. Key words: antioxidants, antioxidant capacity, pre-eclampsia, retroplacental blood, chemiluminescence

Objective. To study the morphological pattern of endometrial pathology in the menopausal women considering clinical symptoms and duration of the menopausal period. Patients and methods. 1032 women in the postmenopause were observed. Clinical data, the results of ultrasound and pathomorphological examination were studied. All patients were divided into the following groups: group 1 consisted of patients with menopausal duration for 1–5 years; group 2 – for 6–10 years; group 3 – for 10–20 years; group 4 – for more than 20 years. Results. Abnormal uterine bleeding (AUB) was registered in 39% of patients from group 1, in 13% of patients both from group 2 and group 3, and in 7% of patients from group 4. Endometrial thickening according to the ultrasound results was observed in 39% of patients from group 1, in 58% of patients from group 2, in 53% of patients both from group 3 and group 4. The combination of AUB and increased endometrial thickness was found in 27% of patients from group 1, in 29% from group 2, in 34% from group 3, and in 40% from group 4. Functional changes in the endometrium represented by the regenerating endometrium, proliferative endometrium, and endometrial hyperplasia were found in 31% of patients from group 1 and in 4% of patients from group 2. The incidence of endometrial carcinoma increased with the increasing duration of the menopause and was 7% in group 1, 12% in group 2, 24% in group 3, and 30% in group 4. Conclusion. The leading cause of AUB in women during the first 5 years of the menopause is functional change in the endometrium. Patients with menopausal duration of more than 10 years and the presence of AUB constitute a risk group of developing endometrial carcinoma. Key words: abnormal uterine bleeding, menopause, endometrial carcinoma

Aim: to study a role of undifferentiated connective tissue dysplasia (uCTD) in etiology of cervical incompetence and its effect on pregnancy and childbirth course.Material and Methods. There were enrolled 60 patients with cervical incompetence. Patients were divided into 3 groups according to the modified CTD scale: group 1 - patients without uCTD (n = 21); group 2 - patients with mild uCTD (n = 25); group 3 - patients with moderate-to-severe uCTD (n = 14). Intensity of CTD clinical signs was assessed based on health status, gynecological and obstetric history, the course of pregnancy, labor and the postpartum period.Results. It was found that patients with more prominent CTD developed earlier (r-Spearman = -0.26) and more marked (r-Spearman = -0.29) cervical shortening and opening of the internal orifice of the uterus (r-Spearman = 0.28). It was also noted that likelihood of occurring preterm labor was significantly higher in patients with CTD (p = 0.02).Conclusion. The data obtained evidence that uCTD affects intensity of manifested cervical insufficiency and rate of preterm delivery.

Objective. To determine the risk of development of placental-related disorders of pregnancy in the presence of single-nucleotide polymorphism rs4065 of the urokinase gene in a mother. Patients and methods. The presence of the genetic variant of the rs4065 urokinase gene was determined in venous blood samples using real-time polymerase chain reaction in patients with placental-related pregnancy disorders and in the control group. Results. Associations between the risk of development of placental-related disorders of pregnancy, such as fetal growth resrtiction and pre-eclampsia, and the maternal rs4065 genotype were found. A correlation between the maternal rs4065 genotype and the degree of fetal growth restriction and the severity of pre-eclampsia was identified. The most unfavorable is the presence of the CC genotype. Conclusion. The presence of single-nucleotide substitutions in the maternal urokinase gene is associated with the development of placental-related disorders of pregnancy. Key words: urokinase-type plasminogen activator, angiogenesis, fetal growth restriction, placental insufficiency, pre-eclampsia, SNP

ABSTRACT Annually, approximately 2 million assisted reproductive technology (ART) procedures are performed worldwide, of which, only ~25% lead to successful delivery. There are two major factors contributing to successful implantation: embryo quality and endometrial receptivity (ER). Although embryo quality might be assessed through morphological and genetic testing, no clinically approved techniques are available to evaluate ER. Mucus in different parts of the female reproductive tract contains many cytokines, chemokines, growth factors, and nucleic acids, which influence and reflect various implantation-related processes. Therefore, the aim of the present review was to summarize available data regarding noninvasively obtained mucosal biomarkers for ER and to investigate their ability to predict the outcome of ART procedures. A broad literature search was performed to define studies related to noninvasive ER assessments. More than 50 biomarkers detectable in endometrial fluid, embryo transfer cannula leftover cells and mucus, menstrual blood, cervicovaginal washings are discussed herein. The remarkable methodological heterogeneity of the reviewed studies complicates the comparison of their results. Nevertheless, certain promising analytical targets may already be identified, such as urocortin, activin A, IL-1β, TNF-α, IP-10, MCP-1, and several oxidative stress biomarkers. The present review contains a collection of currently available mucosal biomarker-related data, which may provide insights for future studies. Abbreviations: ART: assisted reproductive technology; ER: endometrial receptivity; IVF: in vitro fertilization; ICSI: intracytoplasmic sperm injection; IUI: intrauterine insemination; MeSH: Medical Subject Headings; hDP 200: human decidua-associated protein 200; ET: embryo transfer; IL-18: Interleukin-18; LRG: leucine-rich α2-glycoprotein; ROC: receiver operating characteristic; AUC: area under the ROC-curve; LH: luteinizing hormone; LIF: leukemia inhibitory factor; TNF-α: tumor necrosis factor alpha; IFN-γ: interferon γ; MCP-1: monocyte chemoattractant protein-1; VEGF: vascular endothelial growth factor; SOD: superoxide dismutase; CAT: catalase; LPO: lipid peroxidation; TTG: total thiol groups; TAP: total antioxidant power; CE: chronic endometritis

Objective. To evaluate long-term outcomes of fetoscopic laser coagulation (FLC) of placental anastomoses in monochorionic twins with feto-fetal transfusion syndrome (FFTS). Patients and methods. The experimental group included live infants after FLC born to 76 women between 2012 and 2017. The control group comprised monochorionic, diamniotic (MCDA) twins with no complications born to 109 women. The following criteria were used in the analysis: gestational age at FLC, FFTS stage (Quintero staging system), gestational age at delivery, and delivery method. During follow-up, we analyzed children’s data at birth and at the age of one and three years. Results. The number of healthy children and children with minimal health problems in the experimental group was 106 (84.8%) by the age of one year and 112 (89.6%) by the age of 3 years. Nineteen children (15.2%) were disabled at the age of one year; by 3 years of age, their number decreased to 13 (10.4%). In the control group, 2 participants (1.8%) had neurological disabilities. Conclusion. The majority of children born after FLC were healthy and socially adapted. The most common disorders after FLC were neurological disorders (8.8%), cardiovascular disorders (14.8%), retinopathy of prematurity (15.7%), and bronchopulmonary dysplasia (10%). The main factor affecting the development of complications in these children was gestational age at delivery. The optimal gestational age was 33–35 weeks, when the risk of disability was similar to that in MCDA twins without complications. Key words: monochorionic twins, feto-fetal transfusion syndrome, fetoscopy

Objective. To study the role of antioxidants in the complex therapy of patients with endometriosis-associated infertility on the example of evaluating the effectiveness of ubidecarenone. Patients and methods. Forty-three patients with endometriosis-associated infertility and nineteen fertile women with complete reproductive function were examined. In order to improve the receptivity of endometrium and correct the antioxidant status in infertile patients with endometriosis after laparoscopy, therapy with Synergin® was administered at a dosage of 2 capsules per day for 3 months. After therapy, an assessment of endometrium and intrauterine perfusion was made. Results. There was a significant decrease in intrauterine perfusion in patients with endometriosis-associated infertility compared to the control group. However, after therapy with Synergin® within 3 months and correction of endothelial dysfunction in infertile patients with endometriosis, an improvement in intrauterine perfusion was revealed. Thus, prior to therapy, subendometrial blood flow was assessed in 13% of patients as satisfactory, in 77% – it was reduced, in 10% – it was absent; after therapy, 86% of patients showed satisfactory blood flow and 14% had decreased blood flow. Endometrial blood flow was reduced in 32% of patients and in 68% were absent prior to treatment, and after treatment, it was assessed as satisfactory in 45% and was reduced in 55%. Conclusion. Pathogenetic antioxidant therapy is necessary in the complex therapy of infertility in patients with external genital endometriosis after surgical treatment. Key words: α-Tocopherol, infertility, coenzyme Q10, endometrium receptivity, endometriosis

The aim of the study was to evaluate the association of gene polymorphism of matrix metalloproteinase 2 (MMP2), MMP3, MMP9, urokinase plasminogen activator (PLAU) and transforming growth factor β 1 (TGF- β 1) with the occurrence of infertility. Material and methods. 84 women planning pregnancy were examined. Of these, 47 did not become pregnant in six months (the first group), 37 had a pregnancy, and lasted more than 22 weeks (second group). The single-nucleotide polymorphisms (SNPs) of rs2285052 and rs243865 of the MMP2 gene, rs3025058 of the MMP3 gene, rs17576 and rs3918242 of the MMP9 gene, rs4065 and rs2227564 of the PLAU gene, rs1800469 of the TGF gene were analyzed in all patients. Statistical analysis of genetic associations was carried out using the SNPStats program. Results. Patients with the A allele rs2285052 and the T allele rs243865 of the MMP2 gene had an increased risk of infertility (for rs2285052 in the group of patients without pregnancy, СС 27.7%, A С 51.1%, AA 21.3%; in the pregnant group СС 54%, A С 40.5%, AA 5.4%; for rs 243865 in the group of patients without pregnancy СС 57.5%, CT 40.4%, TT 2.1%; in the pregnant group СС 81.1%, CT 18, 9%, TT 0%). With the log-additive variant of inheritance, the OR (95% CI) was 0.38 (0.19–0.77) (p = 0.0043) for rs2285052 and 0.32 (0.12–0.84) (p = 0.015) for rs243865. No statistically significant differences were found between the main group and the comparison group in allele frequencies rs3025058 of the MMP3 gene, rs17576 and rs3918242 of the MMP9 gene, rs4065 and rs2227564 of the PLAU gene, rs1800469 of the TGF- β 1 gene. Conclusions. In the studied sample of patients SNPs rs2285052 and rs243865 of the MMP2 gene were associated with a risk of infertility: the presence of the A allele rs2285052 and the T allele rs243865 of the MMP2 gene were associated with an increased risk of infertility.

Relevance. Despite the assisted reproductive techniques being widely used in modern gynaecology, the challenge of restoring fallopian tube patency in patients with hydrosalpinx, distal tubal occlusion, peritubal and periovarial adhesions remains relevant.Objective. The aim of this study was to evaluate the effectiveness of laparoscopic surgery in restoring fertility in patients with tubal factor infertility.Materials and methods. We included 99 patients, who underwent laparoscopic surgery for tubal factor infertility. During the follow-up we assessed the rate of spontaneous pregnancy and pregnancy after IVF.Results. Pregnancy occurred in 41 (41.4%) patients with a history of tubal factor infertility. Moreover, after reconstructive plastic surgery on the fallopian tubes out of 66 patients, in 17 cases (25.8%) pregnancy occurred spontaneously. In 33 patients tubectomy was performed due to impossibility of adequate fallopian tube reconstruction. In 24 (24.2%) patients, pregnancy occurred after IVF (after salpingo-ovariolysis or after tubectomy). The frequency of pregnancy after IVF in these patients was 1,5 times higher than in patients that underwent IVF in the same medical institution during the same period (42.5% and 27.8%, respectively).Conclusion. In patients with tubal factor infertility younger than 35 with preserved ovulation and the absence of pathospermia in a partner, laparoscopy is an effective method for restoring patency of the fallopian tubes. If a severe falopian tube lesions are present in patients with infertility, bilateral tubectomy should be considered, since bilateral tubectomy in such patients increases the effectiveness of IVF.