Aim: to analyze the association of the ESR1 gene polymorphic loci rs2234693, rs9340799, and rs3798577 with developing preeclampsia (PE) with fetal growth retardation (FGR).
Materials and Methods. The study was performed while analyzing a sample of 400 women: 76 pregnant women with PE and FGR and 324 with a physiological course of pregnancy. Three polymorphic loci of the ESR1 gene (rs2234693, rs9340799, and rs3798577) were genotyped. Functional effects of polymorphic loci were evaluated by using the online programs HaploReg (epigenetic effects) and GTEx Portal (relation to gene expression).
Results. The development of PE and FGR is associated with the G allele and GG genotype rs9340799 of the ESR1 gene (OR = 1.38; p_perm = 0.04 and OR = 2.00; p_perm = 0.04, respectively), the T allele rs3798577 of the ESR1 gene (OR = 1.46; p_perm = 0.01), and the TG haplotype of the polymorphic loci rs2234693–rs9340799 of the ESR1 gene (OR = 2.08; p_perm = 0.009). Polymorphic locirs2234693, rs9340799 ESR1 gene and rs3798577 have an important functional significance in human body being located in the evolutionarily conserved DNA region, affect affinity of regulatory DNA motifs to the eight transcription factors as well as ESR1 gene expression in the thyroid gland, which are positioned in the promoter and enhancer region, DNAse 1 hypersensitivity motif within diverse organs and tissues, and display an important pathogenetic effect for development of PE and FGR.
Conclusion. Polymorphic loci rs2234693, rs9340799 and rs3798577 of the ESR1 gene are associated with developing PE and FGR.

Introduction. Antiphospholipid syndrome (AРS) is a multisystem disease characterized by elevated levels of antiphospholipid antibodies (AРA), arterial and/or venous thrombosis, thrombocytopenia, and habitual miscarriage. Various AРA types have multifactorial and indirect effects on pregnancy course from the earliest stages, leading to termination of pregnancy and putting the prerequisites for further obstetric complications.
Aim: determine rate and relative risk of pregnancy complications in AРA carriers.
Materials and Methods. The retrospective study, conducted between 2017 and 2019, included 268 pregnant women. All women underwent a comprehensive study consisting of clinical examination and laboratory methods. AРA of IgM and IgG classes were measured by using ELISA, lupus anticoagulant (LA) was estimated by using a coagulometer.
Results. APA were detected in 213 (79.48 %) women examined; 55 (20.52 %) patients (n = 55) lacked APA. Failed in vitro fertilization attempts were 2 times more common in women with AРA (10.33 vs. 5.45 %, respectively; p < 0.001). Also, significant differences were found in this group in antenatal fetal death (4.23 vs. 1.82 %, respectively; p < 0.001) and chronic placental insufficiency without fetal malnutrition (23.47 vs. 18.18 %, respectively; p < 0.05). Of 165 women with early pregnancy loss syndrome, AРA were found in 130 (78.79 %), late pregnancy loss – in 29 (76.32 %) and antenatal fetal death – in 9 (90.0 %) women carrying serum AРA. The relative risks of unfavorable pregnancy outcomes have been identified for various AРA subtypes.
Conclusion. Identifying clear-cut relative risks of adverse pregnancy outcomes for various subtypes of antiphospholipid antibodies will allow to determine risk groups and develop a special treatment algorithm for preventing pregnancy complications and perinatal losses.

Introduction. Perinatal mortality in multiple pregnancies increases by 8–10 times compared to singletons. Stillbirth is a significant part of all complications of multiple pregnancies. Although the incidence of perinatal mortality in multiple pregnancies has decreased consistently compared to extremely high rates in the past, it remains relatively high, despite significant positive changes in the management of such pregnancies.
Aim: to assess the diagnostic potential of the first trimester's biochemical screening in multiple pregnancies for predicting antenatal fetal death.
Materials and Methods. As part of a retrospective study, a cohort of twin pregnancies after in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), or spontaneous conception underwent screening of the first trimester at 11⁺⁰–13⁺⁶ weeks of gestation as recommended by the Fetal Medicine Foundation. Determination of pregnancy-associated plasma protein-A (PAPP-A) in blood serum with subsequent calculation of the relative PAPP-A MoM (multiples of median) – a multiple of the median (an indicator of how much the individual test result deviates from the reference values) was performed.
Results. Prenatal screening and outcomes of 302 multiple pregnancies showed that with PAPP-A MoM < 0.5, antenatal fetal death occurred with a frequency of 42.86 % (6/14), with PAPP-A MoM within the reference values – In 12.67 % (28/221), with PAPP-A MoM > 2.0 – in 6.7 % (2/30). Differences between patients with PAPP-A MoM < 0.5 and PAPP-A MoM within the reference values, as well as PAPP-A MoM < 0.5 and PAPP-A MoM > 2.0 were statistically significant (p = 0.002 and p = 0.004, respectively). No differences were detected between spontaneous and assisted reproductive technology (ART) pregnancies.
Conclusion. In women with multiple pregnancies resulting from ART or spontaneous, PAPP-A MoM values below the reference interval (< 0.5) in the first trimester are associated with an increased risk of antenatal fetal death.

Aim: to study ABS parameters, blood gas composition and complete blood count in newborns upon multiple pregnancy depending on the order of twin birth, neonate weight, and accompanying chronic hypoxia.
Materials and Methods. Laboratory parameters assessed in the twin-collected venous blood were analyzed: hemoglobin (Hb) and hematocrit (Ht) level, count of red blood cells (RBC), platelets (PLT) and white blood cells (WBC), base excess (BЕ), partial pressure of oxygen (рО₂) and carbon dioxide (рСО₂), оxygen saturation (sО₂), standard and total carbon dioxide level (НСО_–3, tСО₂).
Results. The second vs. first twin after vaginal delivery had decreased level of рН (7.30 ± 0.08 and 7.35 ± 0.09; р = 0.03, respectively), рО₂ (18.2 ± 13.1 and 27.1 ± 10.7 mm Hg; р = 0.03), sО₂ (29.7 ± 22.7 and 41.8 ± 20.3 %; р < 0.001). Metabolic acidosis exacerbated in case of birth interval extending more than 30 minutes. The hypotrophic vs. normotrophic neonates had a decreased WBC (14.2 ±5.9 vs. 15.9 ± 6.5×109/L; р = 0.02), рО2 (19.3 ± 13.6 vs. 22.6 ± 10.6 mm Hg; р = 0.03), sО₂ (27.9 ± 19.5 vs. 33.8 ± 20.6 %; р = 0.04). PH and PLT level were lower in newborns with intraventricular hemorrhages (7.29 ± 0.07 and 243.1 ± 75.4×109/L), whereas ВЕ magnitude was higher (–4.9 ± 5.2 mmol/L) than in those lacking intraventricular hemorrhages (7.34 ± 0.06; р = 0.03; 265.4 ±71.6×109/L; р < 0.001; –3.2 ± 4.2 mmol/L; р = 0.02, respectively).
Conclusion. During the vaginal delivery, a birth interval should not exceed 30 minutes. In case of diagnosing fetal growth retardation and hypoxia during pregnancy, caesarean section is an optimal option.

Aim: to comparatively assess sexual function and intensity of vulvovaginal symptoms in patients with vulvar lichen sclerosus and mixed vulvar dystrophy.
Materials and Methods. There were examined 57 patients with vulvar lichen sclerosus and 63 patients with mixed vulvar dystrophy, with mean patient age 35.0 ± 0.6 (18–45) years. Prior to therapy, the study participants completed the Female Sexual Function Index (FSFI) and the Vulvovaginal Symptoms Questionnaire (VSQ).
Results. Severe sexual dysfunction (FSFI score 2) was detected in 14 % of cases (n = 8) in group 1 (sclerotic lichen vulva) and 17 % (n = 11) in group 2 (mixed dystrophy). Remaining respondents had total score below the normal cut-off. The mean FSFI score for group 1 and 2 was 17.68 and 16.78, respectively. VSQ testing found that most common complaint in both groups was itching (91 and 95 %, respectively). The majority of patients also noted a deteriorated emotional state and disease-related limitations in everyday life. The maximum VSQ score was 20 corresponding to the peak negative disease impact found in 23 % and 37 % patients in group 1 (n = 13) and group 2 (n = 23), respectively. Many patients also noted lack of lubrication most likely associated with discomfort and pain during intercourse, as well as worsened relationship with partner.
Conclusion. The vulvar dystrophy negatively affects sexual function in young women. Symptoms typical to such conditions impose marked restrictions on intimate life, relationships and quality of general life. It accounts for why it is important to include questionnaires in the set of measures to assess sexual function and vulvovaginal symptoms both before and after treatment.

Aim: to assess the effects of several symptoms on the quality of life (QoL) in perimenopausal women with endometrial hyperplasia and abnormal uterine bleeding (АUB).
Materials and Methods. This study was conducted from September, 2019 to June, 2020. In total, 50 women aged 45–55 years who visited gynecological department with complaints of AUB were randomly interviewed by using relevant questionnaire. MENQOL (Menopause-Specific Quality of Life Questionnaire) was used to assess and evaluate perimenopause related symptoms. Menopausal status was classified according to the definition of menopause proposed by the World Health Organization.
Results. The majority (the total of 97.14 %) of women experienced at least five or more menopausal symptoms. Vasomotor symptoms were recorded as hot flushes (80 %), sweating (70 %), and night sweating (62 %). The most common physical symptoms were frequent back pain in the lumbar region (96 %), decreased physical strength (92 %), generalized weakness, tiredness (90 %), weight gain (80 %), and pain in the neck (90 %). Among participants, there were reported various problems such as depressive feeling of unknown reasons (20 %), anxiety and nervousness (20 %), dissatisfaction with personal life (44 %), poor memory (14 %), low mood (14 %), as well as impatience and irritability (12 %). Sexual problems were reported as changed sexual drive (20 %), vaginal dryness (10 %), and few avoided intimate contacts with the partners (10 %). Menopausal status, educational level and body mass indexes as well as marital status were also studied as those among the multi-factors significantly associated with the frequency and severity of menopause related symptoms.
Conclusion. The severity of perimenopausal symptoms decreases the QoL in everyday life of women aged 45–55 years with endometrial hyperplasia and АUB.

Aim: to assess an effect of medicinal magnesium-containing composition on gelatinase B expression intensity and morphological parameters of chronic experimental endometrial inflammation.

Materials and Methods. There were conducted experiments with 60 sexually mature female Wistar rats to determine an effect of medicinal magnesium-containing composition (contains magnesium chloride – a natural polymineral Bischofite) on gelatinase B activity in endometrial tissues (counting number of gelatinase-B-positive cells and intensity of gelatinase B expression), morphological parameters of cell infiltration, as well as amount of magnesium in red blood cell mass collected from the inferior vena cava and subclavian vein. All such parameters were assessed in experimental animals from 4 groups: group 1 – animals in baseline state, group 2 – control, group 3 – experimental chronic endometritis (CE), group 4 – experimental CE after treatment with medicinal magnesium-containing composition.
Results. It was found that use of medicinal magnesium-containing composition increased amount of erythrocyte magnesium up to the baseline level and increased both number and expression intensity of stromal gelatinase B-positive cells. In addition, magnesium level in erythrocyte mass from the inferior vena cava was increased and accompanied with restored eosinophil-plasmacyte as well as significantly elevated macrophage-lymphocyte infiltration in endometrial tissues compared to CE animals lacking therapy.
Conclusion. The results of this study allow us to conclude about importance of gelatinase B in pathogenesis of experimental chronic endometrial inflammation as well as an opportunity of regulating gelatinase B activity by applying medicinal magnesium containing drug in pathogenetic therapy of experimental CE.

Introduction. Management and the prevalence of labor complications in patients with premature rupture of the membranes (PROM) is a pressing issue.
Aim: to assess the features of childbirth course in patients with PROM during a full-term pregnancy and a favourable cervix.
Materials and methods. А prospective analysis of labor course and the postpartum period was performed in 189 patients with a singleton pregnancy with occipital presentation, at least 37-week gestation, of low and moderate risk groups, without contraindications for vaginal delivery. PROM as complicated pregnancy was found in 89 subjects (main group), whereas 100 having labor onset with intact fetal membranes were enrolled into comparison group. The features of labor course were analyzed.
Results. Primiparous patients dominated in the main group (66.7 %). The latent period between amniotic fluid discharge to labor onset comprised 4.15 ± 3.48 hours and 3.40 ± 2.13 hours in primiparous and multiparous women, respectively, whereas labor activity in 19 % of women did not develop after 6 hour-latent period. The average duration of labor did not depend on the patient parity and was longer in the group with PROM: 8.06 ± 3.51 hours – in primiparous females, 7.21 ± 2.56 hours – in comparison group (T = –1.99; p = 0.04) due to prolonged first stage of labor. In patients with and without PROM, rate of poor uterine contraction strength was 24.7 % and 18.3 % (p = 0.29), cervical dystocia – 2.25 % and 0 % (p = 0.13), use of oxytocin in childbirth – 35.9 % and 18.3 % (p = 0.007), respectively. Caesarean sections in the main group were recorded in 15 cases (16.85 %), fetal vacuum extraction – 6 cases (6.74 %), whereas in the comparison group – per 2 (2,0 %) cases, respectively (χ2 = 16.13; p < 0.001).
Conclusion. Patients with PROM and favourable cervix were shown to have duration of labor, occurrence of operative delivery, rupture of the cervix, and use of oxytocin lasting substantially longer compared to those with the rupture of membranes after onset of the labor. PROM with a favourable cervix occurs more often in primiparous females, which is also coupled to peak rate complications. A 6-hour expectant management is considered as insufficient, because an onset of labor activity in 15.7 % of patients developed after latent period lasting more than 6 hours.

Aim: conduct a systematic analysis of pregnancy development, investigate clinical and laboratory data affecting development of labor abnormalities in women residing in the Belgorod region.
Materials and Methods. From 2014 to 2018, 484 women were examined and divided into 2 groups: main group consisted of those who had childbirth complicated with labor abnormalities (n = 344), whereas control group consisted of women lacking complications during delivery (n = 140). The following methods were used in the study: questionnaires, general clinical methods, biochemical blood tests in pregnant and postpartum women, populational statistics as well as methods of standard and multivariate statistics.
Results. In the second half of pregnancy in women with labor abnormalities revealed higher rate of moderate preeclampsia (34.30 ± 2.56 % vs. 10.71 ± 2.61%; p < 0.05), polyhydramnios (11.34 ± 1.71 % vs. 5.71 ± 1.96 %; p < 0.05), chronic intrauterine hypoxia (29.6 ± 2.46 % vs. 12.86 ± 2.83 %; p < 0.05), chronic utero-placental insufficiency (60.47 ± 2.64 % vs. 20.00 ± 3.38 %; p < 0.05), sexually transmitted infections (3.78 ± 1.03 % vs. 0.71 ± 0.71 %; p < 0.05), acute respiratory viral infection (8.72 ± 1.52 % vs. 3.57 ± 1.57 %; p < 0.05) as well as a combination of several types of pathology (8.72 ± 1.52 % vs. 13.57 ± 2.89 %; p < 0.05). Laboratory parameters in women with labor abnormalities compared with control antepartum group were noted to have significantly decreased count of red blood cells (3.89 ± 0.38×1012/L vs. 3.99 ± 0.40×1012/L; p = 0.006), eosinophils (0.95 ± 0.69×109/L vs. 1.20 ± 0.67×109/L; p = 0.026) and platelets (226.29 ± 62.71×109/L vs. 245.44 ± 60.32×109/L; p = 0.0003). Blood biochemical parameters in women with labor abnormalities vs. control group were featured with significantly decreased level of bilirubin (6.76 ± 3.16 μmol/L vs. 9.88 ± 3.60 μmol/L; p < 0.05) and alanine aminotransferase (13.94 ± 10.08 U/L vs. 19.41 ± 14.40 U/L; p = 0.004). Analyzing coagulation parameters in the main group showed significantly reduced fibrinogen level (4.30 ± 1.00 g/L) compared with control group (4.71 ± 1.14 g/L; p < 0.05) as well as elevated international normalized ratio (1.07 ± 0.11 vs. 1.03 ± 0.10; p = 0.001).
Conclusion. Our study data found that pregnant women with labor abnormalities had altered clinical and laboratory parameters observed as early as in the second half of gestation, which may be used to calculate an individual risk of such labor complication.

Endometrial cancer holdzone of the lead positions in the pattern of female oncological diseases, affecting annually around 300,000 women worldwide. Compared to other cancers of the female reproductive system, this pathology has been extensively investigated by conducting large-scale randomized controlled trials, which proved safety and efficacy of using laparoscopic surgery for such patients. In the last years, robotic-assisted surgery has been actively developed globally, including gynecological oncology. Minimally invasive technologies can reduce the volume of blood loss, shorten hospital stay, lower rate of postoperative complications and shorten rehabilitation period. It is necessary to conduct randomized prospective studies assessing robotic-assisted surgery for treating endometrial cancer, especially due to concerns about postoperative prognosis in cancer patients. In addition, studies on developing clinical guidelines to select proper surgical intervention, including robotic-assisted access for surgeons-oncologists are required.

Administration of menopausal hormone therapy (MHT) in patients with genital endometriosis (GE) is a controversial issue requiring a patient-personalized approach. Current principles for MHT selection and prescription in patients with anamnestic endometriosis are presented, which are based on the guidelines of the International Menopause Society (IMS), The European Menopause and Andropause Society, local and foreign publications retrieved from electronic data bases PubMed, Cyberleninka. The data of our study on observing 724 patients with GE treated with diverse MHT types were presented and analyzed (428 women in perimenopausal period, 296 in postmenopausal period). Patients with endometriosis in perimenopausal and postmenopausal periods showed more prominent manifestations of climacteric and post-ovariectomy syndromes, as well as high risk of reduced bone mineral density (BMD) due to repeated surgery on the ovaries and preceding long-term “antiestrogen therapy”. Custom-compounded MHT based on components combinations, dosage and administration route provides a significantly improved quality of life for patients with endometriosis, prevents loss of BMD and reduces risk of cardiovascular diseases. Using low and ultra-low dose estrogen bioidentical to natural substances in this patient group minimizes a risk of disease recurrence.

Here we review Russia-wide and international publications released over the last 5 years dedicated to phytoestrogens used in treatment of climacteric syndrome. Effects of isoflavones as the most examined agents are discussed acting on vasomotor, cognitive, psychological, urogenital and sexual symptoms as well as on the cardiovascular system, bones, and metabolic age-related changes. Despite obtaining controversial data resulting from the analysis, it may be concluded phytoestrogens hold promise as an alternative to menopausal hormone therapy. It is reasonable to conduct further extensive studies to evaluate efficacy and safety of using plant-derived compounds in postmenopausal women.

Ovarian cystadenofibroma (CAF) is a rare ovarian tumor originating both from epithelial and stromal components being, however, classified as epithelial tumors. CAF prevalence among all ovarian tumors does not exceed more than 1.7 %. CAFs are commonly asymptomatic, in extremely rare cases of large tumor or ovarian torsion pain sensation may be noted. External genital endometriosis (EGE) is a chronic gynecological disorder that occurs in women of reproductive age and cause infertility and pelvic pain. EGE prevalence comprises around 10 % in women of reproductive age, 20–50 % in women with infertility, and almost 90 % in women with chronic pelvic pain. Magnetic resonance imaging (MRI) is method of choice in diagnostics of such pathology due to the high natural soft tissue contrast and functional techniques such as diffusion-weighted images (DWI) and dynamic contrast enhancement (DCE). Surgery planning, necessity for systemic therapy or follow-up directly depend on imaging and diagnostic laparoscopy results. Here we present a clinical case of rarely combined serous papillary CAF with extended EGE accompanied with consequences of intra-tumoral hemorrhage. Case study demonstrates main visualization characteristics that provide correct differential diagnosis and exclude malignancy transformation.

Open letter of MD, Dr Sci Med, Professor, Academician of RAS Nikolay N. Volodin, President of Russian association of specialists in perinatal medicine (RASPM) regarding the case of Elina Sushkevich.

Per request of MD, Dr Sci Med, Professor, Academician of RAS Nikolay N. Volodin, President of Russian association of specialists in perinatal medicine (RASPM) one of leading specialists in obstetrics, gynecology and perinatal medicine in the world prof. Gian Carlo Di Renzo have prepared the Expert Report on the Elina Sushkevich case. Taken into account the importance of this case for healthcare professionals, we publish the full text in the original and translated into Russian.