No 3 (2022)

Premature ovarian failure (POF) is a term that has acquired particular significance in recent years. It occurs in 1% of women who are under 40 years old. The typical manifestation of this syndrome is episodic or stable hypergonadotropic amenorrhea. It is diagnosed in about 10-28% of women with primary amenorrhea and in 4-18% of women with secondary amenorrhea. Unlike postmenopausal women, many patients with POF ovulate intermittently; there is resumption of regular periods in some cases; and spontaneous pregnancy can occur in 5-10%. But in one way or another long-term menstrual irregularities lead to irreversible cessation of ovarian function at a relatively young age, despite the fact that modern treatment approaches, timely diagnosis, and menopausal hormone therapy (MHT) can improve a woman's quality of life at the present time. This paper discusses the theoretical and practical aspects of the diagnosis and etiological features of POF, highlights key issues and choice of approaches to managing patients with POF in order to correct the symptoms of estrogen def iciency, to possibly restore fertility and m inim ize cardiometabolic risks. Conclusion: Women with POF need a special approach and specific therapy depending on their future reproductive plans. Timely MHT remains the main way to relieve the symptoms of estrogen deficiency and leads to an improvement in the level of biochemical and functional markers of endothelial dysfunction. This suggests that MHT is first-line therapy in patients with POF contributing to the normalization of the lipid profile and the functional state of the endothelium, and also confirms the need for its mandatory implementation as the primary prevention of cardiovascular diseases in women with POF.

Aim: Analysis of pregnancy complications and outcomes in women with COVID-19. Materials and methods: The retrospective study included 34pregnant women aged 16-40years, who underwent treatment for COVID-19 in hospital. The diagnosis of COVID-19 infection was confirmed by positive PCR test results for SARS-CoV-2 RNA detection in all pregnant women. Results: Most pregnant women (52.9%) had mild symptoms, 20.7% had moderate symptoms and 17.6% had severe symptoms. Pneumonia was diagnosed in 67.1% of pregnant women. Obesity was predominant in the structure of extragenital disorders. It was in 44.1% of women. With COVID-19, iron deficiency anemia (44.2%), preeclampsia (38.2%), risk of preterm birth (35.3%) were predominant in the structure of pregnancy complications. Preterm birth occurred in 36.8% of cases. Cesarean section was performed in 73.3% of cases. The incidence of complications in newborns was 11.6%. 8.8% of newborns were referred to the neonatal intensive care unit. Conclusion: It was found that most pregnant women had mild cases ofCOVID-19. Pregnant women with COVID-19 had high incidence of preeclampsia, preterm birth and cesarean section versus pregnant women without COVID- 19. Intrauterine vertical transmission of infection was not detected. The incidence of complications in newborns was in compliance with general population indicators.

Objective: To investigate the mRNA expression levels of transcription factor genes (GATA3, RORC2, FOXP3) in the cervical canal, placenta, and fetal membranes in term gestation depending on the presence of histologic chorioamnionitis. Materials and methods: The expression of GATA3, RORC2, and FOXP3 mRNAs was detected in 42pregnant women with a healthy pregnancy who underwent a planned cesarean section for fetal malpresentation and/or uterine scar at 37-41 weeks' gestation. The analysis was performed using RT-PCR and a morphological study of placentas. Results: Histologic chorioamnionitis was detected in 28 (66.7%) patients without clinical manifestations. In the presence of funiculitis/funisitis (7.1%), there was a 10-fold increase in the expression of GATA3 mRNA in the placenta and a 4-fold decrease in the fetal membranes. Parietal chorioamnionitis (64.3%) was associated with a 2-fold increase in expression levels of RORC2 FOXP3 in the placenta. Leukocyte infiltration of the fetal membranes (26.1%) was associated with a 10-fold decrease in the expression of GATA3 mRNA in the cervical canal. Conclusion: The present study showed that more than half of women with a healthy term pregnancy had histological chorioamnionitis. Analysis of the expression of transforming factors GATA3, RORC2, FOXP3 represents a promising direction in diagnosing placental and fetal membranes inflammatory process.

Recently, exosomal microRNA has been considered a potential noninvasive biomarker of various proliferative processes, particularly affecting the female reproductive system. Objective: To investigate the potential of plasma exosomal microRNA expression in patients with serous ovarian cancer, extragenital endometriosis, and ovarian endometriotic cysts (OEC) as potential markers of these diseases. Materials and methods: The study included seven patients with histologically confirmed high-grade serous ovarian cancer, six women in a control group without this pathology ("Control-ovarian cancer"), six patients with OEC, and five women of reproductive age without this pathology ("Control-OEC"). The exosomes were isolated from the blood, and the composition of plasma-derived exosomal microRNAs was determined using next-generation sequencing. Results: Pairwise comparison of miRNA content in the groups "ovarian cancer" - "Control-ovarian cancer" and "OEC" - "Control-OEC" identified 22 and 13 differentially expressed miRNAs (DEM) with statistically significant 2-fold or more differences. Potential markers for ovarian cancer included miR-141-3p, -199a-5p, -200b-3p, -203a-3p, -224-5p, and -4488and for OEC, miR-92b-5p, -486-5p, -3184-3p, -4732-5p, and -4235p. Potential target genes were identified for DEM in each pair of groups. The intracellular signaling pathways most likely involved in the pathogenesis of ovarian cancer and OEC were searched based on their lists. Potential target genes of several signaling pathways regulated by one or more DEMs in ovarian cancer and OEC included AKT1, ATM, BARD1, BAX, BCL2, BRCA1, CASP3, CDK4, CHEK1, CHEK2, JAK1, MDM2, PLK1, PTEN, RB1, SMAD2, SMAD3, and TP53. Functional clustering of target genes showed their involvement in regulating signaling pathways of growth factors, cell cycle, apoptosis, and DNA repair. Conclusion: The detection of unique DEMs in plasma exosomes indicates the presence of specific changes in the microRNA profile characteristic of ovarian cancer and OEC. The listed exosomal microRNAs can be considered candidates for markers of the studied proliferative processes. Multiple interactions between the identified microRNA target genes indicate their significant contribution and joint involvement into proliferative processes in ovarian cancer and OEC.

Objective: To investigate the feasibility of using quantitative assessment of the MT-ND1 gene copy number in culture medium as a marker of successful implantation and embryo quality. Materials and methods: We analyzed the level of MT-ND1 gene copy number in the spent culture medium as a function of embryo quality, maternal age, and the outcome of embryo transfer into the uterine cavity. Results: A total of 142 embryos were obtained, including 102 blastocysts and 40 embryos with arrested development. There was no statistically significant difference between these groups in the distribution of mtDNA copies (p=0.919). Depending on morphological characteristics, all blastocysts were divided into Group 1 (60 excellent and good embryos) and Group 2 (42 average and poor embryos). The distribution of mtDNA copies in these groups did not differ statistically significantly (p=0.082). All blastocysts were divided into groups depending on patient age, including Group 1 (<35years, 63 embryos) and Group 2 (>35.39years, embryos). The number of mtDNA copies was statistically significantly higher in the group of patients aged under 35 (p=0.001). Embryo transfer was performed in 24patients. Depending on the embryo transfer outcome, patients were divided into Group 1 (negative result, 17 patients) and Group 2 (clinical pregnancy, seven patients). The distribution of mtDNA copies in these groups had no significant difference (p=0.234). Conclusion: Spent culture medium contains mtDNA derived from embryos that can be detected and analyzed by quantitative PCR. The level of mtDNA in the spent culture medium might serve as a promising marker for selecting the best embryos for transfer into the uterine cavity.

Objective: To study the distribution of genotypes of the main genes that control the functions of folate cycle enzymes, such as MTHFR-677C>T, MTHfR-1298A>C, MTR-2756A>G, MTRR-66A>G in the Russian population and to analyze their relationship to the plasma level of folates, homocysteine, vitamin B12. Materials and methods: An observational study was conducted in an outpatient setting, which enrolled 194 women aged 20 to 38 years, who had sought advice for pregravid preparation. The polymorphic loci of MTHFR-677C>T, MTHFR-1298A>C, MTR-2756A>G, MTRR-66A>G were genotyped by polymerase chain reaction and melting curve analysis. The levels of folate, homocysteine, and vitamin B12 were quantitatively analyzed by chemiluminescence immunoassay. The oftware package of IBM SPSS Statistics 26 and computing environment R 4.0.5 were used for statistical processing. Results: The prevalence of genotypes in the examined women was as follows: MTHFR-677CT (48.5%), MTHFR-1298AC (27.3%), MTR-2756AG (32.5%), MTRR-66AG (68.6%), MTHFR-677TT(7.7 %), MTHFR-1298CC (12.9%), MTR 2756GG (15%), and MTRR-66GG (4.1%). It was statistically significantly established that the genotypes MTHFR-677TTand MTR 2756GG were associated with the low mean levels of folates (3.6±0.3 and 4.3±0.3 ng/ml, respectively), vitamin B12 (124.3 ±4.0 and 136.8±1.0pg/ml, respectively) and with the high mean level of homocysteine (15.1±0.2 and 15.2±0.3 iimol/l, respectively); the genotypes MTHFR-1298CC, MTHFR-1298AC, MTR-2756AG, and MTRR-66GG were related to the low level of folates (3.5±0.2, 5.6±0.4, 5.8±0.3, and 4.5±0.6 ng/ml, respectively) and to the elevated level of homocysteine (15.3±0.2, 14.3±0.3, 13.5±0.3, and 14.4±0.6imol/l, respectively). Conclusion: The findings indicating the prevalence of polymorphisms in the genes of the folate cycle enzymes in the study participants are similar to the global general population indicators. The genotypes MTHFR-677TT and MTR-2756GG are associated with the elevated level of homocysteine and the reduced levels of folates and vitamin B12; the genotypes MTHFR-1298CC, MTHFR-1298AC, MTR-2756AG, and MTRR-66GG are related to the low level of folates and to the elevated level of homocysteine. The presented data can be taken into account when predicting the risks of obstetric complications and designing a personalized micronutrient support regimen.

Objective: To reduce recurrence rates in patients with severe forms of female genital prolapse (FGP), by introducing the enhanced recovery after surgery (ERAS) protocol. Materials and methods: The ERAS protocol was applied to 72 patients aged 62.6 (8.2) years, operated on for grade II-III FGP according to the international Pelvic Organ Prolapse Quantification (POP-Q) classification. A comparison group consisted of 26 patients of the same age who had been treated by the traditional procedure. Postoperative quantitative and qualitative indicators were estimated. The duration of the follow-up was 12 months. Results: The early postoperative period was uncomplicated in both groups, however, the recovery time of urination was 24 (20;48) hours in the study group versus 48 (36;72) hours in the comparison group, and a cleansing enema was not required. The postoperative length was 2.1 bed-days shorter in the study group than in the comparison one. In the study group, 96% and 93% of the operated women were observed to have no recurrences and to be satisfied with their quality of life at 3 and 12 months after surgery. Conclusion: The clinical introduction of the ERAS protocol could decline the number of postoperative complications by 3.3 times and reduce the length of stay in hospital, the financial costs of treatment by 10,593 rubles, and also the number of FGP recurrences by 1.7 times.

Pelvic floor dysfunction is a complex of abnormal functioning of the pelvic floor muscles and ligamentous apparatus, which leads to disruption of work and descent/prolapse of the pelvic organs. Damages to the support structures of the pelvic floor can contribute to pelvic floor dysfunction. The prevalence of genital prolapse increases with age. According to demographic indicators, there is an increase in women’s life expectancy, including the duration of the menopause period in the female population, which is associated with a decrease in estrogen levels and a worse connective tissue quality, which contributes to the formation of pelvic floor dysfunction. Consequently, genital prolapse is becoming more common. The suggestions have been made that the incidence of genital prolapse will double in the next 30 years. Currently, the problem of genital prolapse is called a hidden epidemic. Among the available diagnostic methods, such as X-rays, computed tomography, magnetic resonance imaging (MRI), and echography, the latter absolutely has an advantage for imaging the pelvic floor. This technique is safe, simple, cheap, readily available, and provides high spatial and temporal resolution. The paper presents the possibilities of modern ultrasound multiparametric visualization of pelvic floor structures. In connection with the improvement of three-dimensional ultrasound technologies, volumetric ultrasound has become a new tool to diagnose the status of the pelvic floor. 3D imaging allows determining the axial plane with good spatial and temporal resolution. Multislice computed tomography, like MRI, promotes layer-by-layer assessment of all structures and differentiation of microtraumas of the pelvic floor muscles. Conclusion: Ultrasound imaging has become an important tool not only for the timely diagnosis of pelvic floor dysfunction, but also for the prevention of genital prolapse.

Background: SARS-CoV-2 enters the cell, by interacting with angiotensin-converting enzyme 2 (ACE-2) receptors, and affects a wide range of tissues and organs. Thus, ACE-2 receptors are found in placental tissues, as conf irmed by the growing number of publications on the detection of virions in cotyledons. To date, the infectious involvement and localization of SARS- CoV-2 in placental tissue are described in a small series of cases and occur with a low frequency of 21 %. The current data show that pregnant women infected with SARS-CoV-2 have a high risk of miscarriage, preeclampsia, preterm birth, and perinatal mortality. In view of the fact that constant efforts are being undertaken to study the placentas of patients who have experienced COVID-19 in order to further predict the effect of SARS-CoV-2 on pregnant women and newborns. Case report: This investigation analyzes data on three clinical cases of the course and outcomes pregnancy in patients after having experienced the novel coronavirus infection in early gestation. It presents in detail the nature of histopathological changes in placental tissue after SARS-CoV-2 infection. Conclusion: Based on the presented clinical cases, by comparing the findings and changes in the fetoplacental complex, there is an idea of its possible damage in pregnant women who have experienced SARS-CoV-2 infection in the early stages of gestation, regardless of the severity of the disease, as demonstrated by these clinical cases.