No 1 (2021)

Until recently, fetal arrhythmias have been a cause of stillbirths and neonatal and infant deaths in many cases, which has given rise to a new interdisciplinary direction in perinatology - fetal cardiology-arrhythmology. Unlike fetal tachyarrhythmias that are actively treatable, even timely therapy for bradycardia does not always provide a favorable outcome. In this connection, to predict and prevent fetal atrioventricular block are still the subject of active study. The review includes scientific publications (mainly systematic reviews and meta-analyses) by foreign and Russian authors over the past 10 years, which have been found in the Pubmed database and other available search systems: Cochrane, Web of Science, MEDLINE, and Google Scholar. The paper presents the modern ideas about the incidence and pathogenesis of fetal bradyarrhythmias and considers various therapeutic and preventive approaches. Conclusion. Further clinical and laboratory studies are needed to develop a comprehensive examination of and optimal management tactics for pregnant women with different types of fetal bradyarrhythmias

Whether the effectiveness of assisted reproductive technology (ART) programs can be enhanced remains relevant, despite the actively continued investigations aimed at identifying the causes of failures and new methods for treatment. One of the main factors influencing the effectiveness of embryo implantation is the state of the endometrium; for its study, investigators used molecular genetic and immunohistochemical studies. Taking into account the changes detected in the endometrium, it is promising to use own platelet-rich plasma (PRP) in the endometrium preparing programs for embryo implantation. Analysis of the literature on the use of PRP in other medical fields indicates the efficiency of this treatment option in terms of both clinical symptoms and a number of laboratory and functional studies. The use of PRP in in vitro fertilization (IVF) programs in patients with failed implantation attempts will affect the structure and functional activity of the endometrium.

The use of combined oral contraceptives (COCs) carries a risk of thrombotic events and phlebopathies. The most common clinical presentation of COC-induced thrombosis is venous thromboembolism of the leg deep veins or pulmonary vessels. Traditional anticoagulants are unsuitable for the routine prevention of COC-induced venous thromboembolic (VTE) events, since they require long-term systematic use. There is a group of proteolytic enzymes, such as subtilisins, that have a pronounced fibrinolytic effect. These enzymes are unique in that they dissolve only denatured or polymerized proteins. For example, subtilisins have no action on fibrinogen, but dissolve cross-linked fibrin. This fibrinolytic action of subtilisins is direct without involving the fibrinolytic system in physiological processes is an important circumstance. Subtilisins have been used to design Trombovazim that has a thrombolytic effect and has been registered for the treatment of venous insufficiency. Several clinical trials have been conducted to prove the high clinical efficacy and safety of Trombovazim used as an oral thrombolytic drug and for the treatment of phlebopathies. To date, the pharmaceutical markets in Russia and other countries lack a similar drug that, when administered orally, is able to dissolve blood clots on its own. Conclusion. The use of Thrombovazim in gynecology is a new method to treat and prevent COC-induced VTE events andphlebopathies.

Pregnancy complicated by placenta previa is associated with a high risk of adverse outcomes, primarily with massive hemorrhage, which is largely due placenta accreta. Aim. To determine prognostically significant risk factors for placenta accreta associated with placenta previa. Materials and methods. Continuous sampling method was used to analyze the cases, when women had deliveries with placenta previa in history. The anamnesis data, birth outcomes, blood loss in patients with placenta accreta associated with placenta previa (n=117) and placenta previa without accretion (n=268) were compared. Results. Placenta accreta occurred in 30.4% of women with placenta previa. Of them in 44.8% of cases, it was due to the presence uterine scars. Among the patients with placenta accreta, parity (p=0.039) and the number of births (p=0.001) was higher. In cases of abdominal delivery, 29.9% of women had obstetric hemorrhage. In patients with placenta accreta, the volume of blood loss was 3 times higher than in women without placenta accreta (p=0,001). The presence of an uterine scar after cesarean section was prognostically more significant in relation to placenta accreta associated with placenta previa (sensitivity - 93.2%, specificity - 76.5%). Conclusion. The women with obstetric hemorrhage in cases of placenta previa are in a high-risk group for the development of massive hemorrhage. The presence of an uterine scar, more than two births in history, and delivery at ≥ 36. 5 weeks are prognostic criteria for placenta accreta in pregnant women with placenta previa.

An optimal ratio of inflammatory (Th1) and anti-inflammatory (Th2) immune responses is required for successful embryo implantation and subsequent fetal development. Allogenic lymphocyte immunization also referred to as cell immunotherapy (CIT) before conception and in the early stages of pregnancy, effectively corrects immunoregulation in women with recurrent spontaneous abortion. However, the time to pregnancy (TTP) after pre-gestational CIT varies significantly. Aim. To investigate the relationship between Th1/Th2 cytokine balance after pre-gestational CIT and the TTP in women with a history of recurrent spontaneous abortion. Materials and methods. The study included 37 women who underwent CIT as monotherapy. TTP was defined as the duration of time expressed in the number of menstrual cycles from contraception discontinuation until conception occurred. Production of pro-inflammatory (IFN-γ, IL-2, IL-6, IL-8, IL-12, IL-18, TNF-α, IL-1β) and anti-inflammatory (IL-4, IL-5, IL-10) cytokines after mitogen-induced activation of maternal peripheral blood cells were analyzed by flow cytometry using FlowCytomix ™ kits (eBioscience). Results. In 22 (59.5%) women, pregnancy occurred within six menstrual cycles, and five (13.5%) women conceived between 7 to 12 menstrual cycles. Ten women (27%) failed to achieve pregnancy within 12 menstrual cycles. Compared to women with TTP ≤ 6 menstrual cycles, those with 6 < ТТР ≤ 12 menstrual cycles and who was unable to conceive had reduced Th1/Th2 cytokine ratio. Conclusion. The TTP after allogeneic immunotherapy may depend on the Th1/Th2 cytokine ratio.

Aim. To investigate vaginal microbiome in pregnant women with preterm prelabor rupture of membranes (PPROM) before 28 weeks' gestation using metagenomic sequencing. Materials and methods. The study comprised 55 pregnant women, including patients with PPRPO before 28 weeks' gestation (group I) and women with a healthy pregnancy (group II). Results. Statistically significant between-group differences were found in the relative abundance of microorganisms for the vaginal microbiome regarding 13 genera of microorganisms including Lactobacillus, Pediococcus, Prevotella, Prevotella 6, Peptostreptococcus, Peptoniphilus, Anaerococcus, Fusobacterium, Parvimonas, Lawsonella, Sutterella, Mobiluncus, and Thermus. Also, there were statistically significant differences in detection rates of microorganisms' genera, including Pediococcus, Prevotella, Prevotella 6, Anaerococcus, Peptoniphilus, Parvimonas, Lawsonella, Sutterella, Mobiluncus, Thermus. Conclusion. The presence of bacteria of the genus Prevotella (especially Prevotella 6), Anaerococcus, Peptoniphilus, Parvimonas, Lawsonella, Sutterella, Mobiluncus, Thermus in the vaginal microbiome of pregnant women with PPRPO, and low relative abundance of bacteria of the genus Lactobacillus and Pediococcus during pregnancy are associated with preterm prelabor rupture of membranes before 28 weeks' gestation, which warrants further investigations.

This was a prospective controlled comparative open-label study of the use of the enterosorbent polymethylsiloxane polyhydrate (Enterosgel) in patients diagnosed with chronic endometritis. Objective. To analyze the effectiveness of modern enterosorption aimed at restoring the reproductive potential of patients with missed abortion and the patients who are at risk for this condition. Materials and methods. The effectiveness of enterosorption was evaluated using the surrogate parameter, namely, normalization of the endotoxin level in the general hemocirculation, development and successful outcome of the subsequent pregnancy. The endotoxin level was used as the primary endpoint due to the fact that there was a relationship between endotoxinemia and changes in the level of proinflammatory cytokines in the peripheral bloodstream with the persistent infectious agent in the genital tract; this relationship was shown to affect the chronization of the inflammatory process in the uterine cavity. To describe the quantitative variables, we used the median, upper and lower quartiles in the Me (LQ;UQ) format. The indicators among two and three or more groups were compared using the Mann-Whitney and Kruskal-Wallis tests, respectively. Results. The enterosorbent Enterosgel was shown to be effective and safe in restoring the reproductive potential of this group of patients, whose level of endotoxin in peripheral blood and cytokines of the first phase of the immune response (IL-1β, IL-6, and TNF-α) was corrected. The most significant results were obtained after the treatment of patients diagnosed with missed abortion who followed a treatment regimen polymethylsiloxane polyhydrate + synbiotic. Conclusion. The obtained data indicate that it is advisable to suppress the inflammatory process in the uterine cavity using broad-spectrum antibiotics and to correct the state of anti-endotoxin immunity with the help of enterosorbent Enterosgel.

Aim. To develop a method for determining the maternal or paternal origin of chromosomal aneuploidies in embryos by performing STR analysis for patients who undergo assisted reproductive technologies (ART) programs. Materials and methods. The development of the method was carried out using biopsy material of the trophectoderm in embryos of 58 couples of patients (116 persons). Preimplantation genetic testing for aneuploidy (PGT-A) was performed using high-throughput sequencing. Determination of the origin of aneuploidy was performed by fragment analysis of STR markers. Results. After After PGT-A, aneuploidy was detected in 67 embryos (41%); euploid embryos were 65 (40%); mosaic forms were found in 28 (17%) embryos. Primers have been developed for the analysis of chromosomes 1, 3, 4. Development of primers for analysis of 1, 3, 4, 5, 6, 7, 9, 11, 12, 13, 14, 15, 16, 19, 22 and X chromosomes was performed. The analysis of chromosome 16 (n = 7 embryos), chromosome 19 (n = 5 embryos) and chromosome 22 (n = 8 embryos) showed that this approach can be used to identify both maternal and paternal origin of aneuploidy. Conclusion. A technological possibility of carrying out STR fragment analysis with purpose of genotyping of embryos using various products of whole genome amplification was shown. It makes possible to carry out PGT-A and PGT-M together with embryo genotyping without the need for repeated biopsies. The study parental contribution to the development of embryonic aneuploidy in future will allow to choose the most optimal tactics for managing patients with repeated unsuccessful attempts of ART and past miscarriages.

Connective tissue dysplasia (CTD) is one of the discussed topics. Female patients with CTD are at risk for pregnancy and childbirth complications: threatened miscarriage, preeclampsia, placental insufficiency, and surgical delivery. Objective. To improve perinatal outcomes with consideration for collagen metabolism in the presence of hypomagnesemia. Subjects and methods. A total of 155 pregnant women were examined and divided into 2 groups according to the presence or absence of CTD signs. Group 1 included 58 (37.4%) pregnant women with non-syndromic CTD (nCTD). Group 2 consisted of97(62.6%) pregnant women who had no signs of CTD manifestations. Each group of the pregnant women was divided into 2 subgroups according to the presence or absence of magnesium deficiency. Results. The investigation revealed that the lower plasma magnesium level in pregnant women substantially worsens the prognosis of pregnancy and childbirth. Correction of magnesium status during pregnancy is ineffective. It is necessary to determine magnesium levels before pregnancy and to timely implement therapeutic and preventive measures including the correction of magnesium deficiency in the patients with nCTD and in those with a family obstetric history; whereas the drugs improving collagen metabolism should be prescribed for the patients with nCTD. This category of patients should plan a pregnancy when they reach the standard magnesium values and the normalized levels of biochemical markers of collagen breakdown, which can considerably improve perinatal outcomes. Thus, there may be more common threatened miscarriage and a high risk for perinatal losses in the patients with nCTD versus pregnant women with normal plasma magnesium levels and normal collagen breakdown values. Threatened miscarriage, preterm delivery, premature amniorrhea, abnormal uterine contractions, and surgical delivery more frequently happen in the pregnant women without nCTD and with magnesium deficiency than in those with normal plasma magnesium levels and normal collagen breakdown values. Conclusion. Thus, optimal methods for the diagnosis and prevention of complications in pregnant women with hypomagnesemia in the presence or absence of CTD were developed on the basis of assessment of the results of standard and special studies, including the determination of the levels of blood magnesium, collagen breakdown markers (urinary deoxypyridinoline and glycosaminoglycans and blood fibronectin).

Cervical cancer is one of the most commonly diagnosed malignant tumors in pregnant women. The existing current standards of therapy for invasive cervical carcinoma during pregnancy include surgery and/or chemotherapy. The tactics for treating patients is determined by gestational age, stage of disease, and a woman’s desire to maintain her pregnancy. Objective. To generalize and analyze the authors’ own experience in managing pregnant women with invasive cervical carcinoma. Subjects and methods. Sixteen cases of invasive cervical carcinoma were retrospectively analyzed in pregnant women with a median age of 34.5 years; the period of initial diagnosis was 21.6 weeks. Results. Pregnancy was complicated by threatened miscarriage in the first trimester in 18.75% of cases; atypical conization was performed in 25%; 2 (12.5%) patients received neoadjuvant chemotherapy. Delivery at term occurred in 62.5% of patients, preterm delivery in 31.2%. The median gestational age at delivery was 36.3 weeks. Cesarean section was performed in 68.7%. Wertheim’s operation following cesarean section was made in 7 (43.7%) patients and with ovarian transposition in 57%. The weight of newborn babies was 3025±312 g. Within 1 year after their birth, the infants developed according to age norms. Conclusion. Due to the introduction of clinical protocols into practice, since 2019 material should be collected from the cervix uteri for cytological examination from all pregnant women when registered at a women’s health center. Compliance with the rules for the collection and transportation of cytological material, as well as its careful interpretation, is the key to the timely identification of patients at risk for cervical cancer. Additional examination of these patients, by carrying out tests for human papillomavirus and colposcopy, and, if necessary, targeted colposcopic biopsy will be able to reduce the frequency of late diagnosis of cervical cancer.

Abnormal uterine bleeding (AUB) is one of the most common complaints encountered in gynecological practice. AUB negatively affects the physical, emotional, sexual, and professional aspects of women’s lives. The paper highlights the current view on the tactics of managing patients with AUB according to the current FIGO classification system. Patient management requires an individual approach to tailoring treatments to individual needs, taking into account not only the etiology of this abnormality, but also the somatic problems of the women and their reproductive plans. After verifying the diagnosis of the abnormality, a physician must pay attention to its pathogenetic validity, when choosing a therapy option, and to the advisability of using one or another method. The paper analyzes various hormonal drugs for AUB, including progestogens and hormonal contraceptives. If there is a need to prevent unwanted pregnancy, oral or intrauterine hormonal contraceptives may be recommended. However, when choosing a drug, in addition to its exerted effects, the safety profile should be taken into account, by assessing the benefit-risk ratio individually for each patient. One of the most preferred and pathogenetically grounded treatments is the use of progestogens. Among them, dydrogesterone occupies a special place due to its high efficacy in reducing the volume of blood loss, as well as its favorable safety profile, which makes it currently the most suitable drug for the treatment and secondary prevention of AUB. Conclusion. Correctly chosen hormone therapy for women who need it makes it possible to improve patients’ health and to minimize the risks of adverse events.

The novel coronavirus infection is a global pandemic with a continuing upward trend for global cases. The virus can infect any person; however, pregnant women may be more susceptible due to physiological changes in the body. This paper describes a clinical case of the rapid course of COVID-19 pneumonia in a pregnant patient without substantial risk factors for a severe, complicated form of the disease. Patient Zh. was infected with COVID-19 at 37-38 weeks’ gestation. The first clinical manifestations of the disease were sore throat accompanied by a rise in temperature up to 38° C. Taking into consideration that the patient felt worse, cough and fever appeared, she was admitted to a specialized hospital on day 5 after the onset of the disease. On day 7 of hospitalization, worsening respiratory symptoms and intoxication syndrome led to the development of acute cardiopulmonary failure that was the cause of death in the pregnant woman and her fetus. Despite the relatively small number of maternal deaths due to COVID-19, obstetricians/gynecologists and other health care workers need additional data on the characteristics of the course of the disease and possible adverse maternal and perinatal outcomes. Conclusion. Physicians should be informed about mortality and its associated clinical characteristics in patients mainly because the median time from the onset of symptoms of the infectious process to the fatal outcome can be as little as two weeks.

Background. Tumors of the external genital organs, vagina, and uterus are rare in childhood and adolescence (8% of all tumors and tumor-like masses of the uterine appendages). Space occupying lesions of the genital organs in girls average 1.5 to 2% of all neoplasms in children of both sexes and tenths of a percent for all cases of female reproductive system tumors. As a rule, they are malignant (sarcoma of the vagina, cervix, or corpus uteri) and primarily manifest themselves as vaginal bleeding that serves as the leading symptom of the disease. When vaginal bleeding appears in young girls, their parents usually quickly go to a doctor. However, girls of early reproductive age seek no medical advice for a long time, and this often leads to the disease being diagnosed at an advanced stage. Case report. The paper describes a clinical case of a teenage girl with benign cervical neoplasm that has been undetected in time, causing multiple recurrences of the disease. Conclusion. Abnormal uterine bleeding in puberty, as well as in all other periods of a woman’s life, requires vaginoscopy in order to exclude vaginal and cervical neoplasms that are rare, but are, nevertheless, possible causes of recurrent vaginal bleeding in girls.