No 8 (2021)

The paper analyzes the results of studies published in recent years on the complement system in preeclampsia and other pregnancy complications. It presents data on changes in complement factors and its regulatory proteins in placental disorders. The results of the studies suggest that uncontrolled complement activation leads to impaired placentation, affects fetal development, and is an important component of the pathogenesis of complications, such as preeclampsia, HELLP syndrome, spontaneous miscarriage, and premature birth. Dysregulation of the alternative complement pathway in the presence of mutations in the genes of regulatory factors H and I, CD46, factor B. and others is known to be associated with atypical hemolytic uremic syndrome, less often with membranoproliferative glomerulonephritis. The similar mutations have been found in patients with severe preeclampsia and HELLP syndrome. Recent studies have shown a pronounced activation of the complement system in 100% of patients with HELLP syndrome and in 90% of those with severe preeclampsia with the formation of the C5b-9 membrane-attack complex and its deposits on activated endothelial cells. C5b-9 transmembrane integrates into the target cell, forming an asymmetric cylindrical channel, through which water molecules and electrolytes freely penetrate the cell, which causes its osmotic lysis. This is one of the most important mechanisms of endothelial damage in preeclampsia. The paper also presents modern therapeutic strategies for blocking excessive activity of the complement system. It is concluded that serious studies are needed to predict pregnancy complications caused by the imbalanced complement system, pharmacological correction, and safety and eff icacy of the drugs used. Conclusion. In addition to the above-mentioned problems, the most important question of what exactly the direct inducer of excessive complement activation is in preeclampsia needs to be solved.

The prevention and treatment of preterm labor remain an unsolved problem in modern obstetrics. Certain successes have been currently achieved in the treatment of threatened preterm labor due to drugs that suppress uterine contractile activity, which include tocolytics. The most widely used tocolytic agents are ß-adrenomimetics; however, they are associated with a high frequency of unpleasant and sometimes severe maternal side effects. Calcium channel blockers may have similar tocolytic efficacy with fewer side effects than ß-adrenomimetics. Oxytocin receptor antagonists also have a low side effect profile. The administration of tocolytic drugs can reduce the strength and frequency of uterine contractions, delay the onset of labor for 48 hours and/or even 7 days, but cannot prolong pregnancy to full-term. The drugs are administered within 48 hours in order to prevent fetal respiratory distress syndrome, to perform magnesium sulfate therapy for fetal neuroprotection, and to transfer a pregnant woman to a Group III hospital. Currently, the choice of a drug for tocolysis remains debatable. Conclusion. It is necessary to continue clinical trials in order to select an effective, and most importantly safe, therapy for threatened preterm labor.

Currently, cancers are of leading importance in the structure of mortality worldwide. Among the female population, malignant endometrial neoplasms occupy the second place in their incidence. Endometrial hyperplastic processes are presently considered to be precursors of malignant transformation, which is especially relevant in able-bodied women. There is evidence that the incidence of endometrial hyperplasia (EH) varies from 10 to 55% and reaches its maximum in the population of perimenopausal women. The paper analyzes an update on clinical risk factors for endometrial hyperplasia in perimenopausal women. Among the most significant background conditions, there are diabetes mellitus, obesity, factors of gynecological history and hormone therapy, including that for malignant breast neoplasms. Changes in the expression of estrogen and progesterone receptors play an important role in the development of pathological effects and their relationship to the development of hyperplastic processes. Conclusion. The use of molecular genetic testing in the study of the course and progression of HE and malignant transformation makes it possible to explain the mechanisms of the effects of risk factors and to clarify their significance for assessing the development of the disease. To select therapeutic tactics and to predict drug therapy success, it seems promising to evaluate the receptor status of patients with HE.

This review analyzes and generalizes the results of the studies characterizing the interaction of peripheral blood platelets and monocytes, which have been conducted to define their role in various physiological and pathophysiological processes. At the same time, special attention was given to reproductively significant processes. Due to the fact that the magnitude, direction, and consequences of the interactions between these types of cells are most strongly characterized by the number, immunomorphological features, and functional activity of platelet-monocyte aggregates (PMAs) resulting from such interactions; particular emphasis was placed on the findings of the investigation of these structural formations. In particular, the review considers the results of studying the mechanisms of interaction between platelets and monocytes, which lead not only to the formation, but also to the stabilization of these structures. It describes the membrane-bound molecules and molecular complexes that provide the formation of PMAs, as well as soluble factors that favor the development of complexation mechanisms at the autocrine, juxtacrine, and paracrine regulation levels. The review contains the characteristics of methods for the isolation and identification of PMAs, such as differential and gradient centrifugation, immunomagnetic separation, electron microscopy, light and fluorescence microscopy, flow cytometry and the latter with visualization. Their advantages and disadvantages are analyzed from the point of view of adequacy, technological effectiveness, and clinical and diagnostic information value of the conducted studies. The data available in the literature on the role of PMAs in reproductive pathologies are assessed. Conclusion. The contact interaction of platelets and monocytes plays an important role in various physiological and pathophysiological processes. The ability to effectively isolate and identify PMAs using modern technologies has created prerequisites for the use of measuring the concentration of PMAs as a diagnostic and prognostic indicator for diseases accompanied by hemostatic disorders. From the point of view of reproductive processes, the study of the effect of PMAs on endometrial and trophoblast cells is of absolute interest. An approach based on the creation of cell models using cell lines of the corresponding origin seems promising.

The authors analyze their own data and the data available in the literature on the negative various effects of stress on the development and functioning of the fetal neuroendocrine, immune, and reproductive systems, leading to disorders in the prenatal and postnatal ontogenetic periods. Poor maternal nutrition and lifestyle during pregnancy, pharmacological effects, and maternal bacterial and viral infections can change the molecular mechanisms of the development of these systems and suppress their functions for a long time. As a result, there is an increased risk for various metabolic, neuropsychiatric, immunological and reproductive disorders in the offspring. Prenatal deficiency of neurotransmitters and hormones, in particular serotonin, dopamine, and gonadotropin-releasing hormone, disrupts the development of the fetal thymus, while this impairs the functioning of T cell immunity in the postnatal period. The influence of infectious agents on the maternal body increases the risk of pathological conditions in the first trimester of pregnancy. Pro-inflammatory cytokines, the synthesis of which increases under the influence of these factors, cause developmental abnormalities in the neuroendocrine and hypothalamic-pituitary-gonadal systems. This leads to a decrease in the reproductive ability or infertility of sexually mature offspring. Conclusion. Timely detection of prenatal and early postnatal disorders caused by intrauterine inflammation opens up opportunities for preventing and correcting the consequences of fetal negative effects. To date, a lot of experience has been accumulated in the use of human immunoglobulins to treat recurrent miscarriage, as well as to prevent infection in premature newborns and low birth weight ones.

Aim. Assessment of the effectiveness of different methods for correction of isthmic-cervical insufficiency (ICI) and pregnancy outcomes in patients with preterm birth (PB) in history and without PB. Materials and methods. Retrospective analysis included 108 women with ICI, who underwent treatment with cervical cerclage and obstetric pessary. The patients were divided into 2 groups. Group I included 74 (66.7%) women with ICI, who had no PB in history: cervical cerclage was used in 35(47.3%) women and obstetric pessary was used in 39 (52.7%) women. Group II included 34 (33.3%) women with ICI an PB and/or spontaneous late-term miscarriage in history: cervical cerclage was used in 24 (70.6%) patients and obstetric pessary was used in 10 (29.4%) patients. Results. The analysis results did not show significant differences between the two techniques for correction of ICI both in the group of patients with PB and with no PB in history. The assessment of gestational age for correction of ICI showed statistically signif icant differences in both groups: in the group of patients with PB in history, the median gestational age at cervical cerclage was 19 (17-20) weeks, and at pessary placement it was 24.5 (20-26) weeks, (p=0.015). In the group of patients with no PB in history - it was 21 (20-22) and 24 (22-26) weeks, respectively (p<0.001). Overall preterm birth rate in the group of women with no PB in history, who underwent cervical cerclage was 31.42%, and 38.46% among those who underwent obstetric pessary insertion. Term births were in 60% and 53.85% of women, respectively. Preterm birth rate in the group of patients with PB in history who underwent cervical cerclage was 45.84%, and 20% among those who underwent pessary insertion; term births were in 45.83% and 70% of women, respectively. Conclusion. In addition to prolonged support with progesterone and elimination of factors contributing to the occurrence of infection, the techniques for correction of ICI - pessary and cerclage showed similar results with regard to pregnancy prolongation, PB rates and perinatal outcomes both in the group of pregnant women with no PB and in the group of women with PB in history.

Aim. The study was aimed at determining antenatal factors associated with brain-derived neurothophic factor and insulin-like growth factor-1 levels in premature infants. Materials and methods. The prospective study included 62 mother-infant pairs. The women and newborns were divided into two groups depending on gestational age at birth: group I included 21 mother-infant pairs with spontaneous preterm birth (PTB), the average gestational age for births was 33.3+1.93 weeks; group II included 41 mother-infant pairs with term birth (TB) at 39,4+1,04 weeks. Enzyme immunoassay (EIA) was performed for quantitative detection of brain-derived neurotrophic factor and insulin-like growth factor-1 levels in blood plasma of newborns. Results. BDNF level was high in the term birth group (р<0.0001), while IGF-1 level was low (р=0.0038). In the preterm birth group, the median BDNF value in women who had treatment for prevention of respiratory distress syndrome (RDS) in newborns was 488.5[70.9; 2295]pg/ml, and 326.5[133.4; 2730]pg/ml in women who did not receive RDS profilaxis, р=0,9644. In the preterm birth group, the median value of IGF-1 was 45.3 [28.3; 58.1] ng/ml in women who received RDS profilaxis, and 90.9 [57.7; 252.3] ng/ml in women who did not receive RDS profilaxis, р=0.0197. Conclusion. The specific features of the course of pregnancy affect BDNF and IGF-1 levels in blood plasma of premature infants, including antenatal prophylaxis of RDS and antibiotic therapy.

Aim. Investigation of the character and extent of changes in endothelial functional activity and metabolic disorders (visceral obesity and insulin resistance, lipid imbalance) in climacteric women, depending on severity of climacteric syndrome (CS). Materials and methods. The study included 168 women in perimenopause and 216 women in early perimenopause with CS. Modified Kupperman-Uvarova menopausal index was assessed. The parameters of lipid metabolism, fasting blood glucose, the level of immunoreactive insulin (IRI) and the HOMA-IR index were assessed. Waist circumference was measured and Waist-Hip Ratio (WHR) was calculated. Flow-dependent vasodilation (FDV) of brachial artery was assessed using the reactive hyperemia test. Enzyme immunoassay was used to assess the levels of endothelial dysfunction (ED) markers - endothelin-1 (ET-1, nitric oxide metabolites, von Willebrand factor antigen (V WF:Ag) and asymmetric dimethylarginine (ADMA) in blood plasma. Results. Significant disturbance of endothelial function was found in women with moderate and severe symptoms of CS in comparison to the women with mild disease: the change in brachial artery diameter (10.1±5.2% versus 12.2±6.5% (р<0.01)) and lower level of NO2 metabolites (12.1fiml/l (10,3;13,8) versus 13.8) μml/l (12.2;15.3, respectively (р=0,042). Along with more severe abdominal obesity and IRI, the progressive intensity of vasomotor symptoms of CS was noted. In women with severe CS compared to a mild disease, obesity and dyslipidemia were more frequent (in 60.2% versus 40% of patients, p<0.001), as well as the metabolic syndrome (in 58.7% versus 41.3%, respectively (p<0.01)). Conclusion. The severity of CS was associated with significant metabolic changes and endothelial dysfunction. The severity of the vasomotor symnptoms of CS may reflect the severity of ED in menopausal women.

Aim. To investigate plasma cytokine profile changes in preterm neonates with respiratory disorders in the early neonatal period. Materials and methods. The study included 105 neonates born in our Center from January 2019 to November 2019. The study group consisted of 92 preterm neonates with gestational age (GA) 32-36 weeks who were admitted to the neonatal intensive care unit (NICU) on the first day of life (DOL). The study group was divided into subgroups of respiratory distress syndrome (RDS) (n=21), transient tachypnea of the newborn (TTN) (n=28), and congenital pneumonia (n=43). The control group included healthy early-term infants (GA 37 weeks). Plasma cytokine profiles of the neonates were analyzed. Blood samples were taken on days 1, 3, and 7 of life in the study group and day 1 of life in the control group. Blood samples were collected into EDTA tubes. Plasma cytokine profiling included pro-inflammatory (IFNy, TNFa, IL-1ß, IL-2, IL-6, IL-12, IL-17) cytokines, anti-inflammatory (IL-4, IL-5, IL-10, IL-13) cytokines, chemokines (IL-8, MCP-1, MIP-1ß), and growth factors (IL-7, G-CSF, GM-CSF). Results. Among preterm neonates, plasma levels of cytokines at the beginning and the end of the early neonatal period differed from those on the first day of life and depended on the type of respiratory disorders. There were statistically significant changes for pro-inflammatory cytokines (IL-6, INF-y, TNF-a), chemokines (IL-8, MCP-1, MIP-1ß), and anti-inflammatory cytokine IL-10. Conclusion. Plasma cytokine profiling in preterm neonates on the first DOL can be used for differential diagnosis and assessment of treatment effectiveness DOL7. An increase in IL-6 concentration on DOL1 is the most informative of the studied markers regarding differential diagnosis between congenital pneumonia, RDS, and TTN. The IL-6/IL-10 ratio can be used as an additional criterion for decision-making regarding discontinuation of antibiotic therapy in preterm infants with congenital pneumonia.

Objective. To study and optimize management tactics for pregnancy and childbirth in women with epilepsy to improve obstetric and perinatal outcomes. Materials and methods. During studies in 2014-2019, the investigators examined 262 pregnant women with cryptogenic epilepsy who delivered infants. Pregnancy and delivery were managed at the Moscow Regional Research Institute of Obstetrics and Gynecology. Special attention was paid to the nature of the course of the underlying disease, to antiepileptic drug therapy, and to the presence of convulsive seizures. The examination included a complete standard clinical and diagnostic testing, a study of fetoplacental complex hormones, antiepileptic drug (AED) concentrations, and immunological and morphological studies. Results. Despite a neurological pathology that requires continuous AED use and the pharmacoresistant form of the disease in some pregnant women, the complicated course of pregnancy and childbirth was not observed in most cases. Labor pain was relieved in women with epilepsy according to obstetric indications; however, a combined method for labor pain relief was used in persistent convulsive seizures in the third trimester, which allowed the maximum sedative and analgesic effects to be achieved. 89% of babies were born in a satisfactory condition owing to the adequate monitoring of a pregnant woman with epilepsy and timely correction of obstetric complications. The birth of babies with congenital malformations (CMs) in two cases was due to the fact that there was no their prevention at the stage of pregnancy planning. Conclusion. The successful course of pregnancy and childbirth in women with epilepsy requires that the pregnant woman should be monitored jointly by an obstetrician/gynecologist and an epileptologist/neurologist, who is competent in the course of epilepsy in females and pregnant women. The most common failure of drug-induced remission was observed in the second trimester of pregnancy, which needed to increase the dose of AEDs or switching to combination therapy. Obstetric complications were treated according to standard clinical protocols.

Objective. The study aimed to characterize the normative AMH levels amongst adolescent girls in Armenia, assess reproductive health, and take preventive measures for infertility. Materials and methods. The study included 700 10-18-year-old adolescent girls randomly selected from different regions of Armenia, including Yerevan. Clinical evaluation included serum levels of AMH, FSH, LH, TSH, anti-TPO, as well as thyroid gland and pelvic ultrasound examination. Results. The individual AMH level in 10-15-year-old adolescent girls ranged from 2.0 to 4.0 ng/ml and among 16-18-year-old adolescent girls from 1.5-4.0 ng/ml. The normal ovarian reserve has the following characteristics: AMH level not less than 2.0 mg/ml, FSH level not more than 10 m U/ml, AFC at least 5 in each ovary, and ovarian volume, not less than 5cm3. A total of 469 (67%) adolescents had a normal AMH level and normal ovarian reserve. 231 (33%) adolescent girls were at high risk for diminished ovarian reserve, menstrual disorders, infertility, and reproductive losses. Conclusion. The study established the normative values for serum AMH and evaluated the normal ovarian reserve of Armenian adolescent girls. Knowledge of low ovarian reserve and its prognostic significance allows identifying risk groups of adolescent girls at an early stage. This enables the determination of reproductive behavior and prevention of reproductive losses and infertility in the reproductive age.

The overactive bladder (OAB) is one of the most important clinical conditions in functional urology for children and adults and а socially significant disease. About 18 million adults in our country are suspected to have OAB symptoms. Selective muscarinic receptor antagonists are considered to be the traditional treatment for OAB. Some mechanisms that lead to urgency are not suppressed by muscarinic receptor blockade. A new area of OAB pharmacotherapy is to affect ß-adrenoptors located in the bladder urothelium and suburothelium. After many years of studies, the innovative and unparalleled drug Mirabegron appeared, which was a ß3-adrenomimetic that acts on the receptors of smooth muscle fibers. Mirabegron has a direct effect on the bladder urothelium. Conclusion. According to some indicators, the efficacy of Mirabegron exceeds that of cholinolytics, whereas the clinical effect can be observed even in a group of patients with unsatisfactory results of previous treatment. Thus, Mirabegron can be considered as the drug of choice for OAB pharmacotherapy.

Placental abruption is one of the most life-threatening and dramatic complications encountered in obstetric practice. The severe form of placental abruption with the formation of a retroplacental hematoma, the so-called Couvelaire uterus, is a serious accident in the second half of pregnancy and during childbirth with severe consequences for the mother and fetus, which often lead to a fatal outcome. The article presents a review of literature on the management tactics for pregnant women and parturients with premature detachment of the normally situated placenta, which is complicated by the development of Couvelaire uterus. Much attention is paid to the possibility of choosing organ-sparing tactics for this pathology. Using six cases from their own clinical practice as an example, the authors demonstrate the possibility of organ-sparing surgery for Couvelaire uterus. Conclusion. The complex process of choosing a surgical intervention directly depends on the amount of blood loss, hemodynamic parameters, and the severity of disorders in the hemostatic system, and uterine contractility. It is also necessary to take into account the general condition of a woman, her desire to preserve the uterus, as well as the level of equipment in the facility, and the capabilities of a surgeon. An individual approach ensures the success of a surgical intervention and the favorable course of the postoperative period.

The issue of increasing nonspecific immunity is becoming particularly relevant in the context of the spread of a new coronavirus infection SARS-CoV-2. Thus, there is question of supplementation with vitamins and micronutrients, especially in reproductive-aged women planning pregnancy, due to socio-economic aspects, geographical latitude, dietary habits, and increased needs associated with the epidemiological situation. The deficiency of certain micronutrients in the diet has been found to impair the chemical, structural and regulatory processes in the body, which can negatively affect the state of the immune system. Certain associations have been identified between sufficiency of micronutrients, the severity of the course and development of complications of COVID-19. Severe course of infection is associated with severe deficiency of vitamin D (<10 ng/ml). Vitamin D contributes to changing the macrophage phenotype from pro-inflammatory Th1 to anti-inflammatory Th2, which may reduce the risk of a cytokine storm. There was a statistically significant decrease in the level of inflammatory markers, including ferritin and D-dimer, a decrease in the risks of multiple organ failure, a tendency to reduce the need for ventilation, vascular damage in patients with acute respiratory distress syndrome with parenteral use of high doses of ascorbic acid. The experimental studies have shown that cations Zn2+ inhibit the activity of SARS-coronavirus RNA polymerase by reducing its replication; this fact opens up prospects for the use of Zn2+ as an antiviral agent in the treatment of COVID-19. Vitamin E and selenium have effects that reduce the risk of infection: they increase the number of Tcells, enhance the responses of mitogenic lymphocytes, increase the secretion of IL-2 cytokines, and stimulate the activity of natural killer cells. The causative agent influences beta-carotene which accelerates the immune response of the body by increasing the activity of macrophages. Conclusion. The strategies for the prevention of COVID-19 provide for the intake of vitamin and mineral complexes containing vitamins D, A, E, zinc, selenium. The optimal intake of micronutrients largely determines the protection of a person from the effects of negative environmental factors including biological agents, namely microbes and viruses.

Background. The problem of treating purulent endometritis after cesarean section remains relevant, since hysterectomy is frequently performed in uterine suture failures, which leads to a woman’s worse quality of life. Timely diagnosis of uterine suture failures makes it possible to perform reconstructive plastic surgery and to preserve the reproductive function. Case report. The paper describes a clinical case of a favorable pregnancy and delivery in a pregnant woman with a uterine suture after three cesarean sections and metroplasty for uterine suture failure in postpartum endometritis. It depicts the complex usage of antibacterial therapy and the intrauterine sorbent VNIITU-1 after metroplasty for postpartum endometritis, which allows the effective elimination of pathogenic microorganisms and local detoxification. The combination application of Zhukovsky uterine and vaginal catheters shows a positive effect in preventing uterine bleeding and pelvic hematomas. Conclusion. An integrated approach to treating postpartum endometritis, by using antibacterial therapy and the intrauterine sorbent VNIITU-1, can improve the outcomes of reconstructive plastic surgeries. The use of Zhukovsky balloon tamponade during delivery in pregnant women with a failed uterine scar after cesarean section permits the amount of blood loss to be reduced during reconstructive plastic surgeries.