Numerous studies have proven a close relationship between inflammatory diseases and the state of hypercoagulability. In fact, thromboembolic complications represent one of the main causes of disability and mortality in acute and chronic inflammatory diseases, cancer and obstetric complications. Despite this, the processes of hemostasis and immune responses have long been considered separately; currently, work is underway to identify the molecular basis for a relationship between such systems. It has been identified that various pro-inflammatory stimuli are capable of triggering a coagulation cascade, which in turn modulates inflammatory responses. Neutrophil extracellular traps (NETs) are the networks of histones of extracellular DNA generated by neutrophils in response to inflammatory stimuli. The hemostasis is activated against infection in order to minimize the spread of infection and, if possible, inactivate the infectious agent. Another molecular network is based on fibrin. Over the last 10 years, there has been accumulated a whole body of evidence that NETs and fibrin are able to form a united network within a thrombus, stabilizing each other. Similarities and molecular cross-reactions are also present in the processes of fibrinolysis and lysis of NETs. Both NETs and von Willebrand factor (vWF) are involved in thrombosis as well as inflammation. During the development of these conditions, a series of events occurs in the microvascular network, including endothelial activation, NETs formation, vWF secretion, adhesion, aggregation, and activation of blood cells. The activity of vWF multimers is regulated by the specific metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Studies have shown that interactions between NETs and vWF can lead to arterial and venous thrombosis and inflammation. In addition, the contents released from activated neutrophils or NETs result in decreased ADAMTS-13 activity, which can occur in both thrombotic microangiopathies and acute ischemic stroke. Recently, NETs have been envisioned as a cause of endothelial damage and immunothrombosis in COVID-19. In addition, vWF and ADAMTS-13 levels predict COVID-19 mortality. In this review, we summarize the biological characteristics and interactions of NETs, vWF, and ADAMTS-13, the effect of NETs on hemostasis regulation and discuss their role in thrombotic conditions, sepsis, COVID-19, and obstetric complications.

Introduction. Rate of factors affecting preterm birth development has not been fully elucidated. The assessment was carried out by identifying 1-2 causes used to build up prognosis.

Aim: to identify most relevant risk factors for preterm birth and assess their impact on pregnancy.

Materials and Methods. The prospective comparative study was conducted that included group 1 - 36 women with term pregnancy, group 2 - 35 with preterm labor. Establishment of the menstrual cycle has been studied by assessing reproductive, somatic history, and course of current pregnancy.

Results. The postpartum women from group 2 were characterized by older age (30.42 ± 6.19 years; p = 0.038). The groups differed by the age of menarche: in group 2, its onset was recorded earlier (11.31 ± 0.79 years), showing shorter duration of menstruation (4.25 ± 1.26 days) as well as menstrual cycle (27.71 ± 3.46 days). Infections in puberty were substantially more frequent in postpartum women from group 2: group 2 vs. group 1 - in 21 vs. 8 postpartum women (p < 0.001); a history of urinary tract infections was also more common in group 2 (in 17 puerperas; p = 0.003), that is also typical for cases resulting in preterm pregnancy. The causative agent of bacterial vaginosis in group 2 was more often presented by Atopobium vaginae (in 17 puerperas; p = 0.0001), with Gardnerella vaginalis found less frequently (in 13 puerperas; p = 0.024), which is important to know for selecting proper therapy. During full-term pregnancy, the Lactobacillus crispatus strain, that determines vaginal health, was excreted significantly more often (in 29 puerperas; p = 0.009). Anemia affecting the antenatal fetal development and the course of labor was significantly more frequent in group 2 (in 22 puerperas; p < 0.001).

Conclusion. While planning pregnancy, it is necessary to take into account the age, menstrual cycle features, history of former infections, vaginal microbiota features, as well as conduct proper therapy and prevention in pregravid period.

Aim: to identify factors predisposing to perinatal losses, assessment of which is available at the first (only) visit of pregnant woman in antenatal clinic.

Materials and Methods. A retrospective analysis of the medical records of 964 women who performed delivery in 2009-2019 in 15 obstetric facilities was carried out. The patients were divided into 2 groups: the main group included 457 women with perinatal losses (stillbirth - 328 children, and 129 children with early neonatal death); the control group consisted of 507 women, whose children survived 7 days during postnatal period. We analyzed parameters routinely determined by an obstetrician-gynecologist at the first visit of woman during within ongoing pregnancy (regardless of gestation age), namely, social status, anamnesis, data of initial examination.

Results. The following significant differences were revealed in pregnant women from the main group: a younger age of pregnancy; no registered marriage and permanent job as well as primary and secondary education; smoking, alcohol and drug use; concurrent diabetes mellitus, hypertensive disorders, blood contact infections, obesity; older menarche age and younger sexual debut age; medical history contains infectious genital pathology, more often pregnancies and childbirths, two or more abortions before repeated childbirth, premature births.

Conclusion. Thus, the anamnestic indicators noted above can be used to create prognostic statistical systems and models to determine high risk of perinatal losses of any nature.

Introduction. A significantly increased frequency of multiple pregnancies including more than two fetuses is a consequence of using assisted reproductive technologies and ovulation stimulations. However, such pregnancies remain poorly investigated. Aim: to study the course and perinatal outcomes of quadruplet pregnancies.

Materials and Methods. 7 pregnant women with quadruplets were examined. A comprehensive examination, including fetometry, monitoring of the cervical length, Doppler examination, and treatment of all complications were performed for all pregnant women. Results. Quadruplet pregnancy belongs to the peak risk group for the frequency of multiple gestational complications: cervical incompetence (85.7 %), anemia (71.4 %), preeclampsia (57.1 %), fetal growth retardation (71.4 %), premature birth (100.0 %), massive bleeding during delivery (33.3 %), extremely low birth weight newborns (30.8 %), respiratory disorders (100.0 %), intraventricular hemorrhages (38.5 %).

Conclusion. Women with quadruplet pregnancies should be monitored and give a birth in level 3 perinatal centers. Delivery should be preferentially performed by caesarean section. The data obtained additionally underline that as few as a single embryo should solely transferred.

Introduction. The risk of pregnancy loss in the first trimester comprises 12.5-18.7 %. It is timely and relevant to develop methods for predicting miscarriage.

Aim: to develop a predictive model for assessing a risk of miscarriage in case of normal embryo karyotype.

Materials and Methods. The single-center cohort retrospective comparative study included 52 women with miscarriage at 6-12 weeks of gestation with normal embryo karyotype (main group) and 126 women with physiologically proceeding pregnancies and favorable perinatal outcomes (control group). All patients underwent general clinical and laboratory examination, analysis of genetic polymorphisms (FGBG -455A, F2 G20210A, F5 G1691A, F7 G10976A, F13 G103A, PAI-1 -675 5G/4G, ITGA2 C708T, ITGB3 T176C, MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G, NOS3 T-786C, NOS3 C894T), spouse examination.

Results. The factors associated with the loss of pregnancy turned out to be presented by a history of infertility, patient adenomyosis, a higher platelet count, as well as abnormal partner spermogram. Significant differences were obtained between the studied groups in the frequency of concurrent polymorphisms PAI-1 -675 5G/4G, MTHFR C677T, MTRR A66G, NOS3 G894T. Based on the identified patterns, a mathematical model has been developed allowing to determine the high risk of pregnancy loss in the first trimester (86.0 % efficiency).

Conclusion. A comprehensive assessment of clinical and anamnestic indicators, molecular genetic parameters, spouse-related health indicators, it is possible to determine risk groups of pregnancy loss in case a normal embryo karyotype. Timely prediction provides the basis for optimizing preconception care and conducting timely prevention of miscarriage.

Data analysis on the pathogenesis and risk factors of neonatal thrombosis was carried out. The main risk factor of any neonatal thrombosis is central catheter installment, but other maternal, fetal and neonatal factors should be taken into consideration. We discuss the epidemiology of neonatal thrombosis and the main features of the hemostasis system in newborns, the most significant risk factors, including genetic and acquired thrombophilia. We consider the von Willebrand factor activity and ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) level in the development of neonatal thrombotic microangiopathy. Finally, we discuss the basic principles of prevented neonatal thrombosis by using low molecular weight heparins.

Antiphospholipid syndrome (APS) is an autoimmune process that increases the risk of arterial and venous thrombosis. The mechanism of damage to the central nervous system (CNS) can be not only due to thrombosis, but also antiphospholipid antibodies (APA) circulating in the peripheral blood. The latter can damage the cerebral vascular endothelium, alter the resistance of the blood-brain barrier and penetrate into the central nervous system, exerting a damaging effect on astroglia and neurons, as evidenced by the release of neurospecific proteins into the peripheral bloodstream. The role of APS in developing cerebral ischemia, migraine, epilepsy, chorea, transverse myelitis, multiple sclerosis, cognitive impairment and mental disorders, as well as the peripheral nervous system is described. It should also be noted about a role of APS for emerging neurological disorders in COVID-19, enabled apart from thrombogenesis due to APA via 2 potential mechanisms - molecular mimicry and neoepitope formation. Further study of the APS pathogenesis and interdisciplinary interaction are necessary to develop effective methods for patient management.

There is a higher incidence of infertility, chromosomal aberrations, poor results of in vitro fertilization, ectopic pregnancies, spontaneous abortion, preeclampsia, placenta previa, gestational diabetes mellitus, caesarean section, chronic diseases with higher rates of admission into intensive care units, and a higher rate of maternal mortality among women who delay pregnancy into advanced age. This is mainly due to socioeconomic causes as well as the increased use of contraceptives. Problems due to advanced maternal age arise also with egg donations. Only chromosome aberrations are related to the age of the donor. Paternal age also appears to play a significant role in the outcome of the pregnancy. However, opinions vary in the literature available. Counseling the couples should be addressed.

Introduction. Issues of etiopathogenesis for various cardiovascular disorders in the structure of extragenital diseases during pregnancy pose an urgent problem and represent a global topic for further scientific research. Due to the high frequency of heart rhythm disorders in pregnant women, it is necessary to improve their management.

Aim: to analyze data from the current literature on the etiopathogenesis of arrhythmias during gestation and effective methods of their correction.

Materials and Methods. Literature sources of electronic databases PubMed/MEDLINE, Medscape, Google Scholar, Embase, Ovid Healthstar, Cochrane, eLibrary, CyberLeninka and scientific articles in peer-reviewed open access journals published across the last 25 years, including basic research on this pathology have been analyzed. The search in databases used keywords and their combinations in Russian and English: "arrhythmias", "arrhythmias in pregnancy", "pathogenesis of gestational arrhythmias".

Results. There have been analyzed major aspects of the etiology and pathogenesis of gestational arrhythmias as well as potential causes for developing first-time rhythm disorders in pregnant women and features of the gestational period as a predictor of emerging arrhythmias in patients with pre-existing pathology of the cardiovascular system are determined. The article describes the most common rhythm disorders and acceptable ways to correct them, taking into account the latest recommendations and research in this area.

Conclusion. The authors concluded that the etiopathogenesis of rhythm disorders during pregnancy and their treatment methods require further examination.

Introduction. Hemostasis is an equilibrium system that performs 2 bidirectional tasks: on the one hand, it prevents bleeding development, whereas on the other hand, it counters thrombogenesis. Shifting the balance leads to development of various complications, and also serves as a key link in the pathogenesis of a number of diseases. Currently, the issue of changing the state of local endometrial hemostasis in various pathologies is of high priority. Unfortunately, publications available on this problem are limited.

Aim: to conduct a literature search and systematize the data analysis to expand understanding regarding a role of local hemostasis disorders in formation of endometrial pathology.

Materials and Methods. There has been performed a systematic analysis of full-text scientific reviews and original articles published in English and Russian in the modern literature. The review includes the 1995-2020 data published in the international abstract and bibliographic databases eLibrary, Google Scholar, Web of Science, Scopus and PubMed/MEDLINE.

Results. Hemostatic changes in the endometrium that occur under the influence of estrogens and progesterone, and create a local hemostatic environment, which disturbance contributes to emergence of various endometrial pathologies, are described. It was found that for the physiological course of pregnancy, complex changes in the local hemostasis are necessary, which are aimed at facilitating the processes of chorionic invasion and maintaining metabolic processes in the mother-fetus interface, whereas alteration of the aforementioned processes contributes to development of abnormal chorionic invasion as the basis for development of insufficient placental function, preeclampsia (PE), and pregnancy termination. Moreover, there have been summarized the data on key changes in the state of local endometrial hemostasis that play a role in the pathogenesis of endometriosis, as well as underlying abnormal uterine bleeding (AUB).

Conclusion. Current research publications provide sparse evidence that the state of the local hemostasis in the endometrium is an important aspect of the physiological course of the menstrual cycle, as well as formation of endometrial pathology. In this review, it is shown that local hemostasis is inextricably linked with the state of the systemic hemostasis, but at the same time, its functioning depends on the level of hormones estrogens and progesterone. Impaired function of local endometrial hemostasis is an important aspect of the pathogenesis of miscarriage, as well as conditions such as PE, endometriosis, AUB.

The work is aimed at discussing pregnancy management for the most thrombogenic genetic thrombophilia - antithrombin III (AT-III) deficiency. A detailed analysis of the literature and clinical case of pregnancy management in a patient with AT-III deficiency, pulmonary embolism and habitual history of miscarriage has been performed and presented. Patients with AT-III deficiency are at high risk for developing thrombotic and obstetric complications even despite using therapeutic doses of anticoagulants. Indications for use and modes of administration of AT-III concentrate have not been currently defined clearly. Monitoring therapy with low molecular weight heparin is largely complicated because a test for determining anti-Xa activity is AT-III-dependent. In addition to standard methods for controlling antithrombotic therapy, we used tests characterizing the dynamic blood clot parameters: thromboelastography and thrombin generation test. The peak risk resulting in both thrombotic and hemorrhagic complications in such patients occurs during period of labor and the postpartum period, when a change in the regimen of anticoagulant therapy is required with its temporary withdrawal and additional administration of AT-III concentrate.

Altered pelvic venous circulation, which may occur due to pelvic venous congestion and varicose veins of the vulva, may be among the causes for developing chronic pelvic pain syndrome. Pelvic congestion syndrome (PCS) is characterized by chronic discomfort in the pelvic area, which may be aggravated during coitus or acquire orthostatic position, and result in severe dysfunction of the pelvic organs. Varicose veins of the vulva develop due to obstruction of the veins, increased venous pressure, and venous insufficiency in the pelvis. Varicose veins may be isolated or associated with varicose veins of the lower extremities. The diagnosis and treatment of such patients are limited by the lack of definitive clinical criteria for early diagnostics, which were discussed in the current study.

Antithrombotic therapy is often used during pregnancy for the treatment and prevention of venous thromboembolism, systemic embolism in patients with heart valve prostheses, for prevention of foetal loss in patients with antiphospholipid syndrome, placenta-mediated complications. In common, low molecular weight heparins (LMWHs) have largely replaced unfractionated heparin as the anticoagulant. However, in case of placenta-mediated complications it has off-label status. The effectiveness and safety of the LMWHs in pregnant women at an increased risk of placenta-mediated complications is discussed in this review. LMWH is effective, safety, easy to administer and associated with a low incidence of foetal and maternal complications.

On July 17, 2021, Advisory Board with the participation of more than 60 leading reproductive specialists and healthcare executives was held. The primary task was to discuss the real world data on the first Russian biosimilar follitropin alfa and the possibilities of import substitution of follitropin alfa drugs. The information about drug development stages, experience of usage in ovarian stimulation for artificial insemination and assisted reproductive technologies (ART), the results of the largest Russian study in reproduction "FОLLITROPIN" (2020), where biosimilar recombinant human follicle stimulating hormone (FSH) was studied in 5484 IVF cycles in real clinical practice, experience of drug use in leading ART medical centers have been provided in research reports. After discussion the Advisory Board Resolution has been developed.