This journal issue presents studies in the field of obstetrics, gynecology and reproductive medicine. The original articles consider the genetic aspects of preeclampsia, including the role of NOS3 gene rs1799983 polymorphism, modern approaches for predicting uterine fibroids using neural network technologies, and vasopressin value as a marker of premature birth. Particular attention is paid to personalized methods of treating coagulopathic bleeding based on thromboelastometry and pregnancy management in chronic kidney pathology. The review articles analyze the pharmacological properties of iron fumarate, the role of the ARID1A gene in gynecological oncology, microbiome impact on the effectiveness of assisted reproductive technologies and the pathogenesis of fetal inflammatory syndrome. Clinical observation describes a rare case of spontaneous uterine rupture, and a historical analysis of forgotten obstetric techniques is presented.

Introduction. Preeclampsia (РЕ) is a complication of pregnancy resulting from a generalized vascular dysfunction. Systemic endotheliopathy also emerges due to a viral infection such as caused by SARS-CoV-2. A verified marker of endothelial damage is a decrease in endothelial cell-produced nitric oxide (NO) level. NOS3 is a gene encoding the enzyme endothelial nitric oxide synthase responsible for NO synthesis.

Aim: to assess an association between rs1799983 single nucleotide polymorphism in NOS3 gene and the risk of developing РЕ as well as susceptibility to SARS-CoV-2 infection during pregnancy in women living in the Republic of Tatarstan.

Materials and Methods. A case-control retrospective observational study with 416 women was conducted at the Sadykov City Clinical Hospital No. 7. Patients were divided into the following groups: group 1 – 119 patients with РЕ, without signs of viral infection; group 2 – 98 pregnant women with moderate SARS-CoV-2 infection without hypertensive disorders. Control group consisted of 199 pregnant women with normotension during gestation period, with no signs of viral infection. Maternal whole blood specimens were analyzed in the study. NOS3 gene rs1799983 polymorphism was genotyped using real-time polymerase chain reaction.

Results. A comparatively assessed prevalence of NOS3 gene rs1799983 genotypes demonstrated statistical significance between group of patients with РЕ and control group (p < 0.05). Carriage of the G allele and the G/G genotype in NOS3 gene rs1799983 polymorphism is associated with risk of developing РЕ. No association between carriage of NOS3 gene rs1799983 polymorphism and susceptibility to SARS-CoV-2 infection in pregnant women was observed (p > 0.05).

Conclusion. The study revealed the association between the carriage of NOS3 gene rs1799983 polymorphism and a risk of developing РЕ but not with SARS-CoV-2 susceptibility during pregnancy in women living in the Republic of Tatarstan.

Aim: to stratify the risk of thrombosis and assess frequency of recurrent venous thromboembolism (VTE) and bleeding during long-term anticoagulant therapy (АСТ) in patients with stage III–IV ovarian cancer (ОС).

Materials and Methods. A prospective interventional comparative non-randomized study was conducted by enrolling 126 patients with stage III–IV ОС, of whom 66 had VTE and received long-term АСТ for 60–72 months, whereas 60 subjects comprised comparison group without thrombotic complications. Risk stratification was performed using the Khorana, Vienna-CATS, and Tic-Onco scales. The frequency of VTE recurrence and bleeding as well as the prognostic significance of the above noted scales were assessed.

Results. It was found that recurrent VTE (deep vein thrombosis – in 12.1 %, pulmonary embolism – in 6.1 %) developed in 18.2 % of patients receiving anticoagulants, so that two thirds of cases occurred within the first year of therapy. In comparison group, VTE incidence was 16.7 %. Major bleeding was recorded in 6.1 % patients, clinically significant moderate bleeding – in 21.2 % cases. The Vienna-CATS (AUC = 0.719) and Tic-Onco (AUC = 0.730) scales demonstrated better predictive ability compared to Khorana model (AUC = 0.671).

Conclusion. 60–72-month-long АСТ in patients with high thrombotic risk allows to significantly reduce the frequency of VTE recurrence with acceptable level of hemorrhagic complications and can be considered as a preferred strategy for secondary prevention in active oncological processes.

Aim: to create a model for predicting emergence of uterine leiomyoma (UL) using neural network analysis of risk factors and to evaluate its prognostic characteristics.

Materials and Methods. A retrospective case-control study with 209 patients aged 20–47 years was performed covering the years from 2022 to 2024. Two groups of patients were identified: 1 – 106 women with UL, 2 – 103 patients without UL. Preliminary data processing was carried out, followed by a quantitatively analyzed relationship between risk factors and UL development using neural network analysis. The multilayer perceptron method was used to create a prognostic model for predicting UL emergence.

Results. During the study, there were selected 12 model-based factors showing statistically significant inter-group differences: body mass index (BMI), age at menarche, number of abortions and spontaneous abortions, age at first birth, presence of arterial hypertension (AH), benign ovarian tumors, history of in vitro fertilization, level of anti-Müllerian hormone, number of pregnancies, serum cholesterol and glucose levels. The prediction accuracy for the developed model was 92.3 %, sensitivity – 90.6 %, specificity – 94.2 %. The predictive value was confirmed using ROC analysis – the area under the curve was 0.93 (95 % confidence interval = 0.91–0.94; p < 0.001), which proves the promise of this method for clinical practice. Modifiable and potentially modifiable factors included increased BMI, AH, benign ovarian tumors, cholesterol and glucose levels. Such factors are considered as most relevant, due to an opportunity to be directly or indirectly affected, which proves an importance for preventive approach to this disease.

Conclusion. The developed model is an effective tool for predicting UL emergence (accuracy 92.3%), the use of which in clinical practice will allow shifting from the established paradigm of radical treatment to a preventive approach.

Introduction. To date, premature birth (РВ) remains one of the main problems in modern obstetrics. The scientific world community continues to search for an affordable, universal, cost-effective method for РВ prediction, which served as the basis for conducting current study.

Aim: assessing an opportunity for diagnosing and predicting an outcome of threatened РВ by studying the blood serum vasopressin level in relation to changes in pain scores analyzed by visual analog scale (VAS). Materials and Methods. A prospective observational randomized study was carried out. In 120 pregnant women, vasopressin level in the venous blood serum was examined in relation to changes in VAS-based pain levels. Main group consisted of 65 patients with complaints of pulling pains in the lower abdomen upon admission to the obstetric hospital, 31 of them with threatened РВ, in whom pregnancy was preserved (main group A) and 34 who gave birth prematurely (main group B). The control group included 55 women with term delivery.

Results. During the development of spontaneous labor, blood serum vasopressin level dynamically increased that was directly proportional to rise in VAS-based pain scores. A statistically significant relation between changes in blood serum vasopressin level and outcome of threatened PB has been established. Thus, a dynamic decrease in vasopressin concentration from the baseline level in patients with threatened PB (from 0.323 ± 0.046 ng/ml to 0.158 ± 0.034 ng/ml) points at possibility of pregnancy prolongation, whereas increase in vasopressin concentration from the baseline level was noted in patients with PB (from 0.117 ± 0.020 ng/ml to 0.364 ± 0.070 ng/ml).

Conclusion. Studying the dynamics of blood serum vasopressin level allows to use this parameter for prediction of threatened PB outcome.

Introduction. Women with chronic kidney disease (CKD) have an increased incidence of pregnancy complications, but few comparative studies on features of pregnancy course during chronic glomerulonephritis (CGN) and chronic tubulointerstitial kidney disease (CTID) are available.

Aim: comparison the frequency of pregnancy complications, proteinuria (PU) and serum creatinine dynamics in patients with CGN and CTID.

Materials and Methods. We conducted an observational single-centre study enrolling 128 pregnant women with CGN (135 deliveries) and 138 with CTID (145 deliveries) by assessing the incidence of complications, diurnal PU, serum creatinine level starting from early gestation to delivery every 4–6 weeks.

Results. Favourable pregnancy outcome was observed in 94.8 % of patients with CGN and in 95.7 % with CTID. The incidence of preeclampsia (PE), placental insufficiency, acute kidney injury, and preterm delivery showed no not inter-group differences, but arterial hypertension, PU > 1.0 g/day were more common in CGN, whereas in CTID – urinary tract infections. During pregnancy, PU increased in both groups, and only in CGN in patients with PE early pregnancy PU was significantly higher than in those without PE. Both groups showed similar serum creatinine dynamics: decrease starting from early pregnancy stages, stabilization in the middle of pregnancy followed by elevation from 28–30 weeks of gestational age until delivery.

Conclusion. High PU level in early pregnancy may help to predict PE in CGN, but not in CTID. In patients with CKD, rise in PU along with serum creatinine increased up to baseline level in late pregnancy, are typically observed and without PE, fetal distress should not be considered as unambiguous indication for early delivery.

Aim: to justify a differentiated approach to the treatment of obstetric coagulopathic bleeding depending on the nature of hemostasis disorders.

Materials and Methods. A prospective cohort study was conducted involving 52 patients with postpartum hemorrhage (PPH) who gave a child birth between 2021 and 2023. Diagnostics and treatment of coagulopathy was carried out according to the algorithm using thromboelastometry (TEM) parameters. Patients were divided into 3 groups depending on blood loss volume: group 1 (n = 19) – blood loss up to 1499 ml; group 2 (n = 14) – blood loss from 1500 to 1999 ml; group 3 (n = 19) – blood loss 2000 ml and more. The following hemostasis parameters were determined: platelet count, prothrombin index, activated partial thromboplastin time (APTT), Claus fibrinogen level, international normalized ratio, and TEM parameters, including clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and maximum clot firmness at 10 minutes (A10) on the EXTEM channels (a test in which recombinant tissue factor is used to activate the extrinsic coagulation pathway), FIBTEM (a test in which platelet activity is suppressed by cytochalasin D, which allows detecting fibrinogen deficiency or qualitative disturbances in fibrin polymerization), and INTEM (a test in which ellagic acid is used as a contact activator of the intrinsic coagulation pathway). Blood samples were collected before administration of blood components and products, tranexamic acid.

Results. Statistically significant differences were found for the fibrinogen level, MCF and A10 parameters on the FIBTEM channel depending on blood loss volume (p < 0.05), indicating a decrease in the quality of fibrin clot upon with increasing blood loss. Highly tight direct relationships were found between the fibrinogen, MCF and A10 values, demonstrating that with a decrease in the fibrinogen level at the time of bleeding by 1.0 g/L, a decrease in MCF by 3.802 mm (the resulting model explains 64.3 % of the observed variance), and A10 by 3.497 mm (the resulting model explains 64.1 % of the observed variance) should be expected. All patients whose blood loss volume reached 2000 ml and more were administered cryoprecipitate, the differences in the parameters were statistically significant between group 3 vs. group 1 and group 2 (p < 0.001). TEM parameters CT and CFT on the INTEM channel also correlated with blood loss volume and had a significant direct correlation between noticeable tightness (according to the Chaddock scale) between APTT and CT (ρ = 0.612; p < 0.001) as well as moderate tightness between APTT and CFT (r_xy = 0.44; p = 0.017). The need for transfusion of fresh frozen plasma (FFP) and prothrombin complex concentrates (PCСs) arose with APTT more than 35 seconds in 77 % of cases (among all patients), with the CT parameter more than 260 seconds – in 63 % of cases and CFT more than 110 sec – in 63 % of cases, respectively; the differences in the indicators are significant while compared with those of patients requiring no introduction of FFP and PPC (p < 0.05). Based on controlled transfusion protocol, in group 1, in 57.9 % of cases it was possible apply no transfusion therapy; the differences in indicators are significant while comparing group 2 and group 3 (p < 0.05).

Conclusion. The use of the TEM method in the diagnostics of hemostasis disorders with PPH allowed for the differential and short-term application of pathogenetically justified therapy with blood components and preparations only in cases where it was required.

Introduction. The use of the safest and most effective methods for iron deficiency (ID) compensation is implicated in current therapy of iron deficiency anemia (IDA). Oral administration of iron salts with organic acid anions is an important field in IDA therapy and prevention. Iron fumarate, being a divalent iron salt and the fumaric acid anion (a tricarboxylic acid cycle metabolite), is absorbed in vivo via gene-encoded molecular mechanisms specialized to interact primarily with fumarate anion.

Aim: to systematize the data from fundamental and clinical studies on iron fumarate pharmacology for ID treatment using topological and metric methods of intellectual analysis.

Results. The results of systematization of studies on iron fumarate pharmacology (more than 500 articles) are presented along and performed categorization of all available publications. The results of the most essential research fields assessing iron fumarate pharmacology are described in detail: (1) comparative pharmacology of iron fumarate and other iron forms; (2) an effect of various iron salts on tissue hemosiderosis; (3) synergism between iron fumarate and folates and other micronutrients; (4) an effect of microbiome state and iron fumarate absorption improved by prebiotics; (5) clinical practice of using iron fumarate for IDA treatment of women in all age groups.

Conclusion. Fumarate-containing preparations are indicated in case where profound substrate-mediated support is required for pillar arms of aerobic and anaerobic energy metabolism ranging from mitochondria and cells to organismal level demanding to mobilize signal-regulatory adaptive reactions. Oral intake of fumarate salt preparations may exert milder and safer effect. In aerobic and hypoxic energy metabolism, which is typical for ID, fumarate salts may act as effective anti-stress and anti-hypoxic agents.

The article is dedicated to outlining the pathogenic mechanisms, diagnostic criteria, and treatment of systemic inflammatory response syndrome (SIRS), thromboinflammation, and septic shock in fetuses and newborns. SIRS is a body hyperreaction to external stress involving biologically active molecules, cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin (IL) IL-1 so that a balance between inflammation and adaptive mechanisms becomes altered. Special attention is paid to fetal inflammatory response syndrome (FIRS). Here, we describe the broad impact of FIRS targeting vital organs and systems. The challenges in diagnosing and treating septic shock in newborns are discussed, highlighting a crosstalk between inflammation and hemostasis. Despite progress in understanding the molecular mechanisms underlying FIRS and sepsis, some obstacles in developing effective therapeutic strategies remain. This underscores a need for conducting targeted research to reduce morbidity and mortality related to thromboinflammation and septic shock.

Infertility is a high-priority medical and social issue, which prevalence reaches 15 % according to the World Health Organization. One of the methods for infertility treatment, which is often resorted to by sub-fertile couples, is the use of assisted reproductive technologies (ART). It is known that the microbiome of the uterine cavity and vagina can affect ART-related fertility potential. The normal vaginal microbiome is characterized by the dominance of Lactobacillus spp. representatives, which ensure the maintenance of optimal pH values and prevent pathogenic microbial penetration and multiplication. It is assumed that the normal endometrial microbiome is characterized by predominance of Lactobacillus spp., but relevant studies are prominently heterogeneous. According to the current hypothesis, the dominance of Lactobacillus spp. and, particularly, Lactobacillus crispatus, in the vagina and uterine cavity is associated with favorable reproductive outcomes in ART programs. Recurrent implantation failures are related to spreading of opportunistic microflora in such niches. Nevertheless, some authors have reported no direct correlation between Lactobacillus spp. level, presence of opportunistic microorganisms and favorable outcomes of ART programs, which underlies a need to conduct further large-scale studies.

Сhromatin remodeling tumor suppressor protein ARID1A (AT-rich interaction domain 1A) is coded by the ARID1A gene that is one of the most frequently mutated genes in human oncological diseases. Inactivating mutations in the ARID1A gene have a pronounced effect on cell survival, chemoresistance, transcription and cell cycle regulation. To date, a large number of studies have focused on assessing the effect of mutations leading to loss of ARID1A function on tumor emergence, progression and therapy resistance. The high frequency of ARID1A mutations in malignant tumors of the female reproductive system opens up unique opportunities for targeted preventive and therapeutic intervention. Clear cell ovarian carcinoma and uterine body cancer bearing ARID1A mutations do not respond well to standard chemotherapy proposing no current effective targeted therapy, which underlines a need for further research in the field. ARID1A can be used as a biomarker of precancerous diseases, as well as a tool for predicting a response to radiation therapy, immunotherapy and targeted therapies. Currently, clinical trials assessing several low molecular weight and epigenetic inhibitors are being conducted in tumors of the female reproductive system with ARID1A deficiency.

Spontaneous uterine rupture during pregnancy is a life-threatening complication that predominantly occurs in the third trimester. A scar resulting from a prior cesarean section represents the primary risk factor for uterine rupture. It is one of the most severe complications in obstetrics, accompanied by bleeding, severe traumatic and hemorrhagic shock, and high perinatal mortality for both the fetus and the woman. Cases of uterine rupture without commonly accepted risk factors, regardless of parity or gestational age, have been described in the literature. Here, we present a clinical case of a complete uterine rupture occurred outside a medical facility at gestational age of 25 weeks in a multiparous woman with a complicated obstetric-gynecological history, lacking uterine scar. This was accompanied by severe hemorrhagic shock, cardiac arrest, and antenatal fetal demise. High-quality specialized care resulted in a favorable outcome for the mother.

Today, understanding physiology of the placental period during normal childbirth, its management, identifying a moment of placental separation and methods for extracting separated and freely-lying birth canal placenta have been well documented. Nevertheless, the history of obstetrics and gynecology keeps everyday work secrets. Here, we would like to uncover one of them to the AGR readers primarily aimed at describing the "unknown" along with the "well-known" moment and restore "historical justice".