Obstetrics and Gynecology

Preeclampsia is the leading cause of maternal and perinatal morbidity and mortality; however, its etiopathogenesis remains unclear, highlighting the need for new conceptual approaches to the study of this complication. In this article preeclampsia is considered as a systemic proteinopathy of the second half of pregnancy, a consequence of a neurogenic, neuroimmune, complement-mediated conflict between the mother and the fetus, associated with the production of barrier-crossing neuron-specific proteins in the fetal brain during the critical period of neurocorticogenesis after 22–24 weeks of gestation.

The aim of this review is to highlight the role of tau protein, particularly its pathological, toxic cis conformation (cis P-tau), in the cascade of pathophysiological changes in preeclampsia, taking into account the structural and functional characteristics of tau protein and the mechanisms of its pathological transformation, systemic spread leading to the formation of cistauosis, impairment of the autophagy process, and the use of tau protein as a target for diagnostic and therapeutic interventions.

Conclusion. The concept presented here describes preeclampsia as a unique multisystem ‘tautopathy’ of perinatal period, based on a neuroimmune conflict mediated by the neuron-specific proteins of the fetal brain, with a key role played by tau protein, which determines the severity and organ-specificity of preeclampsia clinical picture. This explains the temporal progression of preeclampsia and the diversity of its manifestations, and opens up entirely new directions for the development of pathogenetically based methods of diagnosis and treatment.

This paper presents an analysis of the literature on the risk factors, pathophysiological mechanisms and fatal outcomes associated with amniotic fluid embolism in women in labor. It highlights the characteristics of the development of life-threatening complications associated with amniotic fluid embolism, including cardiopulmonary shock, anaphylactoid syndrome and disseminated intravascular coagulation (DIC). It is emphasized that there are no pathognomonic clinical or laboratory manifestations of the disease; consequently, the clinical diagnosis of amniotic fluid embolism is based on the principle of exclusion, which requires a differential diagnosis to be carried out with a whole range of conditions. The article presents the principles of management and the criteria for establishing the final clinical diagnosis in case of maternal death due to amniotic fluid embolism. Objective diagnosis and verification of amniotic fluid embolism are only possible through microscopic examination of histological and immunohistochemical sections of lung tissue obtained from an autopsy.

Conclusion. Amniotic fluid embolism remains a rare but life-threatening complication of pregnancy requiring intensive care.

The widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes and obesity in women of reproductive age highlights the importance of investigating their potential impact on fertility. This review summarizes the current evidence on the role of the incretin system in the regulation of female reproductive function. The most convincing data obtained from patients with polycystic ovary syndrome (PCOS) demonstrate the ability of GLP-1 receptor agonists to reduce insulin resistance and hyperinsulinemia that can be associated with the restoration of a regular menstrual cycle, an increase in the frequency of ovulatory cycles and a higher likelihood of pregnancy. The effects on the reproductive system are due to both systemic improvement in metabolism and weight loss, and to direct action on tissues expressing GLP-1 receptors (the hypothalamic-pituitary axis, the ovaries and endometrium). Direct mechanisms include modulation of steroidogenesis, increased endometrial receptivity, and a reduction in inflammation and oxidative stress.

The safety of using GLP-1 receptor agonists during the periconceptional period remains a matter of debate. Despite data obtained from preclinical studies on potential embryotoxicity, available clinical observations have not revealed a statistically significant increase in the risk of congenital malformations following accidental exposure to the drug during the first trimester of pregnancy. Nevertheless, current guidelines recommend discontinuing treatment before conception.

Conclusion. To expand the clinical use of GLP-1 receptor agonists in gynecological and reproductive medicine, further research is needed to investigate their effectiveness in women without PCOS, to develop standardized protocols for periconceptional safety and to assess the potential of new generations of incretin-based drugs.

Objective. Exploration of the role of vascular endothelial growth factor receptors (VEGFR1, VEGFR2) in formation of placental insufficiency in women with recurrent miscarriage (RM).

Materials and methods. A total of 347 pregnant women were examined: 247 women with RM, and 104 with a history of pregnancy without RM. Of the total number of women, 75 placental samples underwent histological and immunohistochemical examinations with antibodies to VEGFR1 and VEGFR2. Placental samples that underwent pathomorphological examination were divided into 3 groups. Group 1 included placentas of women with RM, who gave birth at term (n=25). Group 2 included placentas of women who gave at 26⁰–36⁶ weeks (n=20). Group 3 (the comparison group) included placentas of 30 patients without a history of RM, who gave birth at 37–40 weeks. Statistical processing of the results was performed using Excel-2010 and STATISTICA 13.0 software packages.

Results. The women with RM had complications during pregnancy. The most common complication of pregnancy was threatened miscarriage in all trimesters of pregnancy that ended with preterm birth. The average gestational age for preterm birth was 31¹ (26^0–36³) weeks. Immunohistochemical analysis of placental samples showed that in preterm birth, expression of VEGFR1 in decidual cells and VEGFR2 in syncytiotrophoblast of chorial villi was significantly lower (p=0.0002) compared with full-term pregnancy. In addition, preterm birth was associated with premature placental abruption, that commonly occurs with failure of physiologic transformation of spiral arteries.

Conclusion. The most frequent pregnancy complications in women with RM miscarriage were threatened miscarriage with high rates of preterm delivery and placental insufficiency. According to our data, the mechanisms of formation of pregnancy complications in women with RM are associated with low expression of VEGFR1 and VEGFR2 in the placenta, leading to impaired gestational restructuring of the uteroplacental arteries and vascularization of the villous chorion, that should be considered as an element of chronic placental insufficiency and taken into account at the pregravid stage.

Preterm birth remains a leading cause of perinatal morbidity and mortality in twin pregnancy.

Objective. To improve perinatal outcomes in twin pregnancies by creating a nomogram to predict the risks of spontaneous preterm births.

Materials and methods. The study included 839 patients with twin pregnancies. Based on pregnancy outcomes, the patients were divided into two groups. Group 1 consisted of women (n=175) whose pregnancies ended in term births. Group 2 included women (n=664) whose pregnancies ended in preterm births. A nomogram for the risk of preterm birth was constructed based on significant predictors, and its predictive performance was evaluated using ROC analysis.

Results. Multivariate analysis identified that independent predictors of preterm birth were twin growth discordance (OR=1.044; 95% CI 1.024–1.064; p< 0.001) and twin chorionicity (monochorionic diamniotic twins: OR=2.993; 95% CI 1.677–5.340; p< 0.001). The nomogram model included these predictors, and was developed to estimate the individual preterm birth risk. ROC curve analysis confirmed satisfactory predictive performance of the model (AUC=0.766).

Conclusion. The risk of spontaneous preterm birth in twin pregnancy is primarily associated with twin chorionicity and twin growth discordance, that is important for personalized high-risk patient management.

Objective. To identify the features of anamnestic data, the course of pregnancy and the results of pathological examination in patients with antenatal death of full-term fetuses depending on the presence of meconium in the amniotic fluid.

Materials and methods. A retrospective analysis of individual pregnancy records, birth histories, and autopsy reports for 83 cases of stillbirth from 2021 to 2023 was conducted. The patients were divided into 2 groups: Group I included the patients with meconium-stained amniotic fluid (MSAF) (n=55); Group II included the patients with clear amniotic fluid (n=28).

Results. The patients in Group I most often had a history of induced abortion (p=0,048), abnormal placental attachment, and oligohydramnios, that can be a marker of MSAF (p=0,041). At the time of fetal death, the length of pregnancy in Group I was longer than in Group II (p=0,003). The frequency of fatty involution of thymus was comparable in stillbirths in both groups. The signs of chronic placental insufficiency and inflammatory-immune disorders were observed in most placental samples collected from both groups.

Conclusion. No direct association was found between fetal distress that led to antenatal death and MSAF. The probability of MSAF increases with increasing gestational age and oligohydramnios. More intensive fetal monitoring is essential in the second half of the third trimester of pregnancy in high-risk patients.

Objective. To evaluate the specific activity of serum immunoglobulins against the matrix metalloproteinase-11 (MMP11) protein in the groups of mothers of many children and patients with uterine fibroids.

Materials and methods. A cDNA fragment containing the MMP11 gene from a cell line with increased expression of this protein was cloned. Recombinant human MMP11 protein produced in E. coli was purified and used to investigate the limit titer of antibodies in blood sera of patients using indirect ELISA. Donor blood serum samples (100 samples) were collected from the patients undergoing treatment at V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology. Informed consent to participate in the study was obtained from the patients. To investigate the immunological activity of sera against the MMP11 protein, four groups of patients were formed. Group 1 consisted of women without diagnosed fibroids who had a history of five or more successful pregnancies. Group 2 consisted of women with fibroids, who also had five or more successful pregnancies. Group 3 included women with recurrent fibroids. Group 4 was the control group of men. An expression construct containing the MMP11 gene was inserted into the E. coli genome. As a result, preparative protein was obtained in sufficient amount to investigate its reaction with antibodies in the blood sera of different patient groups.

Results. Western blot analysis showed that the blood sera of women without fibroids, who had many children, contain antibodies to the MMP11 protein, that provided grounds for a broader study of the immunological reactivity of the blood sera in different groups of patients against this protein. In gentral, the highest protein reactivity was shown in the sera of women with many children. However, the average value for the group of women with fibroids, who had many childeren, was higher, but not statistically significant. In patients with fibroids the reactivity was lower than in group 1, and the lowest was in the control group of men. At the same time, statistical analysis showed significant differences between the groups using different dilutions, that is, there was a dose dependence of the immunological response. The obtained results confirm statistically significant differences in serum reactivity between the studied groups. At the same time, the identified dose-dependent dynamics corresponds to the expected immunological patterns.

Conclusion. Our study showed that the MMP11 protein reacts with antibodies from the sera of different patient groups. At the same time, higher immune response to this protein was found in the group of mothers with many children. The MMP11 protein may further be useful in the development and testing of new targeted preventive therapy for uterine fibroids.

Objective. To evaluate the effectiveness of photodynamic therapy (PDT) combined with traditional hormone therapy on reproductive outcomes, the frequency of clinical manifestations, and the recurrence rate in women of reproductive age with endometrial hyperplasia (EH) and adenomyosis.

Materials and methods. A retrospective single-center comparative study was carried out from 2021 to 2023. The sample was formed using a consecutive sampling method. The study included 48 women aged 25 – 45 years with the established diagnosis of adenomyosis based on clinical findings, ultrasound examination, and hysteroscopy, as well as non-atypical EH confirmed by histological examination. Two groups were formed: hormone therapy (n=21) and combination therapy using endometrial PDT (n=27). Assessment of reproductive outcomes included pregnancy rate, the time before getting pregnant, clinical symptoms before and after treatment, and the recurrence rate of EH based on follow-up histology of endometrial biopsy specimens. The follow-up period was up to 36 months.

Results. Combination therapy using PDT led to statistically significant increase in pregnancy rate (p=0.002), whereas the time before getting pregnant did not differ significantly between the groups (p=0.750). Reduced frequency of clinical manifestations after treatment was in both groups. Despite low frequency of abnormal uterine bleeding, heavy menstrual bleeding, and dysmenorrhea in the group of combination therapy using PDT, no statistically significant differences between the groups in these outcomes were observed. The recurrence of EH was less common in the group of women who were treated with combination therapy compared with the group of women who received traditional hormone therapy (3/18 [16.7%] vs 6/13 [46.2%]; RR=0.36; 95% CI 0.11–1.18; p=0.114).

Conclusion. In patients with EH and adenomyosis, combination therapy using PDT was associated with higher pregnancy rate compared with hormone therapy alone. It suggests that this approach is promising for treatment of combined hormone-dependent pathology. The trend was observed in favor of combination therapy with PDT regarding the recurrence rate of EH and persistence of clinical symptoms after treatment. However, no statistically significant intergroup differences were found for these indicators.

Objective. To evaluate embryological and clinical outcomes in IVF cycles among couples with unexplained infertility following conventional in vitro fertilization (IVF) versus intracytoplasmic sperm injection (ICSI).

Materials and methods. This single-center prospective comparative study included 116 assisted reproductive technology cycles in couples with unexplained infertility, treated between January 2024 and January 2026. Conventional IVF was performed in 58 cycles and ICSI were performed in 58 cycles each. Cycles with split insemination and those involving preimplantation genetic testing for aneuploidy (PGT-A) were excluded from the analysis. The primary outcome was the normal fertilization rate. The secondary outcomes included the blastulation rate, proportion of good-quality blastocysts, implantation rate, pregnancy rate, and clinical pregnancy rate. To account for potential confounding, adjusted analyses were performed using generalized linear models, and pregnancy rates were compared using Fisher's exact test.

Results. Baseline clinical characteristics were generally comparable between the groups, although the starting gonadotropin dose was higher in the ICSI group. Sperm concentration, total motility, and proportion of mature oocytes were higher in the conventional IVF group. No statistically significant between-group differences were observed in the primary outcome, the normal fertilization rate. Likewise, no significant differences were found in the blastulation rate or the proportion of high-quality blastocysts. Implantation, pregnancy, and clinical pregnancy rates were numerically higher in the ICSI group; however, these differences were not statistically significant. After multivariable adjustment, ICSI was not associated with an increased normal fertilization rate (adjusted odds ratio [aOR] 0.96; 95% confidence interval [CI] 0.74–1.25; p=0.763), blastulation rate (aOR 0.77; 95% Cl 0.59–1.01; p=0.063), good-quality blastocyst formation (aOR 0.80; 95% Cl 0.49–1.31; p=0.370), or implantation rate (aOR 1.01; 95% CI 0.003–330; p=0.962).

Conclusion. In patients with unexplained infertility, ICSI was not associated with improved normal fertilization rates or most embryological outcomes compared with conventional IVF. These findings do not support the routine use of ICSI in couples with unexplained infertility and suggest that a selective approach to choosing a fertilization method is warranted.

Objective. To identify approaches to the concept of ‘reproductive health’ based on a comprehensive analysis of regulatory legal documents and to formulate a modern definition of reproductive health.

Materials and methods. Using the search module of the ‘Consultant Plus’ legal reference system, 1,279 documents relating to reproductive health were selected. The study examines the ‘Russian Legislation’ section, which presents 41 regulatory legal documents governing the issues under study.

Results. The content analysis revealed that the concept of ‘reproductive health’ in regulatory legal documents is frequently associated with terms such as ‘assisted reproductive technologies,’ ‘reproductive age,’ ‘reproductive system’ and ‘center for adolescent reproductive health’.

Since it was first used in 1995, the term ‘reproductive health’ and approaches to its understanding have undergone significant changes, driven by socioeconomic conditions and demographic policy. Over the decades, the term’s interpretation has broadened. Initially, reproductive health was considered solely in terms of women’s health and the prevention of abortions. Subsequently, children and adolescents were taken into account in the interpretation of the concept. The adoption of an evidence-based approach in the early 2010s led to the inclusion of issues relating to male fertility and the possibility of reproductive choice for each individual.

Conclusion. The concept of ‘reproductive health’ has gradually expanded to include additional components reflecting the importance of assessing the reproductive potential of the population. This definition is now viewed from a multidisciplinary perspective.

Endometriosis is a chronic disease that dramatically worsens a woman's quality of life and impacts her fertility. Selection of appropriate therapy for stabilizing the process and preventing its progression is a challenging clinical task for gynecologists, especially when surgical treatment is not indicated. In recent years, the use of progestogens, and in particular dienogest, has demonstrated a sustained positive effect on various manifestations of this disease.

Objective. To study the positive effect of the use, tolerability and adherence to each “DlyaJens metri” drug (dienogest 2 mg) in patients with endometriosis requiring hormonal therapy.

Materials and methods. The observational study comprised 740 patients aged 20–45 with stages I–II of endometriosis. The analysis of menstrual bleeding patterns, dysmenorrhea severity, changes in body mass index (BMI), adverse reaction rates, adherence, and patient and physician satisfaction was conducted.

Results. During the therapy we observed a significant reduction in the frequency of heavy menstrual bleeding, as well as its duration, and various manifestations of pain syndrome (dysmenorrhea, dyspareunia, chronic pelvic pain). After 6 months of treatment only 16.2% of women patients complained of endometriosis-associated symptoms. No clinically significant changes in weight or BMI were identified in patients taking “DlyaJens metri” drug throughout the study. We also noted high treatment satisfaction among both physicians and patients. The low incidence of adverse reactions confirms the safety of long-term dienogest therapy.

Conclusion. Our study demonstrated the efficacy and high satisfaction rates of the “DlyaJens metri” Russian dienogest drug among patients with endometriosis during a six-month follow-up in a routine clinical practice. Furthermore, the low incidence of adverse reactions and the absence of weight and libido changes ensured high adherence to such hormone therapy.

Rationale. Magnesium is known as a cofactor for over 600 enzymatic reactions and plays a key role in maintaining women's reproductive health. Magnesium deficiency is associated with dysmenorrhea, premenstrual syndrome (PMS), menstrual irregularities, and, in the long run, with pregnancy complications (preeclampsia, premature birth, fetal growth restriction). Despite its clinical significance, there is a lack of studies on the prevalence of magnesium deficiency among youth in the Republic of Bashkortostan. Given that pregravid preparation is a key period for preventing reproductive losses, timely detection and correction of magnesium deficiency in girls of early reproductive age are of primary importance.

Objective. To assess the prevalence of magnesium deficiency among students of the Republic of Bashkortostan, analyze its link with nutritional status and reproductive health indicators in girls (menstrual cycle regularity, severity of dysmenorrhea and premenstrual syndrome), and show the laboratory and clinical trends during three months of magnesium citrate therapy in patients with verified magnesium deficiency.

Materials and methods. A total of 606 students (480 girls, 126 boys) aged 15–19 were examined. Serum magnesium levels were identified (reference values 0.77–1.03 mmol/L). Menstrual cycle regularity, dysmenorrhea intensity using a visual analog scale (VAS, 0–10 points), and PMS severity using a total score (10 symptoms, 0–30 points) were assessed. Magnesium citrate (Solgar) at a dose of 400 mg of elemental magnesium per day per os was prescribed to 135 girls with hypomagnesemia (< 0.77 mmol/L) for 3 months.

Results. Magnesium deficiency (< 0.77 mmol/L) was detected in 240/480 (50.0%) girls and 55/126 (43.7%) boys aged 15–19. The frequency of deficiency did not differ between the age subgroups of 15–17 and 18–19 years. The median magnesium level in girls with deficiency was significantly lower than in boys: 0.64 [0.50; 0.71] versus 0.70 [0.58; 0.75] mmol/L (p< 0.05). The highest frequency of magnesium deficiency was associated with regular fast food consumption (35.9%) and low intake of fruits and vegetables (27.6%).

During three months of therapy with magnesium citrate (400 mg/day) in 135 girls with hypomagnesemia, normalization of magnesium levels was achieved in 129 (95.5%) patients. The median magnesium level increased from 0.65 [0.52; 0.70] to 0.85 [0.78; 0.93] mmol/l. The intensity of dysmenorrhea according to VAS scale decreased from 7 [5; 8] to 3 [2; 5] points. The total score of PMS symptoms decreased from 18 [15; 22] to 8 [5; 12]. The proportion of girls with a regular menstrual cycle increased from 68.8% (93/135) to 95.5% (129/135)

Conclusion. Magnesium deficiency is common situation among students of the Republic of Bashkortostan and is associated with menstrual irregularities, dysmenorrhea, and PMS. Three months of magnesium citrate therapy (400 mg/day) effectively corrects the deficiency and improves indicators of reproductive health in girls aged 15–19, justifying the need for magnesium status screening as part of preconception care.

The article presents the latest findings on the structural and functional organization of the extracellular matrix (ECM), its role in maintaining tissue homeostasis, regulation of cell proliferation, migration, differentiation and apoptosis. ECM is considered as a dynamic, actively remodeling system that ensures not only the mechanical integrity of tissues but also cell-matrix interaction. The main components of ECM are described in detail: fibrillar proteins, adhesive glycoproteins, proteoglycans, glycosaminoglycans and remodeling enzymes. The paper discusses the concept of chronological aging of ECM caused by the age-related decrease in the synthetic activity of fibroblasts and an increase in the activity of matrix metalloproteinases.

This article examines the pathogenetic aspects of stress urinary incontinence and genitourinary syndrome of menopause associated with the degradation of the collagen-elastin matrix, impaired collagen ratios, imbalance in metalloproteinases and their tissue inhibitors, as well as estrogen deficiency and chronic inflammation. The therapeutic strategy for matrix-oriented regeneration has been established using multicomponent biomimetics of ECM that can replicate the composition, architecture and signaling properties of the native matrix.

The paper describes a range of domestically produced biomimetic hydrogels, a multicomponent biomimetic ECM ‘SPHEROgel’ designed for matrix-oriented regeneration that restores tissue architecture and cell-matrix interaction. The LIGHT, MEDIUM, and LONG variants are available, differing in particle size and bioresorption kinetics, which allows for a personalized choice depending on the clinical requirement. Clinical observations are presented demonstrating the effectiveness of personalized approach to selecting modifications of biomimetic hydrogel, which is a pathogenetically sound and safe method of matrix-oriented therapy for chronic diseases of the urogenital tract.

Conclusion. ECM is not a passive scaffold, but an active dynamic system that determines cellular fate, tissue homeostasis and reparative potential.

Rationale. Managing pregnancy complicated by cancer remains of high relevance. Analysis of case studies on pregnant women with tumors of various localizations is of great importance.

Case report. A 34-year-old female patient underwent a renal ultrasound in the second trimester of pregnancy, which revealed a retroperitoneal extraorgan mass by the right renal hilum and the L2–L3 vertebrae. The pregnancy progressed withoutt any complications, and the patient delivered vaginally at term. Postpartum, a contrast-enhanced CT scan was performed. The tumor was removed laparoscopically, and histological and immunohistochemical examination revealed a schwannoma.

Conclusion. The case report on retroperitoneal schwannoma detected during pregnancy deserves attention due to the rarity of the pathology, the complexity of diagnosis and management.