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Obstetrics, Gynecology and Reproduction

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Vol 19, No 4 (2025)

EDITORIAL

470-475 13
Abstract

This issue focuses on the translation of molecular and clinical-instrumental indicators into personalized solutions in obstetrics and gynaecology. In gynaecological oncology, the discussion covers integrated biomarkers of thrombotic risk (vWF/ADAMTS-13 axis, antiphospholipid antibodies) and the potential for organ-preserving interventions, including robot-assisted procedures. In reproductive medicine, the issues addressed include preconception care of deficiencies (e. g. iron and folate), assessment of the uterine cavity in older patients and predictors of adverse perinatal outcomes in cases of premature rupture of membranes. Reviews on the Wnt/β-catenin cascade in endometriosis, molecular genetic markers of breast cancer, and nanotechnology provide a foundation for developing diagnostic panels and targeted approaches. A clinical case study of vaginal reconstruction and a historical essay complement the practical and educational content of the issue.

ОRIGINAL ARTICLES

476-487 10
Abstract

Aim: to evaluate a prognostic significance for the vWF/ADAMTS-13 (von Willebrand factor/a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) ratio as an integral biomarker for stratifying the risk of venous thromboembolic events and for monitoring the effectiveness of prophylactic anticoagulant therapy (АСТ) in gynecologic oncology patients receiving chemotherapy.

Materials and Methods. This prospective cohort interventional comparative study included 74 patients with ovarian cancer (OC) or cervical canal adenocarcinoma who were undergoing chemotherapy. The patients were divided into groups depending on whether they had experienced thrombotic complications earlier. Levels of vWF, ADAMTS-13, and the vWF/ADAMTS-13 ratio, as well as D-dimer, were assessed. Laboratory parameters were analyzed before chemotherapy, after 1–2 courses, and during prophylactic ACT. Variation statistics, ROC analysis and the Youden criterion were used to determine the threshold values.

Results. Significant disturbances in vWF/ADAMTS-13 axis parameters were detected in patients with pre-chemotherapy thrombotic history, compared to control group: the ratio reached 1.59–1.65 (p < 0.05), compared to 0.65 in control group. During chemotherapy, such alterations worsened (up to 2.04 in OC patients), accompanied by elevated D-dimer level. Administering prophylactic ACT based on low molecular weight heparin normalized the vWF/ADAMTS-13 axis parameters and decreased D-dimer level, reflecting a reduced prothrombotic potential. The incidence of thrombotic complications upon anticoagulant prophylaxis was twice as low as without it (13 % vs. 25 %). ROC analysis confirmed the high diagnostic significance for the vWF/ADAMTS-13 ratio (AUC = 0.87), with an optimal threshold value of ≥ 1.6 for identifying the high-risk group.

Conclusion. The vWF/ADAMTS-13 ratio is a sensitive, integral marker of hypercoagulability. It allows to justify stratification of thrombotic complication risk and monitor the effectiveness of anticoagulant prophylaxis in gynecologic oncology patients receiving chemotherapy. Including vWF/ADAMTS-13 ratio in clinical algorithms can improve the accuracy to select patients for anticoagulant prophylaxis and facilitate treatment personalization.

488-505 340
Abstract

Introduction. Approximately 10 % of patients with preterm labor exhibits signs of intra-amniotic inflammation, which often occurs subclinically and results in increased risk of premature rupture of membranes (PROM).

Aim: to identify predictors of unfavorable perinatal outcomes associated with PROM.

Materials and Мethods. The single-center retrospective cohort study was conducted from January 1 to November 1, 2023 by enrolling patients between 28 0/7 and 36 6/7 weeks of gestation with PROM. A total of 176 maternal and neonatal medical records were analyzed. Two groups of neonates were identified: Group 1 – neonates with favorable outcomes at the time of hospital discharge; Group 2 – fetuses or neonates with unfavorable outcomes at discharge (including antenatal fetal death, neonatal death, grade 3 intraventricular hemorrhage, periventricular leukomalacia, severe bronchopulmonary dysplasia, or surgical-stage necrotizing enterocolitis). There were analyzed maternal medical histories, pregnancy and delivery data, amniotic fluid index (AFI), maximum vertical pocket of amniotic fluid, severity of respiratory failure and central hemodynamic disturbances in premature neonates, as well as incidence rates for those born to mothers with PROM. Multivariate analysis was conducted to identify factors associated with neonatal outcomes.

Results. Antenatal fetal death was recorded in 7 of 176 cases (3.9 %), and neonatal mortality among live-born infants comprised 7 of 169 (4.1 %). Median gestational age at delivery in Group 2 was 193.0 days [IQR: 180.0–198.0], significantly lower than in Group 1 (238.0 days [IQR: 223.5–247.0]; p < 0.001). Chorioamnionitis (p < 0.001) and anhydramnion (p = 0.003) were significantly more frequent in Group 2. Neonates in Group 2 required tracheal intubation (p < 0.001), surfactant therapy (p < 0.001), mechanical lung ventilation (p = 0.029), and high frequency oscillatory ventilation (p < 0.001) more often within the first 72 hours of life. NEOMOD (Neonatal Multiple Organ Dysfunction) scores were significantly higher in this group (p < 0.001). In Group 2, Ureaplasma parvum in nasopharyngeal swabs was more frequently found by using polymerase chain reaction (p = 0.015).

Conclusion. Predictors of adverse outcomes in fetuses and preterm neonates with PROM consisted of anhydramnios, chorioamnionitis, lower gestational age and birth weight, cesarean delivery, elevated maternal C-reactive protein (CRP) and white blood cell count prior to delivery, an AFI ≤ 32.0 mm, higher NEOMOD scores, presence of diffuse ecchymosis at birth, detection of neonatal Ureaplasma parvum, lower hemoglobin levels, as well as increased procalcitonin and CRP levels within the first 72 hours of life.

506-513 214
Abstract

Introduction. Successful completion of in vitro fertilization (IVF) program is characterized by pregnancy achievement, suggesting that an implantation-competent embryo has reached a receptive endometrium. Chronic endometritis (CE) often being asymptomatic or presented with non-specific symptoms represents one of the main causes for impaired endometrial receptivity. CE treatment and normalization of CD138 expression are related to improved outcomes in assisted reproductive technology (ART) programs, primarily in women of advanced reproductive age.

Aim: to analyze the frequency and severity of pathological endometrial changes by using hysteroscopy with biopsy and immunohistochemical examination (IHC) in women of advanced ( 35 years old) vs. younger (< 35 years old) reproductive age.

Materials and Methods. A retrospective descriptive continuous cross-sectional study was conducted to analyze 569 hysteroscopy protocols with biopsy and IHC performed at the "PERSONA" clinic in 2020–2022. Clinical and anamnestic data (age, frequency of primary and secondary infertility), frequency, structure and severity of uterine cavity pathology, age-related pattern were assessed according to histological and IHC studies in two age groups: < 35 years and ≥ 35 years.

Results. CE was identified in 80.47 % of younger and 85.3 % of older patients. Severe CE was significantly more common in ≥ 35-year-old women (12.73 % vs. 3.6 %; p = 0.021). No significant inter-group differences were found in CD138 expression levels. Common endometrial abnormalities included fibrosis and mixed lesions.

Conclusion. While overall endometrial pathology was commonly observed in both age groups, severe CE forms were significantly more frequent in women of advanced reproductive age. Office hysteroscopy is recommended prior to ART initiation in this population to optimize outcomes.

514-523 7
Abstract

Aim: to identify the key pathogenic factors and triggers associated with recurrent venous thromboembolic events (VTE) in gynaecological oncology patients.

Materials and Methods. There was conducted a retrospective cohort study with three groups of gynaecological oncology patients: 155 women with a history of thrombosis episodes (Group I), 66 patients with recurrent thrombosis and stage III–IV ovarian cancer (Group II), and 72 patients with tumours of the female genital organs who had previously contracted SARS-CoV-2 infection (Group III). All patients underwent comprehensive assessments for congenital thrombophilia (FV Leiden, prothrombin G20210A, MTHFR C677T, PAI-1 and platelet glycoproteins), acquired thrombophilia (anti-β2-GP1 antibodies, anti-annexin V antibodies, and anti-prothrombin antibodies), and markers of endothelial dysfunction – von Willebrand factor (vWF) and metalloprotease ADAMTS-13, and thromboinflammatory syndrome (D-dimer). Statistical analysis was performed using non-parametric tests at a significance level set at p < 0.05.

Results. Recurrent VTE in gynaecological oncology patients was found to develop upon high prevalence of congenital and acquired thrombophilia, vWF/ADAMTS-13 axis disorders, and activation of the thromboinflammatory syndrome. In group I, genetic thrombophilia was detected in 145 patients (93.6 %), with multigenic variants occurring in 113 patients (72.9 %); antiphospholipid antibodies (aPL) circulation was found in 87 patients (55.8 %). In group II, genetic thrombophilia was detected in 44 (66.7 %) women and aPL circulation in 31 (47.0 %); the median vWF level was 1513 IU/L (p < 0.05); D-dimer levels exceeded 1500 ng/ml in 48 patients (72.7 %) with median 2700 ng/ml. In group III, recurrent VTE were observed in 39 (54.2 %) patients. The median vWF level was 3450 IU/L and ADAMTS-13 level was reduced down to 220 IU/L (p < 0.01) compared to group I and group II. The D-dimer level exceeded 1500 ng/ml in 33 patients (84.6 %) with median 2900 ng/ml. Circulating aPL was detected in 28 patients (71.8 %) with relapses. COVID-19 convalescent patients had 70 % higher recurrence risk (relative risk (RR) = 1.7; 95 % confidential interval (CI) = 1.1–2.8; p < 0.05).

Conclusion. Recurrent VTE in oncogynaecological patients has a multifactorial etiology, collectively accounted for by congenital and acquired thrombophilia, endothelial dysfunction, and thromboinflammatory syndrome, which may be profoundly exacerbated by previous SARS-CoV-2 infection. The data obtained emphasize a need for comprehensively assessing risk factors and applying an individualized approach to prevent VTE recurrence in this patient group.

524-533 339
Abstract

Aim: to study the features of lichen sclerosus (LS) epidemiology in girls from the Republic of Bashkortostan (RB).

Materials and Methods. A retrospective cohort study was conducted. The authors analyzed LS incidence in girls aged 0 to 18 years, the data provided by two pediatric gynecological department, which in different years served all RB girls with gynecological pathology. A comparison of indicators recorded during the two equal and comparable time periods was carried out: the first 9 years of operation (from 1996 to 2004) at the Department of Pediatric Gynecology of the Clinical Hospital of Emergency Medical Care, Ufa and the first 9 years of operation (from 2015 to 2023) at the Gynecological Department of the Republican Children's Clinical Hospital, Ufa.

Results. Lichen sclerosus in RB girls can be attributed to orphan disease, since its incidence rate over the past 9 years comprised 0.46 ‰. Over the 19-year follow-up (2004–2023), the accumulated LS incidence in RB girls aged 0 to 18 years increased from 0.22 to 0.46 ‰, and in Ufa – from 0.35 to 0.65 ‰.

Conclusion. In recent years, a significant increase in LS incidence in girls has been observed in the RB. Most LS patients are in the prepubertal childhood period.

REVIEW ARTICLES

534-544 116
Abstract

Endometriosis is a chronic estrogen-dependent disease characterized by the ectopic growth of endometrium-like tissue outside the uterus. In recent years, increasing attention has been paid to the role of the Wnt/β-catenin signaling pathway in endometriosis pathogenesis, wherein it regulates cell proliferation, migration, invasion, and fibrosis. Hyperactivation of the Wnt/β-catenin cascade promotes disease progression, chronic inflammation, and adhesion formation. MicroRNAs modulating this signaling pathway are of particular interest, offering potential for endometriosis diagnostics and targeted therapy. Further research may lead to new treatment approaches and improved quality of patients’ life.

545-560 964
Abstract

Aim: to systematize and analyze current data on the use of minimally invasive and robot-assisted interventions in the treatment of gynecologic malignant tumors in reproductive age women who wish to preserve fertility.

Materials and Methods. The search was conducted in the PubMed/MEDLINE, Scopus, Web of Science, and eLibrary databases among the primary sources published from 01.01.2000 tо 28.02.2025. There were retrieved keywords and MeSH (Medical Subject Headings) terms including: “robotic surgery”, “robot-assisted surgery”, “fertility preservation”, “gynecologic cancer”, “cervical cancer”, “endometrial cancer”, “ovarian cancer”, “reproductive age”, “minimally invasive surgery”, “uterine transplantation”, as well as the corresponding Russian terms. Original studies focusing on oncologic and reproductive outcomes in women under the age of 45 were included in the analysis. The methodology followed the PRISMA guidelines. The final analysis included 53 publications.

Results. The data evidence about the effectiveness and oncologic safety of fertility-preserving approaches in early-stage cervical, endometrial, and ovarian cancer. Robot-assisted interventions vs. conventional techniques demonstrated comparable or superior outcomes in fertility preservation with fewer complications and faster recovery. Additional topics addressed include ovarian transposition, uterine transplantation, and alternative fertility preservation strategies.

Conclusion. Robot-assisted surgery extends the potential for fertility-sparing treatment of gynecologic malignant tumors in reproductive age women. Such interventions should be performed in specialized centers by multidisciplinary teams. Further research is needed to standardize treatment protocols and evaluate long-term oncologic and reproductive outcomes.

561-573 18
Abstract

Information published over the last decade on using iron supplements has been collected and systematized. The need for long-term iron supplementation and patient compliance has been updated and emphasized. The main requirements for current iron supplements today have been formulated, and the advantages of combining organic iron salts with folic acid as the most optimal and contemporary approach to the prevention and treatment of iron deficiency during pregnancy have been emphasized.

575-589 629
Abstract

 

Introduction. Breast cancer (BC) is the most common oncology pathology that holds a leading place among the causes of cancer death. Early diagnosis is critically important for successful treatment. Current molecular genetic research has revolutionized oncology allowing to classify breast cancer into various subtypes and, thereby, radically changing the approach to therapy.

Aim: to analyze the literature data on up-to-date information regarding the molecular genetic BC markers and the prospects of their use for BC diagnostics and treatment.

Materials and Methods. In accordance with the PRISMA guidelines, a systematic search was conducted in the PubMed/ MEDLINE, eLibrary, and Google Scholar databases using Russian and English keywords: «breast cancer», «early breast cancer», «molecular markers of tumor cells», «chemotherapy», «hormone therapy», «estrogen and progesterone receptors», «triple-negative breast cancer», «neoadjuvant chemotherapy», «complete pathological response», «immunohistochemistry». Peer-reviewed publications in Russian or English containing original data on BC molecular diagnostics were included, with total of 39 publications selected for analysis.

Results. High diagnostic and prognostic value was found for mutations in the BRCA1/2, PIK3CA, TP53, CHEK2, PALB2, and ESR1 genes, as well as for the expression of PD-L1, TIL (tumor-infiltrating lymphocytes), and Foxp3+ regulatory T cell levels. Modern technologies such as liquid biopsy, analysis of circulating tumor cells, and circulating tumor DNA allow for real-time tumor molecular profiling. This markedly expands the potential for personalized treatment strategies. HER2-low subtype and ESR1 mutations require individualized therapeutic approaches.

Conclusion. BC molecular markers have become a cornerstone for accurate diagnosis, risk stratification, and personalized therapy. Despite substantial research advances, the accessibility of molecular diagnostics, standardization of procedures, and integration of innovative technologies into clinical practice remain pressing issues. Systemic support is needed to implement molecular techniques into standard care protocols and ensure their broader application in real-world oncology settings.

590-607 945
Abstract

Introduction. By enhancing detection accuracy, therapeutic effectiveness and minimizing side effects, nanotechnology may contribute to improve diagnostics and treatment of patients with female reproductive system cancer.

Aim: to summarize current literature data and assess а role of nanotechnology in treatment of cervical cancer (CC), ovarian cancer (OC), endometrial cancer (EC) and reveal gaps requiring further research.

Materials and Methods. The search was carried out in the electronic databases PubMed/MEDLINE, Google Scholar and eLibrary using the following keywords: “gynecological cancer”, “targeted therapy”, “cervical cancer”, “ovarian cancer”, “endometrial cancer”, “nanotechnology”, “nanoparticles”. All works were published between 2011 and 2024.

Results. Nanocarrier-based drug delivery systems represent a promising approach to the treatment of female reproductive system oncology, providing precise drug delivery directly to tumor cells. Such systems, including liposomes, nanoparticles, micelles, and dendrimers, are characterized by advanced efficiency, reduced toxicity, as well as the opportunity for controlled release of active components. Nanotechnologies increase the effectiveness of vaccines by prolonging their half-life, affect the СС microenvironment and potentiate the antitumor immune response with minimal toxicity. Nanovaccines are capable of delivering antigens and adjuvants directly to immune cells, enhancing immune response and improving ОС treatment results. Nanotechnologies show prominent potential in improving EC treatment despite that their role in this context remains understudied compared to other types of female reproductive system cancer.

Conclusion. Nanoparticles can carry both conventional drugs as well as protein- and nucleic acid-based systems directly to cancer cells. However, only a few nanoparticle-based treatments for female reproductive system cancer have been approved for use. The field is making significant progress toward more effective and widely available treatments.

CLINICAL CASE

608-613 8
Abstract

Secondary vagina atresia is a quite rare pathology, and due to its low incidence, the lack of standardized recommendations for the management of this group of patients, as well as the insufficient number of relevant randomized trials, the analysis of individual clinical cases is of special relevance. An analysis of the clinical case of a female patient with acquired vaginal atresia underwent surgical treatment – vaginal reconstruction with a Martius-Symmonds flap is presented. In dynamics, after the surgical intervention, good healing and autograft adaptation were noted, without necrosis and ulceration in the area of Martius-Symmonds flap transplantation, with neovagina sized up to 6.5 cm long and 3 to 4 cm wide in different localization. Due to the lack of standardized recommendations for management of patients with acquired vaginal atresia, it is necessary to continue examining and discussing such cases in clinical practice.

FROM HISTORY

614-618 9
Abstract

The article presents the historical background and professional achievements done by François Morisot, an outstanding French obstetrician from the 17th century who played a key role in the development of modern obstetric science. The authors recount significant events in Morisot's life and career at the Hotel-Dieu de Paris maternity hospital, emphasizing the importance of Dr. Morisot's seminal work “Diseases of pregnant women and postpartum women”, which formed the foundation for obstetric education at that time. Moreover, we also discuss Morisot's innovative practical approaches, including his description of the first ectopic pregnancy, use of manual aids for breech presentations and his technique for puncturing the amniotic sac in cases of bleeding. In addition, Dr. Morisot's critical attitude towards cesarean section and his emphasis on the importance of deep knowledge on anatomy and physiology are additionally noted. Overall, François Morisot's has substantially contributed to the field and his impact has everlasting importance to medical science and obstetric practice.



ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)