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Obstetrics, Gynecology and Reproduction

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ORIGINAL ARTICLE

280
Abstract

Introduction. Azoospermia, defined as the absence of spermatozoa in the ejaculate after centrifugation, is one of the leading causes of male infertility, affecting approximately 1,0 % of men in the general population and up to 15,0 % of infertile patients. Timely differentiation between obstructive (ОА) and non-obstructive (NOA) azoospermia is critical for selecting appropriate treatment strategies, determining prognosis, and applying assisted reproductive technologies (ART).

Aim: to investigate the prevalence of different azoospermia forms of azoospermia in infertile men, within the context of real-world clinical practice at a non-specialized endocrine outpatient department, including personal observations, with consideration of/in comparison with the results of international and Russian epidemiological studies.

Materials and Methods. A comprehensive analysis of literature, clinical guidelines, and original data was performed. The study included 450 men aged 25–45 years with confirmed azoospermia. All patients underwent a comprehensive examination, including collection of anamnesis (reproductive, somatic, surgical); physical examination with assessment of secondary sexual characteristics, size and consistency of the testicles; double examination of ejaculate (centrifugation, microscopy); examination of blood hormone levels (follicle-stimulating hormone, luteinizing hormone, total testosterone, prolactin, anti-Müllerian hormone, sex hormone-binding globulin, inhibin B; if indicated – estradiol, thyroid-stimulating hormone, thyroxine); scrotum ultrasound examination with Doppler ultrasonography; genetic testing – karyotyping, testing for microdeletions of Y chromosome azoospermia factor (AZF) of the Y chromosome, CFTR (cystic fibrosis transmembrane conductance regulator) gene testing; when indicated, testicular sperm extraction (TESE) biopsy was performed.

Results. NOA and OA were identified in 63.3 % and 30 % of patients, respectively. Among NOA cases, the leading causes were idiopathic forms (19.6 %), Klinefelter syndrome (8.4 %), Y-chromosome microdeletions (5.8 %), and hypogonadotropic hypogonadism (6.7 %). Varicocele was associated with NOA in 12 % of cases. These findings are consistent with global data, although minor ethnic and methodological differences were observed.

Conclusion. Azoospermia is a clinically and etiologically heterogeneous condition. Timely differentiation between its forms and the inclusion of genetic testing improve diagnostic accuracy and help optimizing management strategies. Standardization of diagnostic algorithms and a personalized approach increase ART effectiveness and the likelihood of fertility restoration.

125
Abstract

Introduction. Preterm birth (PTB) remains one of the most serious complications of pregnancy, being the leading cause of neonatal mortality and contributing to long-term disability along with chronic morbidity in newborns, as well as imposing substantial socioeconomic costs. Despite preventive efforts, the global PTB rate has remained largely unchanged comprising 5–18 %, underscoring a need for developing more effective prediction tools to enable timely prevention.

Aim: using an independent sample to develop and validate a PTB risk-assessment tool based on machine learning (ML) and routinely collected clinical data retrieved from electronic health records (EHRs) of pregnant patients.

Materials and Methods. We analyzed a dataset of 10,000 de-identified EHRs entries containing 54 variables, including historical, clinical, laboratory, and instrumental (diagnostic/imaging) data. The predictive system comprised two interconnected ML components: (1) an NLP model based on RuBERT (а pre-trained ML model for processing Russian texts) for extracting PTB-relevant features from unstructured Russian-language clinical text, and (2) a downstream predictive ML model, for which 14 algorithms were benchmarked.

Results. The NLP model demonstrated high performance with a median sensitivity = 0.998, F1-score = 0.976, and AUC-ROC = 0.974. Among the ML algorithms, the algorithm based on gradient boosting – CatBoost classifier (Categorical Boosting Classifier) achieved the best risk-prediction results: accuracy = 0.81, sensitivity (recall) = 0.87, precision = 0.76, F1-score = 0.81, and AUC-ROC = 0.82.

Conclusion. The developed model showed performance comparable to that of international counterparts, and validation confirmed its robustness to previously unseen data, indicating strong potential for use in routine clinical practice. This study represents the first step toward an integrated PTB risk-assessment solution combining NLP and ML. Future work will include incorporation of additional predictors (e.g., biochemical markers) and multicenter validation studies.

113
Abstract

Introduction. Preeclampsia (PE) remains one of the leading causes of maternal and perinatal morbidity and mortality, while most cases are still diagnosed at the stage of clinically overt disease. Complex prediction algorithms incorporating biochemical biomarkers and Doppler velocimetry demonstrate high accuracy but are poorly suited for large-scale screening in resource-limited settings.

Aim: to develop, internally and externally validate mathematical models for predicting PE risk at gestational age of ≤ 16 weeks based on routine electronic medical records (EMRs) data and machine learning methods.

Materials and Methods. A retrospective cohort study was conducted using de-identified EMRs of pregnant women from eight regions of the Russian Federation spanning 2010–2025. The analytical dataset included 19,955 visits at gestational age ≤ 16 weeks. The composite outcome comprised PE, eclampsia and HELLP syndrome identified by ICD-10 codes. A broad spectrum of clinical, medical history and anthropometric variables was evaluated as potential predictors. Models (logistic regression, gradient boosting, Random Forest, Extra Trees) were trained with adjustment for class imbalance; feature selection was based on SHAP values (SHapley Additive exPlanations indices). Internal performance was assessed on a held-out test set, and independent external validation was performed on a subsample from healthcare facilities of the Republic of Karelia (n = 918).

Results. The final Extra Trees model including 35 clinically interpretable predictors achieved a ROC-AUC (Receiver Operating Characteristic curve; Area Under Curve) of 0.871 (95 % confidence interval (CI) = 0.811–0.923) and 0.862 (95 % CI = 0.833–0.892) in internal and external validation set, respectively. At a probability threshold of 0.04, sensitivity in the external cohort was 0.886, specificity 0.631, and negative predictive value exceeded 0.99. Probability calibration was moderate (mean absolute calibration error was 0.245–24.5 percentage points). The strongest contributors to PE risk were chronic hypertension, history of PE, blood pressure parameters, antiphospholipid syndrome and diabetes mellitus.

Conclusion. The Extra Trees model developed on routinely collected EMRs data demonstrates acceptable discriminative ability, high sensitivity and very high negative predictive value and may be considered as a screening tool for early PE risk stratification, provided local calibration assessment and further clinical evaluation.

128
Abstract

Aim: to compare international and Russian epidemiological data on the causes of oligozoospermia and to develop differential diagnostics and patient management algorithm by taking into account endocrine, genetic and immunological factors.

Materials and Methods. A retrospective observational study included 210 men aged 25-45 years with confirmed oligozoospermia and infertility complaints. All patients underwent semen analysis according to the World Health Organization standards (2021), blood hormone testing (follicle-stimulating hormone, luteinizing hormone, total testosterone, prolactin, thyroid-stimulating hormone, estradiol, inhibin B, anti-Müllerian hormone, 17-hydroxyprogesterone), scrotal ultrasound, as well as genetic testing (karyotyping and Y-chromosome microdeletions). The data provided by international clinical guidelines, European Association of Urology (EAU, 2024), American Urological Association/American Society for Reproductive Medicine (AUA/ASRM, 2024), publications in Russian and English retrieved from PubMed/MEDLINE, Scopus and eLibrary databases were analyzed.

Results. A wide spectrum of causes of oligozoospermia was identified: endocrine disorders (hypo- and hypergonadotropic hypogonadism), Klinefelter syndrome, Y-chromosome microdeletions, varicocele, and obstructive forms. The pathophysiological mechanisms of hypogonadism, the clinical significance of Klinefelter syndrome, features of AZF deletions, and the role of varicocele as a potentially reversible cause of male infertility are discussed in detail.

Conclusion. Differential diagnosis of oligozoospermia requires a comprehensive, stepwise approach. Incorporating repeated semen analysis, hormonal profiling, ultrasound, and genetic testing into the diagnostic algorithm enables identification of reversible causes (varicocele, hypogonadotropic hypogonadism) as well as timely diagnostics of genetic forms (Klinefelter syndrome, Y-chromosome microdeletions). This ensures a personalized therapeutic strategy and improves the effectiveness of assisted reproductive technologies.

REVIEW ARTICLE

889
Abstract

Malignant neoplasms of the female reproductive system remain a significant global health concern, ranking among the leading causes of cancer incidence and mortality in women. Despite advances in the field of gynecologic oncology, early diagnosis and prognosis of such diseases continue to pose substantial challenges. In recent years, extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, have been increasingly attracted attention as key mediators of intercellular communication and carriers of biologically active molecules. EVs transport microRNAs, long non-coding RNAs, proteins, and other molecules that influence critical carcinogenic processes such as proliferation, angiogenesis, metastasis, and the development of chemoresistance. This review summarizes current data on the EVs role in the pathogenesis and progression of cervical, endometrial, and ovarian cancers. The diagnostic and prognostic potential of EV-associated biomolecular components is examined, with evidence from preclinical and clinical studies highlighting their promise as biomarkers. The review also discusses the prospects for clinical application of EVs, emphasizing the challenges of methodological standardization and the need for multicenter studies to validate their clinical utility. Additionally, the importance of integrating omics technologies and bioinformatics approaches is underscored as essential for improving patient stratification and advancing personalized therapy.

871
Abstract

Glucose metabolism plays a pivotal role in fueling the energetic and biosynthetic demands in rapidly proliferating cells. In gynecologic malignancies (GMs), including ovarian cancer (OC), endometrial cancer (EC), and cervical cancer (CC), metabolic reprogramming occurs to support tumor growth, invasion, metastasis, and drug resistance. The current review provides a comprehensive analysis of the molecular mechanisms underlying glucose metabolism dysregulation in tumors of the female reproductive system, covering glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway (PPP). Special attention is paid to key enzymes such as hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), which are central to the Warburg effect. The review also addresses transcriptional regulators such as hypoxia-inducible factor 1-alpha (HIF-1α) and metabolic sensors like pyruvate dehydrogenase kinase 1 (PDK1) and isocitrate dehydrogenase 1 (IDH1) that play important roles in the adaptation of tumor cells to hypoxic conditions and in disease progression. Expression profiles of glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT3), sodium glucose cotransporter 1 (SGLT1) and PPP enzymes – glucose-6-phosphate dehydrogenase (G6PD), transketolase-like 1 (TKTL1), are discussed in the context of redox homeostasis maintenance and the development of chemoresistance. Understanding these metabolic alterations opens avenues for identifying potential therapeutic targets and prognostic biomarkers. Incorporating molecular profiling into clinical practice may facilitate the development of personalized therapeutic strategies and improve the prognosis of patients with gynecologic cancers.

922
Abstract

Introduction. According to the World Health Organization, infertility affects approximately one in six reproductive-age people. Assisted reproductive technologies (ART), particularly in vitro fertilization (IVF), have been available for more than three decades and have resulted in the birth of millions of children worldwide. Cryopreservation allows for the storage of large numbers of cells and tissues and is used in medicine for various purposes, including IVF.

Aim: to analyze literature-based data on physical principles, methods, and prospects of cryopreservation in reproductive medicine.

Materials and Methods. A review of scientific publications reported by domestic and international authors was conducted using the PubMed/MEDLINE, Google Scholar, and eLibrary databases from 1953 to September 2024. The following keywords were retrieved: “infertility”, “assisted reproductive technologies”, “in vitro fertilization”, “cryopreservation”, “cryoprotectants”, “cryoprotective agents”, “vitrification”, “gamete selection”, “sperm cryopreservation”, “female gamete cryopreservation”, “embryo cryopreservation”. There were predominantly reviewed full-text articles in Russian and English published in peer-reviewed scientific journals, containing original data or systematic analysis, as well as information on the effectiveness, safety, and biological impact of cryopreservation methods. For historical and contextual coverage of the topic, selected monographs, reviews, regulatory documents, and conference materials were also used, provided their relevance to the subject matter. These sources were not included in the assessment of method effectiveness but were considered in the context of the timeline for the technologies and ethical-legal aspects. A total of 5,876 publications were analyzed, of which 74 were included in the final review.

Results. The physical and chemical principles of cryopreservation, classification of cryoprotective agents (CPA), as well as comparative effectiveness for various freezing methods (slow, rapid, ultra-rapid, and vitrification) were systematized. It was established that vitrification provides the highest survival rates for oocytes and embryos compared to conventional freezing, particularly when high-concentration CPAs are used in combination with non-penetrating agents. An effect of alternative carriers and biomaterials (e.g., hyaluronan-phenolic hydroxyl microcapsules, Volvox globator) for single-sperm cryopreservation was examined. Approaches to assessing gamete quality after thawing were summarized, including promising methods such as cell-free DNA analysis and the application of artificial intelligence for embryo morphology assessment. Unresolved issues were identified, including high CPAs-related toxicity, lack of standardized clinical protocols, as well as ethical and legal concerns regarding cryomaterial handling. The need for further research aimed at developing safe and effective ART-related cryopreservation protocols is emphasized.

Conclusion. The analysis revealed knowledge gaps related to the optimization of clinical cryopreservation protocols for embryos and female gametes. Currently, vitrification remains the preferred method, providing the highest survival rates for biological material.

959
Abstract

Introduction. Nectin-4, a cell adhesion molecule of the immunoglobulin superfamily (IgSF), has been extensively studied in oncological diseases. Nectin-4 is involved in the formation of intercellular connections and promotes tumor cell proliferation, migration and chemoresistance. Upregulated nectin-4 expression has been detected in various malignant neoplasms, including tumors of the female reproductive system – ovarian, endometrial, cervical cancer, as well as rare tumors of the vulva, vagina and fallopian tubes.

Aim: to summarize current data on nectin-4 role in the pathogenesis, diagnostics, prognosis and therapy of malignant tumors of the female reproductive system, and to assess the prospects for its clinical use in personalized medicine.

Materials and Methods. A search for relevant publications was conducted in the PubMed/MEDLINE, Scopus, Web of Science, Embase and eLibrary.ru databases beginning from January 2000 to December 2024. The inclusion criteria covered original and review articles devoted to nectin-4 in gynecological oncology. Key words in Russian and English, Boolean operators, and filtering by full-text, subject matter, and quality of research were used. From the 3955 identified publications, 65 were included in the review.

Results. Nectin-4 expression is associated with enhanced tumor cell proliferation, migration, and chemoresistance, whereas its involvement in generating tight intercellular junctions promotes the development of chemoresistant spheroids. In ovarian cancer, upregulated levels of nectin-4 messenger RNA (mRNA) and serum protein demonstrated high diagnostic and prognostic significance, especially in combination with traditional markers such as cancer antigen 125 (CA-125). In endometrial cancer, nectin-4 expression correlates with a deficiency of the mismatch repair system (MMR genes) MSH2/MSH6 genes and lowered progression-free survival. In cervical carcinoma, nectin-4 is related to drug resistance, thereby positioning it as a promising target for novel treatment strategies. The latter using nanoquinacrine and antibody-drug conjugates (ADCs) such as 9MW2821 and ADRX-0706, are currently undergoing clinical trials. Additionally, nectin-4 has shown relevance in non-malignant reproductive disorders such as endometriosis and preeclampsia.

Conclusion. Nectin-4 demonstrates high clinical significance as a diagnostic and prognostic marker in gynecological malignancies. Its expression is associated with aggressive disease progression and drug resistance, especially in ovarian, endometrial and cervical cancers. Clinical trials with nectin-4-targeted drugs, including ADCs, are underway. Thus, nectin-4 represents a promising target for the development of personalized diagnostic and therapeutic strategies in gynecological oncology.

858
Abstract

Sexual dysfunction is one of the most common and underestimated issues observed in women undergone treatment for malignant neoplasms of the female reproductive system. Here, we review current data on the impact of surgical treatment, radiation therapy, and chemotherapy on patients’ sexual health, including symptoms such as vaginal dryness, dyspareunia, decreased sexual desire, and dissatisfaction with intimate life. Special attention is paid to the importance of screening for sexual dysfunction at all stages – from diagnosis to long-term survival. We discuss modern approaches to managing sexual dysfunction, including hormonal and non-hormonal therapies, vaginal moisturizers and lubricants, use of vaginal dilators, pelvic floor physical therapy, psychosocial counseling, and local anesthetic application. The effectiveness of multidisciplinary programs implemented in specialized sexual health clinics is highlighted, along with the growing importance of telemedicine and online resources for patients living in areas with limited access to specialized care. The article also addresses sexual health inequity access to services among marginalized groups, including individuals with low socioeconomic status, residents of rural areas, and members of sexual and gender minority communities. The need to increase awareness among healthcare professionals, integrate sexual health screening into routine oncology practice, and develop individualized rehabilitation programs to improve the quality of women’s life after gynecologic cancer treatment is emphasized.

1112
Abstract

Introduction. Malignant neoplasms of the female reproductive system (ovarian, endometrial, and cervical cancers) account for a significant proportion of female oncology morbidity and mortality. Standard treatment methods, including surgery, chemotherapy, and radiotherapy, show limited efficacy in recurrent and drug-resistant tumors. The development of immunotherapy, particularly immune checkpoint inhibitors (ICI), has opened new therapeutic avenues; however, their clinical effectiveness in gynecologic oncology remains suboptimal. In connection with this, it has increased an interest in novel targets, notably TIGIT (T-cell immunoglobulin and ITIM domain), a co-inhibitory receptor expressed on T-cells and natural killer cells (NK-cells), which plays a key role in establishing an immunosuppressive tumor microenvironment.

Aim: to systematize current data on the biological function of TIGIT and relevant ligands, its role in immunosuppression in malignant neoplasms of the female reproductive system as well as evaluate a therapeutic potential of its blockade during a personalized immunotherapy.

Materials and Methods. This review was conducted according to the PRISMA methodology. There was performed a systematic literature search for publications from 2013 to 2024 in the databases PubMed/MEDLINE, Scopus, Web of Science, Embase, Google Scholar, and ClinicalTrials.gov. A total of 91 scientific sources and 7 registered clinical trials were included. Original studies, meta-analyses, reviews, guidelines, and clinical trial reports were analyzed.

Results. TIGIT interacts with several ligands (CD155, CD112, Nectin-4, Fap2), leading to suppression of NK-cells and CD8+ T-cells activity, macrophage polarization toward M2 phenotype, activation of regulatory T-cells (Treg), and impaired antigen presentation. TIGIT is co-expressed with PD-1 (programmed cell death protein 1) and CD96, forming a suppressive signaling network. Its elevated expression is associated with disease progression in ovarian, endometrial, and cervical cancers, reduced cytotoxicity of tumor-infiltrating lymphocytes (TIL), and poor prognosis. TIGIT blockade, especially in combination with PD-1/PD-L1 (programmed cell death ligand 1), restores effector cell function and enhances antitumor immunity in preclinical and clinical studies.

Conclusion. TIGIT is a promising immunotherapeutic target in malignant neoplasms of the female reproductive system. Its blockade may improve treatment outcomes in patients with recurrent and resistant cancert ypes. Combined approaches involving anti-TIGIT agents require further clinical validation but even today they offer new directions in targeted therapy and personalized management in gynecologic oncology.

905
Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert prominent metabolic and immunomodulatory properties that make them promising agents for the correction of reproductive disorders in obese women. Weight loss, increased insulin sensitivity, normalization of androgen profiles, and restoration of ovulatory function are primarily relevant in polycystic ovary syndrome (PCOS) and unexplained infertility. At the level of immune regulation, GLP-1RAs contribute to downregulated pro-inflammatory cytokine expression, increased percentage of regulatory T cells (Treg), and recovered Th17 (T helper 17 cells)/Treg balance, thereby improving endometrial receptivity and conditions for successful implantation. A close association has been established between obesity, insulin resistance, and chronic inflammation collectively contributing to reduced fertility and increased risk of recurrent miscarriage. GLP-1RAs target key pathogenic mechanisms underlying these conditions, extending beyond their glucose-lowering effects. Furthermore, their potential in decreasing the incidence of immune-related reproductive losses has been observed. Despite high efficacy before pregnancy, the use of GLP-1RAs during gestation remains limited due to potential embryotoxicity. The lack of large-scale randomized clinical trials in reproductive cohorts restrains the broad integration of these agents into clinical protocols. A promising direction is introduction of GLP-1RAs in preconception preparation regimens for women with obesity, PCOS, and immune imbalance.

724
Abstract

Ophthalmictoxicity has become increasingly relevant upon introduction of novel anticancer agents – targeted therapies, immunotherapies, and endocrine treatments. Women with malignancies of the reproductive system, including ovarian, endometrial, and cervical cancers have been receiving treatments associated with potential visual impairments more frequently. This review consolidates the data on ocular adverse events associated with key drug classes used in gynecologic oncology: BRAF (B-Raf proto-oncogene, serine/threonine kinase) inhibitors, MEK inhibitors (mitogen-activated protein kinase kinase) inhibitors, immune checkpoint inhibitors (ICIs), including PD-1 (programmed cell death protein 1), PD-L1 (programmed cell death-ligand 1), and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), antiangiogenic agents targeting VEGF (vascular endothelial growth factor) and VEGFR (vascular endothelial growth factor receptor), as well as selective estrogen receptor modulators (SERMs), aromatase inhibitors, and PARP (poly(ADP-ribose) polymerase) inhibitors. Particular attention is paid to the most common and clinically significant toxicities, including uveitis, keratitis, dry eye syndrome, macular edema, retinopathy, optic neuritis, and rarer but severe complications such as retinal vein occlusion and retinal detachment. In addition, it also presents differentiated approaches to diagnosing and managing ophthalmic toxicity related to the specific drug class. The importance of multidisciplinary collaboration between oncologists, gynecologists, and ophthalmologists is emphasized to ensure timely identification and management of visual impairments. Practical recommendations are provided for screening, monitoring, and managing patients at risk of ocular complications, including referral algorithms and treatment modification strategies. The article aims to increase awareness among gynecologic oncologists regarding ocular toxicity and optimize the clinical management of affected patients.

748
Abstract

Uterine natural killer cells (uNK) represent the dominant population of immune cells in the decidual tissue during early pregnancy, playing a key role in embryo implantation, spiral artery remodeling, and the establishment of proper uteroplacental blood flow. Unlike peripheral natural killer cells (pNK), uNK cells exhibit limited cytotoxicity and pronounced regulatory functions mediated through the production of cytokines, growth factors, and adhesion molecules. An imbalance in uNK cell activation or inhibition is associated with developing several pregnancy complications, including recurrent pregnancy loss, preeclampsia, and infertility associated with endometriosis. Here, we analyze current concepts assessing uNK cell phenotype and functional activity, crosstalk with trophoblasts and regulatory T cells (Treg), as well as the role for key receptors – NKp46 (natural killer protein 46), NKp44 (natural killer protein 44), NKp30 (natural killer protein 30), CD16 (cluster of differentiation 16), NKG2A (natural killer group 2 member A receptor), and cognate ligand HLA-E (human leukocyte antigen E). Special attention is paid to biomarkers reflecting uNK cell status and their prognostic value in reproductive medicine. Therapeutic approaches aimed at modulating uNK cell activity are also considered. In particular, it has been shown that the use of glucocorticoids (e.g., prednisolone) reduces endometrial CD56⁺ uNK cell counts and is applied in patients with recurrent pregnancy loss and repeated implantation failure. Granulocyte colony-stimulating factor (G-CSF) is capable of stimulating angiogenesis, enhancing endometrial receptivity, and increasing the clinical pregnancy rate in women with impaired uNK function. Monoclonal antibodies targeting activating NK cell receptors (NKp46, NKp44, NKp30, CD16) are considered an experimental approach to alleviate excessive uNK cytotoxicity in endometriosis and recurrent miscarriage. Another promising direction relies on applying targeted intervention in immune checkpoints, particularly modulating interaction between the NKG2A receptor and its ligand HLA-E, which may optimize spiral artery remodeling and uteroplacental blood flow.

591
Abstract

Female reproductive system malignancies are frequently associated with a high risk of abdominopelvic complications, arising both from the tumor process itself and due to therapeutic interventions, including surgery, radiotherapy, chemotherapy, and immunotherapy. Such complications may profoundly worsen prognosis, impair quality of life, and hinder further treatment. Imaging diagnostics plays a crucial role in their timely detection, providing an opportunity not only to evaluate an extent and distribution of pathology but also to differentiate expected post-therapeutic changes from true complications. This article reviews the most common complications encountered after surgical procedures, such as lymphatic complications, fistulas, and infectious processes, as well as those following pelvic exenteration. Radiation-induced toxic effects are described, including both early and late changes affecting the gastrointestinal tract, urinary system, and musculoskeletal structures. Particular attention is paid to complications associated with chemotherapy and contemporary systemic therapies, including targeted agents and immunotherapy, which may result in hepatobiliary, pancreatic, gastrointestinal, vascular, and skeletal toxicities. Typical radiological manifestations related to such complications are discussed primarily outlining those following computed tomography (CT) and magnetic resonance imaging (MRI) exerting an essential role for early diagnosis, treatment planning, and follow-up. A comprehensive understanding of imaging features for abdominopelvic complications in patients with gynecologic malignancies is required for accurate diagnosis, prevented misinterpretation, and patient care optimization.

406
Abstract

Elective fertility preservation (EFP) has emerged as a crucial strategy for women seeking to maintain reproductive potential in the context of delayed childbearing. Among the available techniques, elective oocyte cryopreservation (ЕOC) is the most established and widely practiced approach, while ovarian tissue cryopreservation has been gaining attention as an alternative with unique advantages, including the restoration of natural fertility and endocrine function. Advances in vitrification have significantly improved survival and fertilization rates of cryopreserved oocytes, yet key questions remain regarding the optimal number of oocytes required, the ideal age for cryopreservation, and the cost-effectiveness of these procedures across different patient groups. It has been consistently evident that younger age at cryopreservation is associated with higher live birth rates and reduced need for multiple stimulation cycles. It was also verified that long-term storage does not negatively impact oocyte viability or offspring health. Importantly, available data suggest no increased obstetric or perinatal risks for children born from cryopreserved oocytes, although long-term and intergenerational outcomes require further investigation. Ethical and legal debates continue to shape practice worldwide. While ЕОС is broadly permitted, regulatory frameworks vary significantly across countries. In the Russian Federation, fertility preservation is legally permitted and widely applied, though formal age limits are not defined. Overall, EFP offers women greater reproductive autonomy, yet requires careful counseling regarding realistic success rates, maternal age–related risks, ethical considerations, and financial barriers. Future directions should focus on standardized clinical guidelines, expanded patient education, and supportive health policies to ensure equitable access and safe implementation of fertility preservation technologies.

295
Abstract

The article summarizes current evidence on the impact of postmenopausal osteoporosis, menopause-related hormonal changes, and hormone therapy on dental implant outcomes. Epidemiology and pathogenesis of bone alterations are reviewed, with particular emphasis on the role of estrogen, progesterone, calcitonin, growth hormone, and insulin-like growth factor-1 (IGF-1) deficiency. Special attention is paid to the effects of menopausal hormone therapy and bioidentical forms of estradiol and progesterone on osteoporosis course and the effectiveness of dental implantation. The analysis highlights the risks of implant loss and the opportunities of interdisciplinary approach in dentistry and endocrinology to optimize implant osseointegration in postmenopausal women.

257
Abstract

Sphingolipids are bioactive lipids that regulate cell proliferation, differentiation, apoptosis, angiogenesis, and inflammation. In recent years, their role in maintaining the ovarian reserve and developing of female reproductive disorders has gained increasing attention. Ceramides (CERs) and sphingosine-1-phosphate (S1P) form a dynamic balance between pro-apoptotic and pro-survival signals, determining the fate of follicles and oocytes. Dysregulation of sphingolipid metabolism has been identified in ovarian cancer, polycystic ovary syndrome, endometriosis, obesity, diminished ovarian reserve, and premature ovarian insufficiency. These conditions are accompanied by a shift in the CERs/S1P ratio, which affects oocyte quality and their susceptibility to oxidative stress, chemotherapy, and inflammation. Emerging evidence indicates that targeted modulation of the sphingolipid pathway — including enzymes such as sphingosine kinases, ceramide synthases, sphingomyelinases, and ceramide transfer protein, as well as S1P receptors may represent a promising approach for preserving ovarian reserve, preventing infertility, and overcoming chemoresistance in ovarian cancer. S1P exhibits protective properties toward oocytes, whereas ceramide analogues and inhibitors of sphingolipid-metabolizing enzymes offer new opportunities for personalized therapy. Summarizing current data on sphingolipid metabolism in reproductive tissues highlights these molecules not only as biomarkers of pathology but also as potential therapeutic targets, which is particularly relevant for developing fertility-preserving strategies and improving the outcomes of gynecological disease treatment.

157
Abstract

Primary hyperparathyroidism during pregnancy is a rare but clinically significant condition associated with a high risk of complications for both the mother and the fetus. The disease is often asymptomatic or masked by physiological changes in calcium-phosphorus metabolism, which complicates timely diagnostics. Biochemical verification is based on the detection of parathyroid hormone-dependent hypercalcemia. Neck ultrasonography is the safest method for preoperative localization of parathyroid lesions, whereas using radionuclide and computed tomography imaging are limited due to potential fetal radiation exposure. Management strategies are determined by gestational age, the severity of hypercalcemia, and the presence of complications. Conservative measures include adequate hydration, limited use of calcitonin, and cinacalcet; however, their efficacy is limited and may be associated with risks for the newborn. Surgical treatment such as parathyroidectomy optimally performed in the second trimester of pregnancy remains to be the «gold» standard. Compared to conservative management, surgery is associated with a lower risk of spontaneous abortion, preterm delivery, neonatal hypocalcemia, and other complications. The postpartum period requires close patient monitoring due to potential sharp increase in serum calcium levels. Newborns require monitoring of blood ionized calcium level and preventive measures to avoid neonatal hypocalcemia.

46
Abstract

Aim: to systematize current data on diagnostic potential and therapeutic approaches to restore fertility in women of advanced reproductive age with diminished ovarian reserve, as well as to identify promising directions for further research.

Materials and Methods. The review includes scientific publications indexed in PubMed/MEDLINE, Scopus, Web of Science, Google Scholar spanning from January 2020 to January 2025 inclusive, according to the indexing status at the time of the literature search. Article selection was performed in accordance with the PRISMA international guidelines. At the initial search stage, 397 publications were identified in PubMed/MEDLINE, 96 in Scopus, 121 in Web of Science, and 28 in Google Scholar. Duplicate and non–full-text records were excluded. After the selection procedure, 60 publications were included in the final review, comprising randomized clinical trials, meta-analyses, systematic reviews.

Results. Literature analysis demonstrated that the assessment of anti-Müllerian hormone levels and the antral follicle count remain the most reliable predictors of ovarian reserve and treatment outcomes. Individualized protocols for controlled ovarian stimulation improve the rate of mature oocyte retrieval; however, their efficacy is limited by age-related decline in oocyte quality. Experimental approaches such as platelet-rich plasma (PRP) therapy, stem cell application, and mitochondrial support show promising results in pilot studies but require further standardization and evaluation of long-term safety. The use of donor oocytes remains the most effective strategy in cases of severe ovarian reserve depletion.

Conclusion. Despite advances in elucidating the pathogenesis of ovarian aging, optimizing fertility restoration in women of advanced reproductive age with diminished ovarian reserve remains a multifactorial challenge. The most promising directions include the individualized selection of stimulation protocols, integration of supportive and experimental methods, as well as development of molecular and genetic biomarkers for personalized therapy.

CLINICAL CASE

543
Abstract

Introduction. According to the average statistical data, the incidence of ovarian tumors in children comprises about 4.6 %. In the adolescent population, ovarian epithelial tumors confidently hold a leading place. One of their histological subtypes is presented by mucinous cystadenoma. Due to the frequent asymptomatic course or the absence of specific clinical features, such cysts can long persist in the abdominal cavity and reach significant sizes. In the latter case they can manifest with the symptoms of serious complications such as obstruction of the urinary tract and the intestines, pedunculated masses torsion, ovarian torsion, rupture of cysts, etc. Thus, the main insidiousness of ovarian tumors lies in the delayed diagnostics and omitted surgical opportunities for ovary preservation.

Aim: to present a clinical case of a teenage girl with giant ovarian cystadenoma complicated by hydronephrosis due to ureteral compression.

Case presentation. A female patient R., 17 years old, was admitted to the surgical department on 12.02.2025, with complaints of abdominal enlargement, abdominal pain lasting over 4 months, frequent urinal miction and algodismenorrhea. Medical history dated of January 2025 showed that imaging research methods performed in different organizations revealed a multilocular cyst of the abdominal cavity – a mucinous cystadenoma of the left ovary, sized 193×195×271 mm, complicated by hydronephrosis of the right kidney. Physical examination revealed a local abdominal pain in the umbilical region as well as increased abdominal volume. General blood test found signs of mild iron deficiency. Blood screening tests for serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and cancer antigen-125 (CA-125) levels allowed to exclude oncological pathology.

Results. Further surgical treatment was performed. On 17.02.2025, patient R. underwent laparoscopic cystectomy. The passage of urine quickly returned to normal after removal of obstruction cause. A follow-up ultrasound examination on the day 7 post-surgery showed that the pelvis of the right kidney was markedly decreased. The postoperative period was unremarkable. Patient R. was discharged on day 8 with improvement. Recommendations were provided.

Conclusion. A clinical case presented here demonstrates an opportunity for developing complication such as hydronephrosis related to bulky ovarian cyst in adolescents. The surgical treatment confirms that even in case of giant cysts, cystectomy along with preserving maximum volume of the ovarian tissue may be performed thereby allowing to exert reproductive function in the future. However, such surgical treatment option should be performed only with confidence in benign tumor origin and presence of viable ovarian tissue.



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