Introduction. To stop obstetric bleeding, organ-preserving surgical methods are used, one of which is ligation of three-layered uterine vessels. The effectiveness of organ-preserving methods comprises up to 94 %. The function of any organ depends on proper blood supply, and therefore the state of the reproductive function in women undergone organ-preserving operations is an object for further investigation.

Aim: study of blood flow in the uterus and ovaries after ligation of three pairs of uterine vessels in women with pathological blood loss.

Materials and Methods. A prospective controlled study was conducted that included main group (41 patients after ligation of three pairs of uterine vessels due to pathological blood loss during operative delivery) and control group (25 women after cesarean section without pathological blood loss and ligation of three pairs of uterine vessels). Doppler study of uterine arteries and central ovarian blood flow was performed by assessing angle-independent parameters – pulsation index (PI), resistance index (RI). Volumetric blood flow in uterine arteries and uterine arterial perfusion index were calculated.

Results. The average age of patients in main and control group was 30.0 ± 0.84 years and 25.96 ± 0.99 years (p = 0.003), respectively. The volume of blood loss in main vs. control group was 2.7 times greater (p < 0.001). Assessing PI and RI in the uterine arteries showed highly resistant blood flow, PI and RI significantly increased by 1.6 and by 1.4 times, respectively, compared with control group (p < 0.001).Calculation of volumetric blood flow in the uterine arteries in patients from main group showed a decline by 18.2–22.6 % compared to control group. It resulted in decreased arterial perfusion index of the uterus in group of patients underwent organ-preserving operations for pathological blood loss by 30.2 %. PI and IR magnitude in intraovarian blood flow turned out to increase by 2 and 1.4 times, respectively (p < 0.05).

Conclusion. The identified highly resistant blood flow in the uterus and ovaries may further result in anovulatory cycle formation due to impaired organ hemodynamics able to lead to developing ovarian insufficiency.

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.

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.

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.

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.

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.

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.

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.

Endocrine-disrupting chemicals (EDC) represent a broad class of exogenous substances capable of interfering with the normal functioning of the hormonal system and exerting profound effects on female reproductive health. One of the most vulnerable targets for EDC action are ovaries, where they initiate a cascade of pathophysiological processes. This review systematizes current data on the key mechanisms of EDC-induced ovarian toxicity, including hormonal dysregulation, oxidative stress, apoptosis, epigenetic modifications, and disruption of intercellular signaling. It has been demonstrated that chronic exposure to the agents such as bisphenol A, phthalates, polycyclic aromatic hydrocarbons, and dioxins leads to impaired folliculogenesis, ovarian reserve depletion, and premature ovarian insufficiency. Furthermore, we also discuss epigenetic inheritance mechanisms through which EDC may exert long-term effects on reproductive function across generations. Special attention is paid to therapeutic strategies aimed at mitigating EDC-induced damage, including the use of antioxidants, signaling pathway modulators, and epigenetic regulators. Case studies are presented, which illustrate the global scale of environmental EDC contamination and their bioaccumulation in biological systems. The collective evidence underscors an urgent need for a multidisciplinary approach to risk assessment as well as development of preventive and therapeutic interventions to alleviate EDC impact on women’s reproductive health and to safeguard the reproductive potential of future generations.

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.

The prevalence of prostate diseases primarily benign prostatic hyperplasia (BPH) and prostate cancer (PC) has been progressively increasing with age being related to dramatic change in hormonal balance. Researchers and clinicians adhere to traditional understanding in developing BPH pathogenesis underlying no prominent achievements in the disease prevention and treatment. The ongoing search for gaining insights into the mechanisms behind development of these pathologies lies beyond assessing progesterone as one of the key hormones that plays an crucial role in the prostate gland functioning that has not been studied in this regard for many years. Until now, it is believed that progesterone is an exclusively "female hormone", despite that the first line therapy for BPH relies on using drugs lowering activity of enzyme 5α-reductase involved in testosterone-to-dihydrotestosterone transformation, wherein progesterone serves this function in male body under normal in vivo settings. In fact, such drugs are presented by chemical analogues of progesterone bearing minor changes in its molecule structure. In other words, to correct the pathophysiological aspects, it is necessary to proceed from the physiological basics. Presuming this, international research data available on the pathogenesis of BPH and PC as well as the effectiveness for various approaches to pathognomonic therapeutic approaches to prevent them have been analyzed.

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.

Neonatal human herpesvirus type 6 (HHV-6) infection is an extremely rare disease. HHV-6 is a unique virus because it is able to integrate into human chromosomes to be further transmitted vertically from parent to offspring. In humans, HHV-6 is associated with a wide range of clinical manifestations and, in children, may present as roseola infantum, febrile seizures, aphthous stomatitis, mononucleosis-like syndrome, or fever of unknown origin. This article reports a rare case of congenital HHV-6 infection in a newborn. To date, both Russian and international publications provide very limited descriptions of such cases, which, in our opinion, reflects a significant knowledge gap among neonatologists regarding this condition. We discuss the clinical forms of HHV-6 infection in neonates, rare case presentations, and current approaches to diagnosis and treatment.