ORIGINAL ARTICLE
Introduction. The GDF9 (growth differentiation factor 9) and BMP15 (bone morphogenetic protein 15) genes encode oocyte‑specific growth factors that play a pivotal role in folliculogenesis and embryonic development. Polymorphic variants of these genes may be associated with the outcomes of assisted reproductive technologies.
Aim: to evaluate a potential association between polymorphic variants of the GDF9 and BMP15 genes and clinical efficacy of in vitro fertilization (IVF) programs in patients with anovulation-related infertility.
Materials and Methods. A prospective study examining 96 women with anovulatory infertility (mean age 30.5 ± 2.5 years) was carried out. Genotyping was performed as part of a genome‑wide study using Infinium Global Screening Array‑24 v3.0 chips (USA) on an iScan system (Illumina) according to the Infinium HTS Assay Guide. Six single nucleotide polymorphisms (SNPs) were analyzed: rs254286 and rs10491279 (GDF9); rs3810682, rs3897937, rs41308602, and rs58995369 (BMP15).
Results. Statistically significant associations were found between BMP15 polymorphic variants rs3810682, rs3897937, and rs58995369 and IVF outcomes. The heterozygous C/G genotype of rs3810682 was associated with reduced odds of IVF success (odds ratio (OR) = 0.212; 95 % confidence interval (CI) = 0.071–0.636; p = 0.003). Similar patterns were observed for the C/T genotype of rs58995369 (OR = 0.212; 95 % CI = 0.071–0.636; p = 0.004). For the rs3897937 polymorphism, the homozygous A/A genotype was associated with a markedly increased likelihood of pregnancy (OR = 7.000; 95 % CI = 2.703–18.129; p < 0.001), whereas the heterozygous A/G genotype was associated with decreased odds (OR = 0.083; 95 % CI = 0.028–0.247; p < 0.001). No statistically significant associations with IVF outcomes were detected for GDF9 polymorphisms (rs254286, rs10491279).
Conclusion. Polymorphic variants of the BMP15 gene (rs3810682, rs3897937, rs58995369) are associated with IVF outcomes in patients with anovulatory infertility and may serve as potential predictors of IVF success.
Aim: to compare the discriminative ability and calibration of nested-architecture machine learning (ML) models and the Fetal Medicine Foundation (FMF) algorithm for predicting early-onset (< 34 weeks) and late-onset (≥ 34 weeks) preeclampsia (PE) in the first trimester of pregnancy in Russian population.
Materials and Methods. with 23,247 singleton pregnancies was carried out. The biophysical sample comprised 22,230 observations, and the biochemical subsample included 7,581 observations. Nested ML models were developed: M0 (maternal characteristics) → M2 [(M0 + biophysical markers – mean arterial pressure (MAP) and uterine artery pulsatility index (UtAPI)] → M4 (M2 + biochemical markers – placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and pregnancy-associated plasma protein-A (PAPP-A)]. A comparison was made with the FMF algorithms – prior FMF risk (FMF prior) and posterior FMF risk (FMF posterior). Metrics included: AUC-ROC (Area Under the Receiver Operating Characteristic curve) with 95 % confidence interval (CI) calculated by the bootstrap method (n = 2000); the observed-to-expected ratio (O:E ratio); incremental value of biomarkers – change in C-statistic (ΔC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and sensitivity at fixed false-positive rates. Statistical significance of AUC differences was assessed using the DeLong test.
Results. The AUC of model M4 for early-onset PE (EOPE) was 0.972 (95 % CI = 0.947–0.991) compared with 0.951 for FMF posterior (p = 0.368); for late-onset PE (LOPE), the AUC was 0.871 (95 % CI = 0.833–0.906) versus 0.822 for FMF posterior (p = 0.009). After Platt scaling recalibration, the ML models demonstrated adequate calibration (O:E ≈ 1.0). FMF posterior demonstrates inadequate calibration for LOPE in the Russian population (O:E = 3.34; 95 % CI = 2.61–4.21), indicating 3.34-fold more LOPE cases than predicted by the model. Biophysical markers provided 4-fold greater incremental value for EOPE (ΔC = +0.029 vs. +0.007), while biochemical markers were more valuable for LOPE (ΔC = +0.020 vs. +0.001). For EOPE the UtAPI was a lead predictor (odds ratio (OR) = 3.28; 95 % CI = 2.68–4.70), for LOPE – previous PE (OR = 1.90; 95 % CI = 1.72–2.09).
Conclusion. ML models significantly outperform the FMF algorithm in discriminating late preeclampsia and provide substantially better calibration in Russian population. The inadequacy of the FMF algorithm for LOPE (O:E = 3.34 indicates 3.3-fold more LOPE cases than predicted) justifies the need for specialized models for this phenotype. Differential incremental value of biomarkers was established: biophysical markers (UtAPI) are critical for EOPE, biochemical markers (PlGF, sFlt-1) – for LOPE, supporting the concept of contingent screening.
Introduction. Prophylactic use of low-dose acetylsalicylic acid (ASA) is widely implemented in pregnant women at high risk for major obstetrical syndromes (MOS); however, the safety profile of the drug regarding fetal and neonatal outcomes remains a subject of ongoing scientific debate.
Aim: to conduct a comparative analysis of obstetric and perinatal outcomes following preventive ASA use in high-risk patients, while evaluating its efficacy in preeclampsia (PE) and fetal growth restriction (FGR) preventing and assessing safety of antenatal exposure on the fetus and neonate.
Materials and Methods. This retrospective case-control study enrolled 236 mother-infant pairs stratified as follows: main group consisted of pairs in which 136 patients at high risk for PE and/or FGR received 150 mg of ASA daily. This cohort was subdivided into two overlapping subgroups: 103 and 77 mothers predisposed to PE and FGR, respectively, including cases with combined risks. In control group, 100 pairs with general population risk profile not receiving ASA were enrolled.
Results. Preventive ASA therapy demonstrated high clinical efficacy, with incidence of FGR in target subgroup (n = 77) comprising 2.6 %, which corresponds to general population levels. In the at high PE risk (n = 103), the rate of its manifestation was 25.2 %, with all cases presenting exclusively as late-onset PE. No statistically significant differences were observed regarding obstetric blood loss volume or incidence of neonatal intraventricular hemorrhage, including cases of preterm birth. Notably, 6 cases of hypospadias were verified in male subgroup of the study cohort (7.0 % vs. 0,0 % in the control group; p = 0.088), which exceeds the standard population rate (0.2–0.8 %).
Conclusion. The initiation of low-dose ASA therapy within the recommended gestational window (12–16 weeks) in high-risk patients provides effective prevention against early-onset PE and FGR, without increasing hemorrhagic risks for either the mother or the fetus. However, the observed elevation in hypospadias incidence above the general population level suggests a potential vulnerability in urethrogenesis during the second trimester, thereby justifying a need for conducting further large-scale cohort studies.
REVIEW ARTICLE
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.
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.
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.
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.
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.
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.
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.
Luteinizing hormone (LH) activity plays a key role in regulating folliculogenesis, ovulation, and luteinization by determining the effectiveness of controlled ovarian stimulation (COS) protocols in assisted reproductive technologies (ART). LH stimulates androgen synthesis in theca cells serving as a platform for estrogen production in granulosa cells driven by follicle-stimulating hormone (FSH), and regulates receptor expression, oocyte meiotic maturation, and luteal phase formation. Current evidence indicates that a balanced combination of FSH and LH activity is essential for optimal follicular growth and full oocyte maturation. LH deficiency leads to decreased estradiol production, impaired steroidogenesis, and reduced fertilization outcomes. The addition of active LH-containing supplements improves treatment efficacy in women with hypogonadotropic hypogonadism, diminished ovarian reserve, ovarian hyporesponsiveness, as well as in older reproductive-age patients and those undergoing gonadotropin-releasing hormone antagonist protocols. The use of human menopausal gonadotropin and its highly purified form, as well as recombinant LH, enhances hormonal balance, improves oocyte and embryo quality, and reduces the risk of ovarian hyperstimulation syndrome. Incorporation of LH activity into COS regimens supports more physiological follicular maturation and a balanced steroid response. Optimization of LH dosing and timing, along with personalized therapy based on patient age, ovarian reserve, and genetic characteristics, increases ART efficacy, improves treatment outcomes, and ensures a safer and more predictable reproductive result.
The transcription factor Yin Yang 1 (YY1) is a multifunctional regulator of gene expression involved in a wide range of physiological and pathological processes. In recent years, increasing attention has been paid to its role in the human reproductive system; however, available data remain fragmented and require systematic analysis. This review summarizes current experimental and clinical evidence regarding YY1 expression and biological functions in both the female and male reproductive systems. In the female reproductive system, YY1 is involved in regulating folliculogenesis and oocyte maturation, early embryonic development, implantation, and placentation. Its role in modulating trophoblast invasiveness and immune properties, as well as in the formation of the maternal-placental interface, has been demonstrated. Dysregulation of YY1 expression is associated with gestational complications such as recurrent pregnancy loss and preeclampsia. A separate section of the review addresses the role of YY1 in the pathogenesis of gynecological malignancies, including ovarian, cervical, and endometrial cancers, where YY1 contributes to the regulation of tumor growth, invasion, cancer stem cell-related properties, as well as sensitivity to anticancer therapy. In the male reproductive system, YY1 plays a key role in spermatogenesis, maintenance of spermatogonial stem cell function, and meiotic progression. In addition, YY1 has been reported to play a role in the molecular mechanisms underlying prostate cancer progression and the development of resistance to apoptosis and pharmacological treatments. Overall, YY1 represents a central regulatory node in reproductive processes in both physiological and pathological conditions. Further investigation assessing YY1-related molecular mechanisms may facilitate development of novel diagnostic markers and targeted therapeutic strategies in reproductive medicine and oncogynecology.
Recurrent pelvic organ prolapse is a pressing issue in modern gynecology due to its high prevalence, considerable impact on quality of life as well as frequent need for repeat interventions. Despite improvements in surgical techniques and conservative treatment methods, recurrence rates after primary repair remain significant and complicate the choice of optimal management. The incidence of repeat treatment varies depending on the type of previous surgery and duration of follow-up. Conservative management includes pessary use and pelvic floor muscle training, which are appropriate for patients with moderate symptoms or contraindications to surgery. Repeat reconstructive procedures are technically demanding and require careful consideration of defect location, characteristics of prior interventions, and patient comorbidities. Revision surgery following sacrocolpopexy is especially challenging due to mesh fixation features and the risk of intraoperative complications. Management strategy is determined by multiple clinical factors, including prolapse severity, patient age, comorbidities, functional needs, and expected long-term outcomes. Individualized treatment improves therapeutic effectiveness and may reduce the odds for further surgical interventions. Continued accumulation of clinical data is essential for clarifying prognostic factors and improving practical management recommendations.
Endometrial receptivity is a key factor in successful embryo implantation and one of the most difficult-to-assess parameters in reproductive medicine. Despite the wide range of diagnostic approaches, their clinical effectiveness remains debated. This narrative review is based on analyzing publications indexed in PubMed/MEDLINE, Scopus, and Web of Science, focusing on systematic reviews, randomized studies, as well as prospective and retrospective cohort studies aimed at evaluating endometrial receptivity in in vitro fertilization programs. The review analyzes morphological functional, molecular, and integrative approaches, and compares their clinical value regarding implantation outcomes, clinical pregnancy, and live birth. It is shown that morphological and ultrasonographic parameters are characterized by limited prognostic value and high interindividual variability. Functional methods, including assessment of blood flow and uterine peristaltic activity, demonstrate a closer relation to implantation outcomes, although their results remain heterogeneous. Molecular and cellular markers in several studies show higher diagnostic accuracy, but this not accompanied by convincingly improved live birth rates. The most studied transcriptomic tests of endometrial receptivity demonstrate no superiority compared with standard embryo transfer timing in the general patient population. Therefore, none of the existing methods has sufficient prognostic accuracy for independent clinical use. A promising approach is development of integrative diagnostic models that combine clinical, functional, and molecular parameters, followed by validation in large prospective studies.
Introduction. The microbiome of the female reproductive tract is considered a potentially important determinant of fertility, endometrial receptivity, implantation, and assisted reproductive technology (ART) outcomes.
Aim: to summarize current evidence on association between the vaginal microbiome and ART outcomes, and to evaluate a potential role of probiotic interventions in restoring the microbial profile, considering differences between Lactobacillus species, diagnostic approaches, and clinical patient subgroups.
Materials and Methods. An analytical review of 73 publications issued in 2011–2026 was conducted using PubMed/MEDLINE, Springer Link, ScienceDirect, eLibrary, CyberLeninka, and Google Scholar databases. Differences between Gram staining with Nugent scoring, culture-based methods and MALDI-TOF, 16S rRNA gene sequencing, and shotgun metagenomics were taken into account.
Results. Lactobacillus-dominated profiles, particularly those enriched with L. crispatus, were more often associated with favorable reproductive outcomes. However, clinical interpretation depended on species- and strain-level composition, co-occurring taxa, community stability, hormonal status, endometrial condition, and the analytical method used. L. iners may be found in both stable eubiotic profiles and unstable or dysbiotic states. The origin of the endometrial microbiota and its dependence on the vaginal niche remain unresolved. Probiotics were generally well tolerated, but their effects on implantation, clinical pregnancy, and live birth were heterogeneous.
Conclusion. Microbiome profiling and probiotic administration cannot yet be recommended as universal components of ART programs. Standardized sampling and analytical protocols, contamination control, strain-specific approaches, and randomized trials with clinically meaningful reproductive endpoints are required.
Introduction. Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder in women of reproductive age associated with high cardiometabolic risk.
Aim: to analyze current data on the prevalence, developmental mechanisms, and clinical significance of cardiometabolic disorders in patients with PCOS, and to substantiate approaches to multidisciplinary prevention and follow-up care.
Materials and Methods. A narrative review of publications from 2017 to 2026 was conducted using PubMed/MEDLINE, ScienceDirect, Google Scholar, and eLibrary databases. For this, international clinical guidelines, systematic reviews, meta-analyses, randomized controlled trials, and clinically relevant cohort studies were prioritized.
Results. Cardiometabolic risk in PCOS is driven by a high prevalence of insulin resistance, dyslipidemia, arterial hypertension, and obesity. In clinical practice, assessment of glycemic status (preferably via an oral glucose tolerance test), lipid profile, blood pressure, and anthropometric parameters, rather than routine calculation of insulin resistance indices should be prioritized. The importance of comprehensive non-pharmacological prevention (diet, exercise, psychotherapeutic support) and the use of metformin or anti-obesity drugs according to indications is substantiated.
Conclusion. PCOS is associated with a high prevalence of cardiometabolic disorders driven by insulin resistance, visceral obesity, hyperandrogenism, and chronic inflammation, warranting a long-term multidisciplinary follow-up model with continuous prevention and pharmacotherapy when indicated.
Introduction. Endometriosis is a chronic multisystem disease associated with decreased quality of life, chronic pelvic pain, infertility, and a wide range of comorbid conditions. Despite the fact that laparoscopy has traditionally held a central place in the diagnosis and treatment of endometriosis, the current role of surgical intervention requires a differentiated assessment, taking into account disease phenotype, the severity of pain, reproductive plans, the risk of damage to ovarian reserve and the likelihood of recurrence.
Aim: to critically compare surgical, medical, and combined approaches to endometriosis treatment and to substantiate a stratified model of long-term patient management accounting for disease phenotype, pain profile, ovarian reserve, comorbidity, and reproductive plans.
Materials and Methods. A narrative literature review was performed by retieving relevant publixcxations found in PubMed/MEDLINE, Embase, Scopus, Web of Science, ScienceDirect, eLibrary.ru, CyberLeninka, and Google Scholar. The primary search window covered 2017–2025; earlier publications were included base on their methodological, historical, or clinical relevance. Eligible sources comprised systematic reviews, meta-analyses, randomized controlled trials, large cohort studies, and clinically relecant observational studies reporting surgical, medical, or combined endometriosis treatment, pain control, recurrence prevention, effects on fertility and ovarian reserve, as well as long-term therapy safety. The review was prepared in accordance to the SANRA criteria (Scale for the Assessment of Narrative Review Articles).
Results. Synthesis of current evidence indicates that surgery is effective for selected indications (large or symptomatic endometriomas, deep infiltrating endometriosis with obstructive manifestations, distorted pelvic anatomy, and certain infertility phenotypes) but guarantees no durable pain control or recurrence prevention. Long-term medical therapy (progestins, combined oral contraceptives, oral gonadotropin-releasing hormone antagonists with add-back therapy, and the levonorgestrel-releasing intrauterine system) provides clinically relevant pain reduction and lowers postoperative recurrence risk; progestogen regimens are associated with a lower need for reoperation and second-line therapy. Unlike repeated ovarian surgery, medical strategies do not involve direct surgical trauma to ovarian tissue; however, their effectiveness and safety depend on disease phenotype, treatment duration, contraindications, tolerability, and reproductive goals.
Conclusion. Surgical treatment remains important in cases of large or symptomatic endometriomas, pelvic anatomy disorders, obstructive complications, suspected malignancy, and certain infertility forms. The most reasonable approach is not to replace surgery with drug treatment, but rather a stratified model in which the sequence and scope of interventions are determined by patient's clinical profile and long-term goals of therapy.
Aim: to systematically evaluate the evidence on psychosocial stress impacting on the microbiocenosis of the female reproductive tract and to delineate the underlying pathogenetic mechanisms.
Materials and Methods. A comprehensive literature review was conducted across PubMed/MEDLINE, Google Academy, and eLibrary databases covering a 25-year period. Search terms for query included "stress," "vaginal microbiome/microbiocenosis/microflora," "cervical microbiome," and "uterine microbiome" in both Russian and English. Original studies, systematic reviews, and meta-analyses were included; animal experiments, conference abstracts, non-full-text publications, and off-topic articles were excluded.
Results. Chronic psychosocial stress activates the hypothalamic-pituitary-adrenal axis and the sympathoadrenal system, leading to hypercortisolemia and elevated catecholamine levels. Key pathogenetic mechanisms include Th1-to-Th2 (T-helpers 1/T-helpers 2) immune shift followed by consequently suppressed cell-mediated immunity, estrogen deficiency-driven reduction of vaginal epithelial glycogen, impaired glucose metabolism, and direct catecholamine-mediated enhancement of bacterial virulence and proliferation. In the lower reproductive tract, stress is an independent predictor of bacterial vaginosis, recurrent vulvovaginal candidiasis, genital herpes reactivation, and high-risk human papillomavirus (HPV) persistence with increased risk of cervical intraepithelial neoplasia and invasive cervical cancer. Stress also elevates susceptibility to sexually transmitted infections. In the upper reproductive tract, depression and anxiety are associated with increased incidence of pelvic inflammatory disease and reduced implantation success in assisted reproductive technology programs.
Conclusion. Psychosocial stress is an independent, modifiable risk factor for reproductive tract dysbiosis. Assessing psychosocial status should be integrated into clinical evaluation of women with inflammatory and dysbiotic conditions of the reproductive tract, and psychological intervention should be considered a component of comprehensive treatment strategies.
Introduction. The perimenopausal transition is accompanied by progressive decline in ovarian function, variability of sex steroid secretion, menstrual cycle disturbances, abnormal uterine bleeding (AUB), and vasomotor and psychoemotional symptoms. Despite age-related decline in fertility, a risk of unintended pregnancy remains in sexually active women of late reproductive age thereby emphasing a choice of effective and safe contraception as a clinically important task.
Aim: to analyze and summarize current literature assessing 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) use during the transition from contraception to menopausal hormone therapy (MHT) in perimenopausal women, focusing on contraceptive efficacy, endometrial protection, safety, tolerability, and its place among alternative strategies.
Materials and Methods. A narrative literature review in PubMed/MEDLINE, ScienceDirect, eLibrary, and Google Scholar databases was carried out. Publications addressing the use of the 52-mg LNG-IUS in late reproductive-age and perimenopausal women were included primarily assessing contraceptive efficacy, AUB control, endometrial protection during estrogen-containing MHT, safety, tolerability, and patient-oriented outcomes.
Results. The 52-mg LNG-IUS is a highly effective long-acting reversible contraceptive method with additional non-contraceptive benefits, including reduction of menstrual blood loss, treatment of heavy menstrual bleeding, and prevention of endometrial hyperplasia. In perimenopause, the system may simultaneously provide contraception and AUB control; when estrogen therapy is initiated, it may serve as a local progestogen component of MHT and protect the endometrium. This approach may be particularly relevant for women with contraindications to estrogen-containing contraception, a need for a long-term delivery method, and concomitant menstrual cycle disorders.
Conclusion. The 52-mg LNG-IUS may be considered a clinically relevant tool for transition from contraception to MHT in perimenopausal women. However, data on long-term oncological, cardiovascular, and metabolic outcomes remain heterogeneous. Chosing this strategy should be individualized according to age, bleeding pattern, endometrial status, risk profile, contraindications to alternative methods, and patient preferences.
Introduction. The development of artificial intelligence (AI) and machine learning methods opens up new opportunities for optimizing clinical and laboratory stages of assisted reproductive technology (ART) programs.
Aim: to evaluate the current level of efficiency, methodological quality, and implementation prospects of AI algorithms in the clinical and laboratory stages of ART programs.
Materials and Methods. A narrative literature review was conducted using PubMed/MEDLINE, eLibrary, and ScienceDirect databases covering the years 2016–2024 (additionally including fundamental 1996–2015 studies). The search was carried out by using Boolean operators: ("artificial intelligence" OR "machine learning" OR "deep learning") AND ("IVF" OR "assisted reproductive technology" OR "embryo selection"). A total of 60 publications containing verifiable quantitative algorithm performance metrics were included in the final analysis.
Results. AI use shows high accuracy in blastocyst segmentation and quality assessment (AUC = 0.86–0.91), as well as in predicting controlled ovarian hyperstimulation outcomes. However, most analyzed models are limited by single-center training datasets and a lack of external validation.
Conclusion. AI algorithms demonstrate high potential as decision support systems, but widespread implementation in ART practice requires prospective multicenter randomized controlled trials.
Preterm birth (PTB) remains one of the most important problems in modern obstetrics and neonatology and is a leading cause of perinatal morbidity and mortality. The most consistent evidence for vaginal progesterone efficacy has been obtained primarily in women with a singleton pregnancy and sonographic short cervical length, rather than in all high-risk pregnant women. This narrative review summarizes current data on the role of vaginal progesterone in PTB prevention, including pharmacological aspects, indications for use, clinical efficacy, contradictory evidence, practical recommendations, and cost-effectiveness. The review is based on 71 sources, including publications from 2019–2026 and key earlier randomized trials, meta-analyses, and clinical guidelines that are methodologically or clinically relevant to evaluating vaginal progesterone for PTB prevention. The most consistent evidence for vaginal progesterone use was obtained in women with singleton pregnancy and short cervical length (≤ 25 mm). In multiple pregnancy, efficacy appears to be limited to the subgroup of women with short cervical length. Evidence regarding vaginal progesterone efficacy in women with former PTB without cervical shortening remains contradictory. International guidelines generally support the use of vaginal progesterone in women with short cervix in singleton pregnancy. In case of shortening, cervical length screening followed by vaginal progesterone administration may be a cost-effective strategy when adapted to local healthcare conditions.
CLINICAL CASE
OHVIRA syndrome (Herlyn-Werner-Wunderlich syndrome) is a combination of unilateral renal agenesis and uterus didelphys with obstructed hemivagina, with populational prevalence comprising 0.1–3.8 %. In emergency gynecological practice, it typically manifests as spontaneous drainage of hematocolpos requiring conducting careful differential diagnosis with abnormal uterine bleeding. The optimal diagnostic methods include gynecological examination, magnetic resonance imaging, 3D ultrasonography, and endoscopic studies.

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