Original research publications

Differentiating sarcoidosis lesions from metastatic lymph nodes is a well-known clinical challenge, particularly in patients with malignancy in whom sarcoid lesions may mimic nodal metastases on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT). We report a 75-year-old woman with concurrent sarcoidosis and vulvar squamous cell carcinoma in whom 18 F-FDG PET/CT demonstrated avid uptake in enlarged lymph nodes throughout the mediastinum, pulmonary hilum, upper abdomen, and right groin. 18 F-fluorothymidine ( 18 F-FLT) PET/CT performed 7 days later showed FLT uptake comparable to FDG uptake in the right groin lymph node (FDG SUV max 5.5, FLT SUV max 5.8), which was subsequently confirmed as a metastatic node at histopathology, whereas the mediastinal lymph nodes showed markedly weaker FLT uptake relative to FDG (FDG SUV max 11.5, FLT SUV max 4.5) and were considered compatible with sarcoidosis on the basis of the patient's known sarcoid involvement and stability on follow-up imaging over 385 days. This case illustrates that the combination of 18 F-FDG and 18 F-FLT PET/CT may aid in distinguishing sarcoid lesions from metastatic lymph nodes in patients with concurrent sarcoidosis and malignancy.

Genitourinary syndrome of menopause (GSM) is a chronic hypoestrogenic condition characterized by diffuse vulvovaginal pallor, epithelial thinning, loss of rugae, and mucosal atrophy, often accompanied by genitourinary symptoms such as dryness, dysuria, urgency, and dyspareunia. Because many vulvar dermatoses share overlapping symptoms with GSM, accurate diagnosis relies heavily on careful clinical evaluation, with particular emphasis on lesion morphology, distribution, and associated mucocutaneous findings. This review provides a practical, morphology-driven framework for distinguishing GSM from common inflammatory, infectious, and neoplastic vulvar conditions. Given the high degree of diagnostic overlap between vulvar dermatoses and GSM, a structured approach incorporating targeted history, focused physical examination, and timely biopsy when indicated is essential. Referral to dermatology or a vulvar specialist is recommended in cases of diagnostic uncertainty, refractory or multisite disease, or scarring or functional impairment or when escalation to systemic or advanced therapies is required. This approach aims to improve diagnostic accuracy, reduce misclassification as GSM, and facilitate earlier, targeted treatment of vulvar dermatoses.

Anti-Müllerian hormone (AMH) is a reliable biomarker for assessing ovarian reserve, offering insight into the quantity of a woman's remaining oocyte pool. As AMH levels naturally decline with age, establishing accurate reference values is crucial for fertility assessment and reproductive planning. While existing nomograms predominantly focus on infertile populations or small cohorts, the current study presents a comprehensive, population-based analysis of AMH levels in 5,230 women aged 25 to under 45 years. Serum samples were obtained through a central laboratory in a large tertiary hospital (Sheba Medical Center) which processes AMH tests collected primarily in the community. This unique setting provides a broadly representative sample of women from a community-based population. Utilizing these community-based serum samples measured using the Elecsys Cobas AMH assay; this cross-sectional study developed age-specific AMH percentiles and z-scores using the general additive model for location, scale and shape (GAMLSS). Participants were randomly split into a learning group ( n = 4,000) and a validation group ( n = 1,230), with similar median age (34.3 vs. 34.2 years, p = 0.499) and AMH (1.83 vs. 1.85 ng/mL, p = 0.584) levels. Median AMH values demonstrated a clear age-dependent decline, ranging from 3.03 ng/mL at age 25 to 0.31 ng/mL at age 44. The generated reference chart enables interpretation of AMH results in relation to age-matched peers, enhancing the clinical utility of AMH testing for counselling and decision-making in both individual and public health contexts. Importantly, this study addresses a gap in current literature by including a community-based population and avoiding the selection biases inherent in studies limited to women with infertility or polycystic ovary syndrome. The mean z-score in the validation group was approximately zero, confirming the model's robustness. These results reinforce the value of AMH as a tool for fertility assessment, while highlighting variability in AMH across populations and emphasising the need for standardised reference ranges. The newly established percentiles may support timely fertility preservation decisions and inform public health strategies aimed at fertility awareness in reproductive-aged women. As AMH testing becomes increasingly accessible, age-specific interpretation using robust population data will become essential in tailoring personalised reproductive care.

We presented a rare case of we reported a case of recurrent vulvar angiomyofibroblastoma (AMFB). The objective is to highlight the unique image findings in the rare circumstance. A 33-year-old woman presented with a pedunculated painless mass on the right vulva for two months. Tumor excision was performed, and the pathological examination revealed AMFB. One year after the surgery, pelvic CT revealed a small irregular enhancing soft tissue lesion in the right vulva, suggesting a recurrent tumor. Four years after the initial surgery, pelvic MRI revealed a large heterogeneous tumor in the right vulva, measuring 6.1 × 4.8 × 2.8 cm, which displayed hyperintensity on T2-weighted imaging (T2WI) and significant enhancement on post-contrast imaging. DWI/ADC demonstrated a heterogeneous signal intensity with evidence of mild diffusion restriction. Excision was performed and pathological examination revealed recurrent AMFB. The patient has remained free of recurrence for four years following the second surgery. In the rare vulvar AMFB, regular monitoring of tumor appearance by MRI is important for recurrent patients concerned about undergoing repeated surgeries.

Polyendocrine Metabolic Ovarian Syndrome (PMOS), formerly referred to as polycystic ovary syndrome (PCOS), is an intricate endocrine disorder, defined by a constellation of hormonal, metabolic, and reproductive irregularities. Vitamin D deficiency and increased levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have been implicated in the pathogenesis of PMOS. Although vitamin D deficiency and low-grade inflammation have each been associated with PMOS, the relationship between vitamin D status and circulating inflammatory cytokines remains incompletely characterized. Thus, this study aimed to investigate the association of Vitamin D and inflammatory interleukins believed to play a key role in the pathogenesis of PMOS. The study involved 94 participants divided into two groups: 44 PMOS patients and 50 healthy controls. Age and BMI were recorded for each patient and plasma levels of Vitamin D, anti-Müllerian hormone (AMH), IL-6, and IL-8 were measured and compared between the two groups using the Enzyme-Linked Immunosorbent Assay. AMH ( p < 0.02), IL-6 ( p < 0.001) and IL-8 ( p < 0.001) levels were significantly higher in PMOS patients than in controls. Lastly, vitamin D levels were found significantly lower in PMOS patients (18.59 ng/mL) than in controls (37.95 ng/mL; p < 0.001). However, no significant correlation was found between IL-6, IL-8 and Vitamin D. Women with PMOS characterized by lower vitamin D concentrations alongside higher AMH, IL-6, IL-8, and BMI compared to healthy controls. Larger longitudinal and prospective interventional studies are required to clarify causality and determine if vitamin D supplementation improves clinical outcomes.

Neuropsychiatric conditions such as depression, anxiety, and stress-related disorders are increasingly associated with Polycystic Ovary Syndrome (PCOS). Evidence suggests that these conditions are not only linked to the metabolic features of PCOS but also share common underlying mechanisms, including hormonal imbalance, neuroendocrine dysfunction, chronic inflammation, and epigenetic changes. Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) regulation, may act as important links between endocrine abnormalities and changes in brain function. In this review, we summarize current evidence connecting PCOS with psychiatric disorders through disruptions in the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes, neurotransmitter imbalance, and metabolic dysregulation. Altered activity of DNA methyltransferases and locus-specific methylation changes in stress-responsive genes, including FKBP5, have been associated with dysregulated HPA function. Similarly, histone-modifying enzymes such as histone deacetylases (HDAC1/2) and enhancer of zeste homolog 2 contribute to transcriptional changes in genes involved in synaptic plasticity and neuroendocrine regulation under conditions of hyperandrogenism and insulin resistance. In addition, epitranscriptomic regulation via N 6 -methyladenosine (m6A) modification, mediated in part by fat mass and obesity-associated protein (FTO), influences neuronal activity of gonadotropin-releasing hormone and neurotransmitter signaling. Dysregulated ncRNAs, including microRNAs (miR-34a, miR-155, miR-93, and miR-221) and long ncRNAs (XIST, H19, and MALAT1), further connect inflammatory and metabolic disturbances with neuronal function. Therefore, this review links PCOS to psychiatric disorders through alterations in the HPG and HPA axes, neurotransmitter imbalance, metabolic dysfunction, and epigenetic reprogramming. We further propose an integrated neuroendocrine-epigenetic framework to explain psychiatric vulnerability in PCOS and discuss future directions for precision-targeted therapeutic strategies.

The widespread use of aspartame has raised increasing health concerns, particularly regarding its potential endocrine-disrupting effects and a possible association with polycystic ovary syndrome (PCOS), a condition marked by endocrine and metabolic abnormalities. This study systematically investigated the molecular mechanisms by which aspartame may contribute to PCOS pathogenesis using a network toxicology approach. A total of 281 common targets between aspartame and PCOS were identified. Protein-protein interaction network analysis and five topological algorithms revealed 20 hub targets significantly enriched in pathways such as endocrine resistance, TNF signaling, and progesterone-mediated oocyte maturation. Eight of these targets showed significant differential expression in PCOS patients. Weighted gene co-expression network analysis (WGCNA) further demonstrated that several of these hub targets are embedded in co-expression modules positively associated with PCOS phenotypes. Transcription factor prediction indicated that these targets are primarily regulated by FOS and JUN. Molecular docking showed favorable binding affinities between aspartame and both transcription factors. Subsequent molecular dynamics simulations supported the dynamic stability of aspartame binding to FOS and JUN. These findings suggest that aspartame may contribute to PCOS by modulating FOS- and JUN-mediated transcriptional programs, thereby disrupting biological pathways related to endocrine regulation and inflammation. Collectively, this study reveals a potential mechanism by which aspartame mediates PCOS and offers novel insights for toxicological assessment of food additives.

Polycystic Ovary Syndrome (PCOS) is a complex hormonal disorder that affects women of reproductive age globally. It is marked by hormonal imbalance, ovarian dysfunction, and metabolic problems, which may lead to serious health complications. Getting diagnosed early is crucial to detecting PCOS, with abdominal ultrasound being the most commonly used imaging modality. The conventional way of diagnosing PCOS relies on manual image assessment, which is time-consuming and can vary from person to person. To address existing limitations, this study proposes two automated PCOS classification frameworks based on deep feature fusion technique. Deep features were extracted from two complementary deep learning models, ResNet-18 and GoogLeNet, and fused to form a unified representation of ovarian characteristics. Then, the fused features were classified using two strategies: (i) an ensemble framework where AdaBoost was the meta-learner, and (ii) a lightweight custom classification head. The frameworks proposed in this study were evaluated against existing state-of-the-art approaches and demonstrated superior performance. The ensemble model achieved an accuracy of 97.36% with a training time of 16.44 s, while the custom classification head attained a higher accuracy of 99.19% with a reduced training time of 13.31 s. The proposed frameworks offer high accuracy and reduced training time for PCOS diagnosis. By integrating deep feature fusion with ensemble and lightweight classification approaches, this study provides an efficient and reliable solution that can support clinical decision-making and facilitate early PCOS diagnosis.

Polycystic ovary syndrome (PCOS) has been associated with adverse pregnancy outcomes, although reported risks vary across studies. Metabolic heterogeneity within PCOS may contribute to this variability. Dysglycemia during pregnancy may identify a subgroup at increased obstetric risk. The study aims to evaluate whether dysglycemia is associated with preeclampsia and other adverse pregnancy outcomes among individuals with PCOS. We performed a secondary analysis of the prospective Fatty Liver in Pregnancy (FLIP) cohort ( n = 1,321). PCOS was defined by chart review of the electronic health record. Dysglycemia was defined as current or prior gestational diabetes, abnormal glucose tolerance testing, hemoglobin A1c > 5.7% during pregnancy, or pregestational diabetes. Participants were categorized as PCOS with dysglycemia ( n = 36), PCOS without dysglycemia ( n = 44), or non-PCOS controls ( n = 1,238). The primary outcome was preeclampsia. Secondary outcomes included gestational hypertension, preterm birth, abnormal neonatal weight, and neonatal hypoglycemia. Multivariable logistic regression adjusted for maternal age and body mass index. Among 80 individuals with PCOS, 45% had evidence of dysglycemia. Preeclampsia occurred in 33% of those with PCOS and dysglycemia, 7% of those with PCOS without dysglycemia, and 12% of controls ( p = 0.005 for PCOS with dysglycemia versus controls). In adjusted analyses, PCOS with dysglycemia was associated with preeclampsia (odds ratio [OR] 2.9; 95% confidence interval [CI]: 1.4-6.1), whereas PCOS without dysglycemia was not (adjusted odds ratio [aOR] 0.53; 95% CI: 0.16-1.73). PCOS with dysglycemia was also associated with increased preterm birth (OR: 2.3; 95% CI: 1.04-5.14), abnormal neonatal weight (OR: 2.87; 95% CI: 1.36-6.10), neonatal hypoglycemia (OR: 2.8; 95% CI: 1.38-5.77), and any adverse pregnancy outcome (aOR: 4.49; 95% CI: 1.94-10.40). In this prospective cohort, dysglycemia was associated with higher rates of hypertensive and metabolic pregnancy complications among individuals with PCOS. These findings suggest that coexisting dysglycemia may contribute to heterogeneity in obstetric risk among individuals with PCOS and warrant confirmation in larger studies.

Polycystic ovary syndrome (PCOS) is a multifactorial endocrinological disorder with a substantial genetic component. However, the role of genes involved in follicular development and androgen regulation remains incompletely understood, particularly in South Indian populations. This study aimed to evaluate how variations in the ERBB4 and SHBG genes affect PCOS risk. A hospital-based case-control study was conducted among 400 South Indian women, comprising 200 women with PCOS and 200 age-matched healthy controls. Genomic DNA was extracted to study SNPs at ERBB4 (rs2178575 and rs1351592) and SHBG (rs1799941 and rs727428) using ARMS-PCR genotyping. The study compared genotype and allele frequencies between cases and controls while assessing their associations with allelic, homozygous, heterozygous, dominant, recessive, and over-dominant genetic models. Genotyping accuracy was confirmed by re-genotyping and Sanger sequencing of a subset of samples. The ERBB4 rs2178575 polymorphism demonstrated a significant association with PCOS, as the AA genotype and A allele combination increased risk across all three genetic models, including homozygous, recessive, and allelic models. The ERBB4 rs1351592 variant was associated with 3-fold higher risk of PCOS in heterozygous and GC carriers. The SHBG rs1799941 polymorphism showed a significant link to PCOS through its effects on heterozygous and allelic states, whereas rs727428 displayed no significant connection due to its monomorphic distribution. These findings suggest that polymorphisms in ERBB4 and SHBG may contribute to PCOS susceptibility in South Indian women in a locus- and model-specific manner, revealing the intricate genetic structure that defines this medical condition.

This review evaluates whether pregestational prediabetes identifies women at risk of subsequent gestational diabetes mellitus (GDM) and examines its association with maternal and offspring outcomes. Prediabetes is common in women of reproductive age and often precedes GDM. The risk factors for prediabetes and GDM are similar, such as higher BMI, polycystic ovary syndrome, advancing age, and genetic susceptibility. Both conditions denote underlying insulin resistance with limited beta-cell reserve. Preliminary evidence indicates that women with pregestational prediabetes have a higher likelihood of developing GDM. Risk rises progressively with increasing glycemia. Prediabetes is also associated with modestly increased risks of hypertensive disorders of pregnancy and preterm birth, though associations with cesarean delivery, macrosomia, and neonatal outcomes are inconsistent. Glycated hemoglobin in the prediabetes range early in pregnancy is associated with a higher risk of progression to type 2 diabetes than GDM diagnosed at 24-28 weeks. These observations support the view that pregestational prediabetes may emerge as an early marker of metabolic risk with implications extending beyond pregnancy. Prediabetes represents a state of increased metabolic risk in women planning pregnancy. It lies along a dysglycemic continuum linking preconception glycemic status to GDM and future diabetes. Incorporating glycemic assessment into preconception care may aid GDM risk stratification. However, the evidence is still evolving, and prospective studies are needed to define the role of pregestational prediabetes in predicting maternal, fetal, and long-term outcomes.

The International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical carcinoma provides a globally accepted framework that guides treatment decisions and prognosticates disease. The 2018 update incorporates imaging and pathologic findings into the schema, reflecting advances in diagnostic modalities and improving stage accuracy. Despite these improvements, significant information gaps remain, and assigning an accurate FIGO stage may be challenging in several situations faced by pathologists. This article uses real world case examples for various clinical situations and presentations of cervical carcinoma, focusing on a practical approach and providing strategies to ensure accurate and clinically relevant FIGO stage designation.

Cervical cancer is a virus-dependent gynaecologic malignancy and according to GLOBOCAN 2022 cervical cancer is the fourth frequent women cancer in all over the world. Despite this frequency it is rarely seen in developed countries because of the enforcement of cervical screening programmes with human papillomavirus (HPV) test and Pap test called cotest. The burden of this women cancer is high despite the implementation of HPV-based vaccines and screening strategies, could nearly eliminate cervical cancer as a public health problem. A retrospective analysis was conducted using non-16/18 high risk human papilloma virus (HR-HPV) genotyping data and cycle threshold (ct) values from women aged ≥18 years that underwent cervical sampling during gynaecological outpatient clinic at a tertiary centre in Turkey, between January 2022 and December 2023. The most frequently detected genotypes were HPV52 ( n = 24), HPV31 ( n = 23), HPV51 ( n = 22) and HPV56 ( n = 22). On the other hand in cervical intraepithelial neoplasia 3 (CIN3) cases, with combinations involving HPV51, HPV52, HPV59, HPV66 and HPV31 commonly detected. Median minimum patient-level Ct values were 22.0 (Interquartile range-IQR 8) in chronic cervicitis, 19.0 (IQR 10) in CIN1, 17.0 (IQR 8) in CIN2 and 19.0 (IQR 7) in CIN3. To the best of our knowledge, there are limited data about cycle threshold values in prediction of viral load. These region-specific, genotype-resolved data may inform extended-genotyping-based risk stratification and support ongoing surveillance of non-16/18 HR-HPV patterns within HPV-based screening programs. Hence this study opens a new perspective in this era.

In women with polycystic ovary syndrome (PCOS), IVF/ICSI outcomes may be influenced by systemic inflammation (neutrophil-to-lymphocyte ratio, NLR) and by sperm preservation method. We retrospectively studied 276 first eligible autologous PCOS IVF/ICSI cycles. NLR was dichotomized at 2.6 (low n = 136; high n = 140), whereas adjusted models used continuous NLR after exploratory spline assessment showed no convincing nonlinearity. Clinical pregnancy was defined cumulatively from the index retrieval cycle, including fresh or frozen transfer(s) derived from that cycle. Male-factor/semen characteristics were summarized by sperm method. Multivariable logistic regression evaluated cumulative clinical pregnancy in all cycles and an exploratory composite adverse pregnancy/neonatal outcome among 144 clinical pregnancies. Sensitivity analyses repeated the adjusted models using the dichotomized high-versus-low NLR grouping. Cumulative clinical pregnancy was lower with high versus low NLR (42.9% vs 61.8%; p = 0.002). Among clinical pregnancies, the exploratory composite adverse outcome was more frequent with high versus low NLR (58.3% vs 27.4%; p < 0.001). In adjusted analyses, each 1-unit increase in NLR was associated with lower odds of cumulative clinical pregnancy (aOR 0.71, 95% CI 0.53-0.95; p = 0.023) and higher odds of the exploratory composite adverse outcome (aOR 2.32, 95% CI 1.44-3.74; p < 0.001). Sensitivity models using dichotomized NLR were directionally consistent for cumulative clinical pregnancy (high vs low NLR: aOR 0.52, 95% CI 0.31-0.86; p = 0.011). Sperm preservation method was not independently associated with either outcome, and NLR × sperm interaction terms were not significant. Exploratory ROC analysis for the pregnancy cohort showed modest discrimination (AUC 0.67, 95% bootstrap CI 0.57-0.76); the Youden-derived cutoff of 3.16 yielded sensitivity 53.4% and specificity 84.9%. Higher baseline NLR was associated with lower cumulative clinical pregnancy and higher subsequent obstetric/neonatal risk in PCOS IVF/ICSI cycles. After accounting for baseline covariates and male-factor differences, fresh versus frozen ejaculated sperm was not independently associated with either outcome in this analysis. The ROC-derived cutoff should be viewed as exploratory only.

Polycystic ovary syndrome (PCOS) is a highly prevalent and phenotypically diverse endocrine disorder in which insulin resistance (IR) serves as a central molecular driver of major metabolic and reproductive complications, including infertility, obesity, and increased long-term cardiovascular risk. This review examines the complex pathophysiology of PCOS, emphasizing how chronic systemic low-grade inflammation, gut microbiome dysbiosis, and oxidative stress interact to worsen hyperinsulinemia and hyperandrogenemia. It also highlights the clinical value of emerging diagnostic and prognostic biomarkers to improve risk stratification and patient management. Systemic biomarkers, such as pro-inflammatory cytokines, circulating endotoxemia arising from increased intestinal permeability, and epigenetic regulators including miR-146a, may provide prognostic insight into the trajectory of metabolic deterioration. In parallel, endometrial biomarkers, including the glucose transporter GLUT4, implantation-associated genes such as HOXA10, and inflammatory mediators like TNF-α, can support evaluation of impaired uterine receptivity, prediction of assisted reproductive technology (ART) outcomes, and stratification of miscarriage risk. By mapping key interactions within the gut-immune-metabolic axis and detailing localized endometrial dysfunction, this review proposes a framework for integrating targeted biomarker profiling into clinical practice to enable personalized, biomarker-informed interventions aimed at restoring fertility and metabolic health in patients with PCOS.

PCOS is frequently associated with metabolic disturbances, including a high prevalence of insulin resistance and compensatory hyperinsulinemia, which can impair reproductive outcomes. Previous evidence indicates that combining myo-inositol and D-chiro-inositol in a specific 3.6:1 ratio may support ovarian physiology and reproductive performance in women with PCOS. This study aimed to evaluate whether taking a 3.6:1 MYO:DCI inositol-based supplement enriched with antioxidants for at least 1 month prior to controlled ovarian stimulation could improve IVF-ICSI outcomes. A retrospective observational cohort study was conducted, including 92 women diagnosed with PCOS according to the Rotterdam criteria. Patients were allocated to 2 groups: those who used the MYO:DCI 3.6:1 antioxidant-containing supplement (Group 1) and those who followed conventional supplementation (Group 2). Outcomes assessed included ovarian response, fertilization rates, blastocyst development and pregnancy results. The number of retrieved oocytes (21.5 in Group 1 vs. 20.7 in Group 2; p = 0.56) and the metaphase II oocyte rate (72.06% in Group 1 vs. 71.23% in Group 2; p = 0.68) were comparable between both groups. Notably, Group 1 achieved higher fertilization rates (77.66% vs. 71.61%; p = 0.0314) and a lower proportion of cycles without at least one good-quality blastocyst to transfer (4.35% vs. 17.39%; p = 0.0450). In addition, both clinical and ongoing pregnancy rates were significantly improved in the supplemented group (54.39% vs. 42.65%; p = 0.0203; 45.61% vs. 36.76%; p = 0.0033). This observational pilot study suggests that a pre-treatment with 3.6:1 MYO:DCI ratio and antioxidant-based supplement taken for at least 1 month prior to ovarian stimulation may improve oocyte quality and increase pregnancy rates. These findings, while promising, require confirmation in larger prospective trials. Polycystic ovary syndrome is a common condition that can make it harder for some women to become pregnant. One reason is that the body may not use insulin properly, which can affect how eggs develop in the ovaries. Certain natural substances called myo-inositol and D-chiro-inositol help the body manage insulin. Previous research suggests that taking them together in a specific balance may support fertility. In this study, we looked at whether taking a supplement containing these two substances in a 3.6 to 1 balance, along with antioxidants, for at least 1 month before fertility treatment could improve results. We studied 92 women with polycystic ovary syndrome who were undergoing treatment to stimulate the ovaries and collect eggs for assisted reproduction. Half took the supplement being tested, while the other half received standard supplementation. Both groups produced a similar number of mature eggs. However, the women who took the study supplement had higher fertilization rates and were less likely to finish treatment without at least one good-quality embryo. They also had higher rates of pregnancy that continued beyond the early weeks. These results suggest that taking this supplement before reproductive assisted treatment may improve the chances of pregnancy in women with polycystic ovary syndrome.

The purpose of the study is to evaluate morbidity, mortality, one-year lethality, and desolation of patients with cervical cancer in the Osh Oblast of the Kyrgyz Republic. The data about patients with cervical cancer in 2010-2023 was included in the study. The average value of morbidity of cervical cancer in the Osh region of the Kyrgyz Republic (over 14 years) made up to 10,3 ±3,6%000. The growth rate of indicator of morbidity of cervical cancer was 51,2%. The increase in mortality from cervical cancer was unsatisfactory in terms of the onco-gynecological service from 0.3%000 in 2010 to 5.3%000 in 2023. The growth rate was very high, exceeding 1 600%. The improvement and refinement of comprehensive therapy of patients with cervical cancer was evidenced by decrease of one-year mortality from 41.0% to 13.0%. The rate of decline was 68.3%. The positive trend is also observed in the rate of desolation of patients with cervical cancer, which decreased from 62.0% to 24.0%, as result of increased number of patients with early stages of the disease in the Osh region. The rate of desolation of patients with cervical cancer was 61.3%. The results of the study can be used to formulate proposals improving the organization of medical care support for patients with cervical cancer, as well as for formation of regional projects or departmental target programs. Цель исследования — оценить заболеваемость, смертность, одногодичную летальность и запущенность при раке шейки матки в Ошской области Кыргызской Республики. В исследовании использованы данные больных раком шейки матки по Ошской области Кыргызской Республики за 2010—2023 гг. Среднее значение показателя заболеваемости раком шейки матки в Ошской области Кыргызской Республики (за 14 лет) составило 10,3±3,6%000. Темп прироста показателя заболеваемости составил 51,2%. Неудовлетворительным в отношении онкогинекологической службы в данном регионе республики явился рост показателя смертности при раке шейки матки: в динамике он имел тенденцию к росту с 0,3%000 в 2010 г. до 5,3%000 в 2023 г. Темп прироста составил более 1600%. Свидетельством улучшения и совершенствования комплексной терапии больных раком шейки матки стало уменьшение показателя одногодичной летальности с 41,0 до 13,0%. Темп убыли составил 68,3%. Положительная динамика отмечена по показателю запущенности: в динамике значение уменьшилось с 62,0 до 24,0% что является результатом увеличения числа больных раком шейки матки на ранних стадиях в Ошской области Кыргызской Республики. Темп убыли показателя запущенности составил 61,3%. Результаты исследования могут быть использованы для формирования предложений по совершенствованию организации оказания медицинской помощи больных раком шейки матки и при формировании региональных проектов или ведомственных целевых программ.

Achieving optimal brachytherapy coverage for bulky cervical tumors (>30 cc) remains challenging, and the ideal treatment approach is unclear. This study describes real-world tumor volume response, brachytherapy dose delivery, and toxicity in patients treated with an INTERLACE-style induction chemotherapy regimen followed by chemoradiation and MRI-guided adaptive brachytherapy. This retrospective, two-institution cohort included eight patients with locally advanced cervical cancer treated with weekly carboplatin/paclitaxel induction chemotherapy followed by cisplatin-based chemoradiation and MRI-guided brachytherapy. All three serial tumor measurements (at diagnosis, after induction chemotherapy, and after chemoradiation/before brachytherapy) were obtained by pelvic MRI. Gross tumor volumes (GTV) were contoured by the treating radiation oncologist; organ-at-risk volumes were delineated by treating physicians. FIGO stage was IIIC1 in 6 patients, IIA in 1, and IB3 in 1. Five patients (62.5%) were PD-L1 positive. Seven patients received tandem-and-ovoid brachytherapy and one received a Syed-Neblett interstitial implant. Median GTV was 88.3 cc (range 18-370) at diagnosis, 15.3 cc (range 0-187.1) after induction chemotherapy, and 2.2 cc (range 0-11.5) after chemoradiation. Median per-patient GTV reduction was 70% (range, 45-100%) after induction chemotherapy alone and 97% (range 74-100%) by completion of chemoradiation. Seven patients presented with bulky disease (>30 cc); three remained bulky after induction chemotherapy and none after chemoradiation. Median high-risk clinical target volume (HR-CTV) D90 cumulative dose in 2-Gy fraction equivalents (EQ.D2) was 90.5 Gy (range 87-93.7) and median HR-CTV D98 was 79.8 Gy EQ.D2 (range 77.2-84.8; n = 7). Grade ≥ 3 hematologic toxicity was more common during chemoradiation than during induction chemotherapy (neutropenia in 3/8 [37.5%] vs 1/8 [12.5%]; leukopenia in 2/8 [25%] vs 0/8 [0%]). Thrombocytopenia (1/8,12.5%) and one case of anemia were observed exclusively during induction chemotherapy. Two patients discontinued cisplatin early because of hematologic toxicity. Seven of eight patients achieved a complete metabolic response on PET at 3 months post-treatment and remained disease-free at last follow-up (median 62.4 months; range 23.0-72.9). In this real-world cohort, INTERLACE-style induction chemotherapy produced substantial tumor regression that facilitated tandem-and-ovoid brachytherapy in most patients while achieving EMBRACE-aligned HR-CTV doses with manageable, phase-specific toxicity. These hypothesis-generating findings warrant confirmation in larger, prospective, and comparative cohorts.

Dehydroepiandrosterone (DHEA)-induced rodent models are widely used in polyendocrine metabolic ovarian syndrome (PMOS; formerly polycystic ovary syndrome [PCOS]) research, yet their reproducibility is limited by substantial methodological variability. While rats are often reported to exhibit diestrus arrest, mouse studies describe estrus-dominant or mixed-stage arrest, differences frequently attributed to species effects; however, heterogeneity in experimental design may also contribute. We synthesized 25 published DHEA-induced rodent studies and characterized estrous-cycle dynamics in a C57BL/6 model using one commonly used DHEA protocol. Key methodological variables-including induction age, DHEA brand and solvent, dosage, administration duration, smear-sampling timing, and cytological criteria-were extracted and examined using a semi-quantitative comparative approach. Estrous-arrest patterns were compared across methodological subgroups to formulate provisional, evidence-informed recommendations. Substantial variability in estrous-arrest patterns was identified across studies, although subgroup differences were not statistically significant. Approximately 60% of C57BL/6 studies reported estrus-dominant arrest when DHEA was administered at 6 mg/100 g body weight, sesame oil was used as the solvent, and induction began before postnatal day 28. Our experiment confirmed that the selected protocol can produce estrus-dominant arrest, but it did not compare alternative doses, solvents, induction ages, or sampling schedules. Directional trends suggested that DHEA dosage, solvent type, and induction age may contribute to estrous outcomes. Overall, methodological factors may contribute substantially to estrous-cycle variability in DHEA-induced mouse models; however, the available evidence does not establish them as dominant or causal determinants. These findings identify candidate methodological contributors and support provisional recommendations to improve reporting and cross-study comparability, while direct comparative experiments integrating endocrine and ovarian endpoints remain necessary for validation.

Polycystic ovary syndrome (PCOS) is a prevalent metabolic and endocrine disorder marked by hormonal imbalances among women, and the specific pathogenesis remains incompletely clarified. Although n-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have benefits in managing PCOS through previous studies, the specific mechanisms require further investigation. We found that DHEA-induced PCOS mice exhibited an impaired intestinal barrier, decreased levels of glucagon-like peptide-1 (GLP-1, P<.05), elevated serum levels of lipopolysaccharides (LPS, P<.05), and upregulated the ovarian TLR4-NLRP3 inflammatory signaling pathway (P<.05). Our in-depth experiments verified that eicosatrienoic acid (ETA) palliated the pathological representative features of PCOS in mice by regulating intestinal GLP-1 levels (P<.01). In detail, ETA upregulated GLP-1 receptor (GLP-1R) levels in the colon, restoring intestinal barrier integrity through modulation of the functions of the gut epithelial and mucosal barriers, and reduced serum LPS levels in PCOS mice (P<.001). In the ovary, ETA upregulated GLP-1R levels, decreased the expression of the TLR4-NLRP3 signaling pathway (P<.05), and reduced the release of inflammatory factors (all P<.05), thereby ameliorating ovarian inflammation and estradiol secretion disorders (P<.01). Here, we propose the mitigation of ovarian inflammation and restoration of intestinal barrier integrity as novel therapeutic targets and strategies for PCOS management, thereby positioning the n-3 PUFA ETA as a promising therapeutic candidate.

Astaxanthin (AST) has been reported to influence oxidative stress, endoplasmic reticulum stress, and apoptosis in women with polyendocrine metabolic ovarian syndrome (PMOS), formerly referred to as polycystic ovary syndrome (PCOS), but its effects on granulosa-cell (GC) autophagy remain unclear. Given the central role of autophagy in follicular development, this triple-blind, placebo-controlled pilot randomised trial evaluated whether AST modulates autophagy-related signalling in GCs and how these molecular effects relate to ovarian response. Fifty women with PMOS-related anovulatory infertility were enrolled between November 2023 and September 2024 and received AST (12 mg/day) or placebo for six weeks prior to oocyte retrieval; forty-four completed the study (21 AST, 23 placebo). Primary exploratory endpoints were molecular markers of adenosine monophosphate-activated protein kinase (AMPK)-autophagy signalling, and primary clinical outcomes included ovarian response indicators and cleavage stage embryo quality. AST supplementation increased autophagy-related gene 7 (ATG7) expression, enhanced autophagy flux, reduced apoptosis, and showed a trend toward increased AMPK activation. Before adjustment, AST improved oocyte maturity rate (OMR) and increased mature (metaphase II; MII) oocyte yield. After adjusting for age, body mass index, and anti-mullerian hormone level, total oocyte and MII oocyte yields remained significantly higher with AST, while OMR became non-significant. Among embryology outcomes, both the top-ranking embryo rate and the number of embryos suitable for cryopreservation were significantly higher with AST after adjustment. Pregnancy outcomes were numerically higher but not statistically significant. This pilot trial suggests that AST activates autophagy- and apoptosis-related pathways in GCs and may enhance oocyte competence and embryo quality in PMOS. Larger studies are needed to confirm these mechanistic and clinical effects.

Primary screening for human papillomavirus (HPV) followed by treatment with thermal ablation (TA) is an important component of the global strategy to eliminate cervical cancer. However, evidence on post-TA outcomes in women living with HIV (WLWH) remains limited. The aim of this study is to evaluate the risk and determinants of post-TA CIN2+. As part of the AIMA-CC study, WLWH from Côte d'Ivoire, Burkina Faso and Cambodia were screened using HPV testing (GeneXpert). All HPV-positive women were biopsied and those with positive triage (positive visual inspection and/or HPV-161845) were treated with TA using a flat probe and followed for 12 months with HPV testing and biopsies. Among the 456 WLWH (age: 30-59 years) treated with TA and with valid histology, 396 (86%) attended the 12-month follow-up visit. HPV persistence (HPV of same GeneXpert channel at baseline and 12-month post-treatment) was 40% and was associated with baseline HPV16 positivity (p = 0.007), age ≥ 40 years (p = 0.03) and CD4 ≤ 500 cells/mm 3 (p = 0.02). CIN2+ was detected at 12 months in 12 (4%) of the 318 WLWH with valid histology and was associated with 12-month HPV positivity (OR: 5.29 [1.46-28.46]). The risk of CIN2+ was particularly high among women with HPV-16 at 12 months (OR: 15.53 [3.49-91.17]). HPV positivity at 12 months had a sensitivity for detecting CIN2+ of 83% but a specificity of 54%. HPV-16 positivity had lower sensitivity (42%) but high specificity (> 90%). In conclusion, there is an urgent need to improve TA management in WLWH who are at high risk of CIN2+ re-occurrence post-treatment.

This comparative study evaluates the applicability of international radiation therapy guidelines in the management of cervical cancer between high-income countries and low- and middle-income countries (LMICs). Understanding differences in clinical practice is essential to identify gaps and areas for improvement in LMICs. A cross-sectional survey was conducted using an online questionnaire distributed among specialists involved in cervical cancer care from France (high-income countries) and Morocco (LMIC). Responses from 77 participants (45 from Morocco, 32 from France), predominantly females aged 40 to 49 years, were analyzed to assess diagnostic, therapeutic, and imaging practices. Significant differences were observed between the 2 countries. Human papillomavirus vaccination coverage was low, with 86.8% of respondents reporting that their patients were not vaccinated. Magnetic resonance imaging use before brachytherapy (BCT) was more frequent in France (90%) compared with Morocco (25%). Positron emission tomography-computed tomography for lumbar-aortic staging was widely used in France (97%) versus 59% in Morocco.Therapeutic approaches for the International Federation of Gynecology and Obstetrics stages IB1 and IB2 varied, with Morocco favoring preoperative BCT more often (34% vs 16%). Image-guided brachytherapy was systematically used in both countries, but combined intracavitary and interstitial applications were more frequent in France (64% vs 9%). In Morocco, dosimetric outcomes were generally satisfactory, with a D90 dose to the high-risk clinical target volume >85 Gy achieved in 78% of cases, supported by volumetric modulated arc therapy and computed tomography-based planning. Our findings highlight the ability of Moroccan teams to adapt their practice to most Western guidelines for cervical cancer, despite resource limitations. However, there is a crucial need for infrastructure development and continuous training to support long-term harmonization of clinical practice. Significant efforts are also required to improve human papillomavirus vaccination coverage, enhance access to magnetic resonance imaging and positron emission tomography-computed tomography, and optimize the use of high-dose-rate BCT.

Cervical cancer is a preventable threat to women's health, and human papillomavirus (HPV) vaccination is key primary prevention. Caregiver hesitancy may affect vaccination of age-eligible girls.We examined caregivers' willingness to vaccinate primary and secondary school girls against HPV and factors in six ethnic autonomous prefectures of Qinghai Province. From December 2024 to February 2025, we conducted a cross-sectional survey of caregivers of girls in selected classes at 12 schools, using multistage cluster convenience sampling. The questionnaire included Health Belief Model (HBM), Theory of Planned Behavior (TPB), and Perceived Social Support Scale (PSSS) items. Factors were assessed with univariable and four-step hierarchical multiple linear regression, sequentially entering sociodemographic, HBM, TPB, and PSSS blocks. Willingness correlated with perceived susceptibility and severity, cues to action, attitudes, perceived behavioral control, and subjective norms. In univariable analyses, all HBM, TPB, and social-support dimensions except perceived barriers were positively associated with willingness. Hui caregivers had lower willingness, while higher education, middle income, and party/government-agency or public-institution employment predicted higher willingness. In hierarchical multiple regression, Hui ethnicity vs. Han ethnicity predicted lower willingness ( B = -0.229, P = .003). Cues to action ( β = 0.121, P = .024), perceived barriers ( β = 0.128, P < .001), attitudes ( β = 0.203, P < .001), perceived behavioral control ( β = 0.107, P = .001), and subjective norms ( β = 0.323, P < .001) were positively associated. HPV vaccination promotion should be tailored to Qinghai's ethnic autonomous prefectures, with authoritative school and primary-care recommendations, clear vaccine information, and vaccination-process support, while identifying barriers. Future qualitative and prospective implementation studies should clarify decision-making mechanisms and assess intervention acceptability and effects on vaccine uptake in resource-limited settings.

This study aims to investigate the therapeutic effects of the Bushen Huatan (BSHT) Formula on non-obese polycystic ovary syndrome (PCOS) rats, and to explore its potential mechanisms of action. A PCOS model was induced in rats via letrozole, a high-fat/high-sucrose diet, and a PEPD inhibitor for 35 days; estrous cyclicity, fasting glucose, and glycated hemoglobin were monitored. After modeling, the animals underwent 28 days of assigned treatment, followed by an oral glucose tolerance test (OGTT) and assays for sex steroids and lipids. Ovarian and hepatic histology and hepatic steatosis were evaluated. Adipose-derived exosomes were characterized for size, concentration, and surface markers (TSG101, HSP70, CD63). Detect the expression levels of adipose tissue-derived exosomal microRNA-27a-3p (AT-EXO-miR-27a-3p) and ovarian Pparg mRNA. Ovarian PPARG, P-AKT, GLUT4, INSR and IRS-1 proteins were quantified. Compared with the model control group, BSHT lowered serum testosterone, elevated E₂ and FSH, ameliorated glucose intolerance, and improved lipid profiles by decreasing TC and TG and increasing HDL-C. Polycystic ovarian morphology and hepatic lipid accumulation were also attenuated. BSHT down-regulated AT-EXO-miR-27a-3p expression (mean ± SD: 5.13 ± 0.27 vs 17.91 ± 1.19; p < 0.001) and up-regulated both Pparg mRNA (0.38 ± 0.03 vs 0.08 ± 0.002; p < 0.001) and protein (0.37 ± 0.10 vs 0.12 ± 0.02; p = 0.001), while markedly increasing INSR protein abundance (1.50 ± 0.11 vs 0.37 ± 0.04; p < 0.001). This study demonstrates that the BSHT prescription may alleviate reproductive endocrine disorders in PCOS rats by mitigating the inhibitory effects of fat-derived exosomal miR-27a-3p on PPARG.