Recently published papers, fresh preprints, newly-posted clinical
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This systematic review and meta-analysis quantified the association between uterine peristaltic frequency measured during embryo transfer cycles and clinical pregnancy rates in in vitro fertilization.
OA: gold
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PURPOSE: Endometriosis is a common chronic inflammatory gynaecological condition characterised by the abnormal presence of endometrial tissue outside the uterus. Different risk factors for endometrios…
OA: hybrid
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📄 Abstract
PURPOSE: Endometriosis is a common chronic inflammatory gynaecological condition characterised by the abnormal presence of endometrial tissue outside the uterus. Different risk factors for endometriosis have been proposed, with some research finding a significant relationship between endometriosis and early life trauma. This study aimed to determine the prevalence, age, and type of early life trauma in a clinical sample of women with existing diagnosis of endometriosis compared with the prevalence in the general Australian female population.
METHODS: Participants were recruited from the Multidisciplinary Alfred Psychiatry research centre Women's Mental Health Clinic (WMHC). Women who self-reported a diagnosis of endometriosis were identified from the WMHC patient database, established in 2017. In patients who reported a presence of early life trauma, information regarding the type and age of the early traumatic experience(s) was recorded. The prevalence of each type of trauma in our participants was compared to the general female population in Australia.
RESULTS: Of 68 included participants, the mean (SD) age was 41.6 (9.7) years. 86.8% of participants (n = 59) reported experience of any early life trauma, most commonly occurring between ages 6-10 (89.8%). The most reported type of trauma was emotional abuse (76.5%). Compared to the general female population, the prevalence of emotional abuse (76.5% vs. 37.3%), neglect (35.3% vs. 10.8%), and sexual abuse (39.7% vs. 37.3%) were higher in our sample.
CONCLUSION: The findings of this study found high prevalence rates of early life trauma, in particular emotional abuse and neglect, in our clinical sample of women with endometriosis.
A patient with oligometastatic hepatoid adenocarcinoma arising from endometriosis achieved durable disease control over 36 months using a multimodal strategy combining surgery, chemotherapy, stereotactic body radiotherapy, immunotherapy, and targeted therapy.
OA: gold
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Abstract Objectives Hepatoid adenocarcinoma (HAC) arising from endometriosis is an extremely rare malignancy with a poor prognosis and no standard treatment. Radical surgical resection followed by chemotherapy is the commonly used treatment for HAC. The role of radiotherapy and immunotherapy has been poorly explored. We report the second case of HAC arising from endometriosis with oligometastatic lung progression to share our experience with a multimodal approach. Case presentation We report a case of an HAC arising from endometriosis in a patient who presented with a pelvic mass and markedly elevated Alpha-fetoprotein (AFP) and underwent surgical resection followed by pelvic radiotherapy and chemotherapy. The patient had satisfactory pelvic control but developed a solitary lung metastasis six months after the completion of first-line therapy, which was treated with stereotactic body radiotherapy (SBRT). The second metachronous lung metastasis subsequently appeared and was also treated with SBRT, followed by immunotherapy and targeted therapy. The lung metastasis achieved a complete response, and the patient remained free of disease for over 36 months. Treatment-related pneumonitis occurred and resolved after corticosteroid therapy and immunotherapy discontinuation. Conclusions HAC arising from endometriosis appears to be prone to metastasis. The multimodal strategy integrating surgery, chemotherapy, radiotherapy, immunotherapy and targeted therapy may offer durable disease control in oligometastatic HAC arising from endometriosis, though the contribution of each component requires further investigation. Clinicians should also be aware of the risk of pneumonitis when combining lung SBRT with immunotherapy.
L-(+)-Ergothioneine ameliorates preeclampsia-associated vascular endothelial dysfunction by modulating the Nrf2-PPARγ-sFlt-1 axis to improve trophoblast function and promote endothelial recovery.
OA: gold
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Background Preeclampsia (PE) is a serious complication of pregnancy, with vascular endothelial dysfunction being a core pathological feature. This study aimed to investigate whether L-(+)-ergothioneine (LET) ameliorates PE-associated endothelial dysfunction by regulating the Nrf2-PPARγ-sFlt-1 axis. Methods A LPS-induced trophoblast dysfunction model was established using lipopolysaccharide (LPS)-induced human trophoblast cells (HTR8/SVneo). Techniques including CCK-8 assay, flow cytometry, wound healing assay, ELISA, qPCR, Western blot, and immunofluorescence were employed to assess the effects of LET on cell viability, apoptosis, invasion, inflammatory cytokine levels, and the expression of key molecules in the signaling pathway. Results LET significantly increased the viability of LPS-induced trophoblasts, promoted migration, inhibited apoptosis, and downregulated pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ) and endothelial dysfunction markers (sFlt-1, ET-1, PAI-1), while upregulating the anti-inflammatory cytokine IL-4 and plasminogen activators (tPA, uPA). Mechanistically, LET inhibited Nrf2 nuclear translocation and promoted PPARγ expression, consequently reducing sFlt-1 levels. The protective effects of LET were mimicked by the PPARγ activator pioglitazone and reversed by the inhibitor FX-909. Furthermore, the supernatant from LET-treated trophoblasts promoted the viability and invasion of human umbilical vein endothelial cells (HUVECs). Conclusions L-(+)-Ergothioneine improves trophoblast function and indirectly promotes endothelial recovery by modulating the Nrf2-PPARγ-sFlt-1 axis, suggesting a potential therapeutic target for preeclampsia.
BACKGROUND: The relationship between endometriosis and cardiovascular disease (CVD) risk remains unclear. This study aimed to evaluate the association between endometriosis and CVD risk, to examine wh…
OA: gold
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BACKGROUND: The relationship between endometriosis and cardiovascular disease (CVD) risk remains unclear. This study aimed to evaluate the association between endometriosis and CVD risk, to examine whether the association was affected by age group, and to exploratorily assess the mediating role of medications in these associations.
METHODS: A historical, population-based cohort study was conducted based on the Beijing Medical Claim Data for Employees between 2010 and 2017. A total of 19,903 women with endometriosis and 79,612 controls were identified by matching age and year of endometriosis diagnosis in a 1:4 ratio. The primary outcome was the incident diagnosis of any CVD events, and secondary outcomes were major CVD and cerebrovascular disease. The hazard ratios (HRs) were estimated by Cox proportional hazards models representing the association between endometriosis and CVD.
RESULTS: Endometriosis was associated with an increased risk of CVD after adjusting for urbanisation, hypertension and diabetes mellitus (HR = 1.69; 95% CI = 1.35-2.12). The adjusted HRs for major CVD and cerebrovascular disease in women with endometriosis were 1.83 (95% CI = 1.32-2.55) and 1.57 (95% CI = 1.12-2.22) compared with controls, respectively. Interaction analyses between endometriosis and age group (18-44 years vs. 45-55 years) yielded P-values of 0.942, 0.552, and 0.211 for all CVD, major CVD, and cerebrovascular disease, respectively, indicating no statistically significant heterogeneity in the associations across age groups. In the overall population, a proportion of the association between endometriosis and all CVD risk was statistically mediated by statins (68.30%) and aspirin (78.15%).
CONCLUSIONS: Endometriosis was associated with an increased risk of CVD.
Earlier examinations of how risk factors relate to endometriosis (EMT) have largely depended on observational designs, which arrived at conflicting conclusions. The present approach seeks to probe the…
OA: gold
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Earlier examinations of how risk factors relate to endometriosis (EMT) have largely depended on observational designs, which arrived at conflicting conclusions. The present approach seeks to probe the causal association between 108 traits and EMT by means of Mendelian randomization (MR) analysis. MR analysis was applied to explore the connections between a range of traits and the development of EMT. Most of the data used in the genome-wide association studies of these characteristics came from the UK Biobank (UKBB), whereas the genome-wide association studies for EMT drew specifically on FinnGen. Using the inverse-variance weighted approach, suggestive relationships emerged between 12 traits and EMT, including “telomere length” (odds ratio [OR] = 1.29; 95% confidence interval [CI]: 1.13–1.47), “triglycerides” (OR = 1.13; 95% CI: 1.05–1.21), and “high-density lipoprotein cholesterol” (OR = 0.89; 95% CI: 0.83–0.95). For most of these traits, sensitivity analyses based on the weighted median and MR-Egger methods yielded concordant results. Overall, our results point to causal associations between the 12 traits and EMT. They furnish a fresh conceptual foundation for preventing or lessening the risks associated with EMT.
2026·European journal of nuclear medicine and molecular imaging
Deep and superficial endometriosis lesions exhibited substantial fibroblast activation protein expression regardless of visibility on magnetic resonance imaging or transvaginal ultrasound, supporting the rationale for FAP-targeted imaging in endometriosis.
OA: closed
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PURPOSE: Fibroblast activation protein (FAP) is expressed in the fibroinflammatory stroma of endometriosis, but its relationship to conventional imaging visibility is unknown. We evaluated FAP expression in deep endometriosis (DE) and superficial endometriosis (SE) and its relationship to lesion visibility on magnetic resonance imaging (MRI) and transvaginal ultrasound (TVUS).
METHODS: We retrospectively analyzed specimens from DE (n = 13) and SE (n = 9) patients who underwent MRI and/or TVUS. FAP expression was assessed immunohistochemically using H-scores. Two abdominal radiologists independently graded the visibility of pathology-confirmed lesions on MRI and TVUS using a study-specific 0-3 scale, with N/A assigned when the lesion location was outside the available imaging field of view. H-scores were compared by phenotype and imaging visibility (lower [0-1] vs higher [2-3]) using nonparametric analyses.
RESULTS: FAP expression did not differ significantly between DE and SE (median H-scores 170 vs 200, p= 0.738). Endometriosis showed substantial FAP expression, although H-scores were lower than colorectal adenocarcinoma controls (p 0.05). On TVUS, 1 and 2 lesions were assigned N/A for Readers 1 and 2, respectively; among evaluable lesions, low-/high-visibility groups included 2/10 and 1/10 lesions, with median H-scores of 48/165 and 20/160, respectively, limiting conclusions regarding visibility and FAP expression.
CONCLUSION: DE and SE showed substantial stromal FAP expression, including SE lesions poorly visible on conventional imaging. These findings provide a histopathological rationale for FAP-targeted imaging in endometriosis.
This study used virtual screening and molecular dynamics simulations to identify Bictegravir as a promising p300 inhibitor for non-hormonal endometriosis treatment, demonstrating its favorable binding stability compared to other FDA-approved drugs.
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Abstract Endometriosis is a gynecological disorder, characterized by debilitating pain and commonly associated with infertility. Medical therapies are often ineffective, with 25–34% of patients exhibit no or poor response, and many experiencing intolerable side effects that limit long term use. P300 is a critical histone acetyltransferase that promotes inflammation and invasion through epigenetic modulation of immune cells, and upregulation of pro-inflammatory gene expression. In this study, we aimed to identify potential inhibitors of p300 for treating endometriosis using computational drug repurposing. We performed a molecular docking-based virtual screening of 2,083 Food and Drug Administration (FDA) approved drugs against the crystal structure of p300 ligand-binding domain, followed by molecular dynamics (MD) simulations and Molecular Mechanics Poisson Boltzmann Surface Area (MM-PBSA) analysis to further assess the stability and the binding interactions of the top-ranked drugs. Three compounds, Naldemedine, Bictegravir and Zavegepant, exhibited favorable docking affinities and interaction profiles. Further evaluation using 300 ns molecular dynamics simulations and MM-PBSA analyses demonstrated that Bictegravir exhibited the most favorable binding in complex with p300. Lastly, these findings underscore the potential of bioinformatics approaches in providing valuable resources and novel perspective on therapeutic strategies that are often overlooked in the context of endometriosis.
Glucagon-like peptide-1 (GLP-1) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are increasingly prescribed for obesity and type 2 diabetes, but eyelid gland pathol…
OA: gold
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Glucagon-like peptide-1 (GLP-1) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are increasingly prescribed for obesity and type 2 diabetes, but eyelid gland pathology has not previously been reported with these agents. We describe what we believe to be the first reported case series of 2 patients who developed multiple simultaneous internal hordeola after starting tirzepatide, a dual GLP-1/GIP receptor agonist. Patient 1, a 44-year-old woman, developed 6 simultaneous hordeola 4 weeks after dose escalation, 5 of which progressed to chalazia; lesions lessened after tirzepatide discontinuation and worsened upon rechallenge, a positive rechallenge providing strong evidence of causality. Patient 2, a 73-year-old woman with mild pre-existing blepharitis, developed 6 simultaneous hordeola 10 weeks after initiation of her 5 mg dose, 2 of which progressed to chalazia. Both patients lacked classic infectious blepharitis signs despite active lesions, supporting a sterile, obstructive meibomian gland process rather than infection, though both found the recurrences bothersome. These cases suggest a possible, previously undescribed association between tirzepatide and simultaneous or recurrent meibomian gland obstruction. Clinicians should be aware of this potential adverse eyelid effect and pursue conservative ophthalmic management before considering medication changes.
Additional File 1: Fig S1: Violin plots of diffusion parameters apparent diffusion coefficient (ADC), diffusivity (D) and pseudo-diffusivity (D*) and perfusion fraction (f) across the three cohorts fo…
OA: green
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Additional File 1: Fig S1: Violin plots of diffusion parameters apparent diffusion coefficient (ADC), diffusivity (D) and pseudo-diffusivity (D*) and perfusion fraction (f) across the three cohorts for all three uterine layers. The central white line indicates the mean value, while the width of the plot reflects the distribution density of participants within that value range. Fig S2: Anterior-Posterior analysis of the myometrium and junctional zone for three participants groups showing the apparent diffusion coefficient (ADC), diffusivity (D) and perfusion fraction (f). *p < 0.05 compared with healthy controls and †p < 0.05 compared with participants with adenomyosis. Fig S3: Plots showing ADC and IVIM parameter variations in adenomyosis cases categorized according to MRI-based adenomyosis classification. The “Other” category includes cases that could not be assigned to a specific MRI subtype but demonstrated imaging features consistent with adenomyosis. Fig S4: Bland–Altman plots to evaluate the robustness of diffusion quantification for each uterine layer and diffusion parameter across cohorts between the repeated scans. The bold line represents the mean difference, and the dotted lines indicate the 95% limits of agreement (±1.96 standard deviations). Fig S5: IVIM model fitting and stability before and after motion correction registration, showing fitted curves in comparison with the measured averaged diffusion signal across the cohort. Derived parameters, diffusivity (D), pseudo-diffusivity (D*), perfusion fraction (f) and corresponding R² values are provided for each case. Table S1 Mean Diffusion and IVIM parameter values (Hormonal contraceptive users). Table S2 Inter-annotator and Intra-annotator variability of ADC and IVIM parameters. Table S3 Percentage of Variability in ADC and IVIM Metrics.
BACKGROUND: While negative neonatal outcomes are more frequent in fetuses with estimated fetal weight (EFW) 25th-<90th percentile.
METHODS: This prospective cohort study took place at the Maternal-F…
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BACKGROUND: While negative neonatal outcomes are more frequent in fetuses with estimated fetal weight (EFW) 25th-<90th percentile.
METHODS: This prospective cohort study took place at the Maternal-Fetal Medicine Department of a tertiary center in Tehran, Iran, from May 2024- March 2026. Low risk pregnant mothers aged 18-39 years, with singleton pregnancies, exhibiting EFW of 10th-90th percentile, were classified into: 10th-25th percentile group and > 25th-<90th percentile group. Both groups underwent biometric ultrasound at 32-33 weeks of gestation and additionally received biometric and fetal vascular Doppler ultrasound three weeks afterwards. We evaluated the two groups on: (1) Doppler parameters including umbilical artery pulsatility index (UA-PI), middle cerebral artery pulsatility index (MCA-PI), average uterine artery PI, and cerebroplacental ratio (CPR), (2) adverse perinatal and neonatal outcomes including fetal growth restriction (FGR), intrauterine fetal demise, oligohydramnios, meconium-stained liquor, low birth weight (LBW), cesarean section due to fetal distress, abnormal cord arterial blood gas (ABG), low APGAR score, neonatal intensive care unit (NICU) admission, respiratory distress syndrome (RDS), and neonatal mortality. We examined whether the Doppler indices had any predictive value for adverse outcomes in 10th-25th percentile weight fetuses.
RESULTS: Of 402 individuals, 320 (79.6%) were in the > 25th-<90th percentile group, while 82 (20.4%) were in the 10th-25th percentile group. The incidence of negative perinatal and neonatal outcomes like FGR (25.60% vs. 2.81%), LBW (20.73% vs. 0.31%), RDS (13.41% vs. 5.31%), low APGAR scores (14.63% vs. 5.31%), abnormal ABG (13.41% vs. 3.75%), and NICU admission (28.04% vs. 9.37%) was higher in the 10th-25th percentile group compared to the > 25th-<90th percentile group. Although abnormal UA-PI, abnormal MCA-PI, and abnormal CPR were more frequently found in fetuses weighing in the 10th-25th percentile group; however, fetal Doppler indices did not successfully predict negative outcomes for fetuses in this weight range.
CONCLUSIONS: Adverse perinatal and neonatal outcomes were higher in fetuses within 10th-25th percentile for birth weight, with abnormal Doppler indices more common, but these indices did not predict negative outcomes effectively.
This retrospective analysis of 142 women found that coexistent adenomyosis in Type 1 endometrial carcinoma was independently associated with earlier-stage disease and reduced cervical stroma involvement.
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OBJECTIVES: Although frequently identified in hysterectomy specimens of women with endometrial carcinoma, the impact of adenomyosis on the prognosis of endometrial carcinoma remains uncertain. Therefore, we aimed to evaluate the prognostic significance of coexistent adenomyosis and endometrial carcinoma, focusing on histopathological features, staging, and recurrence rates.
METHODS: We conducted a retrospective analysis of 142 women treated during 2013-2023 for endometrial carcinoma, categorized as Type 1 or Type 2. Clinical, histopathological, and recurrence data were compared between those with and without adenomyosis.
RESULTS: Adenomyosis was identified in 32/142 women (22.5%). Among 119 with Type 1 endometrial carcinoma, 26 (21.8%) had adenomyosis. FIGO stage I-II disease was present in all of these and in 76/93 (81.7%) of those without adenomyosis (p = 0.022). Cervical stroma was less frequently involved in the adenomyosis group (1/26; 3.8% vs 17/93; 18.3%, p = 0.05). Among the 23 women with Type 2 endometrial carcinoma, stage and recurrence rates did not differ significantly between those with and without adenomyosis. In histopathological assessment, malignant cells within adenomyotic foci were identified in six patients: five with Type 1 and one with Type 2 carcinoma. All of these involved deep diffuse adenomyosis. Strong PAX8 positivity was found in four women, and estrogen receptor positivity in five.
CONCLUSION: We report an independent association of adenomyosis in Type 1 endometrial carcinoma with earlier-stage disease and reduced cervical stroma involvement. These findings highlight a potential association between adenomyosis and favorable tumor characteristics, warranting further studies to clarify the prognostic significance.
Pelvic magnetic resonance imaging (MRI) plays a pivotal role in evaluating gynecologic diseases, offering superior soft-tissue characterization, multiplanar imaging, and functional assessment compared…
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Pelvic magnetic resonance imaging (MRI) plays a pivotal role in evaluating gynecologic diseases, offering superior soft-tissue characterization, multiplanar imaging, and functional assessment compared to ultrasound and computed tomography. This article proposes evidence-based, standardized MRI protocols and a reproducible interpretative framework to enhance diagnostic accuracy, reduce misdiagnoses, and support multidisciplinary management in routine clinical practice. Key insights cover MR imaging of major gynecologic diseases: endometriosis, adnexal masses including the O-RADS MR scoring system, and pathological hypothesis as well as uterine diseases including endometrial, cervical, and myometrial benign and malignant conditions. For all situations, we present typical and atypical presentations as well as mimickers. This article will give some tips and tricks to help the radiologist in clinical routine for detecting and differentiating the main issues that impact patient management. By adopting standardized protocols and reports with adequate pathology knowledge, radiologists can improve patient outcomes through precise staging, surgical planning, and personalized care. KEY POINTS: Question How can radiologists avoid common diagnostic errors and pitfalls when interpreting pelvic MRI for gynecologic diseases, including endometriosis, uterine tumors, and adnexal masses? Findings Knowledge of common pitfalls, standardized MRI protocols with Dixon-based T1-weighted sequences, diffusion-weighted imaging, and dynamic contrast enhancement, if necessary, combined with structured reporting frameworks including O-RADS MRI and FIGO 2023, reduces misdiagnosis across gynecologic conditions. Critical Relevance Statement This article critically reviews typical and atypical presentations alongside common mimickers of major gynecologic diseases on pelvic MRI, providing radiologists with practical evidence-based strategies to improve diagnostic accuracy, reduce unnecessary interventions, and support multidisciplinary clinical decision-making.
Epithelial ovarian cancer is not a single disease but a group of biologically distinct malignancies that include serous (high-grade and low-grade), endometrioid, clear cell, and mucinous carcinomas, a…
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Epithelial ovarian cancer is not a single disease but a group of biologically distinct malignancies that include serous (high-grade and low-grade), endometrioid, clear cell, and mucinous carcinomas, along with other rare subtypes. Integrating clinicopathological analyses, genomic and multiomic data, and experimental investigations in model systems has revealed the pathogenesis of the various histologic subtypes. A unique feature of epithelial ovarian cancer is that most of these tumors are now recognized to arise not from ovarian tissue but from the fallopian tube or endometrium, the latter in the context of ovarian endometriosis. Studies of precursor lesions have revealed complex evolutionary trajectories and the earliest molecular events in their development. Recent single-cell and spatial technologies further elucidate the roles of intratumoral heterogeneity and the tumor microenvironment in disease progression. This review summarizes these advances from the perspective of tissue of origin and highlights their implications for prevention, early detection, and therapeutic development.
0.55-T MRI diffusion metrics distinguished adenomyosis from healthy uteri through reduced myometrial apparent diffusion coefficient and increased perfusion fraction, while also capturing menstrual phase and hormonal therapy effects.
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OBJECTIVE: To investigate and analyze the microstructure of uterine layers and to evaluate the feasibility and physiological variability of uterine diffusion metrics at 0.55-T MRI in healthy volunteers and participants with adenomyosis.
MATERIALS AND METHODS: In this prospective study, 106 women, including healthy controls without (n = 47) and with hormonal contraception (n = 37), and patients diagnosed with adenomyosis (n = 22), underwent uterine diffusion MRI at 0.55 T. Apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) were modeled using nine b-values in the myometrium, junctional zone, and endometrium. Quantitative intergroup differences, intragroup comparisons, and anterior-posterior wall analyses were performed. Evaluation of scan repetitions, intra-annotator and inter-annotator variability, and IVIM fit quality assessments were performed in subcohorts.
RESULTS: The intergroup analysis was performed on 106 women aged 27.2 ± 5.9 years (mean ± standard deviation) without bowel preparation or antispasmodics. A reduced median myometrium ADC (p = 0.024), reduced endometrial mean diffusivity (p = 0.017), and increased perfusion fraction (p = 0.014) were observed in the cohort with adenomyosis compared to healthy volunteers. Interindividual and intra-individual analysis of healthy volunteers demonstrated increased diffusivity in the endometrium during the luteal phase (p = 0.024). Additionally, differences in diffusion and IVIM parameters were observed in adenomyosis participants undergoing hormonal therapy. Repeat measurements, intra-annotator and inter-annotator agreement, and IVIM metric stability demonstrated good consistency.
CONCLUSION: This study provides early evidence that uterine diffusion and IVIM at 0.55 T enable robust, non-invasive characterization of uterine microstructure sensitive to menstrual phase, hormonal status, and adenomyosis, providing insight into uterine physiology and pathology.
KEY POINTS: Question Can 0.55-T MRI characterize functional changes associated with adenomyosis compared with healthy uteri? Findings 0.55-T uterine diffusion MRI without bowel preparation quantified uterine microstructure, with layer-specific ADC and IVIM distinguishing adenomyosis, hormonal effects, menstrual phase, and anterior-posterior differences. Relevance statement Quantitative diffusion and IVIM metrics at 0.55-T distinguish adenomyosis from healthy tissue through reduced myometrial ADC, endometrial diffusivity, and increased perfusion fraction. These biomarkers hold promise in clarifying diagnosis and supporting future studies assessing hormonal therapy response and treatment monitoring.
This exploratory mixed-methods study found weak, context-dependent associations between lifestyle factors and endometriosis symptom burden, with psychosocial well-being showing the most consistent relationship in women with the condition.
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BACKGROUND: Endometriosis affects approximately 10% of reproductive-age women worldwide, with symptom burden significantly impacting quality of life. While current treatment guidelines focus primarily on hormonal and surgical interventions, the role of lifestyle factors in symptom management remains underexplored. Major clinical guidelines acknowledge insufficient evidence for specific lifestyle recommendations, highlighting the need for exploratory research. Therefore, our aim is to explore potential associations between lifestyle factors (nutrition, physical activity, psychosocial well-being) and symptom burden in women with endometriosis using a mixed-methods approach.
METHODS: A convergent mixed-method design combining a cross-sectional online survey (n = 378) with semi-structured expert interviews (n = 5) was conducted between January and March 2025. Lifestyle factors were assessed using study-specific composite indices for dietary habits, physical activity, and psychosocial well-being. Symptom burden was evaluated using validated endometriosis-related items informed by established assessment tools and 11-point numeric rating scales for symptom frequency and intensity.
RESULTS: In exploratory analyses, the Dietary Habits Index was not significantly associated with overall symptom burden in the study cohort. However, subgroup analysis revealed a weak negative correlation in participants without food intolerances (β = -0.144, p = 0.021). Physical activity and psychosocial well-being indices showed weak associations with symptom burden (physical activity: β = 0.133, p = 0.010; psychosocial well-being: β = -0.261, p < 0.001). Expert interviews emphasized the importance of individualized, multimodal approaches and highlighted psychosocial factors as particularly relevant for symptom management.
CONCLUSIONS: This exploratory study identified weak and context-dependent associations between selected lifestyle factors and endometriosis symptom burden, with psychosocial well-being showing the most consistent relationship. The findings highlight the potential relevance of individualized lifestyle support as an adjunct to conventional medical care. Given the cross-sectional design and methodological limitations, these hypothesis-generating findings require confirmation in longitudinal and intervention studies.
Curcumin alleviates endometriosis in female mice by directly inhibiting protein kinase A, which suppresses de novo estrogen synthesis and reduces ectopic lesion formation.
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Background: Endometriosis is an estrogen-dependent disorder with limited treatment options. The precise molecular targets of curcumin and its effects on local estrogen synthesis in this disease remain unclear. Methods: We investigated curcumin’s efficacy and mechanism via network pharmacology, in vitro functional assays in ectopic endometrial cells, an allogeneic mouse model, and target validation through molecular docking, thermal shift, and hydrolysis stability assays. Results: Curcumin significantly inhibited ectopic cell malignant phenotypes, reducing migration distance by 55.60 ± 7.32%, 80.34 ± 11.19%, and 82.88 ± 13.67% at 5, 10, and 15 μM, respectively, and decreasing invasive cell numbers by 40.38 ± 7.67%, 58.33 ± 12.70%, and 60.18 ± 9.07%, respectively (all p < 0.05). In a mouse model, curcumin (200 mg/kg/day) reduced lesion number by 38.46% (2.167 ± 0.752 vs. 1.333 ± 0.516, p = 0.0493) and lesion volume by 59.73% (0.0497 ± 0.0173 vs. 0.0200 ± 0.0130 mm3, p = 0.00732). It also suppressed de novo estrogen synthesis and modulated the estrogen receptor α (ERα) and β (ERβ) ratio. Mechanistically, curcumin directly bound to and inhibited protein kinase A (PKA), a key kinase in the cAMP signaling pathway. Conclusions: We first demonstrate that curcumin alleviates endometriosis by targeting PKA to inhibit local estrogen synthesis, identifying PKA as a novel therapeutic target and curcumin as a promising treatment candidate.
This matched case-control study found no significant difference in anogenital distance measurements between adolescents with laparoscopically confirmed endometriosis and controls, suggesting AGD is not a biomarker for the condition in this cohort.
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Objectives To determine whether anogenital distance (AGD), a potential non-invasive biomarker reflecting prenatal androgen exposure, differs between adolescents with laparoscopically confirmed endometriosis and matched controls. Methods This IRB-approved, matched case–control study was conducted at a single pediatric hospital between March 2024 and June 2025. Twenty adolescents aged 13–25 years were enrolled: 10 with laparoscopically confirmed endometriosis and 10 controls (three asymptomatic, seven laparoscopically confirmed without endometriosis), matched by age (±1 year) and body mass index (BMI) (±2 kg/m 2 ). AGD was measured under anesthesia from the clitoral surface to the anus (AGD-AC) and from the posterior fourchette to the anus (AGD-AF). Within-pair mean differences were calculated using paired t -tests. Results The mean AGD-AC was 9.4 ± 1.2 cm in cases versus 9.7 ± 1.4 cm in matched controls; the mean AGD-AF was 3.5 ± 0.5 cm in cases versus 3.2 ± 0.8 cm in matched controls. Paired t -tests showed no significant differences in either [mean difference AGD-AC = 0.297, 95% CI (−0.85 to 1.44) p = 0.57; AGD-AF = −0.327, 95% CI ( −0.88 to 0.23) p = 0.22]. Substantial overlap was observed across groups, and no significant differences were identified for either AGD measure. Conclusion We did not detect a difference in AGD measurements between adolescents with laparoscopically confirmed endometriosis and age and BMI-matched controls; however, with only 10 matched pairs, this study was powered to detect only a large effect, and therefore, these null findings should be interpreted cautiously. Larger longitudinal studies are warranted to assess whether AGD correlates with disease onset, severity, or progression.
In patients with ovarian endometriomas, the ultrasound sliding sign was associated with surgically confirmed complete pouch of Douglas obliteration, though evidence regarding performance differences between transvaginal and transrectal routes remained inconclusive.
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Background and Objective: The ultrasound sliding sign dynamically assesses pouch of Douglas (POD) obliteration in suspected endometriosis. Transvaginal (TVS) and transrectal (TRS) ultrasound are used in patients with and without a self-reported history of vaginal intercourse, respectively, and thus in clinically distinct populations. We evaluated sliding sign performance for predicting surgically confirmed complete POD obliteration in patients with ovarian endometriomas and described findings in route-defined TVS and TRS groups. Materials and Methods: This retrospective cohort study enrolled 318 patients with surgically and pathologically confirmed ovarian endometriomas; intraoperative POD status was evaluable in 309. Patients with and without a self-reported history of vaginal intercourse underwent TVS (n = 247) and TRS (n = 71), respectively. A negative sliding sign (absent movement between the uterus and rectum) was the positive index test result for complete POD obliteration. The unadjusted full-cohort diagnostic accuracy analysis was the primary analysis. Because no parous patient underwent TRS (a lack of overlap in examination-route assignment among parous patients), exploratory adjusted analyses were restricted to nulliparous patients, using overlap weighting (principal adjusted analysis) and 1:1 propensity score matching (sensitivity analysis). Results: In the primary unadjusted analysis of the full cohort (n = 309), the negative sliding sign showed limited to moderate discriminative ability (sensitivity 0.71, 95% CI 0.63–0.78; specificity 0.60, 95% CI 0.52–0.67; PLR 1.78, 95% CI 1.44–2.20; NLR 0.48, 95% CI 0.36–0.64) and was associated with complete POD obliteration (p < 0.001). The between-route sensitivity difference was inconclusive (0.19, 95% CI −0.01 to 0.38). In the exploratory overlap-weighted analysis of nulliparous patients (n = 217), the association remained significant (weighted OR = 2.80, 95% CI 1.17–6.69; p = 0.021), without significant sliding sign-by-route interaction (p = 0.302); findings were consistent in the matching sensitivity analysis (66 pairs). Conclusions: The sliding sign was associated with surgically confirmed complete POD obliteration in patients with ovarian endometriomas, but evidence that this association differed between route-defined groups was inconclusive. Route-specific findings are exploratory because the examination route was determined by sexual history rather than randomization. Whether TRS offers performance comparable to TVS remains undetermined, because the two techniques were not evaluated in the same population and TRS feasibility was not formally assessed.
This paper reports the safety and efficacy of anti-CD19 CAR T-cell therapy in six pediatric patients with refractory autoimmune diseases, demonstrating clinical remission and favorable immune reconstitution profiles.
OA: gold
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Background: Adenomyosis is a benign gynaecological condition characterised by the presence of endometrial glands and stroma within the myometrium and may manifest clinically with pelvic pain and heavy…
OA: hybrid
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Background: Adenomyosis is a benign gynaecological condition characterised by the presence of endometrial glands and stroma within the myometrium and may manifest clinically with pelvic pain and heavy menstrual bleeding. Ultrasonography is an important non-invasive modality for its assessment. Clinical findings: A 46-year-old female presented with abdominal pain and heavy menstrual bleeding. Her menstrual cycle was approximately 22 days, with bleeding lasting 3–5 days. Ayurveda assessment revealed Vata-Pittaja Prakriti, Vishamagni and Krura Koshtha. Initial ultrasonography demonstrated a mildly retroflexed, bulky and globular uterus measuring 82 × 51 × 54 mm, with heterogeneous myometrium and loss of endometrial–myometrial differentiation. The radiological impression was early adenomyosis of the uterus. Intervention: The patient was administered a multimodal Ayurveda regimen comprising Chandraprabha Vati twice daily, Indukanta Ghrita 5 mL with milk in the early morning, Indukanta Kashaya 15 mL in the afternoon and at night after food, and equal quantities of Triphala Churna and Avipattikara Churna at night. Outcome: Follow-up ultrasonography, demonstrated an anteverted uterus measuring 48 × 42 × 51 mm. The previously reported bulky globular morphology, heterogeneous myometrium and loss of endometrial–myometrial differentiation were not described in the follow-up report. A 10 × 12 mm intramural fibroid was reported in the right lateral uterine wall. Conclusion: The case demonstrates an interval change in clinical and ultrasonographic findings following multimodal Ayurvedic intervention.
This comparative analysis of immune disorders in external genital endometriosis and premature ovarian failure identified distinct autoantibody profiles and lymphocyte subsets, highlighting different pathogenic mechanisms within a shared chain of immunological alterations.
OA: closed
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External genital endometriosis (EGE) and premature ovarian failure (POF) are among the most common and socially significant gynecological diseases, impairing patients' quality of life and forcing women to resort to assisted reproductive technology (ART) programs for infertility treatment. The immune system is recognized as a key player in the development of these pathologies. Objective. To conduct a comparative analysis of immune disorders in common forms of external genital endometriosis and premature ovarian failure and to identify characteristics common to these diseases. Material and methods. An immunological examination was conducted in 47 women with grades III-IV EGE, 46 women with POF, and 31 women in a comparison group undergoing surgical treatment in the gynecology department of the Department of Operative Gynecology and General Surgery of the V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatal Gynecology, Ministry of Health of the Russian Federation. Peripheral blood lymphocyte phenotyping was performed using flow cytometry, and the serum autoantibody profile (M, G) to endometrial antigens, steroid hormones, and steroidogenic enzymes was assessed using enzyme-linked immunosorbent assay. Results. A systemic clinical blood test revealed higher levels of all NK cell subsets, a high level of Th17 cells, and a low level of Tregs in patients with EGE, reflecting the prevalence of chronic processes. In contrast, patients with POF exhibit a predominantly enhanced Th1 response, mediating impaired steroidogenesis. The autoantibody profile in EGE is characterized by a predominance of antibodies (M, G) to tropomyosin-3, tropomodulin-3, α-enolase-1, and estradiol, whereas in POF, autoantibodies (G) to steroidogenic enzymes (aromatase, 20, 22-desmolase, 21-hydroxylase) predominate. Conclusion. Adaptive immune responses, reflecting the imperfections of central T-lymphocyte selection in patients with this pathology, determine complications associated with prolonged sterile inflammation, the development of autoimmune reactions, and the formation of a background that impedes reproductive function. The presence of a characteristic autoantibody profile in external genital endometriosis and premature ovarian failure opens the prospect of developing diagnostic antibody panels for more accurate early diagnosis and the identification of high-risk groups for these diseases.
This reproducibility package presents Model A0, a deterministic threshold model for early evaluation of AI-assisted endometriosis pathway activation in Brazil's health system, using Appropriate Endometriosis Pathway Activation as its primary operational outcome.
OA: green
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Reproducibility package for Model A0, a deterministic threshold model developed for evidence-constrained early evaluation of Health AI and applied to AI-assisted endometriosis pathway activation in Brazil's Unified Health System (SUS). Model A0 separates algorithm performance, reach, clinical translation, system realization, baseline usual-care pathway activation, and proximal pathway outcomes. The model uses Appropriate Endometriosis Pathway Activation (AEPA) as a model-defined proximal operational outcome and deliberately excludes unsupported downstream clinical and economic consequences. The package contains the frozen scientific Face Sheet, computational implementation specification, R code, model outputs, computational verification materials, evidence reference materials, and an Evidence Search and Classification Log. Evidence is classified according to its legitimate modeling role as parameterized evidence, contextual anchor, threshold variable, or excluded downstream evidence. Model A0 is an early health technology assessment and methodological proof-of-concept. It does not evaluate a specific commercial AI product and does not establish clinical effectiveness, cost-effectiveness, a value-based price, reimbursement recommendations, or readiness for adoption. No individual-level participant data were generated or analyzed. Version 4.1 — 16 September 2026
This study found that combining clinical predictors like severe pain and dyspareunia with CA-125 levels effectively identifies patients at high risk for deep infiltrating endometriosis, potentially reducing diagnostic delays.
OA: closed
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Background. One of the key challenges in modern gynecology remains the diagnostic delay in endometriosis, which averages 7 to 12 years from the onset of first symptoms to the establishment of the diagnosis. This delay is primarily due to the polymorphism of clinical manifestations, insufficient awareness among primary care physicians, and the operator-dependent nature of imaging methods, particularly in deep infiltrating forms of the disease, where a high correlation between radiological descriptions and surgical findings is mainly achieved in specialized centers. Objective. To assess the significance of clinical predictors (dysmenorrhea, severe pain ≥7 on the visual analogue scale [VAS], dyspareunia, and reproductive disorders) and the laboratory marker CA-125 in identifying patients at risk for deep infiltrating endometriosis (DIE). Materials and Methods. A single-center study was conducted including 86 women of reproductive age (18—42 years) with a clinical suspicion of endometriosis. The diagnosis was confirmed surgically. Two groups were formed: patients with ovarian endometriosis combined with deep infiltrating endometriosis (n=23) and patients with ovarian endometriosis without deep forms (n=63). Results. In the overall cohort, dysmenorrhea was present in 81.3% of patients, severe pain ≥7 on the VAS in 46.5%, and dyspareunia in 38.3%. The mean serum CA-125 level was 55.2 U/ml. These features were more frequently observed in patients with deep infiltrating endometriosis, supporting their role as markers for referral to expert imaging modalities and specialized endometriosis centers. Conclusion. The integration of clinical predictors with CA-125 measurement represents a simple and practical tool for the early identification of patients at high risk of deep infiltrating endometriosis. This approach may help reduce diagnostic delays and ensure timely selection of optimal management strategies.
Surgically induced endometriosis and tamoxifen-induced adenomyosis models in Wistar rats reproducibly mimic key pathological features, validating their use for investigating disease mechanisms and assessing novel pharmacological treatments.
OA: closed
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Background. Endometriosis and adenomyosis occupy a significant place in the structure of gynecological diseases and are associated with chronic pelvic pain, impaired reproductive function, and a marked reduction in patients’ quality of life. The limited effectiveness of existing treatment approaches, the potential for adverse effects, and the high risk of recurrence necessitate the search for novel pathogenetically grounded therapeutic strategies. This, in turn, underscores the importance of using reproducible experimental models. Objective. To evaluate the potential of experimental models of endometriosis and adenomyosis in Wistar rats based on studies of disease pathogenesis and the preclinical assessment of promising pharmacological treatment strategies. Material and methods. An analysis of original experimental data was performed using a surgically induced model of endometriosis and a tamoxifen-induced model of adenomyosis in Wistar rats. Results. The applied experimental models were shown to provide reproducible development of pathological changes comparable to the key morphological features of endometriosis and adenomyosis. The findings confirm the validity and informativeness of these experimental platforms for investigating pathophysiological mechanisms and for the selection of promising therapeutic approaches. Conclusion. Experimental models of endometriosis and adenomyosis in Wistar rats represent highly informative tools for both fundamental and preclinical research. Their use enables not only the elucidation of key pathogenetic mechanisms but also the substantiation of novel pharmacological treatment strategies, including personalized and non-hormonal approaches.
Background/Objectives: Clinical prediction models may support staged triage in acute pelvic pain, but simplified integer scores can lose information and destabilise point assignments. We evaluated a t…
OA: gold
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Background/Objectives: Clinical prediction models may support staged triage in acute pelvic pain, but simplified integer scores can lose information and destabilise point assignments. We evaluated a tiered clinical–ultrasound prediction pathway and the stability of its simplified score within an ultrasound-documented acute-pelvic-pain cohort. Methods: This single-centre retrospective cohort included 4800 encounters in 4320 women. Encounters from 2013 to 2019 formed the development cohort (n = 3360), and patient-separated encounters from 2020 to 2022 formed the temporal-evaluation cohort (n = 1440). M1 contained clinical and laboratory predictors without imaging variables, M2 added ultrasound descriptors, and M3 added cross-sectional-imaging descriptors. Multiple imputation, ridge logistic regression, patient-level cluster bootstrap, calibration, decision-curve analysis, reader reproducibility and score-stability analyses were used. Results: Urgent pathology occurred in 20.0% of development and 18.0% of temporal encounters. Temporal AUC was 0.841 for M1 and 0.845 for M2 (difference 0.004; 95% CI 0.001–0.009). Because inclusion required documented ultrasound, this difference estimates incremental information from the selected ultrasound descriptors within an already ultrasound-documented pathway and does not estimate the pathway-level benefit of performing ultrasound. The locked integer rule classified 2.9% as low risk, with 99.6% sensitivity and 3.5% specificity. Categorisation accounted for 0.057 of the total 0.060 AUC loss, and 798 distinct score cards arose in 800 bootstrap resamples. Conclusions: Continuous M2 retained good temporal discrimination, but the small M1-M2 difference does not establish whether ultrasound improves pathway-level triage or can safely alter subsequent management. The integer score had low rule-out yield and highly variable point assignments; independent evaluation should prioritise local calibration, clinical utility and score-card stability before implementation.
This prospective cohort study found that primary unilateral ovarian endometriomas under 4 cm significantly reduce mature oocyte retrieval, blastocyst formation, clinical pregnancy rates, and live birth rates compared to tubal factor infertility.
OA: closed
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The incidence of ovarian endometrioma (OMA) among patients undergoing assisted reproductive technology (ART) programs ranges from 10.5 to 21.8%. Despite data on the possible gonadotoxic effect of OMA, their impact on the outcomes of ART programs remains a subject of debate. In this regard, the current study’s key objective was to conduct a comparative analysis of the parameters of the ovarian response and the embryological stage in patients with OMA and in women with tubal-peritoneal factor infertility (TPF) in order to assess the possible impact of OMA on the effectiveness of IVF. Objective. To evaluate the impact of primary OMAs measuring up to 4 cm on the processes of folliculogenesis, oogenesis, early embryogenesis, pregnancy rate (PR), and live birth in ART programs. Material and methods. A prospective cohort study was conducted in the Department of Assisted Reproductive Technologies in the Treatment of Infertility named after Professor B.V. Leonov at the National Medical Research Center for Obstetrics, Gynecology, and Perinatology named after V.I. Kulakov of the Ministry of Health of Russia between 2023 and 2025. Group 1 (the main group) consisted of patients with primary unilateral ovarian cyst <4 cm in size at the time of ovarian stimulation (n=120); Group 2 (comparison group) consisted of patients with tubal factor infertility (n=144). Results. An analysis was conducted of clinical and anamnestic data, parameters of the embryological stage, and outcomes of ART cycles in 264 patients aged 23 to 35 years with preserved ovarian reserve (OR). Patients with primary unilateral EC were characterized by statistically significantly lower levels of antral follicles, a lower frequency of obtaining mature oocytes (MII), and a lower frequency of blastocyst formation, as well as a lower frequency of embryo cryopreservation compared to women with TPF infertility (p<0.05). In group I, cancellation of the treatment cycle was more commonly observed due to the absence of cleavage, unsatisfactory embryo quality, or arrest of embryo development (p<0.001). The CPR per ovarian stimulation cycle, as well as the live-birth rate, in patients with OMA were statistically significantly lower than in the group of patients with TPF infertility (24% vs 40.6%, p=0.005, and 18.7% vs 31.6%, p=0.019, respectively). Conclusions. The presence of primary unilateral OMA up to 4 cm in size in women under 35 years of age with preserved ovarian function.
This narrative review synthesizes evidence that gut and reproductive tract microbiota dysbiosis activates the TLR4-NF-κB-NLRP3 inflammasome axis, driving inflammation and neuroimmune sensitization in endometriosis-associated chronic pelvic pain.
OA: gold
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Introduction Endometriosis (EMs) is increasingly recognized as a chronic inflammatory disease in which innate immune dysregulation plays an important role. Its immunopathological features include macrophage polarization imbalance, with M1-skewed activation in inflamed peritoneal fluid and lesions, reduced natural killer (NK) cell cytotoxicity, adaptive immune alterations including Th2/Treg-skewed profiles reported in some studies, and persistently elevated pro-inflammatory cytokines. The disease affects approximately 10% of women of reproductive age worldwide, and 70%–80% of these patients experience chronic pelvic pain (CPP). Conventional hormonal therapies provide limited relief and are associated with high recurrence rates after withdrawal, yet the immunological drivers of CPP remain incompletely understood. Methods We conducted a narrative review of peer-reviewed literature identified through PubMed, Web of Science, and Scopus up to August 2026. Search terms covered endometriosis, chronic pelvic pain, microbiota/dysbiosis, Toll-like receptor 4, NF-κB, NLRP3 inflammasome, IL-1β/IL-18, neuroinflammation, and immunotherapy. Reference lists were screened for additional relevant studies, and evidence was synthesized by mechanistic theme and appraised according to study design, directness, and consistency. Results Convergent preclinical and observational evidence suggests that dysbiosis of the gut and reproductive tract microbiota may activate TLR4 via lipopolysaccharide, triggering NF-κB signaling and promoting NLRP3 inflammasome priming and activation. This cascade may contribute to M1-skewed pelvic inflammation, adaptive immune alterations, pyroptosis, and neuroimmune sensitization that could facilitate CPP chronification. Host-derived damage-associated molecular patterns and metabolic stress appear to be the principal immediate Signal 2 sources, whereas microbiota-derived signals mainly provide priming and indirect contributions. Direct causal evidence in humans remains incomplete, and conflicting microbiome findings may reflect sampling site, disease stage, and methodological differences. Discussion The microbiome-inflammasome axis represents one potentially important and testable mechanism in EMs-associated CPP rather than a dominant explanatory framework. Promising therapeutic avenues include probiotics/postbiotics, TLR4 antagonists, NF-κB inhibitors, NLRP3 inhibitors, and IL-1β/IL-18-directed therapies, but most remain exploratory and require validation in prospective, mechanism-based trials. Refining this framework may inform immune stratification and precision immunomodulatory therapy for endometriosis-associated pelvic pain.
An Expert Council resolution supports enzyme therapy with bovhyaluronidase azoximer as a promising adjunct to surgical and hormonal treatments for endometriosis, targeting inflammatory, fibrotic, and adhesive components.
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This Resolution was prepared following the Expert Council meeting entitled «Endometriosis as a Fibro-Inflammatory Disease: The Role of Enzyme Therapy in the Comprehensive Management of Endometriosis-Associated Conditions,» held on June 3, 2026, at the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, as part of the XXIX International Congress «New Technologies in the Diagnosis and Treatment of Gynecological Diseases» with an International Course in Endoscopy. The document summarizes current evidence on the clinical heterogeneity of endometriosis, the mechanisms underlying inflammation, fibrogenesis, and postoperative adhesion formation, and addresses surgical and conservative treatment, chronic endometritis, endometriosis-associated infertility, and preparation for assisted reproductive technology programs. Following the discussion, the Expert Council noted the pathophysiological rationale for including bovhyaluronidase azoximer in the comprehensive treatment of endometriosis and associated conditions. Experimental and clinical evidence supports considering enzyme therapy as a promising adjunct to surgical and hormonal treatment targeting the inflammatory, fibrotic, and adhesive components of the disease. Potential areas of its application include postoperative management, pelvic adhesions, and concomitant chronic inflammatory diseases of the pelvic organs.
This Cochrane review assessed progesterone receptor modulators for endometriosis, finding that mifepristone may improve dysmenorrhoea but increase hot flushes, while gestrinone showed variable efficacy compared to other treatments with low-certainty evidence.
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RATIONALE: Endometriosis is defined as the presence of endometrium-like tissue developing outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects on the endometrium, progesterone receptor modulators (PRMs) have been advocated for the treatment of endometriosis. This is an update of a Cochrane review previously published in 2017.
OBJECTIVES: To assess the effectiveness and safety of progesterone receptor modulators (PRMs) in the management of endometriosis.
SEARCH METHODS: To identify studies, we searched online sources, including the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, ClinicalTrials.gov and the WHO (World Health Organization) trial registry up to 16 April 2026. We also checked reference lists and contacted study authors and experts.
ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) comparing PRMs with placebo, no treatment or other medical treatment, in women with symptomatic endometriosis.
OUTCOMES: Our critical outcomes were overall pain; improvement in the most troublesome symptom, including dysmenorrhoea and dyspareunia; and adverse events resulting from the PRM intervention. Our important outcomes included quality of life (QoL) and patient satisfaction with treatment.
RISK OF BIAS: We used the Cochrane tool RoB 2 to assess the risk of bias in the outcomes of this review.
SYNTHESIS METHODS: Two review authors independently assessed studies against the inclusion criteria, extracted data and assessed risk of bias, consulting a third review author where required. We analysed dichotomous outcomes using Mantel-Haenszel odds ratios (ORs), 95% confidence intervals (CIs) and the fixed-effect model. We analysed continuous outcomes using the mean difference (MD) between groups, presented with 95% CIs. We employed the GRADE approach to assess the certainty of the evidence as high, moderate, low or very low.
INCLUDED STUDIES: No new studies were eligible for inclusion in this update. Of the nine studies (922 women) already included in the review, two compared mifepristone versus placebo or compared different doses of mifepristone, and four either compared gestrinone versus danazol, gestrinone versus gonadotropin-releasing hormone (GnRH) analogues or compared different doses of gestrinone. One study compared asoprisnil versus placebo. The asoprisnil study did not provide extractable numerical data and was included in the narrative synthesis only. Two of the studies did not report any of the review's prespecified outcomes.
SYNTHESIS OF RESULTS: Certainty of the evidence We judged the certainty of evidence as low to very low. The main limitations of the evidence were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition), very serious imprecision (associated with low event rates and wide confidence intervals, with some large effect estimates) and serious indirectness (outcomes assessed in selected subgroups). PRM versus placebo Mifepristone versus placebo These results are based on one study (360 participants) that measured outcomes after three months. The study did not report overall pain. At three months, mifepristone may improve dysmenorrhoea (OR 0.07, 95% CI 0.03 to 0.15; 1 study, 342 participants; low-certainty evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. We are uncertain whether mifepristone improves dyspareunia (OR 0.23, 95% CI 0.10 to 0.51; 1 study, 223 participants; very low-certainty evidence). However, mifepristone may increase hot flushes (OR 28.79, 95% CI 3.93 to 210.73; 1 study, 360 participants; low-certainty evidence). Mifepristone may make little or no difference after three months of treatment to the prevalence of nausea (OR 1.72, 95% CI 0.20 to 15.03; 1 study, 360 participants; low-certainty evidence). PRM versus other medical treatment Gestrinone versus danazol These results are based on two studies (302 participants) that measured outcomes after six months. We are uncertain of the effects of gestrinone relative to danazol on the improvement of overall pain (dichotomous outcome: participants reporting no or mild pelvic pain counted as 'improved') (OR 0.47, 95% CI 0.04 to 5.70; 1 study, 38 participants), dysmenorrhoea (Not estimable; 1 study, 38 participants), or dyspareunia (OR 1.00, 95% CI 0.13 to 7.94; 1 study, 38 participants (all very low-certainty evidence). We are uncertain about the effects of gestrinone relative to danazol on hot flushes (OR 0.79, 95% CI 0.50 to 1.26; 2 studies, 302 participants; very low-certainty evidence). There may be little or no difference between gestrinone and danazol in rates of nausea (OR 1.36, 95% CI 0.84 to 2.19; 2 studies, 302 participants; low-certainty evidence). Gestrinone versus a GnRH analogue (leuprorelin) These results are based on one study (55 participants) that measured outcomes after six months. There may be little to no difference between gestrinone and leuprorelin in non-menstrual pain (MD -0.41, 95% CI -1.76 to 0.94; 1 study, 55 participants; low-certainty evidence). Women taking gestrinone may have higher dysmenorrhoea scores than those taking leuprorelin (MD 0.82, 95% CI 0.15 to 1.49; 1 study, 55 participants; low-certainty evidence), but gestrinone may improve dyspareunia more than leuprorelin (MD -1.16, 95% CI -2.08 to -0.24; 1 study, 52 participants; low-certainty evidence). There may be lower rates of hot flushes with gestrinone than leuprorelin (OR 0.20, 95% CI 0.06 to 0.63; 1 study, 55 participants; low-certainty evidence). There may be little or no difference between gestrinone and leuprorelin in rates of nausea (OR 1.04, 95% CI 0.06 to 17.49; 1 study, 55 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS: Mifepristone may improve dysmenorrhoea in women with endometriosis, but it might increase the prevalence of adverse events, such as hot flushes. The evidence is very uncertain regarding its effect on dyspareunia. Gestrinone may be less effective than leuprorelin in treating dysmenorrhoea, but it may improve dyspareunia. It may be associated with lower rates of hot flushes and similar rates of nausea. We are uncertain about the effect of gestrinone compared to danazol. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.
FUNDING: This Cochrane review had no dedicated funding.
REGISTRATION: Protocol (2012) DOI: 10.1002/14651858.CD009881 Review (2017) DOI: 10.1002/14651858.CD009881.pub2.
The authors provide clinical reflections regarding the use of menopausal hormone therapy following endometriosis-related hysterectomy.
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Dear Editor,We read with great interest the nationwide Finnish register-based study by Sipilä et al. on menopausal hormone therapy (MHT) use after hysterectomy among women with surgically verified ...
This retrospective analysis of 150 patients found that pelvic MRI parameters, including junctional zone thickness in adenomyosis and FIGO classification with apparent diffusion coefficient values in leiomyoma, are independently associated with symptom presence.
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Abstract Objective To evaluate the relationship between pelvic MRI findings and symptom presence in patients with leiomyoma and adenomyosis, and to determine whether these imaging parameters are independently associated with the presence of symptoms. Methods This single-center retrospective study enrolled 150 patients who underwent pelvic MRI and were stratified into three groups based on pathological diagnosis: leiomyoma only ( n = 75), adenomyosis only ( n = 36), and concurrent pathology ( n = 39). Leiomyoma assessment included International Federation of Gynecology and Obstetrics (FIGO) classification, maximum diameter, cavity distortion, and apparent diffusion coefficient (ADC) values; for adenomyosis, junctional zone (JZ) thickness and involvement pattern served as primary parameters. Composite MRI burden scores were constructed for each pathology. Imaging features independently associated with symptom presence were identified by binary logistic regression, and model discrimination was assessed with internal validation by bootstrap resampling. Results Symptom prevalence differed substantially across groups — 64.0% in the leiomyoma group, 72.2% in the adenomyosis group, and 97.4% in patients with concurrent pathology ( p < 0.001). Each 1 mm increase in JZ thickness raised the odds ratio (OR) of symptoms 1.31-fold in the adenomyosis group (OR = 1.31; 95% confidence interval [CI]: 1.08–1.58; p = 0.006), with JZ thickness correlating with pelvic pain at r = 0.61. FIGO type 0–2 location was the imaging feature most strongly associated with abnormal uterine bleeding (AUB) among leiomyoma patients (OR = 6.82; 95% CI: 2.87–16.21; p < 0.001). ADC values were markedly lower in symptomatic leiomyomas (0.91 vs. 1.14 × 10⁻³ mm²/s; p < 0.001). The apparent area under the curve (AUC) was 0.809 for the symptom model and 0.821 for the AUB model, with optimism-corrected values of 0.785 and 0.796, respectively, on bootstrap internal validation. Conclusion Pelvic MRI findings in leiomyoma and adenomyosis are independently associated with the presence of symptoms, with JZ thickness, leiomyoma localization relative to the endometrial cavity, lesion size, and cavity distortion showing the strongest associations. Because these associations were derived and tested within a single cross-sectional sample, they should be regarded as hypothesis-generating and require prospective, externally validated confirmation before they can guide treatment decisions.
An evaluation of fifteen endometriosis scenarios found that artificial intelligence generated recommendations with 93.3% overall concordance to ESHRE guidelines, demonstrating strong alignment in most domains despite variability in complex fertility cases.
OA: hybrid
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Objective: This study aimed to evaluate how closely artificial intelligence (AI)- generated clinical recommendations correspond with established international guidelines for endometriosis management, using structured clinical scenarios.Methods: This study assessed the consistency of AI-generated responses with the 2022 ESHRE Endometriosis Guideline. Fifteen predefined clinical scenarios were designed to reflect the main areas of endometriosis management. Each scenario was submitted using a standardized prompt to ensure consistency. AI responses were evaluated using predefined guideline-based assessment matrices to determine concordance and to explore performance differences across clinical domains.Results: A total of 45 AI-generated responses across 15 clinical scenarios were evaluated. Overall concordance with ESHRE guideline-based reference answers was 93.3% (42/45). Diagnostic scenarios demonstrated 88.9% concordance, while medical management, surgical/multidisciplinary, and high-risk scenarios demonstrated 100% concordance. Fertility-related scenarios showed 83.3% concordance. Complete inter-run consistency was observed in 13 of 15 scenarios (86.7%), with variability limited to Cases 2 and 3. Fleiss’ kappa indicated a high level of inter-run agreement within the evaluated scenarios (κ = 0.831; 95% CI, 0.583–1.000).Conclusion: Artificial intelligence systems show meaningful alignment with evidence-based guidance in fundamental aspects of endometriosis management. However, variability in complex scenarios reveals important limitations. Although AI tools may support education or serve as an adjunct in clinical decision-making, they cannot replace expert clinical judgment in specialized gynecologic care.
BackgroundVitamin D deficiency is a global public health concern, and women of reproductive age represent a particularly vulnerable population. Accurate measurement of serum 25-hydroxyvitamin D [25(OH…
OA: gold
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BackgroundVitamin D deficiency is a global public health concern, and women of reproductive age represent a particularly vulnerable population. Accurate measurement of serum 25-hydroxyvitamin D [25(OH)D] is therefore essential for reliable clinical assessment. This study aimed to evaluate the analytical performance of the Innodx vitamin D assay for 25(OH)D measurement and to investigate the prevalence of vitamin D deficiency among women of reproductive age in southeastern China.MethodsThis cross-sectional study enrolled women of reproductive age (20-45 years) who sought medical services at Xiamen Maternal and Child Health Hospital in China between November 2023 and September 2025. Serum 25(OH)D levels were measured to determine vitamin D status using the Innodx vitamin D assay (Xiamen Innodx Biotech Co., Ltd., Xiamen, China). The analytical performance of the assay was validated according to Clinical and Laboratory Standards Institute (CLSI) guidelines, covering precision, accuracy, linearity, and interference. A method comparison was performed against liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the Roche electrochemiluminescence assay. Based on the measured levels, vitamin D status was categorized as deficient (< 20 ng/mL), insufficient (≥20, < 30 ng/mL), or sufficient (≥ 30 ng/mL).ResultsThe intra-assay coefficients of variation (CV) were 3.18%, 2.09%, and 1.86% at three concentration levels (5, 25, and 100 ng/mL), while intermediate precision CVs were 4.34%, 3.64%, and 3.17%, respectively. Accuracy testing showed bias of 4.20% and 3.26% at 20 and 50 ng/mL. The assay demonstrated excellent linearity (R2 = 0.998) across the range of 4.0-150.0 ng/mL. No significant interference was observed from hemoglobin (100 mg/dL), bilirubin (40 mg/dL), triglycerides (400 mg/dL), or rheumatoid factor (600 IU/mL). In method comparison with LC-MS/MS, the Innodx vitamin D assay demonstrated strong concordance with a Pearson correlation coefficient of r = 0.970. When compared with the Roche vitamin D assay, the Innodx showed better correlation with LC-MS/MS. Among 495 women, the mean 25(OH)D concentration was 20.50 ± 7.88 ng/mL, with 88.9% (95% CI: 86.1%, 91.7%) having vitamin D deficiency or insufficiency. Women aged ≤ 25 years showed significantly lower levels (18.38 ± 6.26 ng/mL) compared to older groups (31-35 years: 23.31 ± 8.97 ng/mL; > 35 years: 23.72 ± 8.56 ng/mL) (P < 0.05).ConclusionThe Innodx vitamin D chemiluminescence assay demonstrated satisfactory analytical performance for clinical use. Our findings reveal a high prevalence of vitamin D deficiency among reproductive-age women in southeastern China, particularly in younger age groups, highlighting the need for public health interventions.
This article titled "Chronic Inflammation and Female Infertility: An Integrative TCM Diagnostic and Therapeutic Approach, with Clinical Case Analysis" is published in the New England Journal of Tradit…
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This article titled "Chronic Inflammation and Female Infertility: An Integrative TCM Diagnostic and Therapeutic Approach, with Clinical Case Analysis" is published in the New England Journal of Traditional Chinese Medicine. 本文《慢性炎症與女性不孕——中醫整合診療思路與臨床病案解析》发表于《新英格兰中医杂志》(New England Journal of Traditional Chinese Medicine)。 Summary:New York TCM Gynecology & Infertility Center, NY 11374 | 2. iHealth Integrative Acupuncture Clinic, CA 95050 Abstract: Chronic low-grade inflammation has been increasingly recognized as a common pathological link across diverse reproductive conditions, including polycystic ovary syndrome (PCOS), endometriosis, chronic endometritis (CE), and unexplained or recurrent pregnancy loss (RPL). Prolonged inflammation impairs folliculogenesis, disrupts steroidogenesis, diminishes endometrial receptivity, and compromises implantation. This paper proposes an integrative TCM approach based on the triad of "Identify the Constitution—Differentiate the Pattern—Correct the Cause" (Shi Ti — Bian Zheng — Jiu Yin). Through two representative clinical cases, we demonstrate that clearing inflammatory heat, transforming phlegm-damp, resolving blood stasis, and tonifying the kidney restore immune homeostasis and optimize reproductive outcomes. Keywords: Female Infertility; Chronic Low-Grade Inflammation; TCM Inflammatory Constitution; Polycystic Ovary Syndrome; Chronic Endometritis; Integrative Chinese and Western Medicine 5. 1 Introduction: Chronic Low-Grade Inflammation in Reproductive Pathophysiology Infertility affects approximately 10%–15% of couples worldwide. Emerging immunological research reveals that sustained low-grade systemic and localized pelvic inflammation acts as a silent destroyer of female fecundity. Elevated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines disrupt the follicular microenvironment, induce granulosa cell apoptosis, impair mitochondrial energetics in oocytes, and alter endometrial decidualization. In traditional Chinese medicine (TCM), while the classical terminology does not encompass "cytokines" or "macrophage polarization," ancient physicians recognized that internal constraint of heat-toxin, damp-heat accumulation, and persistent blood stasis injure the Ren and Chong vessels and destabilize the uterine threshold (Bao Gong). ... 内容简介:English中文 Guoping Zheng¹*, Yuxin Wang² · Corresponding author: Guoping Zheng 1. 慢性炎症與女性不孕——中醫整合診療思路與臨床病案解析 鄭國平¹*,王宇歆² · 美國 1. 紐約中醫婦科及不孕症中心;2. 加州愛康針灸診所;* 通訊作者:鄭國平(health. com) 【摘要】 近年來,慢性低度炎症(chronic low-grade inflammation)被認爲是多種慢性疾病的重要共同病理基礎。 越來越多研究發現,多囊卵巢綜合徵(PCOS/POMS)、子宮內膜異位症、反覆種植失敗(RIF)、反覆妊娠丟失(RPL)等多種女性生殖疾病的發生發展,均可能與慢性炎症、免疫失衡及代謝異常密切相關。 本文首先從現代醫學角度概述慢性炎症的病理生理及與女性不孕關聯機制;探討體質、生活方式及環境因素等在慢性炎症形成中的作用;繼而結合中醫體質學說,引出"炎性體質"的概念,認爲中醫所論之寒、熱、痰、瘀等內生病邪,可能是慢性炎症在不同體質背景下的表現形式之一。 在此基礎上,作者根據多年臨牀經驗總結提煉出"識體—辨證—糾因"與"治標爲先—標本同治—治本收功"相結合的中醫整合診療思路。 前者強調識別體質偏頗、辨析病機特點並糾正導致炎症持續存在的生活方式及環境因素;後者強調根據疾病不同階段分層幹預,在改善局部病理狀態的同時,逐步恢復整體功能穩態。 通過多囊卵巢綜合徵(PCOS)及免疫性反覆妊娠丟失(RPL)兩個臨牀病案,本文展示了上述診療思路在不孕症臨牀中的具體應用,其結果提示:改善代謝異常、降低炎症負荷、調節免疫失衡及重建有利於受孕和妊娠維持的整體內環境,與患者生殖功能恢復及妊娠成功密切相關。 ...
This paper reviews gynaecological causes of acute pelvic pain in women, specifically addressing conditions such as endometriosis and adenomyosis alongside other twists, tears, and tumours.
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This review evaluates the endocannabinoid system as a therapeutic target for endometriosis-associated pain, finding that cannabinoids suppress pain signaling, inflammation, and lesion proliferation through interactions with receptors in endometriotic tissue.
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Endometriosis is a chronic gynecological disorder affecting approximately 10% of reproductive-age women, characterized by the ectopic growth of endometrial tissue and severe pain, including dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, and dyschezia. Current treatments are limited in efficacy and associated with significant side effects, underscoring the urgent need for novel therapeutic strategies. The endocannabinoid system (ECS) has emerged as a promising therapeutic target, given its well-established roles in pain modulation, inflammation, and immune regulation. Epidemiological evidence demonstrates that women with endometriosis increasingly use cannabis for symptom self-management, yet the underlying mechanisms remain poorly characterized. This review integrates preclinical and human evidence to comprehensively evaluate the mechanistic basis of cannabinoid efficacy in endometriosis-associated pain. Evidence from in vitro studies and animal models indicates that cannabinoids target three main mechanisms of endometriosis-associated pain, including inflammation, nociceptive signaling, and lesion proliferation. Cannabinoids suppress pain signaling and sensitization by interacting with cannabinoid and non-cannabinoid receptors expressed in endometriotic lesions. Cannabinoids attenuate endometriosis-induced inflammation by inhibiting proinflammatory cytokine signaling and reducing the release of inflammatory mediators by mast cells and peritoneal macrophages. Cannabinoids also exert antiproliferative effects in endometriosis models, thereby suppressing the growth of endometriotic lesions. In conclusion, the ECS is a promising therapeutic target for endometriosis-associated pain, as it regulates nociception, inflammation, and proliferation. These promising findings highlight the potential therapeutic benefits of cannabinoids for endometriosis-associated pain, warranting the need for clinical trials to evaluate the safety and effectiveness of cannabinoid therapies in endometriosis.
This paper details the translation of expert endometriosis MRI guidelines into structured radiology reporting using generative AI to enhance clinical utility and standardization.
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This one-year observational study at Kathmandu Model Hospital characterized 65 patients undergoing laparoscopic surgery for endometriosis, finding that advanced-stage disease was prevalent and the procedure demonstrated safety with low complication rates.
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Introduction Endometriosis is a common gynaecological condition affecting women of reproductive age group. It is a significant cause of dysmenorrhea and subfertility. Laparoscopy remains the gold standard for diagnosis and management. However, data on patient profiles and surgical characteristics are limited. This study was conducted with an aim to study about the profile of patients undergoing laparoscopic surgery for endometriosis at Kathmandu Model Hospital. Methods This is an observational study conducted in the department of obstetrics and gynaecology at Kathmandu Model Hospital Institute of Health Sciences over one year period from January to December 2025 among all patients who underwent Laparoscopic surgery for endometriosis. Data regarding demographic characteristics, symptoms, revised American Society of Reproductive Medicine (rASRM) staging, type of surgery, perioperative complications were collected in predesigned proforma and then entered in SPSS version 20. Results The rate of endometriosis surgery was 10.48 % (65 cases out of a total of 620 gynaecological surgery) during the study period. The mean age of the patient was 34.5±7.9 years. Dysmenorrhea was the most common presenting symptom (84.6%) followed by heavy menstrual bleeding and subfertility (38.5% each). Majority of patients (98.4%) belonged to advanced stage disease with 66.2% in stage IV and 32.2% in stage III. Fertility preserving surgery was performed in 55.4% while 44.6% underwent radical surgery. History of previous surgery for endometriosis was seen in 21.5%. Overall complication rate was 6.1%. The mean duration of hospital stay was 3.37±0.65 days. Conclusions Endometriosis has with varied clinical presentation occurring mainly in reproductive age group. Laparoscopic surgery for endometriosis is safe even in advanced stage disease and those with previous abdominopelvic surgery with low complication rates.
In women with colorectal endometriosis, laparoscopic resection improved gastrointestinal and endometriosis-related quality of life over 24 months, with pain severity being a stronger predictor of long-term outcomes than bowel dysfunction.
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OBJECTIVES: To assess changes in bowel function, pain symptoms, and endometriosis-related quality of life over 24 months after laparoscopic colorectal resection with natural orifice specimen extraction (NOSE) and conventional abdominal specimen extraction (CASE) in patients with colorectal endometriosis. Secondary objectives were to investigate the impact of bowel dysfunction and pain severity on gastrointestinal quality of life.
MATERIAL AND METHODS: This prospective cohort study included 73 women with colorectal endometriosis who underwent laparoscopic colorectal surgery with NOSE or CASE between 2019 and 2020. Outcomes were assessed preoperatively and at 6, 12, 18, and 24 months postoperatively using the low anterior resection syndrome (LARS) score, Gastrointestinal Quality of Life Index (GIQLI), Endometriosis Health Profile-30 (EHP-30), and Visual Analog Scale (VAS) pain scores. Linear regression analyses were performed to evaluate the possible interaction of bowel dysfunction and pain symptoms preoperatively and 24 months after surgery.
RESULTS: A total of 73 patients were included in the analysis. Bowel function followed a characteristic temporal pattern after surgery. Mean LARS scores increased from 12.62 ± 10.72 preoperatively to 15.66 ± 13.54 at 6 months (p = 0.011), followed by significant decreases at 12 months (10.77 ± 10.61, p < 0.001) and 18 months (7.39 ± 7.61, p < 0.001), with stabilization thereafter at 24 months (7.31 ± 7.46 at 24 months, p = 0.380). Gastrointestinal quality of life improved significantly, with GIQLI scores increasing from 98.75 ± 23.68 preoperatively to 111.48 ± 17.70 at 6 months (p < 0.001) and remaining stable at 12 months (114.72 ± 18.60, p = 0.059), 18 months (114.38 ± 18.13, p = 0.443), and 24 months (112.81 ± 18.81, p = 0.181). Mean EHP-30 pain scores decreased markedly from 12.04 ± 12.40 preoperatively to 0.33 ± 0.85 at 6 months (p < 0.001). Although a modest increase was observed between 6 and 12 months (2.82 ± 6.00, p < 0.001), pain scores remained substantially lower than baseline at 24 months (2.40 ± 5.61, p = 0.074). Linear regression analysis demonstrated significant associations between both pain severity and bowel dysfunction with GIQLI. EHP-30 pain scores explained a greater proportion of GIQLI variance than LARS scores both preoperatively (adjusted R² = 0.63 vs 0.046) and at 24 months (adjusted R² = 0.275 vs 0.182).
CONCLUSIONS: Laparoscopic colorectal resection for deep endometriosis was associated with favorable 24-month outcomes, including improved gastrointestinal quality of life, endometriosis-related quality of life, and pain symptoms, with bowel function recovering after transient early postoperative deterioration. Long-term GIQLI was more strongly associated with residual pain than with LARS-defined bowel dysfunction, emphasizing pain control as a key determinant of patient-reported outcomes after colorectal surgery for endometriosis.
2026·American journal of physiology. Endocrinology and metabolism
This meta-analysis found that BDNF levels are dysregulated in endometriosis and other infertility conditions, although substantial heterogeneity and publication bias limit the robustness of these findings.
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Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival and development, and is also involved in oogenesis, follicle recruitment, and germ cell survival, which could impact reproduction. However, in humans, the relationship between BDNF levels and infertility remains controversial. The aim of this systematic review and meta-analysis was to explore the available evidence on the variation of BDNF levels in the body fluids of women and men and their interface with different conditions that could affect reproductive functions. Data were independently extracted by 2 reviewers. A systematic search was performed on six databases. Of the 1,735 studies identified, 20 were included in the qualitative synthesis and 15 in the meta-analysis. Meta-analysis was performed for all studies regarding infertility markers, and then, specifically, only for studies that evaluated endometriosis and other cases of infertility. Of the 20 studies included in the systematic review, only 1 evaluated sperm dysfunction in men. Of the 19 studies conducted in women, 13 evaluated endometriosis, 4 evaluated amenorrhea, 1 evaluated premature ovarian failure, and 1 evaluated different outcomes on childbirth. In the meta-analysis, BDNF levels were associated with endometriosis and other conditions that lead to infertility. Our findings confirm that BDNF levels are dysregulated in infertility conditions. However, the analyses showed substantial heterogeneity and, in some cases, evidence of publication bias. Further studies evaluating infertility in men and that include BMI, estrogen levels, and the menstrual cycle phase at the time of collection in women are crucial for obtaining more robust results.
Integrative bioinformatics and experimental validation identified SLC12A8 as a biomarker for the malignant transition from endometriosis to endometriosis-associated ovarian cancer, where its elevated expression modulates cell proliferation, invasion, and migration.
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Endometriosis (EM) is a chronic inflammatory, estrogen‑dependent benign gynecological disorder. A subset of patients with EM may subsequently develop endometriosis‑associated ovarian cancer (EAOC), implying a biological continuum between these two conditions. Nevertheless, the molecular events underlying the progression from benign endometriotic lesions toward EAOC remain incompletely characterized. In this study, transcriptomic datasets retrieved from the GEO database were interrogated through differentially expressed gene screening, functional enrichment analysis, and weighted gene co‑expression network analysis (WGCNA) to identify key genes and pathways relevant to EM and EAOC. Candidate genes were further prioritized by integrating survival analysis via the Kaplan‑Meier Plotter, LASSO regression, random‑forest modeling, and CIBERSORT immune‑infiltration profiling. Loss and gain‑of‑function cellular models were established using siRNA and overexpression plasmids, and in‑vitro functional assays were performed to characterize the phenotypic effects of target genes.We identified several candidate genes associated with EM and EAOC and evaluated their discriminatory performance. Among them, SLC12A8 elevated expression across EM and EAOC tissues and exhibited moderate diagnostic capacity. Higher SLC12A8 expression was also associated with poorer prognosis in EAOC patients. In‑vitro experiments further demonstrated that SLC12A8 modulates proliferation, invasion, and migration in both EM and EAOC cell lines. Collectively, our exploratory research findings support SLC12A8 as a candidate functional mediator and potential biomarker linked to EM‑EAOC pathological progression, thereby extending the mechanistic understanding of these disorders.
This protocol outlines a scoping review to map global evidence on the associations between environmental and climatic factors and human fertility-related outcomes.
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BackgroundIncreasing attention has been directed toward environmental and climatic exposures as potential factors influencing reproductive function and fertility-related outcomes. However, the available evidence is dispersed across populations, study designs, and exposures.ObjectiveThe primary objective of this scoping review is to map and synthesize the extent, range, and nature of the global evidence on how environmental and climatic factors influence human fertility outcomes. We aim to capture the environmental and climatic exposures that have been studied, characterize the fertility-related outcomes assessed, and summarize the associations reported between these exposures and outcomes.MethodsThe present scoping review will systematically map global evidence on environmental and climatic factors in relation to human fertility-related outcomes. We will include human studies examining associations between environmental or climatic exposures and fertility-related outcomes, including measures of reproductive function, fertility potential, and reproductive success. A comprehensive search will be conducted across major electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library. Covidence will be used for screening and data management. Reviewers will independently screen studies for eligibility, with disagreements resolved through discussion or consultation with a third reviewer. Data will be extracted using a standardized form, which will be piloted and refined. Furthermore, the methodological quality of included studies will be appraised using the relevant JBI critical appraisal checklist according to study design. Findings will be synthesized using narrative synthesis, structured tables, and appropriate visual methods. The review will be reported in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines.ResultsTitle and abstract screening was completed in May 2026, and full-text screening is underway. Data extraction and synthesis will be conducted after completion of study selection. The review will provide a structured synthesis of available human evidence, summarizing the range of environmental and climatic exposures studied, fertility-related outcomes assessed, and characteristics of included studies. It will also describe the direction and significance of reported findings, including consistent, mixed, or inconclusive evidence, and identify key gaps in the literature to inform future research priorities.ConclusionsAs global fecundity trends evolve and concerns about environmental exposures and climate change intensify, understanding how the environment influences reproductive potential is urgent. This work aligns with global development priorities by addressing the intersection of Sustainable Development Goals 3 (good health and well-being) and 13 (climate action).
Background and aimsSleep disturbances are increasingly recognized in women with polycystic ovary syndrome (PCOS), but the evidence remains inconsistent. We conducted a meta-analysis to evaluate object…
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Background and aimsSleep disturbances are increasingly recognized in women with polycystic ovary syndrome (PCOS), but the evidence remains inconsistent. We conducted a meta-analysis to evaluate objective sleep abnormalities and subjective sleep complaints in women with PCOS.MethodsWe systematically reviewed and meta-analyzed observational studies comparing women with PCOS and women without PCOS. Primary outcomes were objective sleep parameters assessed by polysomnography, while secondary outcomes included subjective sleep quality and daytime sleepiness measured using validated questionnaires, including the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI).ResultsTwenty-one studies involving 1,255 women with PCOS and 1,523 controls were included. Women with PCOS had a significantly higher apnea-hypopnea index compared to controls (SMD = 1.030, 95% CI: 0.408 to 1.653, p = 0.001). Additionally, women with PCOS exhibited significantly higher scores on both PSQI and ESS questionnaires compared to the control group (SMD: 0.435; 95% CI: 0.190 to 0.680, p = 0.001, and SMD: 1.263; 95% CI: 0.335 to 2.191, p = 0.008, respectively). Meta-analysis demonstrated longer stage 1 sleep in PCOS group (SMD: 2.356; 95% CI: 0.224 to 4.488, p = 0.03). However, REM sleep, stage 2, and stages 3 and 4 showed no significant differences between groups.ConclusionThis study highlights significant differences in some sleep-disordered breathing indices, sleep structure, and objective sleep quality measures between women with PCOS and control groups. Subjective sleep measures demonstrated more pronounced differences than some objective assessments, suggesting a greater impact on perceived sleep disturbances.
2026·Nigerian medical journal : journal of the Nigeria Medical Association
This cross-sectional study of Nigerian women found a 34.4% infertility prevalence, identifying male factors as the primary cause and noting endometriosis in 9.7% of cases.
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BACKGROUND: Infertility is a major reproductive health problem with significant social, psychological, and economic consequences. In Nigeria, cultural expectations surrounding childbearing may intensify stigma and emotional distress, particularly among women. This study aimed to determine the prevalence and causes of infertility among women attending the Gynaecology Clinic of Central Hospital Agbor.
METHODOLOGY: This cross-sectional study involves all women presenting with infertility who completed the basic fertility investigations at the CHA gynecology clinic between January 1st and December 31st, 2024. Participants were recruited after obtaining informed consent using a consecutive sampling technique over a period of one year. A data extraction form was used to document the sociodemographic characteristics, clinical history, and investigation results. The data were analyzed using IBM SPSS for Windows, version 25.
RESULTS: The average age of the participants in the study was 32.5 ± 5.8 years. The study found an infertility prevalence of 34.4%, with primary and secondary infertility comprising 41.3% and 58.7%, respectively. The commonest associated factor responsible for infertility in this study was male factor infertility, 37.4%, while female, combined, and unexplained factors made up 33.0%, 16.0%, and 13.6%. Tubal blockage was the most commonly identified factor associated with female infertility (19.4%), while Anovulation, endometriosis, and uterine fibroids were the associated factors in 14.1%, 9.7%, and 8.7%, respectively.
CONCLUSION: This study highlights a high infertility rate of 34.4% among women presenting to a gynecology clinic in South-South Nigeria, with male infertility being the predominant factor. This underscores the need for comprehensive evaluation and management of both partners in infertility cases, emphasizing the importance of male factor assessment in addressing this significant public health concern.
This narrative review addresses diagnostic and therapeutic challenges in endometriosis, highlighting the shift from invasive laparoscopy to non-invasive multimodal imaging and discussing strategies to improve symptom control and treatment outcomes.
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Endometriosis is a multifactorial inflammatory disease associated with altered estrogen signaling, immune dysregulation, and the presence of endometrial-like tissue outside the uterine cavity. It affects nearly 10% of women of reproductive age and can substantially reduce quality of life through chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. Despite its prevalence, diagnosis and treatment remain difficult because symptoms are heterogeneous and frequently nonspecific, contributing to an average diagnostic delay of seven to ten years. This review summarizes the shift from invasive diagnostic laparoscopy toward non-invasive multimodal imaging, particularly transvaginal sonography (TVS) and magnetic resonance imaging (MRI), for disease assessment. It also discusses current medical, surgical, and fertility-preservation strategies aimed at improving symptom control and treatment outcomes in affected patients. Early diagnosis and a multidisciplinary approach may help reduce delays in treatment and improve long-term clinical outcomes.
This supplementary file provides the COREQ checklist for a qualitative interview study exploring the experiences of individuals living with adenomyosis and involuntary childlessness.
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This qualitative study identified coping strategies employed by 20 women living with adenomyosis and experiencing involuntary childlessness through electronic supplement analysis.
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Electronic supplement 2: Coping strategies described by participants, n = 20 (own illustration). Note: Multiple answers possible.
This supplementary file provides the interview guides used for patients and gynecologists in a qualitative study on living with adenomyosis and involuntary childlessness, along with the complete coding systems employed.
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Electronic supplement 1: Interview guides and coding systems. Part 1: Interview guide for patients and gynecologists. Part 2: Complete coding systems.
This meta-analysis investigates genome-wide DNA methylation patterns in endometriosis to identify potential epigenetic biomarkers associated with the disease.
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