What's new in endo & adenomyosis research

Patient-level extracted dataset compiled for a systematic review of primary cutaneous umbilical endometriosis (Villar’s nodule) reported in the literature. Data were extracted on a per-patient basis from published case reports and case series.

Introduction We report an unexpected case of mesonephric-like adenocarcinoma initially treated as a diffuse adenomyosis in a patient presenting with primary infertility. The aim of this report is to raise clinical awareness about the risk of a diagnostic pitfall where an unexpected malignancy can mimic diffuse adenomyosis. The patient’s main concerns and important clinical findings: A 41-year-old patient referred to a tertiary minimally invasive gynecological center in June 2023 for primary infertility, heavy menstrual bleeding, and a 5 x 6 cm myometrial mass diagnosed as diffuse adenomyosis on ultrasound scan. The primary diagnoses, interventions, and outcomes An open cytoreductive resection of adenomyosis with uterine cavity reconstruction was planned due to worsening abnormal uterine bleeding and two failed in vitro fertilization attempts. An unexpected Mesonephric-like adenocarcinoma with only small foci of healthy tissue was identified on histopathological examination, and immunohistochemical staining. Consequently, the patient had a total abdominal hysterectomy with bilateral salpingo-oophorectomy and systematic pelvic lymphadenectomy. This was followed by six cycles of paclitaxel and carboplatin plus pembrolizumab-based immunotherapy. Conclusions This case highlights the importance of thorough evaluation of all atypical myometrial lesions, including adenomyosis, where pre-conception surgical excision and histopathological evaluation are often deferred in most patients.

PURPOSE OF REVIEW: Adenomyosis is increasingly diagnosed in reproductive-aged patients, particularly those undergoing assisted reproductive technology, due to advances in imaging and standardized diagnostic criteria. Its association with infertility and adverse obstetric outcomes has prompted growing interest in understanding disease mechanisms, prognostic features, and optimal fertility-focused management strategies. This review summarizes recent evidence on the pathophysiology, diagnosis, and treatment of adenomyosis in the context of reproductive outcomes. RECENT FINDINGS: Emerging data highlight multifactorial mechanisms linking adenomyosis to impaired implantation and placentation, including hyperestrogenism, progesterone resistance, junctional zone disruption, immune dysregulation, and chronic inflammation. Studies evaluating imaging features suggest that disease phenotype, lesion size, uterine volume, and junctional zone involvement may influence reproductive outcomes, though findings remain inconsistent. Treatment strategies are evolving, with gonadotropin-releasing hormone agonists, levonorgestrel intrauterine systems, and aromatase inhibitors widely used, and growing evidence supporting pretreatment with prolonged gonadotropin-releasing hormone agonists. Adjunct approaches targeting inflammation, uterine contractility, and hormonal pathways are under investigation. Fertility-preserving procedures, including high-intensity focused ultrasound and adenomyomectomy, show promising but heterogeneous reproductive results. SUMMARY: Adenomyosis remains a clinically heterogeneous condition requiring individualized fertility management. Standardized diagnostic frameworks and well designed prospective studies are needed to clarify prognostic factors and optimize therapeutic strategies to improve reproductive outcomes.

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Background Elagolix and Myfembree are gonadotropin-releasing hormone (GnRH)-pathway therapies used for endometriosis, but their post-marketing safety reporting patterns remain incompletely characterized. Because spontaneous reporting databases are susceptible to reporting bias and differential market exposure, comparative analyses require cautious interpretation. Methods We analyzed quarterly data from the FDA Adverse Event Reporting System (FAERS) from 2015Q3 to 2026Q1. Deduplicated female reports with endometriosis-related indications were identified and classified as elagolix, Myfembree, or other endometriosis-related reports. The primary analysis consisted of drug-specific case-noncase disproportionality analyses for elagolix and Myfembree separately within the female endometriosis reporting background. A direct elagolix-versus-Myfembree head-to-head analysis was performed as a secondary analysis. Reporting odds ratios (RORs), proportional reporting ratios (PRRs), and information components (ICs) were calculated at the preferred term (PT) level. Sensitivity analyses included serious-report-only, healthcare-professional-only, physician-only, complete-age, reporter-type-stratified, overlapping-market-period, and bootstrap analyses. Results A total of 4,428 deduplicated female endometriosis-related reports were included, comprising 1,744 elagolix reports, 280 Myfembree reports, and 2,404 other endometriosis-related reports. Serious reports accounted for 31.2% of elagolix reports and 26.8% of Myfembree reports. In drug-specific case-noncase analyses, elagolix showed robust disproportionality signals for hot flush, night sweats, and suicidal ideation. Myfembree showed distinct reporting signals for reproductive and bleeding-related PTs, including heavy menstrual bleeding and intermenstrual bleeding. In the secondary head-to-head analysis, selected PTs including hot flush, nausea, headache, depression, arthralgia, and suicidal ideation showed higher reporting signals for elagolix, whereas alopecia showed a lower reporting signal for elagolix. Sensitivity analyses using alternative algorithms, reporter-type restrictions, overlapping-market-period restriction, complete-age restriction, and bootstrap validation generally supported the direction of the main selected reporting patterns, although some estimates were limited by small cell counts. Conclusions Elagolix and Myfembree showed distinct post-marketing reporting signal profiles among female endometriosis-related FAERS reports. Elagolix was characterized mainly by vasomotor and selected neuropsychiatric reporting signals, whereas Myfembree was characterized mainly by reproductive and bleeding-related reporting signals. These findings represent hypothesis-generating reporting differences rather than clinical incidence rates or causal risk estimates. Further pharmacoepidemiologic studies with denominator data and adjustment for patient-level confounding are needed to clarify comparative safety profiles.

Background: Accessory cavitated uterine mass (ACUM) is an uncommon, non-communicating uterine abnormality often misdiagnosed as endometriosis or a rudimentary horn due to overlapping clinical and radiological features.It typically affects young women and presents with dysmenorrhea, chronic pelvic pain, and occasionally infertility.Objective: To highlight three instances of ACUM through a case series approach in patients who underwent successful laparoscopic management, and to highlight the diagnostic challenges, surgical findings, and outcomes of the same.Cases: We report three cases of young females in the age-group of 15-31 years presenting with severe dysmenorrhea and/or infertility.Imaging studies initially suggested endometriosis or cystic uterine lesions.Diagnostic laparoscopy revealed isolated, cavitated uterine masses mostly close to the insertion of the round ligament, separate from the normal cavity of the uterus.All cases were managed by laparoscopic excision.Histopathology confirmed endometrial-lined cavities without features of adenomyosis.Postoperative outcomes were favorable with complete pain resolution and no recurrence.Conclusion: Accessory cavitated uterine mass should be considered in young patients presenting with intractable dysmenorrhea and atypical uterine lesions.Magnetic resonance imaging (MRI) and 3D ultrasound enhance diagnostic accuracy, but laparoscopy remains a definitive diagnostic and therapeutic tool.Complete laparoscopic excision is curative and provides significant symptomatic relief with good reproductive outcomes.

Data was taken from post operative endometriosis patient on Hasan Sadikin Hospital in the span of 3 years (2021 - 2024). Patient identity was hidden using initials, all the patients record from menstrual cycle & habit, family history and operation detail are available from the dataset. Data has been converted from Bahasa to English for broader audiences.

Endometriosis (EMs) is a prevalent, estrogen-dependent gynecological disorder characterized by the ectopic implantation and proliferation of endometrial-like tissue outside the uterine cavity, affecting approximately 10% of reproductive-aged women globally. Despite its high incidence, the exact pathogenesis of EMs remains incompletely elucidated, and current clinical treatments are often limited by suboptimal efficacy and adverse effects. Accumulating evidence over the past decade has revealed a strong observational association between gut microbiota dysbiosis and EMs development, suggesting that the gut microbiota may serve as a novel potential target for understanding and managing this disease. This review systematically summarizes the potential mechanistic links underlying the interplay between gut microbiota dysbiosis and EMs progression, focusing on three core pathways: intestinal barrier dysfunction and microbial translocation, immune dysregulation and ectopic lesion immune escape, and estrogen metabolism disorder mediated by microbial enzymes and metabolites. In addition, this review stratifies gut microbiome profiles by EMs clinical subtypes (peritoneal, ovarian, deep infiltrating), clarifies anatomical correlations of the gut-lesion axis, and discusses confounding factors and causal inference methodologies. Beyond mechanistic insights, this review also discusses emerging gut microbiota-targeted therapeutic strategies for EMs, including probiotic supplementation, prebiotic intervention, fecal microbiota transplantation (FMT), and dietary modulation, with supplementary ethical considerations for FMT. Collectively, this review provides a comprehensive overview of the gut microbiota-EMs axis, highlighting current evidence levels and offering perspectives for the development of innovative, effective, and safe therapeutic approaches for EMs patients.

Aims: To explore early symptoms and lived experiences of endometriosis during adolescence, as recalled by adult women diagnosed with endometriosis, to identify indicators for a screening questionnaire for high school girls.Background: Endometriosis is a chronic, estrogen-dependent inflammatory disease affecting 10% of women of reproductive age.It manifests as dysmenorrhea, pelvic pain, and infertility.Among adolescents, early symptoms are often dismissed as normal menstrual pain, leading to diagnostic delays of 7-10 years.In Indonesia, limited awareness and the absence of adolescent-focused screening tools further contribute to underdiagnosis, particularly in cities like Palembang, where reproductive health education is minimal.Materials and methods: This qualitative study involved 15 women aged 30-45 years with confirmed endometriosis at Dr. Mohammad Hoesin Hospital, Palembang.Through in-depth interviews, participants recalled their adolescent menstrual experiences.Thematic analysis was conducted to identify recurring symptoms and contextual influences.Key findings informed the development of preliminary questionnaire items for screening.Results: Most participants reported menstrual pain starting from menarche, described as stabbing, squeezing, or radiating to the lower back and pelvis.Pelvic pain outside menstruation, painful defecation, and daily activity limitations were frequently reported.Few experienced urinary symptoms.Some noted a maternal history of similar complaints.Menstrual issues negatively impacted school attendance, social interaction, and mental well-being.These narratives were translated into 24 structured screening questions.Conclusions: Menstrual symptoms in adolescence may signal early endometriosis.Structured school-based screening using symptom-driven questionnaires could promote earlier recognition and reduce diagnostic delay, ultimately improving reproductive health outcomes in adolescents.

STUDY QUESTION: How is endometrial and systemic immunity modulated throughout the menstrual cycle and are there changes in women with endometriosis? SUMMARY ANSWER: Endometriosis is associated with reduced endometrial early natural killer (NK) cells and increased mucosal-associated invariant T (MAIT)-like CD8+ T cells, with cyclical variation. WHAT IS KNOWN ALREADY: The endometrial mucosa contains innate and adaptive immune cells that fluctuate across the menstrual cycle. Immune dysregulation is found in endometriosis, however few studies have broadly assessed endometrial immune single-cell proteome phenotypes. STUDY DESIGN, SIZE, DURATION: This observational cross-sectional immune phenotyping study included 40 participants (28 with surgically confirmed endometriosis and 12 controls). PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial and peripheral blood samples were analysed by spectral flow cytometry using a 36-parameter immune phenotyping panel and a 13-parameter MAIT-specific panel. Totals of 1 950 292 circulating and 1 023 215 endometrial immune cells were profiled. Full-thickness uterine biopsies (n = 3) underwent multiplex immunohistochemical imaging to assess spatial organization across the menstrual cycle. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with controls, patients with endometriosis exhibited decreased endometrial early NK cells (P.adj = 0.006, log2FC = -1.369) and increased MAIT-like CD8+ T cells (CD161+CD8+CD3+) (P.adj = 0.033, log2FC = 1.415). The MAIT cells (CD161+Va7.2+CD3+) peaked during ovulation and the implantation window (P.adj < 0.05). Peripheral immunity also showed cyclical variation with increased early NK cells (P.adj = 0.001, log2FC = 1.052) and decreased effector CD4 T (P.adj = 0.002/log2FC = -2.010) and effector CD8 T cells (P.adj = 0.002, log2FC = -1.180) in the endometriosis group. LIMITATIONS, REASONS FOR CAUTION: The cytometric panel design was biased towards acquired immunity, and the endometriosis patient sample size prevented subtype analysis. WIDER IMPLICATIONS OF THE FINDINGS: MAIT cell dysregulation represents a novel feature of endometriosis, potentially contributing to subfertility and providing new avenues for therapeutic development. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Nuffield Department of Women's and Reproductive Health, University of Oxford, and also supported from the University of Oxford Medical Sciences HIDI Internal Fund Award (0010398), Academy of Medical Science Award (SBF007\100078) and, British Society for Immunology Career Enhancing Grant. C.M.B. has a consultancy role with ObsEva, Theramex, Roche Diagnostics, Sumitovant, Gedeon Richter, Gesyntha, and they have Research Grants from Bayer, Gesyntha, and Serac Life Services. K.Z. is a Board member (non-remunerated) of the World Endometriosis Research Foundation. She has consultancy status with Roche Diagnostics and Gedeon Richter. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Background/Objectives: This study evaluates the 1-year follow-up outcomes after minimally invasive nerve-sparing surgery for the complete excision of deep endometriosis (DE), with a specific focus on deep dyspareunia. Cases with undesirable outcomes were explored in detail to better understand the evolution of this cornerstone endometriosis-related symptom. This approach supports personalized medicine initiatives by seeking to stratify patients into likely surgical responders and non-responders. Methods: This is an interdisciplinary retrospective observational study assessing 195 consecutive cases. Inclusion criteria comprised women with an established diagnosis of DE who had been sexually active in the 6 months prior to surgery. Because pregnancy and postpartum can interfere with the longitudinal assessment of deep dyspareunia, women in these phases during follow-up were excluded. Additionally, individuals who had not been sexually active in the preceding 6 months for reasons unrelated to deep dyspareunia were excluded. Deep dyspareunia was measured using an 11-point (0–10) self-reported Numerical Rating Scale (NRS). Hierarchical clusters were established based on preoperative scores: NONE (NRS = 0), MILD (1 ≤ NRS ≤ 3), MODERATE (4 ≤ NRS ≤ 6), and SEVERE (NRS ≥ 7). Results: In the SEVERE cluster, 82.2% (95% CI: 72.4–92.0) of women improved by ≥3 points. In the NONE cluster, 70.1% (95% CI: 60.3–79.2) remained asymptomatic. Although improvements in deep dyspareunia were statistically significant across the total sample, individual trajectories were not uniform; the response was considered undesirable in 34 cases (17.4%; 95% CI: 12.1–22.8). The frequency of preoperatively asymptomatic women (NRS = 0) developing De Novo deep dyspareunia (NRS ≥ 3) at the 1-year follow-up was estimated at 14.9% (95% CI: 8.0–22.7). These results highlight the marked phenotypic and clinical heterogeneity in patient trajectories and the inherent unpredictability of adverse responses. Conclusions: Postoperative pain outcomes likely result from a complex interplay among surgical, myofascial, neurological, psychological, inflammatory, and hormonal factors. While surgery remains an effective and safe approach for treating pain, our findings underscore that even preoperatively asymptomatic patients should receive targeted counseling regarding the unexpected risk of developing postoperative deep dyspareunia.

The aim of the present study was to analyze the mediating role of self-compassion between trait optimism and beliefs about woman identity, motherhood and infertility among women with endometriosis, adjusting for endometriosis stage and operation status. The participants were 139 women diagnosed with endometriosis ( M age = 33.32, SD = 6.61) from a community sample who completed the scales online. The results showed positive correlations between trait optimism and self-compassion and negative correlations between trait optimism, self-compassion and beliefs about woman identity, motherhood, and infertility. The mediation analyses showed that self-compassion mediated the effect of trait optimism on beliefs about woman identity, motherhood and infertility. Neither the endometriosis stage nor the operation status was significant when included as covariates. These results suggest that self-compassion might serve as an important strategy when facing chronic illnesses such as endometriosis and its effects, such as infertility.

Endometriosis is defined as the ectopic proliferation of endometrial cells. Aberrant signal transduction is present in ectopic endometriotic lesions, and bacteria also contributes to the development of endometriosis by transmitting pathogenic signals through bacterial extracellular vesicles (BEVs). Here, we review the relationship between endometriosis and signal transduction, including classical hormonal, inflammatory, and angiogenic signaling pathways, as well as emerging microbial and epigenetic pathways. We further discuss future challenges from the perspective of molecular signal transduction tools such as extracellular vesicles. Improved understanding of signal transduction in endometriosis will be valuable to develop novel therapies for endometriosis.

Endometriosis (EMs) is an estrogen-dependent inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, yet its precise pathogenesis remains incompletely elucidated. TICAM1, a key adaptor protein in the Toll-like receptor (TLR) signaling pathway, is known to be involved in inflammatory responses; however, its specific role in EMs has not been defined. This study integrated evidence from clinical tissue samples of patients with ovarian endometriomas, in vitro studies, and in vivo models to explore the role of TICAM1 in EMs. TICAM1 expression was significantly upregulated in both eutopic and ectopic endometrium, with the highest levels observed in ectopic lesions, where it was primarily localized to stromal and glandular epithelial cells. Functional experiments showed that TICAM1 overexpression promoted the proliferation, migration, and invasion of human endometrial stromal cells (hESCs), while TICAM1 knockdown suppressed these activities. Concurrently, TLR3 and TLR4 were also upregulated in EMs tissues, and their activation increased TICAM1 expression. Knockdown of TICAM1 attenuated the enhanced cellular activities induced by TLR3/TLR4 activation. Mechanistically, IRF3 and IFN-β levels were elevated in both EMs tissues and TICAM1-overexpressing hESCs, while TICAM1 knockdown inhibited TLR3/TLR4-induced IRF3 phosphorylation and subsequent IFN-β production. These findings were further corroborated in a mouse model of EMs. Together, our findings suggest that TICAM1 may enhance the proliferation, migration, and invasion of hESCs by mediating TLR3/TLR4 signaling and promoting IRF3 phosphorylation and subsequent IFN-β production, thereby potentially contributing to EMs progression. Therefore, targeting TICAM1 may represent a potential therapeutic direction for ovarian endometrioma-associated EMs, while its relevance to superficial peritoneal and deep infiltrating EMs requires further investigation.

Objective: To compare follicular fluid (FF) cytokine and homocysteine profiles in women with poor ovarian response (POR) undergoing in vitro fertilization (IVF), with and without sonographic endometrioma, and to explore potential inflammatory alterations associated with endometrioma in this population. Materials and Methods: This prospective comparative study was conducted among 60 women diagnosed with POR who were undergoing IVF treatment. Participants were divided into two groups according to the presence of sonographic endometrioma: Group I included women without sonographic endometrioma (n=30) and Group II included women with sonographic endometrioma (n=30). FF samples were collected during oocyte retrieval and analyzed for inflammatory biomarkers. Concentrations of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon-α2 (IFN-α2), IFN-γ, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and homocysteine were measured using LEGENDplex multiplex assays and flow cytometry. Cytokine and homocysteine levels were compared between groups. Results: Most inflammatory cytokines, including IL-1β, IL-6, IL-8, IFN-γ, and MCP-1, showed lower levels in women with sonographic endometrioma compared with women without sonographic endometrioma. In contrast, TNF-α and IL-33 levels tended to be higher in the endometrioma group. Homocysteine levels were also lower in women with sonographic endometriomas. However, none of the observed differences reached statistical significance. Overall, the findings suggested distinct, albeit non-significant, inflammatory trends in the FF microenvironment of women with POR and sonographic endometrioma. Conclusion: Women with POR and sonographic endometrioma showed altered trends in FF inflammatory-marker profiles compared with women without sonographic endometrioma; however, these differences were not statistically significant. Since the absence of sonographic endometrioma does not exclude endometriosis, the findings should be interpreted cautiously. Larger prospective studies that include IVF and assess embryological and reproductive outcomes are required to clarify the clinical significance of FF biomarkers in women with POR and endometrioma.

Integrative WES–RNA‑seq profiling highlights a coordinated invasion‑like program in endometriosis with functional dependence on PI3K/AKT signaling, supporting PI3K/AKT as a mechanistically grounded target for anti‑invasive strategies in endometriosis.

Endometriosis is a chronic inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, affecting up to 10% of women of reproductive age. Despite extensive research, its pathogenesis remains incompletely understood, and clinically useful non-invasive diagnostic tools are still lacking. Increasing evidence identifies hypoxia as a key microenvironmental factor promoting lesion establishment and persistence. Cellular responses to hypoxia are mediated by hypoxia-inducible factor 1 alpha (HIF-1α), which coordinates transcriptional programs involved in angiogenesis, inflammation, estrogen biosynthesis, extracellular matrix remodeling, and cell survival. A critical consequence of this hypoxia-driven signaling is the dysregulation of cell adhesion molecules (CAMs), which directly facilitates ectopic implantation and lesion progression. Adhesion-related molecules implicated in endometriosis include integrins, selectins, cadherins (E-cadherin, N-cadherin, CDH12, T-cadherin), claudins, intercellular adhesion molecules (ICAMs), matrix metalloproteinases (MMPs), and anthrax toxin receptor 2 (ANTXR2). Altered expression and activity of these molecules enhance attachment to the peritoneum, immune cell recruitment, angiogenesis, and extracellular matrix remodeling, thereby sustaining chronic inflammation and lesion growth. Beyond their pathogenetic role, CAMs are increasingly recognized as clinically relevant diagnostic and therapeutic targets in endometriosis. Within this group, P-selectin emerges as a particularly promising candidate, as its association with disease-related inflammatory activity supports its potential utility as a non-invasive biomarker and as a therapeutic target, exemplified by preclinical studies using the monoclonal antibody inclacumab. In parallel, growing evidence supports the diagnostic relevance of other adhesion-related molecules, including N-cadherin, ICAM-1, and MMP-9. Furthermore, therapeutic strategies targeting adhesion-related pathways - either directly or through modulation of hypoxia-responsive signaling - have demonstrated promising results in preclinical studies. This review highlights cell adhesion molecules as central effectors of hypoxia-driven mechanisms in endometriosis and underscores their relevance for the development of mechanism-based diagnostic and therapeutic approaches, complementing existing hormonal and symptomatic treatments.

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Ovarian endometrioma cystectomy may compromise ovarian reserve through inadvertent excision of ovarian cortex. We compared inadvertent cortical removal between robotic-assisted and conventional laparoscopic cystectomy using digital pathology. We retrospectively analyzed 81 patients (40 laparoscopic, 41 robotic) who underwent single-surgeon cystectomy (January 2020-December 2025) with digitized hematoxylin and eosin-stained slides available. Ninety-eight ovary/side specimens were classified as follicle-containing cortex, cortex without follicles, or fibrosis, and excised cortical area (mm²) was quantified. The primary analysis used log-linear regression adjusted for cyst length and width with patient-clustered robust standard errors. Tissue-type distribution did not differ by approach (P = 0.611). Excised cortical area was smaller with robotics (median 34.6 mm², interquartile range 16.9-82.3) than laparoscopy (median 65.4 mm², interquartile range 39.5-81.6; P = 0.011). In the adjusted model, robotics was associated with a smaller excised cortical area (robot-to-laparoscopy ratio 0.55, 95% confidence interval 0.32-0.93; P = 0.029). Follicle counts and antral follicle presence among follicle-containing specimens were comparable. Robotic-assisted cystectomy was associated with less inadvertent excision of ovarian cortex after accounting for cyst dimensions, while follicle-based specimen metrics did not differ.

Background Endometriosis is a chronic inflammatory disease with immune dysregulation in which angiogenic, and hematopoietic mediators are thought to contribute to ectopic lesion establishment and persistence. Whether circulating immune cells are intrinsically primed to secrete higher levels of pro-angiogenic growth factors remains unclear. This study evaluated in vitro secretion of fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and granulocyte–macrophage colony-stimulating factor (GM-CSF) by peripheral blood mononuclear cells (PBMCs) from women with and without endometriosis. Methods In a case–control design, women with laparoscopically and histopathologically confirmed endometriosis ( n = 36) and laparoscopically confirmed controls without endometriosis ( n = 44) were enrolled. PBMCs were isolated from peripheral blood and cultured for 24 h under basal conditions or after non-specific mitogenic activation with phytohemagglutinin (PHA, 5 μg/mL). Supernatant concentrations of FGF, PDGF, VEGF and GM-CSF were quantified using a multiplex bead-based immunoassay (Bio-Plex/Luminex). Between-group comparisons used nonparametric tests; univariate logistic regression explored associations with endometriosis status; and false discovery rate (Benjamini–Hochberg) adjustment was applied for multiple testing. Results Baseline secretion of FGF, PDGF, VEGF and GM-CSF by PBMCs did not differ significantly between women with endometriosis and controls after correction for multiple comparisons. PHA stimulation induced marked shifts in secretion profiles across participants— characterized by increases in FGF, PDGF and VEGF and a decrease in GM-CSF—but neither stimulated concentrations nor percent changes differed significantly between groups following false discovery rate adjustment. In univariate logistic regression analyses, none of the baseline growth-factor measures significantly predicted the presence of endometriosis. Conclusion Under standardized in vitro culture conditions, PBMCs from women with endometriosis do not show a generalized increase in secretory capacity for the evaluated pro-angiogenic/hematopoietic growth factors compared with PBMCs from controls without endometriosis. These data do not support systemic PBMC hypersecretion of FGF, PDGF, VEGF and GM-CSF in endometriosis and are consistent with a compartmentalized model in which disease-relevant pro-angiogenic signaling is predominantly shaped within local peritoneal and lesion microenvironments.

Introduction:Endometriosis is a chronic, hormone-dependent condition affecting up to 15% of women of reproductive age. It is associated with pain, infertility, and a significant reduction in quality of life. Despite increasing awareness, the average diagnostic delay remains between 7 and 11 years. The disease is characterized by chronic pelvic pain, fatigue, dyspareunia, and emotional distress, which may contribute to depression, anxiety, decreased self-esteem, and social isolation. Sexual dysfunction arises from both physical symptoms and psychological factors. Endometriosis is also recognized as a leading cause of infertility. Objective:The aim of this review is to evaluate the impact of endometriosis on women’s mental health, sexual functioning, and fertility, with particular emphasis on diagnostic delays and social stigma. Methods and materials: A literature review was conducted using publications available in the PubMed and Google Scholar databases from 2017-2025. The most relevant and recent studies were selected using appropriate keywords. Conclusions:Endometriosis requires a holistic and multidisciplinary approach that integrates medical management with psychological and sexual health support. Addressing mental health and social well-being is essential for improving overall quality of life in affected women. Early diagnosis and the reduction of stigma remain key challenges in contemporary clinical practice.

Adenomyosis is a common condition among women of reproductive age; however, its clinical presentation and distribution patterns are not uniform. In some patients, the disease is confined to a single uterine wall, whereas in others it presents as a diffuse process. Differences in age, body weight, daily habits, and environmental factors may contribute to these variations. This study descriptively and analytically evaluated data from 30 women with adenomyosis confirmed by ultrasound (US) and/or magnetic resonance imaging (MRI). Age, body mass index (BMI), uterine wall localization, previous uterine interventions, low physical activity, chronic stress, sleep deprivation, tobacco exposure, and unhealthy dietary habits were assessed. A risk index ranging from 0 to 5 points was developed based on five lifestyle-related factors. Women aged 30–39 years accounted for 66.7% of the cohort. Regarding localization, diffuse or multi-wall involvement was observed in 40.0% of cases, posterior wall involvement in 26.7%, and anterior wall as well as lateral-fundal localization in 16.7% each. Chronic stress was identified in 60.0% of patients, low physical activity in 53.3%, and sleep deprivation in 50.0%. Among the nine patients with a high-risk index, seven had diffuse adenomyosis. In this group, the mean number of ultrasound findings was 4.9 ± 0.8, and the MRI-measured junctional zone thickness was 14.7 ± 1.8 mm. In the low-risk group, these values were 2.9 ± 0.9 and 9.8 ± 1.4 mm, respectively. These findings suggest that, in addition to clinical symptoms and imaging examinations, a targeted assessment of lifestyle-related factors and medical history plays an important role in the evaluation of patients with adenomyosis.

Endometriosis is a common gynecologic disorder often associated with chronic pelvic pain, infertility, and reduced quality of life. Conventional imaging modalities, such as transvaginal ultrasound and MRI, may underestimate the extent of disease, particularly in deep infiltrating endometriosis. Fibroblast activation protein (FAP) is highly expressed in remodeling endometrium and has been implicated in endometriotic lesions. This study investigates the feasibility of integrating FAP-targeted PET/MRI to improve endometriosis detection. Methods: This retrospective study included 18 premenopausal women. The test cohort consisted of 9 patients with suspected or confirmed endometriosis who had undergone FAP-targeted PET/MRI or PET/CT with the FAP inhibitor (FAPI) [68Ga]BED003 (previously known as [68Ga]Ga-OncoFAP-DOTAGA). The reference cohort consisted of 9 premenopausal women without known endometriosis who had undergone FAPI PET/MRI or PET/CT with either [68Ga]BED003 or [68Ga]Ga-FAPI-46 for initial staging of breast cancer. Examinations were not scheduled with regard to the patients’ menstrual cycles. Lesions were assessed using a segment-based analysis derived from the #Enzian classification. Focal radiopharmaceutical uptake was semiquantitatively assessed using SUVmax and SUVmean. Clinical assessments and laparoscopic findings, when available, served as reference standards. Results: In the test cohort with available PET/MRI data (7 patients and 91 segments), MRI alone identified endometriosis-suspicious findings in 19% of segments. In contrast, combined PET/MRI identified findings in 49% of segments. Among all PET datasets (108 segments per cohort), focal extrauterine FAP uptake was observed in 41% of the test cohort’s segments compared with 13% of the reference cohort’s segments (P < 0.01). The mean number of PET-positive segments per patient was higher in the test cohort than in the reference cohort (4.9 ± 2.4 vs. 1.7 ± 1.3, P = 0.009), with the greatest difference observed in peritoneal, ovarian, and tubal segments. Uterine SUVmax did not differ significantly between the 2 cohorts (P = 0.489). Where available, PET/MRI findings showed substantial concordance with laparoscopic results. Conclusions: FAPI PET/MRI increased the detection of lesions suggestive of endometriosis compared with MRI alone. These findings support further prospective evaluation of FAPI PET/MRI as an adjunct imaging modality for preoperative assessment of endometriosis.

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Endosure does not appear to have a role in diagnosing endometriosis, with current diagnosis relying on imaging techniques and confirmed through laparoscopy.

Background Adenomyosis (AM) is described as a benign invasion of the endometrium into the myometrium, which impacts a large number of childbearing age women. The diagnosis of AM relies on imaging and histological examinations. Although carbohydrate antigen 125 (CA125) has served as a blood indicator for AM diagnosis, its utility is limited to being effective in only approximately half of patients. Currently, there are no reliable blood diagnostic indicators available for AM. Methods Data of 23 blood indicators examined for 143 patients with AM and 143 age-matched healthy women were collected, including six sex hormones, two tumor biomarkers, nine routine data, two inflammatory and coagulation indicators, and four lipid-related indicators. Wilcoxon rank-sum test was applied to identify differentially changed indicators (DCIs) for AM versus controls. Similarly, Wilcoxon rank-sum test was conducted to determine the DCIs associated with the MRI subtypes of AM. Univariate and multivariate analyses were performed to select the DCIs that might differentiate severe from mild AM. Least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVMRFE) were used to determine the key DCIs for AM. Logistic regression was carried out to develop a diagnostic model, and the area under the receiver operating characteristic (ROC) curve (AUC) was calculated to evaluate the performance of the model. A nomogram was constructed to predict the risk of AM. Results We identified 15 DCIs for AM. Four DCIs were found in all three MRI subtypes. CA125 and estradiol could distinguish severe from mild AM. The hemoglobin (HGB) concentration, lymphocyte percentage, neutrophil count, neutrophil percentage, and testosterone were different between diffuse AM and adenomyoma. Based on these DCIs, neutrophil count, HGB concentration, and high-density lipoprotein (HDL) were selected using the LASSO and SVMRFE methods, which could discriminate AM cases with CA125&lt;35 and ≥35 U/ml from the controls with AUCs of 0.812 and 0.928, respectively. Similarly, CA125, neutrophil count, HGB concentration, and HDL were screened and a diagnostic model built for AM, which could differentiate all AM cases from the controls with an AUC of 0.935 (sensitivity = 0.902, specificity = 0.888). Conclusion To our knowledge, these indicators are reported here for the first time as combined biomarkers for the diagnosis of AM. Our findings might provide clues for the pathogenesis research of AM and supply potential blood indicators to assist in its diagnosis.

Sewar Khatib,1 Haya Hassan,2 Suzan Abd Elgani,2 Ari Reiss,2 Batya Engel -Yeger1 1Department of Occupational Therapy, University of Haifa, Haifa, Israel; 2Department of Obstetrics and Gynecology, Emek Medical Center, Afula, IsraelCorrespondence: Sewar Khatib, Department of occupational therapy, university of Haifa, Haifa, Israel, Tel +972-509967091, Email [email protected]: To examine (1) group differences in executive functioning, disease burden, occupational balance and quality of life between women with endometriosis and healthy controls; (2) associations between pain-related and psychological disease burden -specifically pain catastrophizing and emotional distress- and occupational balance and quality of life; and (3) whether executive functioning mediates the relationships between disease burden and quality of life and occupational balance.Patients and Methods: This cross-sectional correlational study included 103 women aged 18– 35 years, compromising 43 women with clinically confirmed endometriosis recruited from a specialized endometriosis clinic and 60 age-matched healthy controls. Disease burden was assessed using measures of pain severity (Visual Analog Scale – VAS), pain catastrophizing (Pain catastrophising scale -PCS), and emotional distress (Depression Anxiety Stress Scale – DASS21). Executive functioning (Barkley Deficits in Executive Functioning Scale–Short Form -BDEFS-SF), occupational balance (Occupational Balance Questionnaire – OBQ11), and quality of life (World Health Organization Quality of Life–BREF - WHOQOL-BREF). Socio-demographic and clinical characteristics were collected to characterize the study sample and inform interpretation of the findings. Mediation analyses were conducted to examine executive functioning as a mechanism linking disease burden to functional outcomes, using Hayes’ PROCESS.Results: Compared with healthy controls, women with endometriosis reported significantly greater pain severity, pain catastrophizing, emotional distress, and executive functioning difficulties, alongside lower occupational balance and reduced quality of life (all p < 0.001). Within the endometriosis group, higher levels of pain catastrophizing and emotional distress were associated with poorer executive functioning, which in turn was associated with lower occupational balance and quality of life (all p < 0.001). Mediation analyses indicated that executive functioning fully mediated the associations between psychological disease burden and both quality of life and occupational balance, such that the direct associations between psychological disease burden and functional outcomes were no longer significant after accounting for executive functioning.Conclusion: Executive functioning represents a central mechanism through which pain-related and psychological disease burden translate into disruptions in daily life among women with endometriosis. These findings extend symptom-based models toward a more integrative, function-oriented understanding of endometriosis and highlight executive functioning as a meaningful target for comprehensive, person-centered assessment and intervention.Keywords: endometriosis, meta-cognition, executive functions, occupational balance, quality of life

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Objective: To investigate the association between delivery/abortion methods, allergy history, and endometriosis (EM) risk. Methodology: This prospective case-control study was conducted at the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), China, from 2018 to 2024. We enrolled 1498 EM patients and 452 non-EM controls. Associations between clinical variables (delivery modes, abortion, allergy history) and EM incidence were analyzed using multivariate logistic regression to adjust for confounders. Results: Cesarean section increased EM risk approximately 2-fold (OR 2.043, 95% CI: 1.489-2.804); this risk remained significant after excluding scar EM (OR 1.944, 95% CI: 1.414-2.674). Induced abortion also correlated with a 2-fold increased risk of EM (OR 2.262, 95% CI: 1.529-3.347). Furthermore, allergic patients with a history of induced abortion had a significantly higher likelihood of developing deep infiltrating endometriosis (DIE). Conclusion: Cesarean section and induced abortion independently increase EM risk. Moreover, induced abortion combined with an allergy history elevates the risk of developing DIE, highlighting the synergistic effect of surgical trauma and immune status on EM pathogenesis.

Background: Cancer antigen 125 (CA-125) is widely used as a tumor marker for epithelial ovarian malignancy. However, significantly elevated CA-125 levels may also occur in benign gynecological conditions such as endometriosis, particularly in cases of ruptured endometrioma. Such marked elevation may mimic ovarian carcinoma and create diagnostic confusion, especially in reproductive-age women. Methods: We report two cases of young unmarried women presenting with acute abdomen and markedly elevated serum CA-125 levels associated with ruptured ovarian endometriomas. Clinical presentation, imaging findings, intraoperative findings, histopathology, management, and postoperative outcomes were analyzed. Results: Case 1 involved a 23-year-old woman with bilateral ovarian endometriomas and hemoperitoneum, with serum CA-125 of 4927 IU/mL and CA 19-9 of 291 IU/mL. Case 2 involved a 26-year-old woman with bilateral endometriomas and hemoperitoneum, with CA-125 of 5704 IU/mL and CA 19-9 of 1401 IU/mL. Both patients underwent laparoscopic surgery, which revealed ruptured endometriotic cysts with chocolate-colored peritoneal contamination. Histopathological examination confirmed endometriosis in both cases. Postoperatively, serum CA-125 levels normalized within three months following surgical management and medical therapy. Conclusion: Extremely elevated CA-125 levels do not always indicate ovarian malignancy. Ruptured endometrioma should be considered in the differential diagnosis of reproductive-age women presenting with acute abdomen, pelvic masses, and markedly elevated CA-125 levels. Careful clinical, radiological, and histopathological correlation is essential to avoid unnecessary radical surgical intervention.

Background: Endometriosis is a chronic, estrogen-dependent inflammatory disease affecting approximately 6-13% of women worldwide, with estimates exceeding 100 million individuals. It presents with heterogeneous symptoms, including chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility, significantly impairing quality of life. Despite its prevalence, endometriosis remains under-recognized and often inadequately addressed at clinical and policy levels. Objective: This review aims to examine the multifaceted burden of endometriosis, including its epidemiology, impact on quality of life and productivity, diagnostic delays, treatment limitations, and health system and policy barriers. Methods: A narrative review of the literature was conducted using major databases, including PubMed, Scopus, and Web of Science. Recent systematic reviews, meta-analyses, observational studies, and policy reports were analyzed to identify key themes and evidence gaps. Results: Endometriosis is associated with substantial physical, psychological, and economic burden, including reduced work productivity and high healthcare costs. Diagnostic delay remains a major challenge due to factors at the patient, provider, and system levels. Current treatments are often limited in effectiveness and accessibility, with high recurrence rates. Fragmented healthcare systems, insufficient specialist training, and a lack of national policies further exacerbate inequalities in care. Conclusions: Endometriosis represents a significant yet often invisible public health issue. Addressing its burden requires integrated care models, improved diagnostic strategies, increased research funding, and comprehensive policy action.

Bowel endometriosis is an uncommon manifestation of endometriosis that can clinically and radiologically mimic colorectal malignancy. Because the disease predominantly involves the deeper layers of the bowel wall with relative sparing of the mucosa, endoscopic findings may be normal, posing a significant diagnostic challenge. A 38-year-old woman presented with abdominal distension, epigastric pain, vomiting, constipation, and loss of appetite for 3 months. Radiological imaging revealed circumferential wall thickening at the rectosigmoid junction with luminal narrowing and features suggestive of distal colonic obstruction suspicious for malignancy. Sigmoidoscopy demonstrated normal mucosa with the inability to negotiate the scope beyond the narrowing. Mucosal biopsy revealed chronic non-specific colitis. Due to persistent radiological suspicion of malignancy, surgical resection was performed. Histopathological examination demonstrated endometrial glands and stroma infiltrating the serosa, muscularis propria, and submucosa of the rectosigmoid colon, confirming the diagnosis of rectosigmoid endometriosis. Rectosigmoid endometriosis may closely mimic colorectal carcinoma on imaging, while endoscopic findings remain non-specific. Awareness of this diagnostic pitfall is essential in reproductive-age women presenting with colorectal obstruction to prevent misdiagnosis and unnecessary radical treatment.

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Background: Endometriosis has potential negative effects on the fertility, mental, and sexual health of women. Since the conducted studies have not comprehensively addressed the needs and strategies to improve sexual health, and to design the necessary programs and interventions for this group of women. Objective: The present study aims to design and implement interventions to improve sexual health of women with endometriosis. Materials and Methods: This sequential mixed-methods study comprises 4 phases. Phase 1 is a qualitative study using semi-structured interviews to explore needs and strategies from the perspectives of women with endometriosis and healthcare providers. Phase 2 involves a systematic review to identify additional evidence-based strategies. Phase 3 integrates findings from phases 1 and 2 with prioritization by a multidisciplinary expert panel using the Delphi technique, to develop a comprehensive intervention program. Phase 4 is a randomized controlled trial to evaluate the effectiveness of the developed intervention on sexual function and sexual quality of life compared to routine care. Conclusion: This protocol aims to develop a comprehensive, evidence-based care program integrating qualitative insights, systematic review findings, and multidisciplinary expert opinions, and to evaluate its effectiveness in improving the sexual health of women with endometriosis.

This study aimed to develop and validate a clinical prediction model for the success of the focused ultrasound ablation system (FUAS) in treating adenomyosis. A retrospective analysis was conducted on 250 patients from Qingdao Women and Children's Hospital (2019-2022). Patients were categorized into success (n = 108) or failure (n = 142) groups based on a post-treatment lesion ablation rate greater than 80%. The dataset was split into training (70%) and validation (30%) sets. The multivariable analysis identified age (OR = 1.10, P = 0.014), depth of adenomyosis (OR = 1.03, P = 0.036), and uterine body (OR = 0.25, P = 0.027) as independent predictors of FUAS efficacy, which were used to build the model. In the training set, the model achieved an AUC of 0.74 for efficacy prediction. The Bootstrap ROC indicates an AUC mean of 0.751 with a standard deviation of 0.036. In conclusion, a model based on age, depth of ademyosis, and uterine body lesions treatment dose accurately predicts FUAS success for adenomyosis. This tool can aid clinical decision-making and promote personalized treatment.

Purpose: Ovarian clear cell carcinoma (OCCC) is strongly associated with endometriosis and shows geographic variation in incidence. We investigated whether OCCC and adjacent endometriosis exhibit distinct transcriptional states and whether these patterns differ between United Kingdom (UK) and Japanese cohorts. Experimental Design: We performed whole-transcriptome spatial profiling on specimens from 16 OCCC cases (8 UK, 8 Japan) in which tumor and endometriosis were both present. Gene expression was analyzed in tumor, endometriosis and stroma. ARID1A status was assessed by immunohistochemistry. Results: Median age was 59 years (range 26-82). 13/16 cases (81.3%) had early-stage disease. Tissue compartment rather than cohort of origin was the dominant source of variation across endometriosis and tumor regions. Endometriosis was enriched for inflammatory and immune-related pathways compared to tumor, whilst there was greater representation of chromatin and protein-DNA complex assembly pathways in tumor regions. These patterns were conserved across both cohorts and after stratification by ARID1A status. Mesenchymal-associated gene expression scores also significantly differed across stroma, endometriosis and tumor with clear compartmental separation. Cell type deconvolution analyses showed clear compositional differences between stromal and epithelial disease compartments. Conclusions: OCCC and coexisting endometriosis are transcriptionally distinct, with the dominant contrast being compartmental rather than geographic. ARID1A alone is unlikely to account for the principal spatial transcriptional states identified here. Further analyses will be required to ascertain whether these differences reflect genuine biological differences between OCCC and coexisting endometriosis or represent different stages of endometriosis-associated tumorigenesis.

Background: Endometriosis affects 10–15% of reproductive-aged women and is a leading cause of infertility through anatomical, inflammatory, and molecular mechanisms. Objective: This review synthesizes current evidence on the pathophysiology of endometriosis-associated infertility and evaluates medical, surgical, and ART strategies to guide individualized management. Methods: We conducted a narrative review (2000–2025; PubMed, Scopus, WoS) synthesizing RCTs, meta-analyses, and observational studies on mechanisms and treatment outcomes. Results: In rASRM stage III–IV, tubo-ovarian distortion and adhesions mechanically impair oocyte pickup and embryo transport. In superficial disease, animal models demonstrate that peritoneal inflammatory mediators and ROS can impair oocyte maturation, though direct causal evidence in humans is lacking. Epigenetic dysregulation has been identified in the eutopic endometrium and linked to progesterone resistance, though its direct causal role in infertility remains unestablished. Hormonal suppression controls pain but does not improve spontaneous conception rates. Laparoscopic surgery in stage I–II remains debated. Prospective evidence supporting fertility benefit from DIE excision without mechanical obstruction is lacking. Cystectomy consistently reduces AMH, favoring IVF over surgery unless symptoms or retrieval barriers exist. IVF/ICSI live birth rates per cycle in stage I–II are comparable to those without endometriosis; cumulative rates after ≤5 cycles reach 43–46% in treated vs. 28% in untreated stage III–IV patients. Conclusions: Management requires two sequential decisions: first, whether to perform a diagnostic laparoscopy to identify minimal disease and adhesions, and second, whether to proceed with surgery or transfer directly to ART. Age ≥ 35, infertility > 2 years, or low AMH/AFC favor immediate IVF. Post-surgical EFI guides timing: high EFI supports expectant management or IUI; low EFI should prompt ART referral. When cystectomy is necessary, tissue-sparing techniques should be prioritized and fertility preservation, including oocyte cryopreservation, discussed preoperatively.

These official ISON Guidelines summarize the current neuropelveological concepts regarding the diagnosis, pathophysiology, differential diagnosis, and surgical management of endometriosis involving the sciatic nerve and sacral plexus. Developed under the auspices of the International Society of Neuropelveology (ISON), the document reflects one of the world’s largest clinical and surgical experiences in pelvic nerve endometriosis, including more than 600 patients treated over more than two decades of neuropelveological practice. The guidelines emphasize the fundamental distinction between sacral plexus endometriosis and isolated intraneural sciatic nerve endometriosis, two entities with major differences in anatomical origin, biological behavior, neurological progression, imaging findings, and surgical implications. The document introduces a neuropelveological classification system and proposes a novel neuropathogenic model for isolated sciatic nerve endometriosis as a primary intraneural neuro-inflammatory and neuro-regenerative disease process. Detailed recommendations are provided for neuropelveological clinical examination, MRI and transvaginal Doppler ultrasound evaluation, neuro-urological assessment, electrophysiological studies, differential diagnosis, surgical indications, laparoscopic nerve decompression, intrafascicular neurolysis, microsurgical nerve-sparing techniques, vascular management, postoperative rehabilitation, and long-term neurological follow-up. Special emphasis is placed on the prevention of irreversible axonal damage and the necessity for highly specialized neuropelveological expertise and reference centers for surgical treatment. These guidelines aim to establish standardized principles for the diagnosis and treatment of pelvic nerve endometriosis and to improve recognition of these frequently overlooked neuropathic disorders among gynecologists, neurosurgeons, neurologists, pain specialists, radiologists, and pelvic surgeons worldwide. Keywords: Neuropelveology; Endometriosis; Sciatic nerve; Sacral plexus; Pelvic neuropathy; Catamenial sciatica; Laparoscopic nerve surgery; Pelvic nerve entrapment; Deep infiltrating endometriosis; Chronic pelvic pain; Pudendal neuralgia; Sacral radiculopathy; Neurofunctional pelvic surgery; LANN technique.

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Endometriosis is a chronic condition often surrounded by taboo, silence, and misunderstanding. Although diagnostic uncertainty and epistemic tensions shape endometriosis care, little is known about how design can address the communicative and relational gaps between patients and gynaecologists. This article investigates how participatory and speculative design can support communication between these groups. Using a Research through Design approach, three co-design workshops were conducted with six individuals with endometriosis and five doctors. Participants created analogue artefacts including empathy maps, body maps, clay representations, written narratives, speculative futures and collective posters that materialised embodied pain, emotional burden and clinical perspectives. The workshops revealed how experiential and clinical knowledge can meet through material and narrative mediation, enabling mutual empathy and discursive practices of care beyond conventional consultation settings. The artefacts acted as mediators that articulated aspects of endometriosis that are difficult to verbalise, while highlighting resonances and divergencies between patients and doctors.

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