What's new in endo & adenomyosis research

Endometriosis (EMs) is a common gynecological disorder affecting reproductive‑aged women, characterized by ectopic endometrial growth and chronic pelvic pain that severely impairs quality of life. Although its pathogenesis remains incompletely understood, accumulating evidence indicates that the tumor suppressor p53 and aberrant epigenetic modifications play critical roles in EMs initiation and progression. p53 expression is significantly reduced in ectopic lesions, leading to apoptosis resistance and hyperproliferation of endometrial cells. Importantly, p53 dysfunction contributes to EMs through at least four epigenetic mechanisms: (1) p53 transcriptionally represses DNA methyltransferases (DNMTs), and its loss indirectly promotes locus‑specific hypermethylation and silencing of tumor suppressors; (2) p53, via its interaction with histone modifiers, influences their recruitment to target genes, and p53 impairment synergizes with histone deacetylase dysregulation to create a pro‑proliferative, anti‑apoptotic microenvironment; (3) p53 functionally interacts with the chromatin remodeler ARID1A, and their co‑dysruption impairs chromatin accessibility and immune homeostasis; (4) p53 coordinates non‑coding RNA networks (e.g. lncRNA MALAT1, miR‑34a) that regulate epithelial-mesenchymal transition, angiogenesis, and apoptosis. This review systematically summarizes the p53‑mediated epigenetic regulatory network in EMs and highlights potential therapeutic opportunities targeting p53-epigenetic crosstalk. Future studies should investigate synergistic mechanisms among different epigenetic layers and validate these findings in multi‑center clinical cohorts.

STUDY QUESTION: How do the three most widely accessible large language models perform in terms of accuracy, consistency, and reliability when answering clinically relevant questions derived from the 2022 ESHRE guideline on endometriosis? SUMMARY ANSWER: Model A achieved the highest accuracy scores, model C demonstrated significantly superior consistency across repeated queries, and all three models showed comparable but suboptimal reliability under free-tier access, while under official API access median accuracy converged across providers and reliability increased. WHAT IS KNOWN ALREADY: Large language models are increasingly consulted by both clinicians and patients as readily accessible sources of medical information. In reproductive medicine, preliminary evidence suggests that individual platforms may retrieve endometriosis-related content with mixed fidelity. However, no study has simultaneously benchmarked multiple models against a single, internationally recognized endometriosis guideline. The extent to which these tools can be trusted to faithfully reproduce evidence-based recommendations on endometriosis diagnosis and management remains largely unexplored. STUDY DESIGN, SIZE, DURATION: Cross-sectional, multi-platform comparative study. Fifty clinically relevant questions covering the diagnostic and therapeutic domains of the 2022 ESHRE endometriosis guideline were simultaneously submitted to all three models during December 2025. Each question was entered in duplicate using independent sessions to assess response consistency and reliability. Subgroup analyses were carried out by submitting the questions to the API version and to the free-tier version of the platforms available in May 2026. PARTICIPANTS/MATERIALS, SETTING, METHODS: The three models were accessed through their respective free web interfaces using new accounts, without prompt engineering, prior training, or retrieval-augmented generation. A zero-shot prompting approach was adopted. Accuracy was evaluated by two independent experts using the Global Quality Score (GQS); consistency was defined as identical responses across the three iterations; reliability was defined as the alignment of each response with the ESHRE guideline. Discrepancies were settled by a third reviewer. MAIN RESULTS AND THE ROLE OF CHANCE: Significant differences in accuracy were observed across models (Kruskal-Wallis H = 37.10, P < 0.001). Model A achieved the highest median GQS (5, interquartile range [IQR] 4-5), followed by model C (4, IQR 3-5) and model B (3, IQR 3-4). Post-hoc analysis confirmed that model A significantly outperformed model B (P < 0.001) but not model C (P = 0.123), while model C also scored significantly higher than model B (P < 0.001). For consistency, model C demonstrated a significantly higher rate of reproducible responses (92.0%) compared with model A (72.0%, P = 0.028) and model B (68.0%, P = 0.008). No significant between-model differences were found for reliability (χ2 = 1.029, P = 0.598), with rates of 76.0% for model C, 68.0% for model A, and 68.0% for model B. In API and free-tier May 2026 subgroup analyses, median GQS converged to 4 across all three providers, and reliability rose to at least 76% for each provider. LIMITATIONS, REASONS FOR CAUTION: Model outputs may change with subsequent updates. GQS retains a degree of subjectivity despite expert adjudication. The study tested factual recall rather than complex clinical reasoning, limiting generalizability to real-world decision-making scenarios. WIDER IMPLICATIONS OF THE FINDINGS: These findings provide the first multi-platform benchmark of large language models against the latest endometriosis guideline. While models A and C retrieved guideline-concordant information with acceptable fidelity, none of the models achieved a level of reliability required for unsupervised clinical use. The dissociation between accuracy and consistency at the free tier, and its attenuation under API and more recent accesses, indicates that both model capability and commercial tier shape user-facing outputs. The dissociation between accuracy and consistency underscores that a model producing high-quality answers does not necessarily do so in a reproducible manner. Expert oversight remains crucial when interpreting their output regarding endometriosis care. Future research should extend this framework to additional endometriosis guidelines and to longitudinal monitoring of models' performance with their upgrades. FUNDING: No external funding was received for this study. DISCLOSURES: The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Background/Objectives: Endometriosis manifests as ectopic endometrial tissue outside the uterine cavity. This lesion can sometimes appear at unusual anatomical sites or within the intestinal tract, growing and mimicking cancer. Such tumor-like endometriosis lesions are relatively uncommon and biologically intriguing. Methods: This study is a retrospective case series of 14 patients presenting with tumor-like endometriosis at a single institution between 2007 and 2023. Laser capture microdissection was used to isolate epithelial cells from endometriotic glands in tissue sections from formalin-fixed, paraffin-embedded blocks, and the microdissected epithelium was analyzed for cancer driver mutations. Results: Unlike conventional endometriosis, these tumor-like lesions were generally sizable and clinically presented in the groin area, aortic wall, omentum, bowel wall, or lymph nodes, all of which raised suspicion for malignancy, despite 11 (78.6%) of the 14 cases having a history of or clinical signs of endometriosis. A total of 11 cancer-driver mutations were identified in 6 of the 14 patients, with four patients harboring multiple mutations. Recurrent mutations included KRAS-activating mutations in four cases and ARID1A-inactivating mutations in two cases. Additional mutations involved PIK3CA, CTNNB1, CHD4, MYD88, and STAG2. Conclusions: This study detected mutations in KRAS, ARID1A, PIK3CA, CTNNB1, and MYD88 in endometriotic lesions, consistent with previous literature, and identified newly reported mutations in CHD4 and STAG2. Not every tumor-like lesion harbored cancer driver mutations.

Aims and Objectives. Non-descent vaginal hysterectomy (NDVH) remains an underutilised route despite being scarless, regional-anaesthesia-compatible, and resource-sparing. In an era dominated by laparoscopic and robotic surgery, its feasibility in contemporary practice deserves re-evaluation. We aimed to (i) assess the feasibility and perioperative outcomes of NDVH in women with benign, non-prolapsed uteri up to 14 weeks in size, and (ii) evaluate whether a composite preoperative feasibility score, built from five routinely available clinical parameters, stratifies anticipated surgical difficulty and observed morbidity.Methods. Retrospective observational case series at a tertiary teaching referral centre (October 2022–October 2024). Consecutive eligible women had a benign indication, a non-prolapsed uterus ≤14 weeks, and no adnexal pathology. A composite score (age, vaginal parity, previous pelvic surgery, comorbidity, uterine size; each 0–2; total 0–10) classified cases as easy (0–3), moderately difficult (4–6), or difficult (7–10). Outcomes were operative time, estimated blood loss (EBL), transfusion, hospital stay, and intra-/post-operative complications. Associations between the score and outcomes were tested with Spearman correlation and, across the three score categories, with the Kruskal–Wallis and χ² tests; individual score components (prior caesarean/pelvic surgery, uterine size) were examined secondarily with Mann–Whitney U and Fisher's exact tests.Results. Thirty women underwent NDVH (mean age 46.4 ± 5.3 years; 96.7% multiparous; 60.0% with prior pelvic surgery, predominantly caesarean). By FIGO PALM-COEIN grouping, leiomyoma-related disease (AUB-L) was the leading indication (20 women, 66.7%), followed by adenomyosis-related disease (AUB-A; 8, 26.7%) and abnormal uterine bleeding not otherwise specified (AUB-NOS; 2, 6.7%). The uterus was removed vaginally in all 30; 1 (3.3%) required laparotomy for haemostasis. Debulking was used in 12 (40%). Mean operative time was 168.5 ± 29.7 min and mean EBL 216.7 ± 64.8 mL; transfusion was required in 5 (16.7%). Any complication occurred in 10 patients (33.3%): post-operative fever- 5 (16.7%), urinary tract infection- 2 (6.7%), transient urinary retention- 2 (6.7%), bladder injury- 1 (3.3%), ureteric injury- 1 (3.3%), and laparotomy for haemostasis- 1 (3.3%); no bowel injury occurred. Outcomes deteriorated monotonically across score categories: complications 16.7% → 28.6% → 100%, EBL 183 → 232 → 262 mL, operative time 161 → 165 → 202 min, and transfusion 0% → 14.3% → 75% for easy, moderate, and difficult groups. The score correlated with EBL (ρ=0.5, p=0.007), operative time (ρ=0.5, p=0.004), hospital stay (ρ=0.5, p=0.002), and complications (ρ=0.5, p=0.005).Conclusion. In appropriately selected women with benign, non-prolapsed uteri ≤14 weeks, NDVH is feasible, but morbidity in this tertiary cohort was substantial and rose steeply with the preoperative feasibility score. The score is therefore best positioned as a graded decision aid: it identifies the low-morbidity majority who are ideal vaginal candidates, and flags the high-difficulty minority in whom either a modified vaginal strategy or an alternative route, senior operator, and prophylactic measures should be planned. External validation in a larger, prospective, multicentre cohort is required.

Current evidence regarding the efficacy of a new endometriosis blood test is limited and indirect, with varying diagnostic performance across studies. Blood biomarkers may support diagnosis but do not replace traditional methods.

Chronic pelvic pain (CPP) severely impacts quality of life, presenting distinct perioperative management challenges. Patients face heightened anxiety, severe postoperative pain, prolonged recovery from fear of movement, and persistent pain amplified by concurrent chronic overlapping pain conditions (COPCs). While data on preoperative pain's precise impact remains limited, surgery often triggers severe flares. Consequently, comprehensive preoperative screening is crucial. Evaluating risk factors-including central sensitization, substance use, smoking, COPCs, specific pain generators, and psychological comorbidities-allows clinicians to manage expectations effectively. Ultimately, this targeted risk assessment equips patients with the necessary strategies and tools to optimize their surgical recovery.

The objective of this work was to compare the perioperative safety and operative efficacy of robotic-assisted surgery (RAS) versus conventional laparoscopy surgery (CLS) in women with symptomatic colorectal endometriosis, with particular focus on to the anatomical disease complexity as defined by the #Enzian system. We retrospectively reviewed 160 consecutive cases operated for colorectal endometriosis at a single referral center between 2022 and 2025. Patients were managed by RAS (n = 59) or CLS (n = 101) in a non-randomized, sequential setting, with CLS performed prior to the implementation of RAS at our center. Intraoperative variables (operative time, blood loss, number of trocars, conversion rate) and perioperative outcomes (length of stay, transfusion, intensive-care admission, complications, reoperation, readmission, anastomotic leakage, and C-reactive protein serum levels on postoperative days 1-3 were analyzed. Anatomical disease extent was assessed using the #Enzian classification, including compartments P, O, T, A, B, C and F-compartments (FA, FB, FI, FU, F-nerves, F-diaphragm). Continuous variables were compared using the Mann-Whitney U test and categorical variables using Fisher's exact test, with p < 0.05 considered statistically significant. Complete excision of colorectal endometriosis and additional lesions was achieved with either route in all cases, with a very low overall rate of anastomotic leakage (2/160; 1.3%). Anatomical complexity was significantly higher in the RAS group, with more frequent peritubal/periovarian adhesions (T) (p = 0.002), advanced rectal (C) lesions (p = 0.003), and increased involvement of the bladder (FB) (8.5% vs. 0.0%, p = 0.006), ureter (FU) (11.9% vs. 2.0%, p = 0.013), and diaphragm (10.2% vs. 0.0%, p = 0.002). Despite this, median operative time was comparable between groups (225 [150-292] vs. 201 [146-251] minutes, p = 0.188). Length of hospital stay was significantly shorter after RAS (5 [4-6] vs. 6 [4-7] days, p = 0.008). Overall complication rates were similar (10.2% vs. 12.9%, p = 0.80), and the reoperation rate was numerically lower in the RAS group (1.7% vs. 6.9%, p = 0.26). RAS and CLS are both safe and effective surgical approaches for excision of symptomatic colorectal endometriosis. Despite being used in anatomically more complex cases, RAS achieved perioperative outcomes comparable to CLS, with a shorter length of hospital stay and a numerically lower reoperation rate. These findings underscore the importance of accounting for anatomical complexity and disease extent when comparing outcomes in deep endometriosis surgery. Prospective risk-adjusted or propensity score-matched studies are warranted to confirm these results.What is new? RAS achieves comparable perioperative outcomes to CLS in colorectal endometriosis and is associated to shorter hospitalization, despite being preferentially used in anatomically more complex cases defined by the #Enzian classification.

This Correspondence is a formal response to the Comment by Dr. Machado regarding our publication "Creatine Promotes Endometriosis by Inducing Ferroptosis Resistance via Suppression of PrP." We address several conceptual concerns raised in the Comment and clarify the physiological relevance of creatine concentrations, the methodological framework for PrP target identification, and the interpretation of human cohort data. We further provide evidence supporting creatine accumulation in endometriotic lesions and peritoneal fluid, and clarify the experimental basis for PrP target identification using integrated biochemical, computational, and functional analyses. Rather than demonstrating a direct molecular interaction, our findings instead provide convergent evidence consistent with PrP acting as a candidate functional target of creatine. We also reinforce the association between creatine exposure, ferroptosis resistance, and lesion progression, while acknowledging that definitive biochemical validation of direct binding remains to be established. Importantly, our study provides translational support for mechanistic investigations in endometriosis, rather than establishing a definitive clinical biomarker. Collectively, we highlight the metabolic significance of creatine-PrP signaling in endometriosis and discuss future directions for mechanistic and clinical validation.

Identification and preservation of pelvic autonomic nerves is essential for preventing postoperative functional disorders during surgery for deep endometriosis (DE); however, nerve-sparing surgery in patients with severe fibrosis and cul-de-sac obliteration remains technically demanding. Herein, we describe a surgical technique and perioperative outcomes of fluorescence-guided intraoperative identification of the hypogastric nerve using indocyanine green (ICG) during robot-assisted nerve-sparing hysterectomy (NSH) for DE. This retrospective cohort study included 41 consecutive patients who underwent robot-assisted NSH for DE between November 2020 and December 2025. A low-dose intravenous bolus of ICG (0.25 mg/kg) was administered intraoperatively, and near-infrared fluorescence imaging was used to facilitate intraoperative identification of the hypogastric nerve. Fluorescence onset was retrospectively assessed via surgical video review. The hypogastric nerve was successfully identified in 38 of 41 cases, yielding an overall identification rate of 92.7% (95% CI, 80.6-97.5%). The median time from ICG injection to fluorescence onset was 25 s (range, 12-42 s). No ICG-related adverse events or major perioperative complications occurred. In the three unsuccessful cases, nerve-sparing surgery was completed under conventional white-light visualization without conversion or additional complications. Real-time near-infrared ICG fluorescence imaging is a simple and minimally invasive adjunctive technique that facilitates fluorescence-guided intraoperative identification of the hypogastric nerve during robot-assisted nerve-sparing pelvic surgery. This approach may improve the reproducibility of anatomical nerve-sparing dissection and facilitate safer anatomical navigation during complex pelvic surgery. Larger prospective studies are warranted to validate these preliminary findings.

BACKGROUND: Benign uterine disorders, including uterine leiomyomas and uterine endometriosis/adenomyosis-related conditions, are common causes of gynecologic morbidity and represent an important women's health issue. Although these conditions are generally non-malignant, a subset of hospitalizations may involve substantial anemia-related clinical burden. Evidence describing severe inpatient anemia, red cell product ordering, intensive care unit (ICU) use, and short-term hospital outcomes in this population remains limited. METHODS: We conducted a retrospective cohort study using hospital data from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Adult female hospitalizations with diagnostic codes related to benign uterine disorders were identified. Hospitalizations with missing hemoglobin data, pregnancy- or obstetric-related diagnoses, and gynecologic malignancy-related diagnoses were excluded. The unit of analysis was hospitalization. Severe anemia was defined as a minimum inpatient hemoglobin level < 8 g/dL during hospitalization. The main outcome was red cell product ordering identified from Blood Bank provider order entry records, which was interpreted as a transfusion-related resource use indicator rather than confirmed red cell administration. Additional hospital burden outcomes included hospital length of stay, ICU admission during hospitalization, in-hospital mortality, and gynecologic procedure-related outcomes. Multivariable logistic regression was used to evaluate the association of severe anemia with red cell product ordering and ICU admission. Models were adjusted for age, race/ethnicity, insurance status, marital status, admission type, and disease group. Sensitivity analyses used hemoglobin < 10 g/dL as an alternative anemia threshold. RESULTS: The final cohort included 1,860 non-obstetric, non-malignant hospitalizations with available hemoglobin data. Severe anemia was present in 425 hospitalizations (22.8%). Compared with hospitalizations without severe anemia, those with severe anemia had a higher proportion of red cell product orders (63.29% vs. 5.09%), longer hospital length of stay [3.436 (1.911-6.389) vs. 2.310 (1.335-3.816) days], and more frequent ICU admission during hospitalization (15.06% vs. 6.13%). In-hospital mortality was uncommon overall and was analyzed only exploratorily. After multivariable adjustment, severe anemia was associated with red cell product ordering [adjusted odds ratio (OR) 33.61, 95% confidence interval (CI) 24.23-47.29] and ICU admission during hospitalization (adjusted OR 2.69, 95% CI 1.84-3.91). In the fibroid-only subgroup, the corresponding adjusted ORs were 35.55 (95% CI 24.96-50.64) for red cell product ordering and 2.68 (95% CI 1.83-3.92) for ICU admission. Sensitivity analyses using hemoglobin < 10 g/dL showed directionally consistent findings. Additional sensitivity analyses using earlier hemoglobin definitions showed that early 24-hour Hb < 8 g/dL remained strongly associated with red cell product ordering (adjusted OR 22.57, 95% CI 15.54-32.80), whereas the corresponding ICU admission estimate was attenuated and not statistically significant (adjusted OR 1.09, 95% CI 0.66-1.80). CONCLUSIONS: Among women hospitalized with benign uterine disorders, severe inpatient anemia was common and was associated with greater red cell product ordering and higher hospital resource use. These findings suggest that severe inpatient anemia may serve as a practical marker of anemia-related hospital burden in this defined hospitalized population, while ICU-related findings and causal interpretation require caution.

Endometriosis is one of the most common causes of chronic pelvic or lower-abdominal pain, yet mechanisms, predictors, and patient-centered treatment pathways remain insufficiently defined. This article summarizes the situation in Germany and presents two complementary research consortia: StEPP-UPP and ENDO-PAIN.StEPP-UPP addresses the clinical heterogeneity of endometriosis pain via a prospective multicenter cohort, standardized patient-reported outcomes, quantitative sensory testing, and multi-omics from blood, stool, and lesions. Explainable artificial intelligence and machine-learning models aim to estimate risk and trajectories of persistent pain, define mechanism-informed subgroups, and support treatment decisions. Preclinical mouse models with non-evoked behavioral metrics plus multiparametric MRI and single-cell analyses provide mechanistic anchoring for clinical signatures.ENDO-PAIN focuses on neuroinflammation and fibrosis as drivers of pain and chronification. Using patient samples, cell cultures, and 3D organoids, it maps immune-stroma interactions, syndecan signaling, and hormone-inflammation axes (for example P4-TGFβ-NFκB-COX-2) to derive biomarker networks and therapeutic targets.Both consortia integrate patient advocacy structurally to ensure patient-relevant endpoints and accessible information. Together they point to three priorities: standardization of data collection and biobanking; stratification along bio-psycho-social profiles and molecular signatures; and interdisciplinary shared decision-making across research, clinics, and people with endometriosis, aiming for mechanistically grounded, data-driven, patient-centered pain medicine.

Deep infiltrative endometriosis involving the bowel is a complex disease in which the optimal minimally invasive surgical approach remains uncertain, particularly regarding long-term fertility, recurrence, and healthcare utilization. We conducted a retrospective propensity score-matched cohort study using the TriNetX US Collaborative Network, including 72 healthcare organizations. Adult women who underwent minimally invasive colectomy for colorectal endometriosis between October 2013 and October 2025 were identified. Patients with prior hysterectomy, malignancy, inflammatory bowel disease, adenomyosis, or conversion to open surgery were excluded. Robotic colectomy was compared with conventional laparoscopic colectomy. After 1:1 propensity score matching, 487 patients were included in each cohort, with balanced baseline characteristics. At 3 years, robotic colectomy was associated with higher pregnancy achievement compared with laparoscopy (7.2% vs 2.9%; RR 2.50, 95% CI 1.36-4.59), lower endometriosis recurrence (4.3% vs 20.1%; RR 0.21, 95% CI 0.14-0.34), and reduced long-term opioid utilization (68.4% vs 89.3%; RR 0.77, 95% CI 0.72-0.82). At 5 years, these benefits persisted, with higher pregnancy achievement (7.8% vs 3.3%), lower recurrence (4.7% vs 18.5%), reduced opioid utilization (68.0% vs 90.3%), and fewer emergency readmissions (26.7% vs 35.1%). No significant differences were observed in urinary dysfunction, urinary incontinence, pelvic or perineal pain, dysmenorrhea, or dyspareunia. In this propensity-matched analysis, robotic colectomy was associated with higher recorded pregnancy and lower recurrence, opioid use, and readmission; given shorter follow-up and no fertility-intent data, these associations are hypothesis-generating.

INTRODUCTION: Our objective was to compare the severity of pelvic inflammatory disease (PID) in hospitalized women with and without endometriosis, and to assess whether deep endometriosis is associated with worse clinical outcomes. MATERIAL AND METHODS: A single-center retrospective cohort study was conducted from January 2018 to December 2023, including women hospitalized for PID in a tertiary care endometriosis center. Patients were classified based on the presence of endometriosis, as diagnosed by transvaginal ultrasound (TVUS). Clinical, microbiological, and imaging data were analyzed. Primary outcomes included treatment failure, length of hospital stay, need for urgent surgery, and recurrence. A subgroup analysis was performed within the endometriosis group to assess the impact of deep endometriosis. RESULTS: Of 159, 48 (30.2%) had endometriosis. Compared to those without the disease, women with endometriosis were older and had significantly higher rates of adnexal findings on TVUS (95.8% vs. 73.8%, p = 0.01), mostly suspected infected endometrioma. Vaginal and endocervical cultures were negative in 72.9% of endometriosis patients, and only one tested positive for sexually transmitted disease, in contrast to 42.3% positivity in the non-endometriosis group (p <0.01). Patients with endometriosis showed significantly higher rates of treatment failure (35.4% vs. 17.1%, p = 0.01), recurrence (31.3% vs. 11.7%, p = 0.01), and longer hospital stays (6.1 vs. 3.9). In the deep endometriosis subgroup, treatment failure and recurrence rates were higher, although these differences did not reach statistical significance. CONCLUSIONS: Endometriosis is a significant risk factor for more severe PID, contributing to worse clinical outcomes, including higher treatment failure, prolonged hospitalization, and greater recurrence. Particularly, those with deep endometriosis seem to have a more severe clinical course.

Introduction: Endometriosis is a chronic inflammatory disorder that depends on estrogen and affects approximately 10% of women of reproductive age. Although the exact cause of endometriosis remains unclear, it is suggested that combination of genetic, hormonal, and immunological factors is involved in its pathogenesis. Studies have shown that impaired immune system function plays a role in the development of endometriotic lesions. One type of immune cells that may contribute to the pathogenesis of endometriosis is the natural killer (NK) cells. NK cells are components of the innate immune system and play a critical role in defending against infections and eliminating abnormal cells, including cancerous cells. They are also involved in maternal-fetal tolerance and maintaining reproductive health. Increasing evidence suggests that both the function and number of NK cells are altered in endometriosis. Furthermore, recent research has shown promising results regarding the potential role of NK cells in the treatment of endometriosis.

To systematically identify, characterize, and critically appraise preclinical studies of berberine in endometriosis and adenomyosis, including studies using disease-related cell, tissue, and animal models.

Endometriosis may rarely present with atypical manifestations that closely mimic intra-abdominal malignancy or severe pelvic sepsis, resulting in significant diagnostic uncertainty. We present two contrasting cases of presumed severe endometriosis with uncommon clinical and radiological presentations. In the first case, a woman in her 30s presented with acute abdominal pain, progressive abdominal distension, and respiratory compromise associated with massive haemorrhagic ascites and markedly elevated cancer antigen 125 levels. Cross-sectional imaging demonstrated extensive deep infiltrative endometriosis with haemoperitoneum and multiple extra-pelvic endometriotic deposits. In the second case, a woman in her 30s presented with a complex adnexal mass, para-aortic lymphadenopathy and inflammatory features initially concerning for tubo-ovarian abscess or underlying malignancy. Following prolonged antibiotic therapy, complete radiological resolution of the adnexal lesion was observed, with subsequent imaging findings considered highly suggestive of an infected endometrioma. These cases emphasise the diverse spectrum of endometriosis presentations, the limitations of non-histological diagnosis and the importance of multidisciplinary assessment, radiological expertise and longitudinal follow-up in complex presentations.

ABSTRACTBackground: Suppurative leiomyoma, also known as pyomyoma, is an extremely rare clinical entitycharacterized by suppuration, necrosis, and abscess formation within a uterine leiomyoma. In the postantibiotic era, this condition is rarely encountered and frequently misdiagnosed preoperatively as pyometra,pelvic inflammatory disease, or uterine sarcoma.Case Presentation: A 50-year-old postmenopausal female (gravida 5, parity 1) presented with irregularvaginal bleeding, purulent discharge, and a significantly enlarged uterus. Preoperative clinical evaluations ledto a diagnosis of uterine leiomyomas complicated by pyometra. An abdominal hysterectomy with bilateralsalpingectomy was performed. Gross pathological examination revealed multiple, well-demarcated, pus-filledencysted cavities (largest measuring 3.0 x 2.5 cm) embedded deeply within a hypertrophic miometrial wall,while the endometrial cavity remained empty and compressed, thereby excluding central pyometra.Histopathology confirmed acute suppurative endometritis-myometritis with multiple encysted myometrialabscesses (pyomyomas) arising in a background of diffuse myometrial hypertrophy, extensive adenomyosis,and bilateral acute-on-chronic suppurative salpingitis.Conclusions: Pyomyoma should be considered in the differential diagnosis of postmenopausal womenpresenting with a pelvic mass, fever, or purulent discharge, especially when imaging suggests myometrialdegeneration. This case highlights how underlying extensive adenomyosis and chronic salpingitis can serveas structural and infectious conduits, facilitating direct bacterial extension into the myometrium to initiatelocalized pyogenic abscessuation. INTRODUCTIONUterine leiomyomas represent the most common benign neoplasms of the female reproductive tract, affecting up to70-80% of women by the fifth decade of life. While these tumors frequently undergo various forms of asepticdegeneration—such as hyaline, cystic, calcific, or red degeneration—suppurative degeneration, or the formation ofa pyomyoma, is an exceptionally rare complication. A pyomyoma occurs when a leiomyoma becomes infarcted,undergoes necrosis, and is subsequently seeded by pathogenic bacteria via hematogenous, lymphatic, orascending cervical routes.Due to its scarcity, clinicians rarely anticipate this diagnosis, and it is frequently misidentified as pyometra(accumulation of pus within the endometrial cavity), tubo-ovarian abscess, or a necrotic uterine sarcoma. Thisdiagnostic confusion is particularly pronounced in postmenopausal women, in whom diminished uterine vascularitypredisposes leiomyomas to ischemic infarction and subsequent pyogenic colonization. Here, we present a clinicallyand pathologically peculiar case of a 50-year-old postmenopausal patient whose preoperative diagnosis ofpyometra was pathologically redefined as a localized suppurative endometritis-myometritis with encystedpyomyomas, orchestrated by coexisting chronic salpingitis and extensive adenomyosis.CASE PRESENTATIONA 50-year-old postmenopausal female (gravida 5, parity 1; LMP: menopausal) presented with a history of irregular,frank vaginal bleeding, purulent vaginal discharge, pelvic discomfort, and a palpably enlarged uterus. Based onclinical findings and imaging indicating uterine enlargement and fluid collections, a presumptive diagnosis of a largeleiomyomatous uterus complicated by pyometra was made. The patient underwent an elective total abdominalhysterectomy and bilateral salpingectomy. Operative findings reported large uterine fibroids associated with asuspected pyometra.Gross Pathological FindingsThe specimen was received in a formalin-filled container, labeled "uterus, both fallopian tubes," containing a totalabdominal hysterectomy specimen with an attached right salpingectomy and a detached left salpingectomy. Theuterus was brown, smooth, firm, and irregularly shaped, measuring 15.0 x 12.0 x 11.5 cm. Upon bisection, the cutsurface revealed multiple, well-demarcated, pus-filled cavities embedded directly within the thick myometrium; thelargest of these encysted abscesses measured 3.0 x 2.5 cm. Crucially, the endometrial cavity itself was empty,lined by light brown, thin tissue, measuring 4.0 x 3.0 cm, with a myometrial thickness of 3.0 cm. The cervical canalwas completely patent, containing no nabothian cysts or fluid accumulation. The bilateral fallopian tubes weredilated and rubbery; the right measured 6.0 x 1.4 x 1.0 cm, and the left measured 3.0 x 1.8 x 1.5 cm, with cutsurfaces revealing lumens filled with organizing, light-brown purulent tissue. Figure 1. Gross pathology of the bisectioned uterusA high-resolution photograph of the bisected uterus. The markedly hypertrophic and dark brown myometrium is seen. Mostnotably, within the thickness of the myometrial wall, there are multiple well-circumscribed, 'encysted' abscess cavities filled withthick, creamy, light-brownish purulent material. The largest cavity measures approximately 3.0 cm in diameter and is surroundedby an intense rim of congested, red-brown inflammatory reaction, characteristic of a localized pyomyoma/myometrial abscess.Adjacent to the uterus, on the left, the dilated left fallopian tube (1.8x1.5 cm) filled with organizing purulent tissue (pyosalpinx) can be identified. Note that the endometrial cavity is compressed and empty of pus, definitively ruling out a central pyometra. Microscopic ExaminationHistopathological evaluation of twelve duplicated slides confirmed a complex infectious and structural process. Theendometrium demonstrated a weakly active proliferative pattern with overlapping peri-menopausal atrophicchanges, characterized by attenuated glands, reduced stromal cellularity, and focal cystic dilatation. Crucially, theunderlying myometrium demonstrated acute bacterial endometritis-myometritis. Within the myometrial wall, multipleencysted abscesses were identified, characterized by central pools of dense neutrophilic infiltrates, cellular debris,and necrosis, bordered by reactive stromal changes and granulation tissue.Adjacent myometrial sections demonstrated diffuse hypertrophy accompanied by extensive, deep adenomyosis,where benign endometrial glands and stroma were seen embedded within hypertrophic smooth muscle bundles.Multiple subserosal leiomyomas were noted, consisting of classic, benign interlacing fascicles of spindle-shapedsmooth muscle cells devoid of cytological atypia, necrosis, or atypical mitotic figures. The cervix exhibited chronicand active cervicitis with reactive epithelial changes and Nabothian cysts. Both fallopian tubes showed mild tomoderate acute suppurative salpingitis, marked by mucosal neutrophilic infiltration, reactive epithelial changes, andvascular congestion, while preserving the overall structure of the tubal wall.DISCUSSIONA pyomyoma is a diagnostic enigma that typically presents with a triad of a palpable pelvic mass, pain, and fever,accompanied by leukocitosis. In postmenopausal women, the clinical picture is easily confused with a malignantprocess, such as leiomyosarcoma, or pyometra, particularly when vaginal discharge is present. In our case, thesurgical team expected a pyometra. However, gross and microscopic examination demonstrated that theendometrial cavity was empty, and the purulent collections were entirely "encysted" within the myometrium aslocalized abscesses.This pathologically peculiar finding prompts an investigation into the route of infection. In patients with pyomyomas,infection usually ascends from the cervix, or spreads hematogenously or lymphatically. We propose that in thispatient, the infection ascended through the cervix, causing an acute but transient endometritis, and subsequentlyutilized two distinct "conduits" to penetrate deep into the uterine wall:1. Adenomyosis as an infectious conduit: The presence of extensive, diffuse adenomyosis provided preexisting anatomical invaginations of endometrial glands and stroma deep into the hypertrophic myometrium.These glands likely acted as a pathway, allowing the ascending bacterial pathogen to bypass the superficialendometrium and seed directly into the deep, hypertrophic myometrium.2. Bilateral acute-on-chronic salpingitis: The significant dilation and active purulent salpingitis suggest aconcurrent pelvic inflammatory process. The fallopian tubes, filled with organizing purulent debris, may haveserved as a persistent reservoir of bacteria, contributing to the infection of the highly vascularized,degenerating leiomyomas. This case is highly educational because it emphasizes that a clinical presentation of pyometra with an enlargeduterus can mask a localized pyomyoma. Recognizing these distinct pathological entities is crucial, as their clinicalcourses, risks of uterine rupture, and surgical complexities differ significantly. Pathologists and gynecologists mustremain aware of this rare presentation to ensure comprehensive diagnosis and timely surgical intervention.CONCLUSIONSIn conclusion, suppurative leiomyoma (pyomyoma) remains a highly unusual, life-threatening complication inmodern gynecology. This case illustrates a unique pathological correlation where extensive uterine adenomyosisand chronic suppurative salpingitis acted as conduits for deep myometrial bacterial entry, culminating in multipleencysted myometrial abscesses. When managing postmenopausal patients with enlarged uteri, purulent discharge,and suspected pelvic infections, clinicians must maintain a high index of suspicion for pyomyoma, as early surgicalintervention via hysterectomy remains the definitive, life-saving treatment.REFERENCES1. Karaman E, et al. Pyomyoma (suppurative leiomyoma) in a postmenopausal woman: a case report and review of the literature.Journal of Medical Case Reports. 2016;10:112.2. Schmid-Tannwald C, et al. Abscess formation in a uterine fibroid (pyomyoma) - a rare cause of acute abdomen: MRI findings.European Journal of Radiology Extra. 2011;79(2):e27-e30.3. Gorny KR, et al

BACKGROUND: Adenomyosis (AM) is frequently associated with compromised embryo implantation. The leukemia inhibitory factor (LIF)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is crucial for endometrial receptivity; however, its mechanistic role in AM-related implantation failure remains insufficiently elucidated. This study aimed to investigate the inactivation mechanism of the LIF/STAT3 pathway in AM and to evaluate a novel nanotherapeutic strategy for restoring implantation capacity. METHODS: Clinical endometrial samples from AM patients and controls were analyzed. A three-dimensional (3D) co-culture system simulating the endometrial microenvironment was established. Interventions were performed using a tofacitinib-loaded biomimetic nanogel (Tofa-NG). Comprehensive analyses included bulk RNA Sequencing (RNA-seq), immunohistochemistry (IHC), RT-qPCR, proteomics, inflammatory cytokine profiling, and metabolomics to dissect the pathological links. RESULTS: The LIF/STAT3 signaling pathway was significantly downregulated in the endometrium of AM patients, correlating directly with implantation failure. Pathologically elevated inflammatory cytokines suppressed LIF expression via NF-κB pathway activation, exacerbating the inflammatory microenvironment. Metabolomic profiling revealed a strong association between LIF/STAT3 pathway inactivation and aberrant cellular energy metabolism. The engineered Tofa-NG facilitated targeted drug delivery, effectively mitigated local inflammation, and successfully reactivated the LIF/STAT3 pathway. Consequently, this intervention significantly improved the embryo implantation success rate in the experimental model. CONCLUSION: This study identifies the inactivation of the LIF/STAT3 pathway as a central mechanism underlying embryo implantation defects in AM, intricately linked to chronic inflammation and metabolic dysregulation. The Tofa-NG strategy demonstrates promising therapeutic potential by rectifying the signaling deficit and ameliorating the endometrial microenvironment. These findings provide a novel theoretical foundation for developing targeted, personalized treatments for infertility associated with AM.

Endometriosis is a chronic, heterogenous disorder in which cyclical hemorrhage and repetitive repair generate ectopic implants that persist, recur, and drive pain and infertility; conventional frameworks emphasizing hormonal aberration and immune failure incompletely explain lesion fibrotic maturation and spatial heterogeneity. We synthesize human, experimental, and emerging spatial-omic evidence to advance a unifying mechanistic paradigm: cyclical bleeding seeds an immunothrombotic niche in which activated platelets and fibrin scaffolds organize immune cells and stromal responders, and platelet-derived signals, including P-selectin, TGF-β and platelet-derived microparticles (PMPs), act as upstream instructors of both immune dysregulation and fibrogenic stromal reprogramming. Quantitative histology and SHG imaging demonstrate spatial platelet hotspots that co-localize with NK suppression, CD163+ macrophage polarization and aligned collagen bundles in human lesions, while PMP proteomics and functional uptake assays link vesicular cargo to myofibroblast and reparative macrophage transcriptional programs. Mechanistically, platelet TGF-β and PMP cargo downregulate NK effector receptors (for example NKG2D), reprogram macrophages toward LOX-enriched matrix-remodeling states, and bias adaptive responses toward tolerance (Treg/Th17 imbalance), creating microdomains permissive for lesion survival. These processes engage a mechanobiological feedback loop: LOX-dependent collagen crosslinking increases stiffness, which amplifies myofibroblast and immune phenotypes and further recruits platelets, consolidating fibrotic architecture. We propose a research and translational roadmap, standardized PMP pipelines, integrated scRNA/spatial cohorts, ex vivo perturbations, and early proof-of-concept trials targeting adhesion (P-selectin), PMP biology, TGF-β activation or LOX, to test causality and enable precision interventions for the "immunofibrotic" endometriosis phenotype. Reframing endometriosis as a platelet-organized immunofibrotic disorder identifies novel druggable nodes and biomarker strategies with immediate potential to change both mechanistic research and clinical management.

BACKGROUND: Longitudinal studies suggest that diets encouraging higher intake of fruits and vegetables and lower intake of red meat are associated with a lower risk of laparoscopically-confirmed endometriosis. However, no studies have examined whether plant-focused dietary patterns are associated with endometriosis risk. OBJECTIVE: To investigate the association between three plant-based diet indices and the risk of laparoscopically-confirmed endometriosis in a predominantly omnivorous population. METHODS: We followed 82,084 premenopausal women participating in Nurses' Health Study II for 30 years. Diet was assessed using a validated food frequency questionnaire every 4 years. We calculated an overall plant-based diet (PDI), a healthful plant-based diet (hPDI), and an unhealthful plant-based diet (uPDI); higher scores indicated greater intake of plant foods and lower intake of animal foods. Laparoscopically confirmed endometriosis was ascertained from 1993. We used Cox proportional hazards models with age in months to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 1,038,888 person-years of follow-up, 3,829 cases of laparoscopically-confirmed endometriosis were reported. We observed no association between PDIs and endometriosis risk. The HR of each plant-based diet index with multivariable-adjusted models comparing participants in the highest quintile of adherence to those in the lowest quintile were 1.01 (CI=0.91, 1.13) for PDI, 1.07 (CI=0.96, 1.20) for hPDI, and 1.05 (CI=0.94, 1.16) for uPDI. Estimates were consistent regardless of infertility status. CONCLUSIONS: This study suggests that variation in the proportion of plant to animal foods, as captured by plant-based diet indices within predominantly omnivorous population is unrelated to risk of laparoscopically-confirmed endometriosis.

BACKGROUND: The management of endometriomata remains a challenge, with current options associated with either high recurrence rates or significant reduction in ovarian reserve. Ethanol sclerotherapy has been suggested as a treatment that is effective while maintaining ovarian reserve. METHODS: PubMed, EMBASE, MEDLINE, SCOPUS and CENTRAL were searched with no restriction on date or language. Keywords and MESH terms for 'endometrioma' AND 'ethanol sclerotherapy' AND 'cystectomy' were used. Studies were included if they made a direct comparison between ethanol sclerotherapy and cystectomy in the management of endometriomata in women of reproductive age. Randomised controlled trials (RCTs), cohort or case control studies were included. Searches were performed 11th February 2025 and repeated 21st August 2025. Risk of bias was assessed using ROB2 for RCTs and ROBINS-I for observational studies. RESULTS: Searches identified 172 studies with 16 of these fitting the inclusion criteria. Unfortunately, a formal analysis of between group change in Anti-Mullerian hormone (AMH) was not possible due to insufficient reporting of change score variance data, as such an exploratory between group pre- and post- analysis was performed instead. This found no significant difference in AMH at baseline (mean difference (MD) 0.02, 95% CI -0.20 to 0.25, p = 0.830) while post procedure AMH was significantly higher in the sclerotherapy arm (MD 0.75, 95% CI 0.43 to 1.06, p < 0.001). Overall risk of bias was high; however, similar results were seen following a sensitivity analysis excluding studies at highest risk of bias (high for ROB2 and critical for ROBINS-I) (MD -0.25, 95% CI -0.57 to 0.08, p = 0.136 and MD 0.60, 95% CI 0.22 to 0.97, p = 0.002, respectively). Studies reporting on Antral Follicle Count (AFC) gave conflicting results and all were assessed as at high or critical risk of bias. No significant difference was seen in recurrence (LogOR 0.28, 95% CI -0.57 to 1.12, p = 0.523). Rates of serious complications were low at 0.24% for sclerotherapy and 0.76% for cystectomy. It was not possible to pool data on symptomatology. Number of oocytes retrieved was higher in the sclerotherapy arm (MD 3.23, 95% CI 1.34 to 5.12, p < 0.001). Number of mature oocytes retrieved was also higher in the sclerotherapy arm (MD 2.79, 95% CI 1.08 to 4.51, p = 0.001), however this became non-significant when studies at the highest risk of bias were excluded (MD 0.79, 95% CI -0.61-2.19, p = 0.27). Data on pregnancy rate could not be pooled due to the wide variation in definition of clinical pregnancy. No significant difference was seen in live birth rate between interventions (logOR 0.59, 95% CI -0.30 to 1.48, p = 0.192). CONCLUSIONS: Our results show ethanol sclerotherapy maintains ovarian reserve when compared to ovarian cystectomy in the treatment of endometrioma, as evidenced by the higher post-procedure AMH levels and increased number of retrieved oocytes at IVF seen following sclerotherapy. However, due to the high risk of bias and flaws in design of included studies, high-quality randomised controlled trials with unified outcome standards are urgently required to confirm these findings and verify the protective benefit of ethanol sclerotherapy. This would support patients and their clinicians in decisions regarding management of endometriomata, particularly when fertility preservation is required. TRIAL REGISTRATION: This review was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO). The registration number is CRD42024625920.

(No abstract on file for this paper.)

Endometriosis (EMS) is a chronic inflammatory disease defined by the presence of endometrial-like tissue outside the uterine cavity. Ovarian EMS is considered the most prevalent disease phenotype. However, the causal relationship between granulysin and ovarian EMS remains unclear. We investigate the potential causal relationship between granulysin and ovarian EMS using a 2-sample Mendelian randomization analysis. Genome-wide association study data for granulysin and ovarian EMS were obtained from publicly available online databases. A 2-sample Mendelian randomization analysis was conducted using the inverse-variance weighted method. The causal effect was further validated through weighted median and MR-Egger regression analyses, and a leave-one-out sensitivity analysis was performed. The odds ratio and its 95% confidence interval were used to evaluate the causal relationship between granulysin and the risk of ovarian EMS. Our findings suggest a direct causal relationship between granulysin expression and ovarian EMS. The inverse-variance weighted analysis revealed that a 1-standard deviation increase in granulysin was associated with a 10.7% reduction in the risk of ovarian EMS (odd ratio = 0.892, 95% confidence interval: 0.824–0.966, P = .004). There may exist a negative causal relationship between granulysin expression and ovarian EMS.

(No abstract on file for this paper.)

Background: Abdominal wall endometriosis (AWE) following cesarean section (CS) is an increasingly recognized complication. Intramuscular involvement of the rectus abdominis and the management of associated fascial defects remain underreported. Methods: We retrospectively analyzed 14 consecutive women with histopathologically confirmed AWE following CS. Clinical presentation, imaging, operative technique, and follow-up outcomes were analyzed. Results: Mean age was 35.4 years (range 29–45). Three cases (21.4%) showed intramuscular rectus abdominis invasion; 11 (78.6%) were subcutaneous. Mean nodule size was 24.1 mm (range 9–45 mm). Cross-sectional imaging (MRI or CT) was obtained selectively in four patients with the largest lesions. Wide local excision with free margins was achieved in all cases. Two intramuscular cases required primary fascial repair (defects ~2 cm) without prosthetic mesh. No recurrences were detected at 12–24 months of follow-up. Conclusions: AWE following CS may involve both subcutaneous and intramuscular planes. Wide local excision with primary fascial repair is effective for small defects. Preoperative sonographic evaluation and individualized operative planning are essential for optimal outcomes.

(No abstract on file for this paper.)

Background: Endometriosis is a chronic inflammatory disease affecting approximately 10% of women of reproductive age and is commonly associated with pelvic pain and infertility. Increasing evidence indicates that lower urinary tract symptoms (LUTS) are more common in women with endometriosis, even in the absence of direct urinary tract involvement; however, the underlying mechanisms remain poorly understood. This study aimed to compare LUTS in women with surgically confirmed endometriosis and symptomatic women in whom endometriosis was surgically excluded, and to investigate their association with urethral ultrasonographic parameters and lesion localization. Methods: This prospective case–control study included 163 women: 81 with surgically confirmed endometriosis and 82 symptomatic controls in whom endometriosis was surgically excluded. Urinary symptoms were assessed using the validated Urogenital Distress Inventory Short Form (UDI-6). Urethral length and mobility were evaluated by transvaginal pelvic floor ultrasonography at rest, during pelvic floor muscle contraction, and during the Valsalva maneuver. Associations between urinary symptoms, ultrasonographic findings, lesion localization, and selected clinical variables were analyzed using appropriate non-parametric tests and multivariable linear regression. Results: Women with endometriosis demonstrated significantly higher total UDI-6 scores than symptomatic controls (p = 0.002), indicating a greater burden of lower urinary tract symptoms. Significant differences were observed only for pain/discomfort and post-void urine leakage, whereas the remaining UDI-6 domains did not differ between groups. Overall urethral ultrasonographic parameters were comparable between groups. However, among symptomatic women (UDI-6 ≥ 1), urethral mobility during the Valsalva maneuver was significantly lower in women with endometriosis than in controls (p = 0.041). Endometriosis localization was not associated with urinary symptom severity or urethral ultrasonographic findings. In multivariable analysis, previous cesarean section, but not endometriosis itself, was independently associated with higher UDI-6 scores. Conclusions: Women with surgically confirmed endometriosis experienced a greater burden of lower urinary tract symptoms than symptomatic women without endometriosis, particularly pain/discomfort and post-void urine leakage. These symptoms were not associated with lesion localization or major differences in urethral morphology, indicating that structural urethral abnormalities alone do not explain urinary symptom severity in this population. Routine assessment of urinary symptoms using validated questionnaires may facilitate comprehensive evaluation of women with endometriosis. Further prospective multicenter studies incorporating standardized pain assessment, urodynamic evaluation, and longitudinal follow-up are warranted to better elucidate the mechanisms underlying lower urinary tract symptoms in this population.

Background: Endometriosis is a common estrogen-dependent inflammatory disorder affecting women of reproductive age, causing dysmenorrhea, chronic pelvic pain and dyspareunia that substantially impair quality of life. Hormonal suppression with combined oral contraceptive pills (OCPs) and dienogest is a widely used medical therapy, yet comparative evidence on their relative efficacy for pain relief remains limited, particularly in South Asian populations. Objective: This study aimed to compare the effectiveness of combined OCP and dienogest in relieving pain and improving quality of life among women with endometriosis over a six-month treatment period. Methods: This retrospective observational study was conducted at the Department of Reproductive Endocrinology and Infertility, Bangladesh Medical University, between February 2023 and January 2024, involving 80 women with laparoscopically confirmed endometriosis divided into combined OCP (n=40) and dienogest (n=40) groups. Pain scores for dysmenorrhea, chronic pelvic pain and dyspareunia were assessed using a visual analogue scale and quality of life was measured using the Endometriosis Health Profile-30 (EHP-30) questionnaire at baseline and six months. Statistical analysis was performed using SPSS version 25.0. Results: Both groups showed significant pain reduction after six months; however, dienogest produced a greater decline in dysmenorrhea (2.4±1.2 vs 3.6±1.4, p<0.001), chronic pelvic pain (2.3±1.1 vs 3.2±1.5, p=0.006) and dyspareunia (2.2±1.3 vs 3.1±1.6, p=0.007), together with better EHP-30 scores (39.8±10.6 vs 46.5±11.4, p=0.008). A greater proportion of women achieved at least 50% dysmenorrhea reduction with dienogest (87.5% vs 70.0%, p=0.048). Irregular bleeding was more frequent with dienogest, whereas nausea and breast tenderness were more common with combined OCP. Conclusion: Dienogest provides superior pain relief and quality-of-life improvement compared with combined OCP in endometriosis management, with a distinct but manageable adverse-effect profile.

Background: Smoking may impair female reproductive health, but its causal role remains unclear. This study evaluated the causal associations of smoking initiation, lifetime smoking index, and smoking cessation with 15 female reproductive disorders. Methods: Linkage disequilibrium score regression (LDSC), Mendelian randomization (MR), and colocalization analysis assessed genetic correlations and causal associations, and detected shared genetic variants between smoking-related phenotypes and female reproductive disorders. Results: Genetic liability to smoking initiation was associated with higher risks of adenomyosis (odds ratio [OR] = 1.57, P = 0.008), dysplastic lesions involving the cervix, vagina, or vulva (OR = 1.34, P = 0.016), inflammatory disease of the uterus (OR = 1.52, P = 0.016), oligomenorrhea (OR = 2.09, P = 0.032), and torsion of ovary, ovarian pedicle, and fallopian tube (OR = 2.43, P = 0.046). A higher lifetime smoking index was associated with increased risks of dysplastic lesions involving the cervix, vagina, or vulva (OR = 1.55, P = 0.020), cervical dysplastic lesions (OR = 1.70, P = 0.007), excessive, frequent, and irregular menstruation (OR = 1.37, P = 0.003), and inflammatory disease of the uteri (OR = 2.66, P < 0.001). Genetic propensity to smoking cessation resulted in a reduced risk of endometriosis (OR = 0.58, P = 0.015). Colocalization revealed two shared genetic loci (inhibitory synaptic factor 1 [INSYN1] and phosphodiesterase 4B [PDE4B]) between lifetime smoking index and inflammatory disease of the uterus. Conclusion: These findings provide genetic evidence that smoking-related behaviors may causally influence several female reproductive disorders.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder characterized by impaired surfactant clearance due to alveolar macrophage dysfunction. Leuprorelin acetate, a gonadotropin-releasing hormone agonist, is widely used in the treatment of ovarian endometriosis; however, pulmonary findings associated with this therapy have not been well characterized. We report a case of PAP diagnosed during leuprorelin acetate therapy for ovarian endometrioma and describe its temporal relationship with treatment. CASE PRESENTATION: A 29-year-old woman underwent laparoscopic surgery for an ovarian endometrioma in August 2025 and initiated leuprorelin acetate therapy three days postoperatively. A routine chest computed tomography (CT) performed one month later revealed scattered bilateral ground-glass opacities (GGOs), which persisted on repeat CT in November 2025. Although the patient remained asymptomatic, video-assisted thoracoscopic surgery (VATS) lung biopsy was performed to obtain a histopathological diagnosis and confirmed PAP. Serum anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody testing was negative (3.2 µg/mL; reference range, ≤ 5 µg/mL), not supporting autoimmune PAP. During treatment, the patient developed transient Common Terminology Criteria for Adverse Events (CTCAE) grade 2 leukopenia (white blood cell nadir, 2.94 × 10⁹/L), which resolved spontaneously after completion of leuprorelin acetate therapy without intervention. Hematological evaluation did not suggest an underlying clonal disorder, including myelodysplastic syndrome. Because baseline chest imaging was unavailable, pre-existing subclinical PAP could not be excluded. Follow-up CT performed three months after completion of therapy showed regression of GGOs. CONCLUSION: This case shows a temporal relationship between leuprorelin acetate therapy and non-autoimmune PAP. However, causality cannot be inferred in the absence of baseline imaging. Only a temporal association can be observed. This observation is hypothesis-generating and highlights a potential rare pulmonary finding observed in the context of gonadotropin-releasing hormone agonist therapy.

INTRODUCTION: Deep endometriosis (DE) involving the bowel presents a complex management challenge. While surgery is often emphasized, limited evidence exists on long-term outcomes of conservative (non-surgical) management. This study aimed to evaluate quality of life (QoL), symptoms, bowel, and urinary function in patients with bowel DE managed conservatively over a nearly 7-year period. A secondary aim was to compare initial characteristics of those who later underwent surgery versus those who remained conservatively treated. MATERIAL AND METHODS: Patients diagnosed with bowel DE and managed conservatively with hormonal therapy were originally enrolled in a prospective study and followed up nearly 7 years later. Follow-up data were collected using validated online questionnaires: Short Form Health Survey 36 (SF-36) and Endometriosis Health Profile-30 (EHP-30) for QoL; the Low Anterior Resection Score (LARS) for bowel function; and the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) for urinary symptoms. Patients who had entered menopause or undergone bowel surgery or oophorectomy were excluded, as were patients pregnant at the time of follow-up. For the analysis related to the secondary aim, data collected 1 year from baseline was used, assessing any differences between those who later required surgery and those who remained conservatively managed. RESULTS: Fifty-two patients remained on conservative management throughout the follow-up. QoL (SF-36 and EHP-30) and bowel/urinary symptoms (LARS, ICIQ-FLUTS) remained stable. A significant reduction in dysmenorrhea was observed, while intermenstrual pain and dyschezia remained unchanged. Painkiller use tended to decrease. At follow-up, 15% reported major LARS. Seventy-three patients were included in the secondary analysis. Among respondents, 19% (n = 14) underwent bowel resection or total oophorectomy during the follow-up. These patients had significantly larger bowel lesions, higher pain scores, and lower SF-36 "bodily pain" scores, reflecting poorer QoL compared to those who remained conservatively managed. CONCLUSIONS: Over nearly 7 years of follow-up, most patients with bowel DE managed conservatively maintained stable symptoms and a relatively high QoL. One fifth required surgery, and these patients exhibited worse pain and QoL years prior to intervention. Conservative hormonal therapy appears to be a viable long-term option in selected patients, underscoring the importance of individualized, symptom-oriented treatment strategies.

Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by highly individualized, multisystemic symptoms, affecting approximately 10% of females. In this work, we present a long-term prospective study in which 34 participants defined personalized symptom sets and severity scales, tracking them daily for up to 12 months using a custom-developed app. This patient-tailored, high-resolution monitoring revealed substantial heterogeneity in the number of symptoms tracked, with participants tracking a median of 24.5 unique symptoms (interquartile range [19.25, 36.5]). To standardize assessment of system-organ involvement, symptoms were mapped to the MedDRA hierarchy, allowing structured analysis of symptom distribution. Based on these data, we propose a framework for characterizing symptom burden, trajectory, and disease burden, concepts that together capture the variability, systemic nature, and complexity of endometriosis. This personalized approach offers a clearer understanding of the disease experience and lays the groundwork for future tools that may improve communication with healthcare providers and inform more personalized and effective treatment strategies.

This matched comparative study investigates whether unoperated ovarian endometriomas (OMAs) influence the prevalence of tubal pathology as detected by hysterosalpingography (HSG) in infertile women. A total of 266 infertile women with unilateral or bilateral OMAs ≥ 2 cm and 539 matched controls without endometriomas were included between January 2021 and October 2024. Diagnosis of OMAs was confirmed by transvaginal ultrasonography and, if necessary, MRI, and all participants underwent standardized HSG assessment. Tubal pathologies were classified into nine distinct categories. The OMA group showed significantly higher rates of tubal abnormalities (31.6% vs. 10.8%, p < 0.001), with unilateral hydrosalpinx and phimosis being notably more common. Logistic regression identified age and OMA presence as independent predictors, and ROC analysis suggested a cutoff of 4.5 cm for increased risk. These findings indicate that unoperated OMAs, especially when ≥ 4.5 cm, are associated with a markedly increased risk of tubal pathology. Early tubal assessment may be beneficial for individualized fertility planning in this population.

Adenomyosis is a chronic gynecological disorder characterized by ectopic endometrial tissue within the myometrium, leading to pelvic pain, menorrhagia, and infertility. Increasing evidence implicates dysregulated Wnt/beta-catenin signaling and aberrant activation of SFRP4+ natural killer T (NKT) cells in disease progression. This study reports the ultrasound-assisted synthesis of a cerium-doped zeolite nanocomplex (Ce-ZNC) and evaluates its therapeutic efficacy in experimental models of adenomyosis. Ce-ZNC was synthesized via an ultrasound-assisted doping approach and characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and polydispersity index (PDI) analysis. In vitro studies were conducted on human peripheral blood mononuclear cell (PBMC)-derived SFRP4+ NKT cells. In vivo efficacy was evaluated in a murine adenomyosis model. IGFBP5 expression and Wnt/beta catenin signaling components were analyzed by RT-qPCR and Western blotting. Histological and cytokine analyses were performed to assess fibrosis and inflammation. Ce-ZNC exhibited spherical morphology with nanoscale dimensions and good colloidal stability. Treatment resulted in a dose-dependent suppression of IGFBP5 expression and inhibition of Wnt/beta-catenin signaling. In vivo administration significantly reduced uterine fibrosis, glandular invasion, and inflammatory cytokine levels. These findings suggest that Ce-ZNC exerts immunomodulatory and anti-fibrotic effects in adenomyosis. While promising, further studies are required to elucidate biodistribution, long-term safety, and translational potential in human models. Key words Adenomyosis " Cerium-doped zeolite " Nanomedicine " Wnt/beta-catenin pathway " IGFBP5 " SFRP4+ NKT cells " Inflammation " Fibrosis " Ultrasound-assisted synthesis.

Introduction Nomograms are intuitive graphical tools that integrate multiple prognostic variables to generate individualized risk estimates. To date, no study has developed a validated prediction model specifically for symptomatic recurrence after uterine-sparing surgery for adenomyosis. Accordingly, this study aimed to construct and validate a nomogram based on retrospective clinical data to predict symptomatic recurrence after laparoscopic adenomyomectomy and to inform individualized postoperative management. Materials and Methods In this retrospective cohort study, 484 consecutive patients who underwent primary laparoscopic adenomyomectomy between December 1, 2017, and March 30, 2022, were included. All patients completed postoperative follow-up. Symptomatic recurrence occurred in 131 patients, while 353 remained recurrence-free. Independent predictors of recurrence were identified using multivariate Cox regression, and a nomogram was constructed. Model discrimination was evaluated using Harrell’s concordance index (C-index) and internally validated using 5-fold cross-validation. Model performance was assessed via receiver operating characteristic curve, calibration curves, and decision curve analysis. A sensitivity analysis using inverse probability of treatment weighting (IPTW) confirmed the robustness of the identified predictors against residual confounding. Results Previous surgical history of ovarian endometrioma, preoperative CA125 level, concomitant ovarian endometrioma, postoperative medication modality, and duration of postoperative therapy were independent predictors of symptomatic recurrence. The nomogram demonstrated good discriminatory ability (area under the receiver operating characteristic curve [AUC], 0.776; 95% confidence interval [CI], 0.728–0.824). The calibration curve also had a good performance, and the DCA indicated that patients achieved a high net benefit for the predicted probability thresholds between 0% and 60%. Conclusion This nomogram provides accurate individualized risk estimation for symptomatic recurrence after laparoscopic adenomyomectomy, which requires multicenter external validation to confirm its clinical utility.

Desmoid tumour or aggressive fibromatosis is a rare abdominal wall mass often confused with other conditions. Though imaging modalities are important for diagnosis of an abdominal wall mass, histopathology gives the definitive diagnosis. Here, we present a case history of a 28-year-old lady who presented with a painful swelling over the previous Caesarean section scar. Local examination was suggestive of a lipoma or scar endometriosis but a pelvic ultrasonography suggested a mass in the right adnexal region. So, with varied differentials in mind, laparotomy was done and ultimately it was diagnosed as a case of abdominal wall desmoid tumour on histopathology. BIRDEM Med J 2026; 16(2): 104-108

Background: Endometriosis is a chronic inflammatory and estrogen-dependent disease in which oxidative stress, immune dysregulation, and lesion-supportive microenvironmental signaling contribute to lesion development. N-acetylcysteine (NAC), a glutathione-replenishing and redox-modulating agent, has been studied as a possible non-hormonal intervention. Methods: Following preregistration in the Open Science Framework (OSF), we performed a PRISMA-compliant systematic review of studies evaluating NAC in endometriosis-related clinical, in vivo, ex vivo, or in vitro settings. We searched PubMed/MEDLINE, EBSCOhost, and the Bielefeld Academic Search Engine (BASE) from inception to 24 May 2026. Risk of bias was assessed with design-specific instruments. Results: Twenty-two studies were included. Clinical evidence comprised six studies and suggested that the findings vary by clinical context. In non-postoperative settings, NAC was associated with reduced pain, decreased NSAID use, and endometrioma shrinkage or stabilization. In contrast, the only postoperative randomized comparison found no added benefit of NAC over continuous oral contraceptive therapy for recurrence or pain. Fertility-related clinical findings were suggestive but preliminary. Across nonclinical models, NAC reduced proliferation, lesion burden, oxidative stress, inflammatory mediators, and, in selected systems, migration-related behavior. Mechanistic studies linked NAC to modulation of ROS-dependent proliferation, TNF-α, COX-2, MMP-2/-9, autophagy-related signaling, oxidation-sensitive nociception, and partial protection of oocyte and embryo competence under endometriosis-associated oxidative conditions. Conclusions: NAC shows biological plausibility and preclinical activity in endometriosis, but clinical evidence is heterogeneous and methodologically limited.

Background. The relevance is due to the high frequency of fertility disorders in patients with endometrioid ovarian cysts, the limitations of existing methods for predicting pregnancy, and the need for an individual approach to managing such patients. Aim. To evaluate the prognostic significance of clinical and laboratory parameters in predicting the likelihood of pregnancy in women who underwent surgical treatment for endometrioid ovarian cyst. Materials and methods. A prospective comparative study of 88 patients operated on for newly diagnosed unilateral endometrioid ovarian cyst was conducted. The patients were followed up for 6 months after surgery and were divided into 2 groups: group 1 – 55 women without pregnancy, group 2 – 33 women with spontaneous pregnancy. Before the operation, all patients underwent ultrasound of the pelvic organs, analysis of the content of sex hormones, standard laboratory tests, evaluation of the visual-analog pain scale. During the operation, peritoneal fluid was taken to determine the levels of vascular endothelial growth factor, tumor necrosis factor α (TNF-α), interleukins-1β, 6, 8, 10. Results. The level of Anti-Mullerian hormone was lower in group 1 – 2.55 [Q1–Q3 1.25–4.33] ng/ml, compared with group 2 – 4.40 [Q1–Q3 2.10–6.90] ng/ml; p=0.028. The level of ferritin was also lower in group 1 – 29 [Q1–Q3 14.75–57] mcg/l, compared with group 2 – 41 [Q1–Q3 22–57] mcg/l (p=0.023). The frequency of detection of ultrasound signs of adenomyosis was higher in group 1 – in 27 (49.1%) women, compared with group 2 – in 9 (27.3%); p=0.044. The Endometriosis Fertility Index (EFI) was 7 [Q1–Q3 7–8] points for group 1 and 9 [Q1–Q3 8–9] points for group 2 (p 0.001). The concentration of TNF-α in the peritoneal fluid was 3.51 [Q1–Q3 1.37–4.18] pg/ml in group 1, compared with group 2 – 2.46 [Q1–Q3 0.66–3.73] pg/ml (p=0.036). Conclusion. The study revealed that successful conception was associated with high serum levels of Anti-Mullerian hormone and ferritin, low concentrations of TNF-α in peritoneal fluid, and absence of adenomyosis on ultrasound examination.

Purpose: We aim to elucidate the impact of endometriomas on oocyte developmental competence and identify genetic alterations that may influence ICSI success rates in women of different ages. Methods: In this retrospective study, two groups of patients have been analyzed: 108 women with a history of severe endometriosis (stages III and IV), who underwent OPU and ICSI after endometriosis surgery, and a control group, built out of 108 women with no endometriosis history. The Turku Endometriosis Database was used for differential gene expression analysis. Results: The number of aspirated oocytes (endometrioma group: 2.75 ± 0.32 vs. control 10.32 ± 0.54) was significantly (p < 0.0001) lower in patients with endometrioma excision, and the number of generated blastocysts was significantly (p < 0.0001) lower when compared to patients without endometriosis (endometrioma group: 1.09 ± 0.13 vs. control group: 3.76 ± 0.23). Additionally, AMH levels were significantly lower (p < 0.001) in the endometriosis-affected group below the age of 35 years (1.65 ± 0.15) than in the unaffected control group (2.99 ± 0.27) within the same age group. The mRNA expression of the following genes related to oxidative stress was significantly (p < 0.05) upregulated in the endometriosis group compared with healthy controls: DES, P2RX1, FOS, SRF, RASD2, SLITRK3, and TEAD3. Gene Ontology and pathway enrichment analyses demonstrated a significant (p < 0.0001) enrichment of oxidative stress–associated biological processes and signaling pathways, including responses to reactive oxygen species and hypoxia, HIF-1, MAPK, PI3K–Akt, NF-κB, and apoptotic signaling, supporting oxidative stress as a central molecular mechanism underlying the observed transcriptomic alterations. Conclusions: In conclusion, this retrospective study provides a holistic perspective on the impact of endometrioma and its oxidative stress effect on oocyte developmental rates and ICSI outcomes across different age groups.

Abstract Uterine polypoid adenomyoma is a rare focal form of adenomyosis that can present as an intracavitary lesion and pose a significant diagnostic challenge, often mimicking more common or concerning entities, such as endometrial polyps or uterine adenosarcoma. We describe the case of a 53-year-old woman who presented with profound anaemia (haemoglobin 3.9 g/dL) secondary to acute on chronic heavy vaginal bleeding. Multimodal imaging, including ultrasound and MRI, prompted the initial diagnosis of uterine polypoid adenomyoma, later supported by surgical pathology. Ultrasound demonstrated diffusely heterogeneous myometrial echotexture and multifocal “venetian blind” artifact consistent with adenomyosis. MRI revealed an ovoid lesion within the endometrial cavity containing numerous T2 hyperintense cystic foci and imaging characteristics similar to the junctional zone, consistent with a submucosal uterine polypoid adenomyoma. Management included blood transfusions, hormone therapy, and ultimately hysterectomy. This case serves to underscore the importance of a combined approach, including both multimodal imaging and histopathology, in guiding the accurate diagnosis and optimal management of uterine polypoid adenomyoma. It is also intended to increase awareness of this rare lesion and encourage its consideration in the differential diagnosis of intracavitary uterine masses, as it may have implications for treatment planning.

Endometriosis is estimated to affect 10% of reproductive-age women: approximately 6.5 million women in the United States, and 190 million women worldwide. Endometriosis is a painful and chronic inflammatory disease characterized by the growth of endometrial-like tissue outside of the uterus. Endometriosis is a difficult disease to diagnose due to nonspecific symptoms, lack of awareness, and symptom normalization. This results in long diagnostic delays; the time from the start of symptoms to diagnosis is estimated to be on average 7 years. Individuals with endometriosis are more likely to have coexisting chronic conditions, including cancer; however, the exact mechanisms remain unclear. Furthermore, the association between endometriosis and both melanoma and colorectal cancer remains unclear due to previous studies with significant bias. To better understand the sequelae of endometriosis, we prospectively investigated the relationship between endometriosis and cutaneous melanoma, and colorectal cancer, in Chapters 1 and 2,respectively. We examined these associations in the Sister Study, a prospective cohort of 49,255 women aged 35 to 76 years old in the United States. To date, the majority of endometriosis research is conducted among Caucasian women, lacking critical information on race and ethnicity. As a result, little is known about the experiences of endometriosis diagnosis among Black, Asian, and Hispanic women. For Chapter 3, we conducted a qualitative study to understand the role of race and ethnicity in the patient's journey to endometriosis diagnosis among 25 Black women.

(No abstract on file for this paper.)

Endometriosis is a chronic, estrogen-dependent inflammatory disease that causes debilitating pain and significantly impairs quality of life. Due to its anti-inflammatory and immunomodulatory properties, vitamin D has been proposed as a potential therapeutic agent, but clinical evidence remains inconsistent. This study aimed to evaluate the effect of vitamin D supplementation on pain symptoms and quality of life in women with endometriosis. This randomized, double-blind, placebo-controlled clinical trial was conducted on 66 women with symptomatic endometriosis and vitamin D levels below 30 ng/mL. Participants were randomly assigned to either the intervention group (n = 33), receiving 4000 IU of vitamin D every other day, or the control group (n = 33), receiving a matching placebo for eight weeks. Crucially, all participants in both groups continued their standard dienogest (Verogest) therapy. The primary outcomes were pain severity, assessed using the Visual Analogue Scale (VAS) and the ENDOPAIN-4D questionnaire, and quality of life as secondary outcome, assessed with the Endometriosis Health Profile-30 (EHP-30). Outcomes were measured at baseline and after the eight-week intervention. All 66 participants completed the trial. Despite baseline imbalances in socio-demographic characteristics (quantified via standardized mean differences), adjusting for these variables as covariates did not yield significant differences between groups. Regarding the ENDOPAIN-4D scores, for the "usual level of pain," the post-intervention mean score was 38.8 (SD = 6.5) in the vitamin D group compared to 50.1 (SD = 7.4) in the placebo group (adjusted mean difference [AMD]: -11.3; 95% Confidence Interval [CI]: -26.2 to 3.5; P = 0.136). For the "worst level of pain," the post-intervention mean score was 23.6 (SD = 3.1) in the vitamin D group and 25.6 (SD = 3.5) in the placebo group (AMD: -2.0; 95% CI: -9.0 to 4.9; P = 0.492). The adjusted mean post-intervention VAS score was 5.8 (SD = 0.3) in the vitamin D group versus 6.2 (SD = 0.4) in the placebo group (AMD: -0.3; 95% CI: -1.3 to 0.5; P = 0.113). No significant differences were observed in the ENDOPAIN-4D scores or in any of the five domains of the EHP-30 questionnaire (all P > 0.05). In women under hormonal suppression with dienogest, eight weeks of adjunctive vitamin D did not yield statistically or clinically significant improvements in pain or quality of life. These null findings likely reflect a "floor effect" from the baseline hormonal therapy and are limited by the lack of biochemical confirmation of repletion. These findings are specific to adjunctive use and may not reflect the potential of vitamin D as a monotherapy.Trial registration: Iranian Registry of Clinical Trials (IRCT) IRCT20120718010324N78. Date of first registration 2023-05-25. URL https//irct.behdasht.gov.ir/trial/68131.

The causal role of established risk factors for premenstrual disorders (PMDs) remains unclear. We used Mendelian randomization (MR) to assess causality for eight known-risk factors identified through a literature review. Summary statistics for these risk factors were from genome-wide association studies (GWAS) with sample size ranging from 129,017 to 1.2 million, and for PMDs from a GWAS of 72,297 participants. Findings were validated using one-sample MR in LifeGene cohort (n = 5674-5937). In two-sample MR, genetic liability to smoking initiation (OR = 1.25 (1.10-1.43)), earlier menarche (OR = 0.94 (0.89-0.98) per year), and higher BMI (OR = 1.19 (1.05-1.34) per kg/m2) were associated with PMD risk. No causal association was indicated for anemia, childhood abuse, childhood asthma, diabetes, and endometriosis. In one-sample MR, point estimates for BMI (OR = 1.10 (0.88-1.38) per kg/m²) and earlier menarche (OR = 0.98 (0.83-1.15) per year) were directionally consistent with the two-sample MR findings, but the confidence intervals included null effects. However, a null association was observed for smoking (OR = 0.94 (0.77-1.16)). The two-sample MR supports causal role of earlier menarche, higher BMI, and smoking in risk of PMDs. The lack of replication in one-sample MR highlights the need for triangulating evidence from future well-powered and methodologically comparable studies to strengthen these findings.