OBJECTIVE:This study aims to assess the surgical outcomes and learning curve of robotic single-port vaginal natural orifice transluminal endoscopic surgery (RSP-vNOTES) for hysterectomy in benign gynecologic conditions. MATERIALS AND METHODS:A retrospective observational analysis was conducted of 97 consecutively enrolled patients who underwent RSP-vNOTES hysterectomy using the da Vinci (single-port) SP system between December 2023 and July 2025 at a single tertiary care center. RESULTS:Median procedural durations included a total operative time of 151 minutes, a port placement time of five minutes, a docking time of two minutes, a robotic console time of 78 minutes, and a hysterectomy time of 35 minutes. One case (1.0%) required conversion to a transumbilical single-incision robotic approach for management of diaphragmatic endometriosis after completion of the vaginal hysterectomy, rather than due to failure of the hysterectomy itself. Fourteen patients (14.4%) experienced perioperative complications. Cumulative sum analysis revealed that hysterectomy time stabilized after approximately 30 cases, while port placement and docking times plateaued after 43 and 37 cases, respectively. CONCLUSIONS:These findings suggest that proficiency in RSP-vNOTES can be achieved with sequential case experience. RSP-vNOTES appears to be a safe and effective surgical approach for hysterectomy, including complex scenarios such as endometriosis. Proficiency is typically achieved after 30 cases, particularly among surgeons with prior experience in robotic-assisted single-site and vNOTES techniques.

Adult stem cells are thought to drive the regenerative potential of the endometrium and contribute to the pathogenesis of endometriosis; however, their identity and defining features remain to be characterized. Here, we used in vivo and in vitro approaches to demonstrate that cells with high aldehyde dehydrogenase 1 activity (ALDHHI cells) were long-lived progenitors in the endometrium with a higher organoid formation capacity, long-term passaging potential, and stemness gene signatures. Using lineage tracing with an Aldh1a1creERT2/+; Rosa26LSL-tdTomato reporter mouse, Aldh1a1+ epithelial cells expanded during postnatal development, Aldh1a1+ stromal cells expanded during estrous cycling, and both populations of Aldh1a1+ cells were present during postpartum repair. In response to ovariectomy or exogenous estradiol, we found that ALDH1A1+ cells localized to glandular crypts of the endometrium or throughout the luminal epithelium, respectively, indicating that their spatial localization is hormone-sensitive. Functionally, we found that selective ablation of ALDH1A1+ cells in Aldh1a1creERT2/+; Rosa26LSL-DTR mice decreased endometrial gland number and FOXA2 expression. These findings were recapitulated in the human endometrium, where endometrial epithelial organoids with high ALDH activity (ALDHHI cells) showed a higher organoid formation capacity than ALDHLO cells and displayed unique transcriptomes with fewer luminal-like ciliated cells. Overall, our studies indicate that ALDH1A1+ cells are hormone-sensitive adult stem cells in the endometrium with regenerative potential that are critical for endometrial development and function.

Endometrial organoids are a powerful, 3D in vitro system for studying reproductive function and disease since they are more physiologically representative than 2D cell models. However, optimal methods for the analysis of individual organoids are still developing and remain inconsistent throughout the field. To independently evaluate and optimize high-throughput analysis tools for human and mouse endometrial organoids, we first assessed several interfaces, OrganoID, OrganoSeg2, and Biodock, for their segmentation capabilities of whole-dome Z projection brightfield microscopy images. The edge detections of OrganoID and OrganoSeg2 were not sufficient to distinguish individual endometrial organoids when multiple organoids were in contact or when debris was present and thus, we did not further evaluate these interfaces for phenotypic quantitative analysis. By creating trained deep learning models on Biodock which performed reliable segmentation, we present methods to classify and quantify organoids with mixed 'round' or 'abnormal' populations, extracting critical information such as area, eccentricity, and brightness from each individual organoid. These analysis parameters were effective in organoids from human endometrial epithelium grown in complete vs. reduced medium and from genetically engineered mice. Additionally, Biodock was used to quantify live and dead cells labeled with fluorescent dyes, showing that it is also useful for quantifying high-throughput live imaging data from drug treatment experiments. Overall, deep learning models trained through Biodock accurately assessed phenotypic properties of human and murine endometrial organoids in brightfield and live-fluorescent microscopy, demonstrating that it is a promising tool for analyzing endometrial organoids to reliably detect phenotypic differences from organoid microscopy.

IntroductionThis study was to evaluate the safety and feasibility of robotic single-port transvaginal natural orifice transluminal endoscopic surgery (RSP-vNOTES) compared with robotic Xi-assisted single-incision transumbilical surgery (RXi-SITS) for hysterectomy.MethodA total of 405 patients was retrospectively analyzed, comprising 278 individuals who underwent RXi-SITS hysterectomy and 127 who underwent RSP-vNOTES hysterectomy.ResultsA significantly higher prevalence of endometriosis-associated concomitant procedures, including ovarian cystectomy, lesion excision, adhesiolysis, appendectomy, bowel shaving, and bowel oversew, was observed among patients undergoing RSP-vNOTES (all p < 0.05). The RXi-SITS group saw uterosacral ligament suspension and ovarian vein ligation more commonly performed (both p < 0.05). A multivariable linear regression approach was employed to account for heterogeneity in procedural complexity. Following multivariable adjustment, estimated blood loss, hysterectomy time, and postoperative pain outcomes were comparable between the two surgical approaches. In contrast, multivariable linear regression accounting for concomitant procedures demonstrated that the RXi-SITS approach was independently associated with a significantly prolonged total operative time, with an adjusted mean increase of 21.8 min compared with RSP-vNOTES (B = 21.83; 95% CI: 6.05-37.61; p = 0.007). This is despite unadjusted analyses showing a longer median operative time in the RSP-vNOTES group (160 [IQR 140-194] vs. 151 [120–200] minutes; p = 0.02).DiscussionCompared with RXi-SITS hysterectomy, RSP-vNOTES hysterectomy demonstrated comparable surgical outcomes, supporting its safety and feasibility across a range of gynecologic procedures. Despite greater procedural complexity in the RSP-vNOTES cohort, the RXi-SITS approach was independently associated with a longer total operative time, suggesting a potential efficiency advantage of RSP-vNOTES in appropriately selected patients.

PURPOSE OF REVIEW:Endometriosis was once thought to affect only reproductive-aged women. However, 2-5% of postmenopausal individuals remain affected. Guidance for this group is limited. This review outlines an updated approach to postmenopausal endometriosis, addressing pathophysiology, diagnostic challenges, and management in both natural and surgical menopause. RECENT FINDINGS:Postmenopausal endometriosis is underrecognized and has many diagnostic challenges. MRI is the preferred imaging modality for detecting lesions and assessing malignancy risk, while surgery with excision remains the diagnostic and treatment gold standard. Medical treatment options are limited, with aromatase inhibitors showing the most promise by targeting main sources of estrogen production; however, research is limited. Hormonal replacement therapy is recommended after surgical or premature menopause (<age 45), and hormone therapy may be considered for symptomatic natural menopause, though optimal regimens and duration remain unclear. Combined estrogen-progestogen therapy or tibolone is preferred due to the possible risk of recurrence or malignancy. Ovarian-sparing surgery may be considered in select younger patients to reduce the need for hormonal replacement therapy given the lack of data. SUMMARY:Evidence on postmenopausal endometriosis remains limited. Further research is needed to guide treatment, refine hormone therapy strategies, and improve long-term outcomes and quality of life.

Adult stem cells are thought to drive the regenerative potential of the endometrium and contribute to the pathogenesis of endometriosis, however, their identity and defining features remain to be characterized. Here, we used in vivo and in vitro approaches to demonstrate that cells with high aldehyde dehydrogenase 1 activity (ALDHHI cells) were long lived progenitors in the endometrial epithelium with a higher organoid formation capacity, long-term passaging potential, and stemness gene signatures. Using lineage tracing with an Aldh1a1cre/ERT2; ROSA26tdTomato reporter mouse, Aldh1a1+ cells expanded during postnatal development, estrus cycling, and following post-partum repair. In response to ovariectomy or exogenous estradiol, we found that ALDH1A1+ cells localized to glandular crypts of the endometrium or throughout the luminal epithelium, respectively, indicating that their spatial localization is hormone sensitive. Functionally, we found that selective ablation of ALDH1A1+ cells in Aldh1a1cre/ERT2; ROSA26-DTRflox/flox mice decreased endometrial gland number and FOXA2 expression. These findings were recapitulated in the human endometrium, where endometrial epithelial organoids with high ALDH activity (ALDHHI cells) showed a higher organoid formation capacity than ALDHLO cells and displayed unique transcriptomes with fewer luminal-like ciliated cells. Overall, our studies indicate that ALDH1A1+ cells are hormone-sensitive adult stem cells in the endometrium with regenerative potential that are critical for endometrial development and function.

Pelvic organ prolapse remains a common condition requiring durable surgical correction, with sacrocolpopexy considered the gold standard. Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) has emerged as a scarless minimally invasive approach, while the integration of robotic single-port technology may further enhance surgical precision and ergonomics. However, data on robotic-assisted single-port vNOTES (RSP-vNOTES) sacrocolpopexy remains limited. We report a case of a 58-year-old Asian woman with symptomatic apical pelvic organ prolapse. The pelvic organ prolapse quantification (POP-Q) assessment demonstrated stage II uterine prolapse. She underwent robotic-assisted single-port vNOTES (RSP-vNOTES) sacrocolpopexy using the da Vinci single-port (SP) platform. The procedure was successfully completed via a transvaginal approach without abdominal incisions. Operative time was 170 min, with minimal blood loss (25 mL), and no intraoperative complications occurred, nor was a conversion required. The patient was discharged on postoperative day two and demonstrated an uneventful recovery with sustained anatomical support at one-year follow-up. This case highlights the feasibility and safety of RSP-vNOTES sacrocolpopexy and underscores its potential advantages, including enhanced visualization, improved instrument dexterity, and the benefits of a scarless approach. As an early application of RSP-vNOTES in pelvic reconstructive surgery, this technique may represent a significant advancement in minimally invasive management of pelvic organ prolapse. Therefore, this case report aimed to describe the surgical technique and perioperative outcomes of RSP-vNOTES sacrocolpopexy using the da Vinci SP platform, while highlighting its potential advantages and clinical relevance. By presenting this early experience, we seek to contribute to the evolving evidence base and inform future adoption of this innovative approach in minimally invasive pelvic reconstructive surgery.

STUDY QUESTION:Does intercornual distance (ICD), as reflected by intrauterine stent size during hysteroscopic adhesiolysis, have an association with reproductive outcomes and provide information for postoperative risk stratification in women with moderate-to-severe intrauterine adhesions? SUMMARY ANSWER:A smaller ICD was independently associated with a lower likelihood of clinical pregnancy within 1 year of the final hysteroscopy and may offer additional information for postoperative risk stratification in women with moderate-to-severe intrauterine adhesions. WHAT IS KNOWN ALREADY:Reproductive outcomes following treatment for moderate-to-severe intrauterine adhesions vary considerably. Existing severity classifications offer limited discrimination within this group. The potential association between ICD and postoperative reproductive outcomes has not been systematically evaluated. STUDY DESIGN SIZE DURATION:Retrospective cohort study conducted at a tertiary academic center from November 2022 to October 2023. A total of 560 women were included, with up to 2 years of follow-up. PARTICIPANTS/MATERIALS SETTING METHODS:Retrospective single-center cohort of women aged 18-44 years with moderate-to-severe intrauterine adhesions (American Fertility Society [AFS] score ≥ 5) undergoing standardized hysteroscopic management with adhesiolysis, intrauterine stent placement, and scheduled second-look hysteroscopy. ICD was reflected by intraoperatively selected stent size, categorized into ordered levels (XXXS-XXXL) and dichotomized using an XS threshold (∼20-22 mm). Postoperative ultrasound-derived ICD was analyzed for supportive evaluation. The primary outcome was clinical pregnancy within 1 year of the final hysteroscopy. Associations were examined using multivariable logistic regression with sensitivity analyses. The incremental predictive value and clinical utility of stent-size classification (≤XS vs >XS) beyond established clinical variables were evaluated using discrimination, calibration, and decision-curve analyses. MAIN RESULTS AND THE ROLE OF CHANCE:Women in the ≤XS group had lower odds of clinical pregnancy within 1 year of the final hysteroscopy compared with those in the >XS group (adjusted odds ratio [aOR] = 0.447, 95% CI 0.255-0.786; P = 0.005). The association was consistent in sensitivity analyses and when postoperative ultrasound-derived ICD was analyzed as a continuous variable. Although improvements in model discrimination were modest, the difference in the probability of clinical pregnancy between the ≤XS and >XS groups was 21.2% (absolute risk difference [ARD] = 21.2%, 95% CI 9.6-32.2; P < 0.001), corresponding to a number needed to benefit (NNB) of 4.7, indicating potential clinical utility for postoperative risk stratification. LIMITATIONS REASONS FOR CAUTION:This single-center retrospective study may limit generalizability and is subject to selection bias and residual confounding. Prospective multicenter validation is required. WIDER IMPLICATIONS OF THE FINDINGS:ICD may provide additional information for postoperative risk stratification in women with moderate-to-severe intrauterine adhesions. STUDY FUNDING/COMPETING INTERESTS:This study was supported by Scientific and Technological Project of Furong Laboratory (Gynecological Disease and Reproductive Health) (No. 2023SK2109) and Key Research Project of National Key Clinical Specialties, Health Commission of Hunan Province (Z2023068), China. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER:N/A.

Endometriosis, defined as the ectopic growth of endometrial tissue outside of the uterine cavity, is an inflammatory and hormone-dependent disease that causes excruciating pelvic pain, infertility, and significantly decreases quality of life in affected patients. The JUN N-terminal kinases (JNKs) are a leading class of nonhormonal therapeutic targets that have been validated in preclinical models of endometriosis and in a Phase 1/2 clinical trial. Despite their therapeutic potential, JNK inhibitors with increased potency and specificity are needed to address the inflammatory pathology of endometriosis and to prevent disease progression. Leveraging a DNA-encoded chemical library collection of ~4 billion compounds, we identified lead inhibitor CDD-2428 and optimized derivatives, CDD-2728 and CDD-3013, with excellent binding affinity to JNK1-3 (K d = 0.12 to 3.7 nM), enhanced selectivity, metabolic stability, and cellular permeability. Crystallographic and biochemical studies confirmed that CDD-3013 exhibited superior kinase selectivity with improved efficacy compared to existing JNK inhibitors. In primary endometriosis cell models, CDD-2728 and CDD-3013 suppressed JNK-dependent inflammatory signaling, dampening pathways linked to pain, invasion, angiogenesis, and macrophage recruitment. In an endometriosis mouse model, both CDD-2728 and CDD-3013 reduced endometriotic lesion size, macrophage infiltration, and cellular proliferation, showing in vivo efficacy. When tested in a lipopolysaccharide-induced hyperalgesia model, CDD-2728 and CDD-3013 decreased markers of induced pain, as measured by changes in a dynamic weight bearing test and Grimace scores. These findings nominate CDD-2728 and CDD-3013 as potent, nonhormonal therapeutic candidates for endometriosis with broad anti-inflammatory and analgesic activity, addressing a critical unmet clinical need.

STUDY OBJECTIVE:To show the feasibility and technique used to perform a right ovarian cystectomy via robot-assisted vaginal natural orifice transluminal endoscopic surgery (vNOTES) using the da Vinci single-port (SP) robotic platform. DESIGN:Single-patient video case report. SETTING:Single academic institution. INTERVENTIONS:We demonstrate the use of the da Vinci SP robotic platform performing vNOTES on a right ovarian cyst. This cyst was adherent to the right upper pelvic brim, and we show the steps in performing adhesiolysis and isolation of the cyst before performing a cystectomy. This video highlights the versatility of the da Vinci SP with 3 articulating instruments, a high-definition angulating camera, a telescoping arm feature, and SP docking globe for specimen placement, in addition to the established benefits of robotic surgery. CONCLUSION:This video highlights the feasibility and strategies used to perform an ovarian cystectomy via robot-assisted vNOTES using the da Vinci SP robotic platform.

BACKGROUND:Intraoperative ureteral injury, although uncommon, can result in significant morbidity and medicolegal consequences, particularly during complex gynecologic procedures such as endometriosis excision and prolapse repair. Conventional ureteral identification techniques, including stents and methylene blue, have recognized limitations. Indocyanine green (ICG) with near-infrared fluorescence (NIRF) imaging enables real-time ureter visualization, but clinical evidence remains scattered. OBJECTIVE:To systematically evaluate the feasibility, safety, and outcomes of intraureteral ICG for ureteral identification in gynecologic surgery. SEARCH STRATEGY:A systematic literature search of multiple databases was performed for studies published between 2000 and 2025 using keywords related to ICG, ureter, gynecologic surgery, and intraoperative fluorescence. SELECTION CRITERIA:Studies reporting intraureteral ICG use for ureteral identification during gynecologic surgery were eligible. Studies involving fewer than 10 patients were excluded. DATA COLLECTION AND ANALYSIS:Data were extracted on ureter visualization success, ureteral injury, ICG-related complications, and operative outcomes. Risk of bias was assessed using the ROBINS-I, and certainty of evidence was evaluated using GRADE. RESULTS:Of 778 records identified, seven studies comprising 299 patients met the inclusion criteria. All studies reported successful ureter visualization, with no ureteral injuries or ICG-related complications. Secondary outcomes, including estimated blood loss and operative time, were inconsistently reported, with very low certainty of evidence. CONCLUSIONS:Intraureteral ICG appears to consistently enable safe, real-time visualization during gynecologic surgery, including complex cases. Although safety and visualization outcomes are encouraging, the evidence is limited. Prospective observational studies with standardized outcome reporting are needed to inform future practice. PROSPERO REGISTRATION:CRD420251110017.

Over the past 500 years,the convergence of three distinct paths-vaginal surgery,laparoscopy,and robotic technologies-has enabled the development of robot-assisted vaginal natural orifice transluminal endoscopic surgery(RA-vNOTES).The ongoing evolution of vaginal surgery has led to contemporary procedures such as hysterectomy,myomectomy,sacrocolpopexy,adnexal interventions,and oncologic operations,applicable to a wide range of diagnoses and pathologies.This approach offers patients significant benefits,including superior cosmetic outcomes,less pain,lower infection rates,and faster recovery of baseline quality of life.Surgeons benefit from improved ergonomics,better visualization,the ability to use multiple instruments,and enhanced tremor control.Robotic assistance has greatly expanded the ability to safely perform more complex cases,such as excision of stage 4 endometriosis with complete posterior cul-de-sac obliteration,as well as other procedures previously considered contraindicated in traditional vaginal surgery.Here,we present current findings and advances in RA-vNOTES and consider future developments in robotic surgery aimed at further improving minimally invasive techniques.

Endometriosis remains an under-researched disease with a wide range of symptoms. Endometriosis reduces a woman's quality of life and professional productivity, yet its exact causes, risk factors, and treatment have yet to be elucidated. Body mass index and endometriosis have been observed to be inversely related; however, this relationship may only be a correlation rather than a causation. Obesity may play a role in the inflammation and cell proliferation associated with endometriosis through the complex signaling pathways of adipokines. A literature review was done on endometriosis and obesity to gain insight and synthesize knowledge about opportunities to improve endometriosis care, its inflammatory pathogenesis, and the treatment potential of glucagon-like peptide-1. A Boolean search was performed via the Texas Medical Center Library with keywords including "endometriosis", "adipose tissue", "obesity", "adipokines", "glucagon-like peptide-1", and "inflammation". After screening titles, abstracts, and full texts, articles were excluded due to irrelevance, lack of access to full-text, and repetition. The literature revealed that at the onset of endometriosis symptoms in obese women, chronic pelvic pain and decreased appetite could cause misdiagnosis and weight loss, lowering the incidence of endometriosis in the obese population. Poor visualization, ventilatory compromise, and conversion to laparotomy during laparoscopy hinders diagnostic quality for obese patients. Interestingly, endometriosis and obesity share similar pathological markers, including leptin, adiponectin, tumor-necrosis-factor-α, and interleukin-6. Finally, glucagon-like peptide-1 was found to decrease pro-inflammatory secretions and macrophage infiltration.

Vaginal natural orifice transluminal endoscopic surgery (vNOTES) for the treatment of gynecologic diseases offers advantages such minimal invasiveness, low surgical complication rates, and faster postoperative recovery. It also achieves a true “scarless” cosmetic outcome and represents a key direction in the development of modern surgery. The latest generation of single-port (SP) surgical robots deploy one electronic endoscope and three robotic surgical instruments through a single mechanical port, allowing high-definition visualization, a wide range of motion and restoration of the surgical triangulation. These characteristics reduce surgical difficulty and improve precision. Single-port robotic-assisted vNOTES (RSP-vNOTES) allows surgeons to perform intricate surgical procedures within confined anatomical spaces, expands surgical indications, enhances surgical precision and outcomes, and instates a new era of minimally invasive gynecologic surgery.

OBJECTIVE:To demonstrate the feasibility and mid-term outcomes of Robotic single-port single-incision laparoscopic surgery (RSP-SILS) for endometriosis management. METHODS:A retrospective analysis was conducted on 50 adult women with endometriosis who underwent RSP-SILS via the da Vinci SP platform between November 2023 and July 2025. RESULTS:Median total operative time was 142 min, robot dock time was 3 min, and robot console time was 99 min. Median estimated blood loss was 25 mL. No conversion occurred. Reported mid-term outcomes included 1 case each of pelvic haematoma, Clostridioides difficile colitis, and umbilical surgical site infection, as well as 3 cases of recurrent pelvic pain. Additionally, learning curve analysis demonstrated that robotic docking time stabilised after approximately 18 cases, suggesting progressive technical familiarisation with the RSP-SILS platform. CONCLUSION:Our findings suggest that the use of RSP-SILS is a feasible and effective minimally invasive approach for performing complex procedures, specifically for endometriosis management.