Background:Midurethral sling placement is often performed during prolapse repair to treat or prevent stress urinary incontinence. However, some women experience persistent or new-onset stress or urgency urinary incontinence after surgery. It is unclear how prolapse repair, with or without a concomitant midurethral sling, alters urethral morphology and support, and how these changes relate to urinary continence outcomes. Objectives:To compare postoperative urethral morphology (dimensions, angles, shape) and support (position, mobility) after transvaginal prolapse repair with vs without a concurrent midurethral sling, and to explore associations between postoperative urethral characteristics and urinary outcomes (stress, urgency symptoms). Study Design:This ancillary analysis used magnetic resonance imaging and urinary outcome data from the Defining Mechanisms of Anterior Vaginal Wall Descent Study conducted across 8 clinical sites within the United States Pelvic Floor Disorders Network. Eighty-two women (median age, 65 years) underwent transvaginal prolapse repair (vaginal mesh hysteropexy or vaginal hysterectomy with uterosacral ligament suspension) with or without a concurrent midurethral sling between April 2013 and February 2015. Postoperative imaging at rest and during strain was performed 30-42 months after surgery (or earlier if they chose reoperation) between June 2014 and May 2018. Prolapse recurrence, defined as descent beyond the vaginal introitus during strain, was recorded. The urethra was segmented from postoperative scans to create 3-dimensional models for measuring urethral diameters, length, surface area, volume, angles, shape (principal component scores from a statistical shape model), position, and mobility (rest-to-strain displacement). Preoperative and 24-48-month postoperative urinary continence outcomes were assessed using validated questionnaires: the Urogenital Distress Inventory, Urinary Impact Questionnaire, and the Incontinence Severity Index. Comparisons of urethral and urinary outcomes by (1) midurethral sling and (2) stress urinary incontinence were made using Wilcoxon rank-sum tests, principal component analysis, and multivariate models as appropriate. Associations between urethral and urinary outcomes were evaluated with Spearman's rank correlation. Results:Forty-six women (22 hysteropexy, 24 hysterectomy) were in the sling group, and 36 (19 hysteropexy, 17 hysterectomy) were in the no-sling group. Among the 48 women without prolapse recurrence (28 sling, 20 no-sling), those with a sling (vs without) had larger urethral dimensions (all P<.03), a more anterior-superior position of the proximal urethra (indicating better bladder neck support) (P=.04), a straighter urethral shape (P=.006), and reported less bothersome postoperative stress incontinence (P=.02). Overall, 14 women (17%) experienced postoperative stress incontinence. Stress urinary incontinence was linked to a more acute proximal urethral sagittal angle (more aligned with axial plane) (P=.01), and a lower proximal urethra position (P=.04) and mid-urethra position (P=.03). Poorer stress and urgency urinary outcomes were associated with a shorter urethral length (P=.01), a more posterior-inferior urethral position (all P<.05), increased "C" or "S"-shaped urethral concavity (P=.008; P=.006), and smaller rest-to-strain displacement of the proximal (P=.03) and distal (P=.009) urethra. Conclusions:Urethral morphology and support differed with concomitant midurethral sling (vs no sling) and stress urinary incontinence after vaginal surgery. Urethral characteristics were also associated with postoperative urinary symptoms. Urethral configuration may influence urinary outcomes and could be considered during prolapse and stress urinary incontinence repairs.

IMPORTANCE:Beta-agonist medication and onabotulinumtoxinA injections are commonly used for the treatment of urgency urinary incontinence (UUI); however, there are limited comparative efficacy data to inform best practice. We describe the design and rationale for the Beta-Agonist versus ONA Trial for Urgency Urinary Incontinence (BEST), which was developed in partnership with engaged patients, stakeholders, and communities. OBJECTIVES:The primary objective is to compare treatment efficacy, as measured by coprimary endpoints symptom severity and treatment satisfaction at 3 months. Secondary objectives include comparisons of quality of life, global improvement, cognitive and sexual function, complications, and to describe barriers to UUI treatment. STUDY DESIGN:BEST is a multisite, single-blinded, randomized trial of beta-agonist versus onabotulinumtoxinA in female participants with UUI. Patient eligibility, primary and secondary outcome measures, and substantive changes in trial design through engagement with patients, stakeholders, and communities are described. Four hundred thirty-two participants will provide 80% power to detect a 15% difference in both coprimary outcomes of treatment satisfaction and symptom severity between treatment arms at a split alpha=0.025, allowing for 20% attrition. Linear mixed-effects models following the intention-to-treat principle are planned. RESULTS:Participant enrollment began in July 2023 across 5 clinical sites. As of January 6, 2026, 396 of 432 participants (92%) have been randomized, 324 (82% of randomized) have reached the primary 3-month outcome with a 98.7% retention rate for completion of the coprimary outcomes, and 213 (54% of randomized) have reached the 12-month outcome with 94% retention rate. CONCLUSIONS:The BEST design was substantively informed by patient and stakeholder input and will provide patient-important comparative efficacy data for beta-agonist versus onabotulinumtoxinA for UUI.

Magnetic resonance imaging (MRI) can evaluate individual components of postsurgical recurrent prolapse that may not be visible on physical examination and provide insights into mechanisms of prolapse recurrence. This planned prospective secondary imaging analysis at nine clinical sites performed in the Study of Uterine Prolapse Procedures-Randomized (SUPeR) trial of the National Institute of Child Health Human Development (NICHD) Pelvic Floor Disorders Network (ClinicalTrials.gov: NCT01802281) randomized 183 women to native tissue repair (NTR-hysterectomy) or vaginal mesh repair (VM-hysteropexy) for uterovaginal prolapse, and assessed for surgical failure. A subset of participants who enrolled in Defining Mechanisms of Anterior Vaginal Wall Descent (DEMAND) underwent MRI at rest, maximal strain, and post-strain rest (recovery) 30–42 months after surgery or prior to 30 months if undergoing reoperation for recurrence. Of the 88 participants analyzed (aged 65 ± 7.7 years), 22 (25.0

Urgency urinary incontinence (UUI) and Alzheimer's disease (AD) are highly comorbid conditions in women, but the underlying molecular mechanisms are largely unknown. Therefore, we used network enrichment analyses and an elaborate literature search to integrate the most significant genes from four genome-wide association studies (GWASs) and other genetic, expression and functional evidence into a molecular landscape of female UUI. This molecular landscape centers around local, i.e., bladder-based, processing of the AD-associated amyloid precursor protein (APP). To further elucidate how APP processing is implicated in the comorbidity between UUI and AD, we conducted polygenic risk score (PRS)-based analyses, which showed that genetic risk factors associated with AD and a decreased amyloid beta 42/40 blood level ratio (also) contribute to UUI susceptibility. In conclusion, APP processing constitutes a putative molecular link between UUI and AD, adding further weight to their clinical comorbidity and having implications for the treatment (and prevention) of both traits.

This prespecified secondary analysis of the Pelvic Floor Disorders Network Study of Uterine Prolapse Procedures-Randomized Trial (SUPER) investigates if there is a difference in treatment failure for vaginal mesh hysteropexy (hysteropexy) vs vaginal hysterectomy with uterosacral ligament suspension (hysterectomy) in women with uterovaginal prolapse. QuestionAt 10 years, is there a difference in treatment failure for vaginal mesh hysteropexy (hysteropexy) vs vaginal hysterectomy with uterosacral ligament suspension (hysterectomy) in women with uterovaginal prolapse?FindingsIn this randomized clinical trial of 175 women included in the intention-to-treat analysis with symptomatic uterovaginal prolapse undergoing surgery, hysteropexy compared with hysterectomy had fewer primary outcome failures.MeaningResults show that although hysteropexy had a better composite primary outcome, there was no evidence that it was increasingly more durable between years 6 and 10 than a native tissue procedure. ImportanceVaginal hysterectomy with suture apical suspension (hysterectomy) is commonly performed for uterovaginal prolapse, and a vaginal sacrospinous hysteropexy with graft (hysteropexy) is a uterine-sparing alternative. Ten-year outcomes for prolapse surgeries are rarely reported.ObjectiveTo compare the efficacy and adverse events of these 2 procedures over 10 years.Design, Setting, and ParticipantsAt 9 clinical sites in the US Pelvic Floor Disorders Network, postmenopausal women with symptomatic uterovaginal prolapse were enrolled in a multisite superiority randomized clinical trial between April 2013 and February 2015. Study data were analyzed from February 2018 to November 2025.InterventionsWomen were originally randomized to vaginal mesh hysteropexy or to vaginal hysterectomy with uterosacral ligament suspension. Participants had 5 years of masked follow-up at 6-month intervals followed by an extended unmasked annual follow-up from 6 to 10 years.Main Outcomes and MeasuresThe primary treatment failure composite outcome (retreatment of prolapse, prolapse beyond the hymen, or prolapse symptoms) was evaluated with time-to-failure models. Secondary outcomes included individual anatomic Pelvic Organ Prolapse Quantification measures, bothersome symptoms measured by validated questionnaires, complications and adverse events.ResultsA total of 183 participants (mean [SD] age, 66 [7] years) were randomized, and 175 were included in the intention-to-treat analysis after ineligibility exclusions (88 hysteropexy group and 87 hysterectomy group), 112 of whom (64%; 55 hysteropexy group and 57 hysterectomy group) participated in the 6- to 10-year follow-up extension. There were fewer failures for hysteropexy (35 of 88 [40%]) compared with hysterectomy (46 of 87 [53%]) through 10 years. Time-to-failure analysis showed lower failure risk in hysteropexy (adjusted hazard ratio, 0.64; 95% CI, 0.41-1.00; P = .05). Both groups had sustained improvements in patient reported outcomes with no group differences demonstrated in patient-reported prolapse, urinary, or bowel symptoms, sexual function, dyspareunia, or clinically important complications.Conclusions and RelevanceResults show that vaginal mesh hysteropexy continued to have a lower composite failure rate through 10 years than vaginal hysterectomy with uterosacral ligament suspension, although an expected increase in durability over the native tissue procedure in years 6 to 10 was not observed. Both procedures are reasonable options for patients. If available, hysteropexy with mesh augmentation for patients who desire uterine preservation is a low risk and effective option.Trial RegistrationClinicalTrials.gov Identifier: NCT01802281

Quality of life can significantly improve following successful surgical repair of obstetric fistula; however, these surgeries may be technically challenging. There are limited consensus data regarding optimal fistula closure techniques and perioperative management. The objective of this study was to identify clinical and anatomical characteristics associated with failure of obstetric vesicovaginal/urethrovaginal fistulas (VVaF/UVaF) closure. In this retrospective cohort study, medical records of patients following VVaF/UVaF surgery at a single fistula center in Niger between 2022 and 2024 were identified. Clinical and demographic data were collected. Successful fistula closure was defined as water-tight visually assessed closure of fistula at discharge from the fistula center. Multivariable logistic regression was used to identify independent factors associated with closure failure. Of 125 women, 28 (22.4

Importance:Vaginal hysterectomy with suture apical suspension (hysterectomy) is commonly performed for uterovaginal prolapse, and a vaginal sacrospinous hysteropexy with graft (hysteropexy) is a uterine-sparing alternative. Ten-year outcomes for prolapse surgeries are rarely reported. Objective:To compare the efficacy and adverse events of these 2 procedures over 10 years. Design, Setting, and Participants:At 9 clinical sites in the US Pelvic Floor Disorders Network, postmenopausal women with symptomatic uterovaginal prolapse were enrolled in a multisite superiority randomized clinical trial between April 2013 and February 2015. Study data were analyzed from February 2018 to November 2025. Interventions:Women were originally randomized to vaginal mesh hysteropexy or to vaginal hysterectomy with uterosacral ligament suspension. Participants had 5 years of masked follow-up at 6-month intervals followed by an extended unmasked annual follow-up from 6 to 10 years. Main Outcomes and Measures:The primary treatment failure composite outcome (retreatment of prolapse, prolapse beyond the hymen, or prolapse symptoms) was evaluated with time-to-failure models. Secondary outcomes included individual anatomic Pelvic Organ Prolapse Quantification measures, bothersome symptoms measured by validated questionnaires, complications and adverse events. Results:A total of 183 participants (mean [SD] age, 66 [7] years) were randomized, and 175 were included in the intention-to-treat analysis after ineligibility exclusions (88 hysteropexy group and 87 hysterectomy group), 112 of whom (64%; 55 hysteropexy group and 57 hysterectomy group) participated in the 6- to 10-year follow-up extension. There were fewer failures for hysteropexy (35 of 88 [40%]) compared with hysterectomy (46 of 87 [53%]) through 10 years. Time-to-failure analysis showed lower failure risk in hysteropexy (adjusted hazard ratio, 0.64; 95% CI, 0.41-1.00; P = .05). Both groups had sustained improvements in patient reported outcomes with no group differences demonstrated in patient-reported prolapse, urinary, or bowel symptoms, sexual function, dyspareunia, or clinically important complications. Conclusions and Relevance:Results show that vaginal mesh hysteropexy continued to have a lower composite failure rate through 10 years than vaginal hysterectomy with uterosacral ligament suspension, although an expected increase in durability over the native tissue procedure in years 6 to 10 was not observed. Both procedures are reasonable options for patients. If available, hysteropexy with mesh augmentation for patients who desire uterine preservation is a low risk and effective option. Trial Registration:ClinicalTrials.gov Identifier: NCT01802281.

BACKGROUND:There is sparse normative data on clitoral-vestibular bulb anatomy and how it changes with aging, despite growing evidence of the latter playing a notable role in female sexual function and other pelvic symptoms. OBJECTIVE:To identify age-related differences in clitoral-vestibular bulb anatomy (dimensions, position, shape) among women across the adult lifespan. STUDY DESIGN:This was a retrospective study of pelvic magnetic resonance images of women (≥18 years) without pelvic floor disorder/dysfunction symptom indications (pelvic organ prolapse, urinary incontinence/pain, fecal incontinence/pain, dyspareunia) and with normal pelvic anatomy (radiographically normal reproductive, genitourinary, or gastrointestinal systems). Participants were categorized into the following age groups: Young Adult (18-34 years), Early Midlife (35-49 years), and Older Adult (≥50 years). Axial images of participants in the supine position at rest were acquired for medical indications. The clitoral-vestibular bulb complex, vagina, and urethra were manually segmented to construct 3-dimensional anatomical models. Computational methods quantified clitoral-vestibular bulb dimensions, position, vaginal-urethral distances, and shape (given by principal component scores obtained from a statistical shape model). Age differences in clitoral-vestibular bulb measures were evaluated using Bonferroni-corrected one-way multivariate and univariate analyses of covariance, with adjustments for body mass index and parity. Age-related correlations were assessed using Spearman's rank correlation. RESULTS:A total of 134 women were analyzed (median [range] age, 39 [19-80] years): 47 Young Adult, 46 Early Midlife, and 41 Older Adult women. All Young Adult and Early Midlife women were premenopausal, whereas 27 (71%) of Older Adult women were postmenopausal. Older Adult women had a shorter clitoral body length than Early Midlife women (24.1 mm vs 27.9 mm; P=.006). Overall, smaller vestibular bulb volume was associated with increasing age (P=.04). Older Adult women had a more caudally positioned (lower in the pelvis) clitoral-vestibular bulb complex than Early Midlife women (-21.0 mm vs -17.6 mm; P<.001) and Young Adult women (-21.0 mm vs -17.9 mm; P<.001). Across the entire cohort, increasing age correlated with a shorter clitoral body length (ρ=-0.21; P=.01), smaller vestibular bulb volume (ρ=-0.20; P=.02), and a more dorsally (ρ=-0.22; P=.01) and caudally (ρ=-0.43; P<.001) positioned clitoral-vestibular bulb complex, whereas clitoral volume remained unchanged (ρ=-0.03; P=.73). The shape analysis revealed that age predominantly affected the vestibular bulbs, which became more medially positioned (closer together) (ρ=-0.28; P=.001) and proportionally smaller relative to the clitoris (ρ=-0.28; P=.001) with advancing age. CONCLUSIONS:Increasing age was weakly correlated with reduced size and moderately correlated with caudal displacement of the clitoral-vestibular bulb complex, with aging primarily affecting the vestibular bulbs compared to the clitoris. Findings suggest age-related atrophy and descent of clitoral-vestibular bulb anatomy, which may contribute to sexual function and other pelvic symptoms.

This joint Clinical Consensus Statement on the safety and feasibility of concomitant urogynecologic and gynecologic oncology surgical procedures reflects statements drafted by content experts from the American Urogynecologic Society and the Society of Gynecologic Oncology. The writing group used a Delphi process to evaluate statements developed from a structured literature search and assessed consensus. A total of 35 statements were assessed in the following categories: (1) background, (2) treatment options, (3) timing of concurrent surgery, (4) risk factors, and (5) value-based care. Of the 35 statements, 28 reached consensus on initial review. Three statements were omitted, and 4 statements were revised and reached consensus following second review utilizing the Delphi process.

IMPORTANCE:Stool metabolites influencing gut motility and sensation may contribute to fecal incontinence (FI). OBJECTIVE:The objective of this study was to test whether FI is associated with higher levels of butyrate and Clostridiales taxa in stool. STUDY DESIGN:Stool metabolites and microbiota were compared between 96 women with FI and 42 controls. FI frequency and subtype (urgency vs insensible) were measured using a 14-day bowel diary, St. Mark's score, and the Accidental Bowel Leakage questionnaire. Metabolite analysis included targeted analysis (8 short-chain fatty acids including butyrate, 17 bile acids, and 8 tryptophan derivatives) and untargeted analysis. Stool microbiota were characterized using 16S rRNA gene sequencing. Multivariable and exploratory multiomics factor analysis were performed with statistical significance defined as false discovery rate (FDR) ≤0.10. RESULTS:The FI group had a higher proportion of Bristol stool types 2 and 6 than controls (P = 0.005). The mean number of leaks for the FI group was 1.7 ± 1.7 per day, 38% had urgency FI, and 39% had insensible FI. There was no significant difference between groups in butyrate levels and Clostridiales taxa. Multiomics analysis identified glycerolipids (monoacylglycerols and diacylglycerols) associated with FI (FDR = 0.08). In addition, insensible FI was associated with glycerolipids, long-chain saturated and monounsaturated fatty acids, phospholipids, and dipeptides (FDR = 0.08-0.09). The top weighted microbiota associated with these metabolites were Lachnospiraceae and Ruminococcaceae; however, these taxa were not directly associated with FI. CONCLUSION:Butyrate and Clostridiales were not associated with FI. Novel stool metabolite signatures were identified, suggesting new biological pathways and potential therapeutic targets for FI.

IMPORTANCE:Older women have a high prevalence of and bother from overactive bladder (OAB) and urgency urinary incontinence (UUI), with unique treatment challenges. It is important to improve care for this long-overlooked and understudied group. OBJECTIVE:The objective was to describe the design and rationale for a randomized controlled noninferiority trial of low-dose (50 unit) versus standard-dose (100 unit) onabotulinumtoxinA (OnabotA) for OAB symptoms in women 70 years or older with UUI. STUDY DESIGN:Study population, injection procedure, and conduct are described. The primary outcome is change in quality of life (QOL) between groups as measured by the OAB Questionnaire (OABq-SF) 3 months posttreatment, including confirmatory heterogeneity of treatment effect analysis by frailty status. Secondary outcomes include patient-reported symptom bother and distress, satisfaction, goal attainment, depression scores, adverse events (AEs), cost analysis, and qualitative interviews. Patients will be assessed monthly for safety and efficacy through 12 months and can receive up to 2 additional treatments. RESULTS:A sample size of 278 is needed to achieve 90% power to detect noninferiority. Assuming a withdrawal of 26%, the target randomization is 376 participants. Adult females aged 70 years and older are recruited if they have urgency or urgency-predominant mixed urinary incontinence. Exclusion criteria include postvoid residual volume >150 mL, need for treatment under sedation, current other treatment for OAB, and conditions that affect bladder emptying. CONCLUSIONS:This trial will contribute important data on symptom-specific and health-related QOL, patient-reported and clinical outcomes, and AEs among older women with UUI being treated with the standard dose versus reduced dose of OnabotA.

Uterine natural killer (uNK) cells are a tissue-resident lymphocyte population critical for pregnancy success. Although mouse models have demonstrated that uNK cell deficiency results in abnormal placentation and poor pregnancy outcomes, the generalizability of this knowledge to humans remains unclear. Here, we compared tissue samples collected from a cohort of human recipients of uterus transplant (UTx) at high risk for pregnancy complications with healthy controls using flow cytometry, immunofluorescence microscopy, and single-cell RNA sequencing (scRNA-seq). Subsets of tissue-resident uNK cells were reduced in endometrial and decidual samples from recipients of UTx compared with healthy control samples. Loss of tissue-resident uNK cells was associated with histopathologic evidence of maternal vascular malperfusion in placentas from recipients of UTx and related pregnancy complications including preeclampsia. scRNA-seq of UTx endometrial biopsies and deciduae further revealed that the NK cell reduction in recipients of UTx correlated with impaired transcriptional programming of NK tissue residency arising from the inhibition of signaling by nuclear factor of activated T cells (NFAT). In vitro culture of uNK cells from healthy controls with the NFAT inhibitor tacrolimus resulted in down-regulation of adhesion molecules. Together, these experiments suggested that NFAT-dependent genes modulate multiple molecular tissue residency programs in uNK cells, including early residency programs involving activator protein-1 (AP-1) family transcription factors and later residency programs characterized by up-regulation of surface integrins by transforming growth factor-β (TGF-β). Collectively, these data identify a previously undescribed role for NFAT in uNK tissue residency and provide mechanistic insights into the biologic basis of pregnancy complications due to alteration of tissue-resident NK cell subsets in humans.

IMPORTANCE:Incorporating community engagement (CE) strategies can inform and enhance study design, recruitment, retention, dissemination, and access for diverse populations; however, these approaches are underutilized in pelvic floor disorders trials. OBJECTIVES:The objectives of this study are to describe the CE methods used in a multisite randomized trial comparing beta-3 adrenergic agonists and intradetrusor onabotulinumtoxinA for the treatment of urgency urinary incontinence (UUI). Specific objectives of engagement methods included identifying barriers to recruitment and retention and improving study access for underrepresented populations. This study enrollment and community engagement are ongoing. STUDY DESIGN:We describe the formation of strategic CE partnerships with patients, clinicians, CE specialists, community organization leaders locally, and at the national level to guide the development of a randomized trial at 5 U.S. academic medical centers. Insight from these various partners have shaped the implementation of CE studios (listening sessions) with patients, caregivers, and clinicians in English, Spanish, and Amharic, focused on participation barriers and culturally appropriate recruitment materials. ENGAGEMENT APPROACH:Completed CE studios identified potential participation barriers, including mistrust, UUI stigma, limited health literacy, cultural and linguistic accessibility, financial and logistical challenges, and clinician constraints. Potential solutions identified in the CE studios included partnering with trusted community organizations, tailored study materials, simplified visit scheduling, appropriate compensation, and clinician resources. We have encouraged variation of recruitment strategies across study sites unified by common engagement principles, including tailored recruitment materials, culturally responsive imagery, outreach efforts by local community liaisons, and bidirectional communication with community partners. Throughout study enrollment, we continue our engagement efforts, and ongoing insight from partners continues to shape this trial, including recruitment, retention, and dissemination efforts. CONCLUSIONS:Including different voices through CE can help identify varied and culturally tailored opportunities for recruitment and retention in randomized trials for UUI, which will help ensure study feasibility and relevance to diverse patients and community partners.

Vaginal reconstruction is limited by the lack of biomaterials that replicate the structure, biomechanics, and biochemistry of the native tissues. Synthetic meshes, xenografts, and autologous skin or bowel grafts are hindered by their immunogenicity, poor integration, and non-physiological properties. We report a scalable platform for the fabrication of patient-specific living vaginal grafts from autologous fibroblasts. Using scaffold-free micromolding and automated assembly, fibroblasts from small full-thickness vaginal biopsies self-assembled into a collagen-rich, highly aligned extracellular matrix. To improve mechanical integrity, we create twisted subunit assemblies that displayed highly aligned collagen, dense cellularity, and a predominantly quiescent fibroblast phenotype with minimal myofibroblast activation. This autologous tissue-specific construct addresses the shortcomings of current materials and offers a customizable and biocompatible solution for regenerative gynecology. By combining tissue specificity, immunologic safety, and modular scalability, this approach has the potential to transform surgical options for congenital anomalies, post-oncologic reconstruction, fistula repair, and pelvic organ prolapse.