Inhibition of NFAT promotes loss of tissue resident uterine natural killer cells and attendant pregnancy complications in humans.

Uterine natural killer cells (uNKs) are a tissue resident lymphocyte population that are critical for pregnancy success. Although mouse models have demonstrated that NK deficiency results in abnormal placentation and poor pregnancy outcomes, the generalizability of this knowledge to humans remains unclear. Here we identify uterus transplant (UTx) recipients as a human population with reduced endometrial NK cells and altered pregnancy phenotypes. We further show that the NK reduction in UTx is due to impaired transcriptional programming of NK tissue residency due to blockade of the transcription factor nuclear factor of activated T cells (NFAT). NFAT-dependent genes played a role in multiple molecular circuits governing tissue residency in uNKs, including early residency programs involving AP-1 transcription factors as well as TGFß-mediated upregulation of surface integrins. Collectively, our data identify a previously undescribed role for NFAT in uterine NK tissue residency and provide novel mechanistic insights into the biologic basis of pregnancy complications due to alteration of tissue resident NK subsets in humans. One Sentence Summary: Role of NFAT in uterine NK cell tissue residency.

Dietary Intake and Symptom Severity in Women with Fecal Incontinence.

INTRODUCTION AND HYPOTHESIS: The goal of this study was to determine whether dietary fat/fiber intake was associated with fecal incontinence (FI) severity. METHODS: Planned supplemental analysis of a randomized clinical trial evaluating the impact of 12-week treatment with percutaneous tibial nerve stimulation versus sham in reducing FI severity in women. All subjects completed a food screener questionnaire at baseline. FI severity was measured using the seven-item validated St. Mark's (Vaizey) FI severity scale. Participants also completed a 7-day bowel diary capturing the number of FI-free days, FI events, and bowel movements per week. Spearman's correlations were calculated between dietary, St. Mark's score, and bowel diary measures. RESULTS: One hundred and eighty-six women were included in this analysis. Mean calories from fats were 32% (interquartile range [IQR] 30-35%). Mean dietary fiber intake was 13.9 ± 4.3 g. The percentage of calories from fats was at the higher end of recommended values, whereas fiber intake was lower than recommended for adult women (recommended values: calories from fat 20-35% and 22-28 g of fiber/day). There was no correlation between St. Mark's score and fat intake (r = 0.11, p = 0.14) or dietary fiber intake (r = -0.01, p = 0.90). There was a weak negative correlation between the number of FI-free days and total fat intake (r = -0.20, p = 0.008). Other correlations between dietary fat/fiber intake and bowel diary measures were negligible or nonsignificant. CONCLUSION: Overall, in women with moderate to severe FI, there was no association between FI severity and dietary fat/fiber intake. Weak associations between FI frequency and fat intake may suggest a role for dietary assessment in the evaluation of women with FI.

Characteristics Associated With Recurrent Urinary Tract Infections: A Case-Control Study.

IMPORTANCE: Recurrent urinary tract infections (rUTIs) affect 2-10% of adult women and are associated with a significant effect on quality of life, daily activities, and mental health. OBJECTIVE: The aim of this study was to identify clinical characteristics associated with rUTIs among women seeking care for pelvic floor disorders at an academic tertiary urogynecology clinic. STUDY DESIGN: A retrospective case-control study of women presenting to an academic tertiary urogynecology clinic was conducted. Cases were women with rUTIs, defined as ≥2 UTIs in 6 months or ≥3 within 1 year. Controls were women with no culture documented UTIs. Cases were matched 2:1 to controls by age and body mass index. Demographic and clinical characteristics were compared between cases and controls, and bivariate characteristics with P values ≤0.2 were assessed for an independent association with rUTIs by multivariable logistic regression. RESULTS: A total of 285 cases with rUTIs were identified, and 150 matched controls had a mean (SD) age of 72 (11.8) years and a body mass index of 29.6 (6.7; calculated as weight in kilograms divided by height in meters squared). Multivariable analysis revealed that prolapse beyond the introitus (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.13-0.60), parity (OR, 1.33; 95% CI, 1.08-1.64), Charlson Comorbidity Index (OR, 1.66; 95% CI, 1.37-2.03), and postvoid residual volume ≥100 mL (OR, 4.05; 95% CI, 2.01, 8.18) were associated with rUTIs. CONCLUSIONS: In this ambulatory urogynecologic population, prolapse through the introitus was negatively associated with rUTIs, whereas parity, increased medical comorbidities, and elevated postvoid residual volume were positively associated with rUTI. Future research should seek an increased understanding of these factors associated with rUTI to implement effective preventive strategies.

Treatment of Cervical Cancer Complicated by Advanced Pelvic Organ Prolapse: A Case Report.

ABSTRACT: Concurrent cervical cancer with advanced pelvic organ prolapse is rare: there are no well-established treatment recommendations. It is hypothesized that chronic irritation, as with long-standing pelvic organ prolapse, may lead to dysplasia and human papillomavirus-independent carcinoma, which represents only 5% of cervical cancers. Two patients with complete uterine procidentia were referred to gynecologic oncology with cervical squamous cell carcinoma; both were clinically staged as International Federation of Gynaecology and Obstetrics IB3. Treatment planning was complicated by procidentia in both cases. Standard definitive treatment of locally advanced cervical cancer is radiation therapy and concurrent chemotherapy; however, the mobility and externalization of the target lesion raised concerns regarding anatomic reproducibility during radiation treatment. After multidisciplinary team discussion (gynecologic oncology, urogynecology, radiation oncology), surgical resection and co-management with gynecologic oncology and urogynecology were successfully performed for definitive management for both patients. Although rare, this case study demonstrates the importance of multidisciplinary coordination in these complex clinical scenarios.

Impact of the Duration of the Second Stage of Labor on Postpartum Pelvic Floor Symptoms.

IMPORTANCE: The associated effect of duration of the second stage of labor (SSL) on pelvic floor symptoms development is not well studied. OBJECTIVE: This study aimed to examine the association between duration of SSL and pelvic floor symptoms at 6 months postpartum among primiparous women. STUDY DESIGN: A planned secondary analysis of a multicenter randomized trial evaluating the impact of immediate versus delayed pushing on vaginal delivery rates, maternal morbidity, and neonatal outcomes was conducted between 2014 and 2018. For pelvic floor arm participants, demographic, pelvic examination, and validated questionnaire data were collected postpartum. Primary outcome was change in Pelvic Floor Distress Inventory 20 (PFDI-20) score from immediate to 6 months postpartum. Secondary outcomes included changes in the Pelvic Floor Impact Questionnaire, Fecal Incontinence Severity Index, Modified Manchester Health Questionnaire scores, and Pelvic Organ Prolapse Quantification measurements at 6 months postpartum. Participants were analyzed by SSL duration ≤60 minutes or >60 minutes. RESULTS: Of the 2,414 trial participants, 767 (32%) completed pelvic floor assessments at 6 months. Pelvic Floor Distress Inventory 20 scores significantly improved at 6 months in the ≤60 minutes SSL group compared with >60 minutes SSL (-14.3 ± 48.0 and -3.2 ± 45.3, respectively; P = 0.04). Changes from immediate postpartum in total and subscale scores for other questionnaires at 6 months did not differ between groups. Prolapse stage did not differ between groups. Perineal body was significantly shorter in the >60 minutes SSL group (3.7 ± 0.7, 3.5 ± 0.8; P = 0.03). CONCLUSIONS: Women with SSL >60 minutes experience less improvement in PFDI-20 scores at 6 months. Greater tissue and innervation trauma in those with SSL >60 minutes may explain persistently less improvement in PFDI-20 scores.

First and Second Stage Risk Factors Associated with Perineal Lacerations.

OBJECTIVE: To determine intrapartum factors associated with perineal laceration at delivery. METHODS: This was a planned secondary analysis of a multicenter randomized clinical trial of delayed versus immediate pushing among term nulliparous women in labor with neuraxial analgesia conducted in the United States. Intrapartum characteristics were extracted from the medical charts. The primary outcome was perineal laceration, defined as second degree or above, characterized at delivery in women participating in longer term pelvic floor assessments post-delivery. Multivariable logistic regression was used to refine risk estimates while adjusting for randomization group, birth weight, and maternal age. RESULTS: Among the 941 women participating in the pelvic floor follow-up, 40.6% experienced a perineal laceration. No first stage labor characteristics were associated with perineal laceration, including type of labor or length of first stage. Receiving an amnioinfusion appeared protective of perineal laceration (adjusted odds ratio, 0.48; 95% confidence interval 0.26-0.91; P = 0.01). Second stage labor characteristics associated with injury were length of stage (2.01 h vs. 1.50 h; adjusted odds ratio, 1.36; 95% confidence interval 1.18-1.57; P < 0.01) and a prolonged second stage (adjusted odds ratio, 1.64; 95% confidence interval 1.06-2.56; P < 0.01). Operative vaginal delivery was strongly associated with perineal laceration (adjusted odds ratio, 3.57; 95% confidence interval 1.85-6.90; P < 0.01). CONCLUSION: Operative vaginal delivery is a modifiable risk factor associated with an increased risk of perineal laceration. Amnioinfusion appeared protective against injury, which could reflect a spurious finding, but may also represent true risk reduction similar to the mechanism of warm perineal compress.

Trial Design for Mixed Urinary Incontinence: Midurethral Sling Versus Botulinum Toxin A.

IMPORTANCE: Mixed urinary incontinence (MUI) is common and can be challenging to manage. OBJECTIVES: We present the protocol design and rationale of a trial comparing the efficacy of 2 procedures for the treatment of women with MUI refractory to oral treatment. The Midurethral sling versus Botulinum toxin A (MUSA) trial compares the efficacy of intradetrusor injection of 100 U of onabotulinimtoxinA (an office-based procedure directed at the urgency component) versus midurethral sling (MUS) placement (a surgical procedure directed at the stress component). STUDY DESIGN: The MUSA is a multicenter, randomized trial of women with MUI electing to undergo procedural treatment for MUI at 7 clinical centers in the NICHD Pelvic Floor Disorders Network. Participants are randomized to either onabotulinumtoxinA 100 U or MUS. OnabotulinimtoxinA recipients may receive an additional injection between 3 and 6 months. Participants may receive additional treatment (including crossover to the alternative study intervention) between 6 and 12 months. The primary outcome is change from baseline in Urogenital Distress Inventory (UDI) at 6 months. Secondary outcomes include change in UDI at 3 and 12 months, irritative and stress subscores of the UDI, urinary incontinence episodes, predictors of poor treatment response, quality of life and global impression outcomes, adverse events, use of additional treatments, and cost effectiveness. RESULTS: Recruitment and randomization of 150 participants is complete and participants are currently in the follow-up phase. CONCLUSIONS: This trial will provide information to guide care for women with MUI refractory to oral treatment who seek surgical treatment with either onabotulinumtoxinA or MUS.

A Motion-based Device Urinary Incontinence Treatment: A Longitudinal Analysis at 18 and 24 Months.

INTRODUCTION AND HYPOTHESIS: There are sparse data regarding the long-term efficacy of pelvic floor muscle training (PFMT) for the treatment of urinary incontinence (UI). The objective of this study was to evaluate the impact of an 8-week PFMT program guided by a motion-based intravaginal device versus a standard home program over 24 months. METHODS: Between October 2020 and March 2021, a total of 363 women with stress or stress-predominant mixed UI were randomized and completed an 8-week PFMT program using a motion-based intravaginal device (intervention group) or a home program following written/video instructions (control group). Participants were not asked to continue training after the 8-week program. At 18 and 24 months' follow-up, the Urogenital Distress Inventory, short-form (UDI-6) and Patient Global Impression of Improvement (PGI-I) were collected. In the original trial, a total of 139 participants in each arm were needed to detect a 0.3 effect size (alpha = 0.05, power 0.8, one-tailed t test) in the difference in UDI-6 scores. RESULTS: A total of 231 participants returned 24-month data. Mean age at 24 months was 51.7 ± 14.5 years, and mean BMI was 31.8 ± 7.4 kg/m2. Mean change in UDI-6 scores from baseline to 24 months was greater in the intervention group than the control group (-21.1 ± 24.5 vs -14.8 ± 19.4, p = 0.04). Reported improvement using PGI-I was greater in the intervention group than in the control group at 24 months (35% vs 22%, p = 0.03, OR 1.95(95% CI 1.08, 3.57). CONCLUSIONS: Pelvic floor muscle training guided by a motion-based prescription intravaginal device yielded durable and significantly greater UI symptom improvement than a standard home program, even in the absence of continued therapy.

Characteristics Associated With Surgical Failure After Native Tissue Apical Prolapse Repair.

OBJECTIVE: To identify clinical and demographic characteristics associated with prolapse recurrence by 12 months after native tissue transvaginal repair. METHODS: This was a planned secondary analysis of a randomized trial including postmenopausal participants with stage 2 or greater apical or anterior vaginal prolapse scheduled for surgical repair at three U.S. sites. Participants underwent vaginal hysterectomy (if uterus was present) and standardized uterosacral or sacrospinous ligament suspension at the surgeon's discretion. The intervention was perioperative (5 weeks or more preoperatively and 12 months postoperatively) vaginal estrogen compared with placebo cream. The primary outcome was time to failure by 12 months after surgery, defined by objective prolapse of the anterior or posterior walls beyond the hymen or the apex descending more than one-third of the vaginal length, symptomatic vaginal bulge, or retreatment. For this analysis, participants were grouped according to failure compared with success, and multiple factors were compared, including age, time since menopause, race and ethnicity, parity, body mass index (BMI), baseline genital hiatus measurement, prolapse stage and point of maximal prolapse, surgery type (uterosacral or sacrospinous ligament suspension), and concomitant procedures. Factors were assessed for association with the hazard of surgical failure using Cox proportional hazards models, adjusted for site and treatment group. Factors with P <.50 from this analysis were considered for inclusion in the final multivariable model; site and treatment group were kept in this model. RESULTS: One hundred eighty-six participants underwent surgery; 183 provided complete data. There were 30 failures (16.4%) and 153 successes (83.4%) at 12 months. On bivariate analysis, failure was associated with decreasing age, shorter duration since menopause, Latina ethnicity, and greater baseline genital hiatus. In the final multivariable model, which included age, BMI, and point of maximal prolapse, only age remained significantly associated with surgical failure (adjusted hazard ratio [per year] 0.92, 95% CI, 0.86-0.98, P =.016). CONCLUSION: Among postmenopausal women, younger age was associated with increased frequency of prolapse recurrence by 12 months after native tissue repair. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02431897.

Perioperative Vaginal Estrogen as Adjunct to Native Tissue Vaginal Apical Prolapse Repair: A Randomized Clinical Trial.

Importance: Surgical repairs of apical/uterovaginal prolapse are commonly performed using native tissue pelvic ligaments as the point of attachment for the vaginal cuff after a hysterectomy. Clinicians may recommend vaginal estrogen in an effort to reduce prolapse recurrence, but the effects of intravaginal estrogen on surgical prolapse management are uncertain. Objective: To compare the efficacy of perioperative vaginal estrogen vs placebo cream on prolapse recurrence following native tissue surgical prolapse repair. Design, Setting, and Participants: This randomized superiority clinical trial was conducted at 3 tertiary US clinical sites (Texas, Alabama, Rhode Island). Postmenopausal women (N = 206) with bothersome anterior and apical vaginal prolapse interested in surgical repair were enrolled in urogynecology clinics between December 2016 and February 2020. Interventions: The intervention was 1 g of conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally nightly for 2 weeks and then twice weekly to complete at least 5 weeks of application preoperatively; this continued twice weekly for 12 months postoperatively. Participants underwent a vaginal hysterectomy (if uterus present) and standardized apical fixation (either uterosacral or sacrospinous ligament fixation). Main Outcomes and Measures: The primary outcome was time to failure of prolapse repair by 12 months after surgery defined by at least 1 of the following 3 outcomes: anatomical/objective prolapse of the anterior or posterior walls beyond the hymen or the apex descending more than one-third of the vaginal length, subjective vaginal bulge symptoms, or repeated prolapse treatment. Secondary outcomes included measures of urinary and sexual function, symptoms and signs of urogenital atrophy, and adverse events. Results: Of 206 postmenopausal women, 199 were randomized and 186 underwent surgery. The mean (SD) age of participants was 65 (6.7) years. The primary outcome was not significantly different for women receiving vaginal estrogen vs placebo through 12 months: 12-month failure incidence of 19% (n = 20) for vaginal estrogen vs 9% (n = 10) for placebo (adjusted hazard ratio, 1.97 [95% CI, 0.92-4.22]), with the anatomic recurrence component being most common, rather than vaginal bulge symptoms or prolapse repeated treatment. Masked surgeon assessment of vaginal tissue quality and estrogenization was significantly better in the vaginal estrogen group at the time of the operation. In the subset of participants with at least moderately bothersome vaginal atrophy symptoms at baseline (n = 109), the vaginal atrophy score for most bothersome symptom was significantly better at 12 months with vaginal estrogen. Conclusions and Relevance: Adjunctive perioperative vaginal estrogen application did not improve surgical success rates after native tissue transvaginal prolapse repair. Trial Registration: ClinicalTrials.gov Identifier: NCT02431897.

Effects of preoperative intravaginal estrogen on pelvic floor disorder symptoms in postmenopausal women with pelvic organ prolapse.

BACKGROUND: Menopause and the decline in systemic estrogen are associated with the development of pelvic floor disorders, such as prolapse, urinary incontinence, overactive bladder, and vulvovaginal atrophy symptoms. Past evidence suggests that postmenopausal women with symptomatic prolapse gain benefit from the preoperative application of intravaginal estrogen, but it is unknown whether they would experience improvement in other pelvic floor symptoms when treated with intravaginal estrogen. OBJECTIVE: This study aimed to determine the effects of intravaginal estrogen (compared with placebo) on stress and urgency urinary incontinence, urinary frequency, sexual function and dyspareunia, and vaginal atrophy symptoms and signs in postmenopausal women with symptomatic prolapse. STUDY DESIGN: This was a planned ancillary analysis of a randomized, double-blind trial, "Investigation to Minimize Prolapse Recurrence Of the Vagina using Estrogen," which included participants with ≥stage 2 apical and/or anterior prolapse scheduled for transvaginal native tissue apical repair at 3 US sites. The intervention was 1 g conjugated estrogen intravaginal cream (0.625 mg/g) or identical placebo (1:1), inserted nightly for 2 weeks and then twice weekly for ≥5 weeks total before surgery and continued twice weekly for 1 year postoperatively. For this analysis, question responses were compared from participants' baseline and preoperative visits: lower urinary tract symptoms (Urogenital Distress Inventory-6 Questionnaire); sexual health questions, including dyspareunia (Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised); and atrophy-related symptoms (dryness, soreness, dyspareunia, discharge, and itching; each scored 1-4, 4 being quite a bit bothersome). Masked examiners assessed vaginal color, dryness, and petechiae (each scored 1-3, total range 3-9, with 9 being the most estrogenized appearing). Data were analyzed by intent to treat and "per protocol" (ie, those adherent with ≥50% of expected intravaginal cream use, per objective tube before and after weights). RESULTS: Of 199 participants randomized (mean age of 65 years) and contributing baseline data, 191 had preoperative data. The characteristics were similar between groups. Total Urogenital Distress Inventory-6 Questionnaire scores showed minimal change during this median time of 7 weeks between baseline and preoperative visits, but for those with at least moderately bothersome baseline stress urinary incontinence (32 in the estrogen group and 21 in the placebo group), 16 (50%) in the estrogen group and 9 (43%) in the placebo group showed improvement (P=.78). In addition, 43% of participants in the estrogen group and 31% of participants in the placebo group showed improvement in urgency urinary incontinence (P=.41), and 41% of participants in the estrogen group and 26% of participants in the placebo group showed improvement in urinary frequency (P=.18). There was minimal change in the Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-IUGA-Revised scores among sexually active women; dyspareunia rates did not differ between intravaginal estrogen and placebo at the preoperative assessment: 42% and 48%, respectively (P=.49). The maximum score for most bothersome atrophy symptom (among those with baseline symptoms and adherent to study cream) improved slightly more with intravaginal estrogen (adjusted mean difference, -0.33 points; 95% confidence interval, -0.98 to 0.31), but this was not statistically significant (P=.19). However, on examination, among adherent participants, objective signs of atrophy were more improved with intravaginal estrogen treatment (+1.54 vs +0.69; mean difference, 0.85; 95% confidence interval, 0.05-1.65; P=.01). CONCLUSION: Despite objective changes in the vaginal epithelium consistent with increased estrogenization among drug-adherent participants, the results were inconclusive regarding whether 7 weeks of preoperative intravaginal estrogen cream in postmenopausal women with symptomatic pelvic organ prolapse was associated with improved urinary function, sexual function, dyspareunia symptoms, and other symptoms commonly attributed to atrophy. Additional study is needed.

Pain Catastrophizing and Impact on Pelvic Floor Surgery Experience.

IMPORTANCE: Understanding patients' perceptions of symptoms and outcomes of urogynecologic surgery is essential for providing high-quality care. OBJECTIVE: The aim of the study was to assess association of pain catastrophizing with pelvic floor symptom distress and impact, postoperative pain, and voiding trial in patients undergoing urogynecologic surgery. STUDY DESIGN: Individuals whose self-identified gender was female and were undergoing surgery March 2020-December 2021 were included. Participants completed the Pain Catastrophizing Scale (range 0-52), Pelvic Floor Distress Inventory, and Pelvic Floor Impact Questionnaire preoperatively. Pain catastrophizing was score ≥30 and describes the tendency to magnify the overall threat of pain. Voiding trial failure was inability to void ≥2/3 of instilled volume (≤300 mL). The association between pain catastrophizing and symptom distress and impact was assessed with linear regression. A P < 0.05 is significant. RESULTS: Three hundred twenty patients were included (mean age, 60 years, 87% White). Forty-six of 320 participants (14%) had a pain catastrophizing score ≥30. The pain catastrophizing group had higher body mass index (33 ± 12 vs 29 ± 5), more benzodiazepine use (26% vs 12%), greater symptom distress (154 ± 58 vs 108 ± 60), and greater urogenital (59 ± 29 vs 47 ± 28), colorectal (42 ± 24 vs 26 ± 23), and prolapse (54 ± 24 vs 36 ± 24) subscale scores, all P ≤ 0.02. The pain catastrophizing group had greater impact (153 ± 72 vs 72 ± 64, P < 0.01) and urogenital (60 ± 29 vs 34 ± 28), colorectal (36 ± 33 vs 16 ± 26), and prolapse (57 ± 32 vs 22 ± 27) subscale scores, P < 0.01. Associations remained controlling for confounders ( P < 0.01). The pain catastrophizing group had higher 10-point pain scores (8 vs 6, P < 0.01) and was more likely to report pain at 2 weeks (59% vs 20%, P < 0.01) and 3 months (25% vs 6%, P = 0.01). Voiding trial failure did not differ (26% vs 28%, P = 0.98). CONCLUSIONS: Pain catastrophizing is associated with greater pelvic floor symptom distress and impact and postoperative pain but not voiding trial failure.

Five-year surgical outcomes of transvaginal apical approaches in women with advanced pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: In women with advanced prolapse, differences in vaginal apex anchoring sites may impact surgical outcomes over time. The primary aim was to compare 5-year surgical outcomes of uterosacral ligament suspension (ULS) versus sacrospinous ligament fixation (SSLF) in women with advanced (stage III-IV) prolapse. METHODS: A secondary analysis was conducted in a subset of women with advanced prolapse from a multicenter randomized trial comparing ULS versus SSLF and its extended follow-up, using publicly accessible de-identified datasets. The primary outcome was time to failure, defined as any one of (1) apical descent > 1/3 into the vaginal canal or anterior/posterior compartment beyond the hymen, (2) bothersome vaginal bulge symptoms, or (3) re-treatment. Secondary outcomes include symptom severity measured by the Pelvic Organ Prolapse Distress Inventory (POPDI) and adverse events. RESULTS: Of 285 women, 90/147 (61.2%) in ULS and 88/138 (63.8%) in SSLF had advanced prolapse. Baseline characteristics did not differ between groups except for median-vaginal deliveries (3.0 [2.0, 5.0] versus 3.0 [2.0, 4.0], p < 0.01). The median time to failure was 1.7 years ULS versus 2.0 years SSLF (p = 0.42). Surgical failure increased over time in both groups with no intergroup difference; by year 5, the estimated failure rate was 67.7% ULS versus 71.5% SSLF (adjusted difference -3.8; 95%CI [-21.9, 14.2]). No differences were noted in individual failure components (p > 0.05). POPDI scores improved over 5 years without intergroup difference (ULS -68.0 ± 61.1 versus SSLF -69.9 ± 60.3, adjusted difference -0.1 [-20.0, 19.9]). No difference in adverse events were observed (p > 0.05). CONCLUSION: In women with advanced prolapse, surgical failure, symptom severity, and adverse events did not differ between ULS and SSLF over 5 years.

Endometrial Cancer Surgery With or Without Concomitant Stress Urinary Incontinence Surgery.

OBJECTIVE: To compare quality of life (QOL) among patients with endometrial intraepithelial neoplasia or early-stage endometrial cancer and stress urinary incontinence (SUI) who chose to have concomitant surgery with cancer surgery alone. METHODS: A multicenter, prospective cohort study was conducted across eight U.S. sites. Potentially eligible patients were screened for SUI symptoms. Those who screened positive were offered referral to urogynecology and incontinence treatment, including concomitant surgery. Participants were categorized into two groups: 1) concomitant cancer and SUI surgery or 2) cancer surgery alone. The primary outcome was cancer-related QOL as measured by the FACT-En (Functional Assessment of Cancer Therapy-Endometrial) (range 0-100; higher score indicates better QOL). The FACT-En and questionnaires assessing urinary symptom-specific severity and effects were assessed before surgery and 6 weeks, 6 months, and 12 months after surgery. Adjusted median regression accounting for clustering was used to examine the relationship between SUI treatment group and FACT-En scores. RESULTS: Of 1,322 (53.1%) patients, 702 screened positive for SUI with 532 analyzed; 110 (21%) chose concomitant cancer and SUI surgery, and 422 (79%) chose cancer surgery alone. FACT-En scores increased for both the concomitant SUI surgery and cancer surgery-only groups from the preoperative to the postoperative period. After adjustment for timepoint and preoperative covariates, the median change in FACT-En score (postoperative-preoperative) was 1.2 points higher (95% CI -1.3 to 3.6) for the concomitant SUI surgery group compared with the cancer surgery-only group across the postoperative period. Median time until surgery (22 days vs 16 days; P <.001), estimated blood loss (150 mL vs 72.5 mL; P <.001), and operative time (185.5 minutes vs 152 minutes; P <.001) were all greater for the concomitant cancer and SUI surgery group compared with the cancer-only group, respectively. CONCLUSION: Concomitant surgery did not result in improved QOL compared with cancer surgery alone for endometrial intraepithelial neoplasia and patients with early-stage endometrial cancer with SUI. However, FACT-En scores were improved in both groups.

Effect of Second-Stage Pushing Timing on Postpartum Pelvic Floor Morbidity: A Randomized Controlled Trial.

OBJECTIVE: To assess whether immediate or delayed pushing in the second-stage results in higher risk of pelvic floor morbidity. METHODS: This study was a planned secondary aim of a multicenter randomized clinical trial that included nulliparous patients at 37 weeks of gestation or greater in labor with neuraxial analgesia. Participants were randomized in the second stage to initiate pushing immediately or wait 60 minutes before pushing. Participants had pelvic floor assessments at 1-5 days postpartum, 6 weeks postpartum, and 6 months postpartum. Rates of perineal lacerations, pelvic organ prolapse quantification (POP-Q) measures, and scores on validated symptom-specific distress and quality-of-life questionnaires (PFDI-20 [Pelvic Floor Distress Inventory], PFIQ [Pelvic Floor Impact Questionnaire], FISI [Fecal Incontinence Severity Index], and MMHQ [Modified Manchester Health Questionnaire]) were compared. It was estimated that 630 participants would provide more than 80% power to detect a 40% difference in second-degree or greater perineal lacerations and approximately 80% power to detect a 40% difference in stage 2 or greater pelvic organ prolapse (POP). RESULTS: Among 2,414 participants in the primary trial conducted between May 19, 2014, and December 16, 2017, 941 (39%) had pelvic floor assessments: 452 immediate pushing and 489 delayed pushing. The mean age was 24.8 years, and 93.4% had vaginal delivery. There were no significant differences in perineal lacerations at delivery and POP at 6 weeks and 6 months postpartum. Changes from baseline in total and subscale scores for the PFDI-20, the PFIQ, and the MMHQ were not significantly different at 6 weeks postpartum and 6 months postpartum. The change in FISI score was higher in the immediate pushing group at 6 months (2.9±5.7 vs 2.0±4.5, difference 0.9, P =.01), but less than the minimum important difference of 4. CONCLUSION: Among nulliparous patients in the second stage with neuraxial analgesia, immediate pushing, compared with delayed pushing, did not increase perineal lacerations, POP-Q measures, or patient-reported pelvic floor symptoms at 6 weeks and 6 months postpartum. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02137200.

Digital Therapeutic Device for Urinary Incontinence: A Longitudinal Analysis at 6 and 12 Months.

OBJECTIVE: To evaluate the long-term efficacy of an 8-week regimen of pelvic floor muscle training guided by a motion-based digital therapeutic device compared with a standard home program in the treatment of stress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (MUI). METHODS: The primary virtual trial was conducted from October 2020 to March 2021; 363 women with SUI or stress-predominant MUI were randomized to complete pelvic floor muscle training using the device (intervention group) or a standard home pelvic floor muscle training program (control group) for 8 weeks. Primary outcomes included change in UDI-6 (Urogenital Distress Inventory, Short Form) score and SUI episodes on a 3-day bladder diary. The PGI-I (Patient Global Impression of Improvement) was also assessed, with "much better" and "very much better" responses considered as improvement. In this planned secondary analysis, symptom and adherence data were collected in follow-up at 6 and 12 months. A modified intention-to-treat analysis was performed using Student's t tests and χ2 tests as appropriate. RESULTS: Of 299 participants analyzed at 8 weeks, 286 (95.7%) returned 6- and 12-month data (151 in the control group, 135 in the intervention group). Mean age was 51.9±12.8 years, and mean body mass index (BMI) was 31.8±7.4; 84.6% of participants were parous, and 54.9% were postmenopausal. Mean change in UDI-6 score from baseline to 6 and 12 months was significantly greater in the intervention group than in the control group (20.2±20.9 vs 14.8±19.5, P=.03 and 22.7±23.3 vs 15.9±20.3, P=.01, respectively). Participants in the intervention group had more than twice the odds of reporting improvement on the PGI-I compared with participants in the control group (OR 2.45, 95% CI 1.49-4.00). CONCLUSION: Pelvic floor muscle training guided by a motion-based digital therapeutic device yielded significantly greater urinary incontinence symptom improvement compared with a standard home pelvic floor muscle training program at 6 and 12 months, although continued improvement waned over time. This technology may facilitate pelvic floor muscle training access and adherence for women with SUI and stress-predominant MUI and represents an effective modality for scaling first-line care. FUNDING SOURCE: Renovia Inc. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04508153.

Characteristics associated with composite surgical failure over 5 years of women in a randomized trial of sacrospinous hysteropexy with graft vs vaginal hysterectomy with uterosacral ligament suspension.

BACKGROUND: Among women with symptomatic uterovaginal prolapse undergoing vaginal surgery in the Vaginal hysterectomy with Native Tissue Vault Suspension vs Sacrospinous Hysteropexy with Graft Suspension (Study for Uterine Prolapse Procedures Randomized Trial) trial, sacrospinous hysteropexy with graft (hysteropexy) resulted in a lower composite surgical failure rate than vaginal hysterectomy with uterosacral suspension over 5 years. OBJECTIVE: This study aimed to identify factors associated with the rate of surgical failure over 5 years among women undergoing sacrospinous hysteropexy with graft vs vaginal hysterectomy with uterosacral suspension for uterovaginal prolapse. STUDY DESIGN: This planned secondary analysis of a comparative effectiveness trial of 2 transvaginal apical suspensions (NCT01802281) defined surgical failure as either retreatment of prolapse, recurrence of prolapse beyond the hymen, or bothersome prolapse symptoms. Baseline clinical and sociodemographic factors for eligible participants receiving the randomized surgery (N=173) were compared across categories of failure (≤1 year, >1 year, and no failure) with rank-based tests. Factors with adequate prevalence and clinical relevance were assessed for minimally adjusted bivariate associations using piecewise exponential survival models adjusting for randomized apical repair and clinical site. The multivariable model included factors with bivariate P<.2, additional clinically important variables, apical repair, and clinical site. Backward selection determined final retained risk factors (P<.1) with statistical significance evaluated by Bonferroni correction (P<.005). Final factors were assessed for interaction with type of apical repair at P<.1. Association is presented by adjusted hazard ratios and further illustrated by categorization of risk factors. RESULTS: In the final multivariable model, body mass index (increase of 5 kg/m2: adjusted hazard ratio, 1.7; 95% confidence interval, 1.3-2.2; P<.001) and duration of prolapse symptoms (increase of 1 year: adjusted hazard ratio, 1.1; 95% confidence interval, 1.0-1.1; P<.005) were associated with composite surgical failure, where rates of failure were 2.9 and 1.8 times higher in women with obesity and women who are overweight than women who have normal weight and women who are underweight (95% confidence intervals, 1.5-5.8 and 0.9-3.5) and 3.0 times higher in women experiencing >5 years prolapse symptoms than women experiencing ≤5 years prolapse symptoms (95% confidence interval, 1.8-5.0). Sacrospinous hysteropexy with graft had a lower rate of failure than hysterectomy with uterosacral suspension (adjusted hazard ratio, 0.6; 95% confidence interval, 0.4-1.0; P=.05). The interaction between symptom duration and apical repair (P=.07) indicated that failure was less likely after hysteropexy than hysterectomy for those with ≤5 years symptom duration (adjusted hazard ratio, 0.5; 95% confidence interval, 0.2-0.9), but not for those with >5 years symptom duration (adjusted hazard ratio, 1.0; 95% confidence interval 0.5-2.1). CONCLUSION: Obesity and duration of prolapse symptoms have been determined as risk factors associated with surgical failure over 5 years from transvaginal prolapse repair, regardless of approach. Providers and patients should consider these modifiable risk factors when discussing treatment plans for bothersome prolapse.

Characteristics Associated With Postoperative Catheterization at Discharge in Women Undergoing Colpocleisis.

IMPORTANCE: Although transient voiding dysfunction is common after surgical correction of pelvic organ prolapse, it has not been well studied in women undergoing colpocleisis. OBJECTIVE: This study aimed to identify characteristics associated with discharge home with a urinary catheter in women undergoing colpocleisis. STUDY DESIGN: This is a secondary analysis of a multicenter prospective study examining the effect of pelvic support, symptoms, and satisfaction in women undergoing colpocleisis. Publicly accessible deidentified data sets of the index study were analyzed. Primary outcome was discharge with a urinary catheter postoperatively. Characteristics associated with discharge with catheter after colpocleisis were assessed via logistic regression. Covariates were selected based on statistical significance at 0.05 and clinical relevance on bivariate analysis. RESULTS: Of the 136 women (mean age, 77.8 ± 5.5 years) undergoing colpocleisis in the index study, 68 (50.0%) were discharged with catheter. Baseline characteristics did not differ, except that the catheter group had lower prior incontinence surgery (7.4% vs 22.1%, P = 0.02) and higher preoperative postvoid residual volume (PVR; 189.8 ± 187.6 vs 91.3 ± 124.2 mL, P < 0.01). Those discharged with catheter had greater estimated blood loss (128.7 ± 88.5 vs 95.3 ± 74.5 mL, P = 0.02), operative time (125.2 ± 56.3 vs 100.8 ± 45.4 minutes, P < 0.01), and concomitant levator myorrhaphy (82.4% vs 58.8%, P < 0.01). Multivariable analysis revealed preoperative PVR (adjusted odds ratio, 1.2; 95% confidence interval, 1.0-1.4 for every 50-mL increase in PVR) and levator myorrhaphy (adjusted odds ratio, 4.3; 95% confidence interval, 1.6-11.3) were associated with postoperative catheterization. CONCLUSIONS: In women undergoing colpocleisis, higher preoperative PVR and levator myorrhaphy were associated with discharge with catheter.

Intravesical Instillation of OnabotulinumtoxinA in the Treatment of Refractory Overactive Bladder in Participants with Urinary Incontinence.

PURPOSE: Intradetrusor injections of onabotulinumtoxinA are efficacious for the treatment of overactive bladder with urgency urinary incontinence in adults refractory to or intolerant of anticholinergics. Delivery of onabotulinumtoxinA via instillation would reduce the need for intradetrusor injections. The objective of this trial was to assess the efficacy and safety of intravesical instillation of an onabotulinumtoxinA + hydrogel admixture. MATERIALS AND METHODS: After review of a stage 1 safety phase by an independent committee, participants were recruited into stage 2 and randomized to either onabotulinumtoxinA 100, 300, 400, or 500 U, or placebo, all with hydrogel admixture. End points included change from baseline to week 12 in the number of urinary incontinence episodes (primary); micturition, urgency urinary, and nocturia episodes/day; volume voided per micturition; proportion of participants with a ≥50% decrease from baseline in urinary incontinence episodes/day; and Overactive Bladder Questionnaire total score. Adverse events were reported. RESULTS: Change from baseline to week 12 in number of urinary incontinence episodes was -2.72 with placebo and ranged from -0.89 to -1.85 in the onabotulinumtoxinA + hydrogel treatment groups. No difference from placebo was observed for any efficacy end point. The proportions of participants with treatment-emergent adverse events were similar among all groups, with asymptomatic bacteriuria the highest reported (6.7%-15.5%). There were no reports of urinary retention or elevated post-void residual volume. CONCLUSIONS: Intravesical instillation of an onabotulinumtoxinA + hydrogel admixture for the treatment of refractory overactive bladder was well tolerated, but it showed no improvement over placebo.