Testosterone use and sexual function among transgender men and gender diverse people assigned female at birth.

BACKGROUND: Testosterone use among transgender people likely impacts their experience of sexual function and vulvovaginal pain via several complex pathways. Testosterone use is associated with decreased estrogen in the vagina and atrophic vaginal tissue, which may be associated with decreased vaginal lubrication and/or discomfort during sexual activity. At the same time, increased gender affirmation through testosterone use may be associated with improved sexual function. However, data on pelvic and vulvovaginal pain among transgender men and nonbinary people assigned female at birth are scarce. OBJECTIVE: This study aimed to assess the association between testosterone and sexual function with a focus on symptoms that are commonly associated with vaginal atrophy. STUDY DESIGN: We conducted a cross-sectional analysis of 1219 participants aged 18 to 72 years using data collected from 2019 to 2021 from an online, prospective, longitudinal cohort study of sexual and/or gender minority people in the United States (The Population Research in Identity and Disparities for Equality Study). Our analysis included adult transgender men and gender diverse participants assigned female at birth who were categorized as never, current, and former testosterone users. Sexual function was measured across 8 Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction domains. RESULTS: Overall, 516 (42.3%) participants had never used testosterone, and 602 (49.4%) currently used testosterone. The median duration of use was 37.7 months (range, 7 days to >27 years). Most participants (64.6%) reported genital pain or discomfort during sexual activity in the past 30 days, most commonly in the vagina or frontal genital opening (52.2%), followed by around the clitoris (29.1%) and labia (24.5%). Current testosterone use was associated with a greater interest in sexual activity (ß=6.32; 95% confidence interval, 4.91-7.74), higher ability to orgasm (ß=1.50; 95% confidence interval, 0.19-2.81), and more vaginal pain or discomfort during sexual activity (ß=1.80; 95% confidence interval, 0.61-3.00). No associations were observed between current testosterone use and satisfaction with sex life, lubrication, labial pain or discomfort, or orgasm pleasure. CONCLUSION: Testosterone use among transgender men and gender diverse people was associated with an increased interest in sexual activity and the ability to orgasm, as well as with vaginal pain or discomfort during sexual activity. Notably, the available evidence demonstrates that >60% of transgender men experience vulvovaginal pain during sexual activity. The causes of pelvic and vulvovaginal pain are poorly understood but are likely multifactorial and include physiological (eg, testosterone-associated vaginal atrophy) and psychological factors (eg, gender affirmation). Given this high burden, there is an urgent need to identify effective and acceptable interventions for this population.

What predicts durable symptom relief of uterine fibroids treated with MRI-guided focused ultrasound? A multicenter trial in 8 academic centers.

OBJECTIVE: To identify variables predictive of durable clinical success after MRI-guided focused ultrasound (MRgFUS) treatment of uterine fibroids. MATERIALS AND METHODS: In this prospective, multicenter trial, 99 women with symptomatic uterine fibroids were treated using MRgFUS. Pelvic MRI was obtained at baseline and treatment day. The Uterine Fibroid Symptom-Quality of Life questionnaire was used to calculate a symptom severity score (SSS) at baseline and 6, 12, 24, and 36 months following treatment. Clinical, imaging, and treatment variables were correlated with symptom reduction sustained through the 12- and 24-month time points using univariable and multivariable logistic regression analyses. A novel parameter, the ratio of non-perfused volume to total fibroid load (NPV/TFL), was developed to determine association with durable outcomes. RESULTS: Post-treatment, mean symptom severity decreased at the 6-, 12-, 24-, and 36-month follow-ups (p < 0.001, all time points). In univariable analysis, three variables predicted treatment success (defined by ≥ 30-point improvement in SSS) sustained at both the 12-month and 24-month time points: increasing ratio of NPV/TFL (p = 0.002), decreasing total fibroid load (p = 0.04), and the absence of T2-weighted Funaki type 2 fibroids (p = 0.02). In multivariable analysis, the NPV/TFL was the sole predictor of durable clinical success (p = 0.01). Patients with ratios below 30% had less improvement in SSS and lacked durable clinical response compared with those between 30-79 (p = 0.03) and ≥ 80% (p = 0.01). CONCLUSION: Increased non-perfused volume relative to total fibroid volume was significantly associated with durable reduction of symptoms of abnormal uterine bleeding and bulk bother. CLINICAL RELEVANCE STATEMENT: Patient selection for sustained clinical benefit should emphasize those with likelihood of achieving high ablation ratios, as determined by imaging (e.g., device access, Funaki type) and by considering the total fibroid load, not just the primary symptomatic fibroid. TRIAL REGISTRATION: Clinical trial ID: NCT01285960. KEY POINTS: • Patient selection/treatment approach associated with durable symptom relief in MRI-guided focused ultrasound ablation of uterine fibroids remains unclear. • The ablation ratio, non-perfused volume/total fibroid volume, was positively associated with sustained symptom relief in both bleeding and bulk bother at 1- and 2-year follow-ups. • Selecting patients with imaging features that favor a high ratio of ablation to total fibroid load (including non-targeted fibroids) is the main factor in predicting durability of symptom relief after uterine fibroid treatment.

Postoperative complications and recurrence rates after rectal prolapse surgery versus combined rectal prolapse and pelvic organ prolapse surgery.

INTRODUCTION AND HYPOTHESIS: Our primary objectives were to compare < 30-day postoperative complications and RP recurrence rates after RP-only surgery and combined surgery. Our secondary objectives were to determine preoperative predictors of < 30-day complications and RP recurrence. METHODS: A prospective IRB-approved cohort study was performed at a single tertiary care center from 2017 to 2020. Female patients with symptomatic RP underwent either RP-only surgery or combined surgery based on the discretion of the colorectal and FPMRS surgeons. Primary outcome measures were < 30-day complications separated into Clavien-Dindo (CD) classes and rectal prolapse on physical examination. RESULTS: Seventy women had RP-only surgery and 45 had combined surgery with a mean follow-up time of 208 days. Sixty-eight percent underwent abdominal RP repair, and 32% underwent perineal RP repair. Twenty percent had one or more complications, 14% in the RP-only group and 29% in the combined surgery group (p = 0.06). On multivariate analysis, combined surgery patients had a 30% increased risk of complications compared to RP-only surgery patients (RR = 1.3). Most of these complications were minor (14/17, 82.4%) and categorized as CD I or II, including urinary retention and UTI. Twelve percent of this cohort had RP recurrence, 11% in the RP-only group and 13% in the combined surgery group (p = 0.76). Preoperative risk factors for RP recurrence included a primary complaint of rectal bleeding (RR 5.5) and reporting stools consistent with Bristol Stool Scale of 1 (RR 2.1). CONCLUSION: Patients undergoing combined RP + POP surgery had a higher risk of complications and equivalent RP recurrence rates compared to patients undergoing RP-only surgery.

Characterizing relaxin receptor expression and exploring relaxin's effect on tissue remodeling/fibrosis in the human bladder.

BACKGROUND: Relaxin is an endogenous protein that has been shown to have antifibrotic properties in various organ systems. There has been no characterization of relaxin's role in the human bladder. Our objective was to characterize relaxin receptor expression in the human bladder and assess relaxin's effect on tissue remodeling/fibrosis pathways in bladder smooth muscle cells. METHODS: Relaxin family peptide receptor 1 (RXFP1) and RXFP2 expression was assessed using quantitative reverse transcriptase-PCR (qRT-PCR) and immunohistochemistry (IHC) on primary bladder tissue. Primary human smooth muscle bladder cells were cultured and stimulated with various concentrations of relaxin. Western blot, qRTPCR, ELISA, and zymogram assays were used to analyze fibrosis/tissue remodeling pathway proteins. RESULTS: There was universal mRNA transcript detection and protein expression of relaxin receptors in primary bladder specimens. Immunohistochemistry demonstrated RXFP1 and RXFP2 localizing to both urothelial and smooth muscle cell layers of the bladder. 24 h of in vitro relaxin stimulation did not affect mRNA expression of selected proteins in human bladder smooth muscle cells. However, 48 h of in vitro relaxin stimulation resulted in upregulation of active (p = 0.004) and latent (p = 0.027) MMP-2 in cell lysate, and upregulation of active MMP-2 in supernatant (p = 0.04). There was a dose dependent relationship with increasing expression of MMP-2 with increasing relaxin concentration. Relaxin stimulation resulted in decreased levels of active and total TGF-ß1 in supernatant and extracellular matrix (p < 0.005 with 100 ng/mL relaxin stimulation). CONCLUSIONS: In the human bladder, relaxin receptors are expressed at the dome and trigone and localize to the urothelium and smooth muscle cell layers. Stimulation of human bladder SMCs with relaxin in vitro affects expression of MMP-2 and TGF-ß1.

Evaluation of the routine use of pelvic MRI in women presenting with symptomatic uterine fibroids: When is pelvic MRI useful?

BACKGROUND: Pelvic ultrasound (US) diagnosis of uterine fibroids may overlook coexisting gynecological conditions that contribute to women's symptoms. PURPOSE: To determine the added value of pelvic MRI for women diagnosed with symptomatic fibroids by US, and to identify clinical factors associated with additional MRI findings. STUDY TYPE: Retrospective observational study. POPULATION: In all, 367 consecutive women with fibroids diagnosed by US and referred to our multidisciplinary fibroid center between 2013-2017. FIELD STRENGTH/SEQUENCE: All patients had both pelvic US and MRI prior to their consultations. MRIs were performed at 1.5 T or 3 T and included multiplanar T2 -weighted sequences, and precontrast and postcontrast T1 -weighted imaging. ASSESSMENT: Demographics, symptoms, uterine fibroid symptom severity scores, and health-related quality of life scores, as well as imaging findings were evaluated. STATISTICAL TESTS: Patients were separated into two subgroups according to whether MRI provided additional findings to the initial US. Univariate and multivariate regression analyses were performed. RESULTS: Pelvic MRI provided additional information in 162 patients (44%; 95% confidence interval [CI] 39-49%). The most common significant findings were adenomyosis (22%), endometriosis (17%), and partially endocavitary fibroids (15%). Women with pelvic pain, health-related quality of life scores less than 30 out of 100, or multiple fibroids visualized on US had greater odds of additional MRI findings (odds ratio [OR] 1.68, 2.26, 1.63; P = 0.02, 0.004, 0.03, respectively), while nulliparous women had reduced odds (OR 0.55, P = 0.01). Patients with additional MRI findings were treated less often with uterine fibroid embolization (14% vs. 36%, P < 0.001) or MR-guided focused US (1% vs. 5%, P = 0.04), and more often with medical management (17% vs. 8%, P = 0.01). DATA CONCLUSION: Pelvic MRI revealed additional findings in more than 40% of women presenting with symptoms initially ascribed to fibroids by US. Further evaluation using MRI is particularly useful for parous women with pelvic pain, poor quality of life scores, and/or multiple fibroids. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019.

Are fibroid and bony pelvis characteristics associated with urinary and pelvic symptom severity?

BACKGROUND: Urinary and pelvic floor symptoms often are attributed to size and location of uterine fibroid tumors. However, direct supporting evidence that links increased size to worsening symptoms is scant and limited to ultrasound evaluation of fibroid tumors. Because management of fibroid tumors is targeted towards symptomatic relief, the identification of fibroid and pelvic characteristics that are associated with worse symptoms is vital to the optimization of therapies and prevention needless interventions. OBJECTIVE: We examined the correlation between urinary, pelvic floor and fibroid symptoms, and fibroid size and location using precise uterine fibroid and bony pelvis characteristics that were obtained from magnetic resonance imaging. STUDY DESIGN: A retrospective review (2013-2017) of a multidisciplinary fibroid clinic identified 338 women who had been examined via pelvic magnetic resonance imaging, Pelvic Floor Distress Inventory questionnaire (score 0-300), and a Uterine Fibroid Symptoms questionnaire (score 1-100). Multiple linear regression analysis was used to assess the influence of clinical factors and magnetic resonance imaging findings on scaled Pelvic Floor Distress Inventory and Uterine Fibroid Symptoms scores. Data were analyzed with statistical software. RESULTS: Our cohort of 338 women had a median Pelvic Floor Distress Inventory of 72.7 (interquartile range, 41-112.3). Increased Pelvic Floor Distress Inventory score was associated with clinical factors of higher body mass index (P<.001), noncommercial insurance (P<.001), increased parity (P=.001), and a history of incontinence surgery (P=.003). Uterine volume, dominant fibroid volume, dimension and location, and fibroid tumor location relative to the bony pelvis structure did not reach significance when compared with pelvic floor symptom severity. The mean Uterine Fibroid Symptoms score was 52.0 (standard deviation, 23.5). An increased Uterine Fibroid Symptoms score was associated with dominant submucosal fibroid tumors (P=.011), body mass index (P<.0016), and a clinical history of anemia (P<.001) or any hormonal treatment for fibroid tumors (P=.009). CONCLUSION: Contrary to common belief, in this cohort of women who sought fibroid care, size and position of fibroid tumors or uterus were not associated with pelvic floor symptom severity. Whereas, bleeding symptom severity was associated with dominant submucosal fibroid tumor and previous hormonal treatment. Careful attention to clinical factors such as body mass index and medical history is recommended when pelvic floor symptoms are evaluated in women with uterine fibroid tumors.

Urodynamic factors associated with the large capacity bladder and incomplete emptying after prolapse repair (2009-2015).

AIMS: To identify the clinical and urodynamic factors associated with the large capacity bladder and incomplete bladder emptying after prolapse repair. METHODS: We identified 592 women who underwent anterior and/or apical prolapse repair at our institution from 2009 to 2015. Women were stratified by urodynamic capacity. The primary outcome was incomplete emptying at the longest follow-up (postvoid residual [PVR] > 200 mL). Data were analyzed in the Statistical Analysis System software. RESULTS: Two hundred and sixty-six women (mean age, 61 years) had preoperative urodynamic tracings available for review. After surgery, there were 519 PVRs in 239 women recorded at up to 2949 days (mean, 396) and nine time points (median, 2; IQR, 1-3). The receiver operator curve for predicted probability of longest follow-up PVR greater than 200 mL (area under curve = 0.67) identified the 600 mL cutpoint which defined large capacity bladder. Large capacity bladders (capacity, >600 mL [n=79] vs ≤600 mL, [n=160]) had a mean: detrusor pressure at maximum flow (21 vs 22 cm H2 O; P = 0.717), maximum flow rate (19 vs 17 mL/s; P = 0.148), significantly elevated PVR (202 vs 73 mL; P < 0.001), and significantly lower voiding efficiency (VE) (74 vs 82%, P < 0.05). Following prolapse repair, elevated PVR was associated with large capacity (PVR 101 vs 49 mL, P < 0.05). Large bladders had a two- to three-fold risk of longest follow-up PVR greater than 200 mL (14.3%-20.3% [capacity, >600 mL] vs 4.1%-7.0% [capacity, ≤600 mL]). VE was similar after surgery regardless of the capacity (87% vs 88%, P = 0.772). CONCLUSIONS: The decision to pursue prolapse repair should be individualized and take into account, the bladder capacity and goals for PVR improvement after surgery.

Evaluation of diet pattern and weight gain in postmenopausal women enrolled in the Women's Health Initiative Observational Study.

It is unclear which of four popular contemporary diet patterns is best for weight maintenance among postmenopausal women. Four dietary patterns were characterised among postmenopausal women aged 49-81 years (mean 63·6 (sd 7·4) years) from the Women's Health Initiative Observational Study: (1) a low-fat diet; (2) a reduced-carbohydrate diet; (3) a Mediterranean-style (Med) diet; and (4) a diet consistent with the US Department of Agriculture's Dietary Guidelines for Americans (DGA). Discrete-time hazards models were used to compare the risk of weight gain (≥10 %) among high adherers of each diet pattern. In adjusted models, the reduced-carbohydrate diet was inversely related to weight gain (OR 0·71; 95 % CI 0·66, 0·76), whereas the low-fat (OR 1·43; 95 % CI 1·33, 1·54) and DGA (OR 1·24; 95 % CI 1·15, 1·33) diets were associated with increased risk of weight gain. By baseline weight status, the reduced-carbohydrate diet was inversely related to weight gain among women who were normal weight (OR 0·72; 95 % CI 0·63, 0·81), overweight (OR 0·67; 95 % CI 0·59, 0·76) or obese class I (OR 0·63; 95 % CI 0·53, 0·76) at baseline. The low-fat diet was associated with increased risk of weight gain in women who were normal weight (OR 1·28; 95 % CI 1·13, 1·46), overweight (OR 1·60; 95 % CI 1·40, 1·83), obese class I (OR 1·73; 95 % CI 1·43, 2·09) or obese class II (OR 1·44; 95 % CI 1·08, 1·92) at baseline. These findings suggest that a low-fat diet may promote weight gain, whereas a reduced-carbohydrate diet may decrease risk of postmenopausal weight gain.

Assessing the use of the IUGA/ICS classification system for prosthesis/graft complications in publications from 2011 to 2015.

INTRODUCTION AND HYPOTHESIS: Complications of pelvic organ prolapse and urinary incontinence surgery have gained increasing attention from both lay media and medical societies. The International Urogynecological Association and International Continence Society proposed the category-time-site system to classify complications in 2011. Our objective is to assess the usage of the category-time-site system in the literature. METHODS: We conducted a systematic review and identified records using PubMed search terms "mesh" and "prolapse or incontinence" and "complication or excision" (February 2011 to December 2015) to select publications following the introduction of category-time-site system. Relevant publications were included and reviewed for study design, initial procedure, number of patients assigned codes, number of unique codes applied, purpose of assigning codes, and duration of clinical follow-up. RESULTS: Of 167 eligible records, 23 (14 %) used the system, 137 (82 %) used no system, and 7 (4 %) used another system. They included three study designs: randomized control trials, case reports, and case series. Given the very limited amount of data, no statistical tests were performed, but trends were noted. CONCLUSIONS: Fourteen percent of the reports in the literature describing complications related to prosthesis/graft use in pelvic surgery utilize the category-time-site system. The system's limited and inconsistent use hinders the ability to draw conclusions useful for clinical practice. Effort should be directed toward improving appropriate usage or revising the system to increase its exposure in related publications. An improved system will better prepare pelvic surgeons for assessing future generations of prostheses/grafts.

Sonographic Evaluation for Endometrial Polyps: The Interrupted Mucosa Sign.

OBJECTIVES: To evaluate the interrupted mucosa sign for identification of endometrial polyps, using pathologic confirmation as the reference standard, compared to other accepted sonographic findings. METHODS: We reviewed 195 patients referred for pelvic sonographic evaluations for suspected endometrial polyps in this retrospective Institutional Review Board-approved study. Of these, 82 had tissue sampling of the endometrium and constituted the final study group. Patient data, including age, menopausal status, last menstrual period, and final pathologic diagnosis, were recorded. Sonograms were reviewed by 2 blinded board-certified radiologists for endometrial features, including thickness, echogenicity, vascularity, presence of a mass, and the interrupted mucosa sign. Descriptive statistics and multivariate logistic regression analysis were performed. RESULTS: The mean age of the patients was 44.99 (SD, 9.88) years, 79.1% of whom were premenopausal. Pathologic diagnosis confirmed polyps in 58 (70.73%). A single feeding vessel was visualized in 36 patients with polyps (62.07%), whereas the interrupted mucosa sign was visualized in 34 (58.62%). The presence of a feeding vessel, the interrupted mucosa sign, or both detected 48 (82.76%) of the polyps. In the multivariate analysis, only the interrupted mucosa sign was a statistically significant predictor of pathologic diagnosis of a polyp (P= .035), with an odds ratio of 3.83 (95% confidence interval, 1.10-13.29). Other sonographic findings were not independent predictors of a polyp: mass (P = .35), single feeding vessel (P = .31), endometrial thickness (P = .88), and endometrial echogenicity (P = .45). The sensitivity, specificity, and positive predictive value of the interrupted mucosa sign were 59%, 75%, and 85%, respectively. CONCLUSIONS: The interrupted mucosa sign is a promising sonographic sign for identification of endometrial polyps, with greater predictive power than previously described signs. It has the potential to improve the diagnostic performance of sonography, especially when used in combination with other described signs.

Challenges and future prospects for tissue engineering in female pelvic medicine and reconstructive surgery.

With advances in material engineering there is now a wide array of new materials for augmentation of tissue repairs in Female Pelvic Medicine and Reconstructive Surgery (FPMRS). However, clinical outcomes are discrepant and long term complications debilitating. In this manuscript, we describe the molecular and cellular host environments and biomechanical considerations that affect optimal integration of implant materials. There is growing interest in biodegradable scaffolds with cellular implants. It is thought that the cellular component could regenerate host tissue while the scaffold provides temporary mechanical properties. Current findings are promising, but detailed in vivo and long term testing is needed before clinical applications.

Histologic characteristics of vaginal cuff tissue from patients with vaginal cuff dehiscence.

STUDY OBJECTIVE: To describe the histologic characteristics of vaginal tissue in patients with vaginal cuff dehiscence (VCD) after robotic hysterectomy and to compare this group with patients without dehiscence. DESIGN: Retrospective analysis (Canadian Task Force classification II-3). SETTING: Academic center. PATIENTS: Seven patients with VCD and 6 patients without VCD. INTERVENTIONS: Vaginal cuff tissue was obtained from all patients and was stained using hematoxylin-eosin and evaluated for acute and chronic inflammation markers including neutrophils, lymphocytes, and plasma cells. Immunohistochemical staining was performed and evaluated using the semiquantitative method for collagen types I and III, smooth muscle actin, and SM22α (myofibroblast) content. Grading was performed by 4 blinded investigators. The Mann-Whitney test was used to evaluate the 2 groups, and correlation coefficients for interobserver variability. MEASUREMENTS AND MAIN RESULTS: The VCD group, compared with the non-VCD group, demonstrated significantly greater numbers of neutrophils (1.71 vs 1.0; p = .04), lymphocytes (2.85 vs 1.33; p = .002), and plasma cells (2.2 vs 1.0; p = .001). There was no statistical difference between the groups in amounts of collagen I (1.71 vs 1.27; p = .09) and collagen III (1.66 vs 1.38; p = .37), smooth muscle actin (1.23 vs 1.33; p = .65), and SM22α (1.85 vs 1.27; p = .09). Interobserver variability was low (κ = 0.86; p = .76). CONCLUSION: Compared with the control group, patients with VCD demonstrated significantly higher levels of acute and chronic inflammatory cells. This finding suggests that a prolonged inflammatory phase may be delaying normal progression to reparation in patients with dehiscence.

Functional outcome of the anterior vaginal wall in a pelvic surgery injury rat model after treatment with stem cell-derived progenitors of smooth muscle cells.

Background : Stem-cell-derived therapy is a promising option for tissue regeneration. Human iPSC-derived progenitors of smooth muscle cells (pSMCs) have limited proliferation and differentiation, which may minimize the risk of in vivo tumor formation while restoring smooth muscle cell deficiencies. Up to 30 % of women who suffer from recurrence of vaginal prolapse after prolapse surgery are faced with reoperation. Therefore, there is an unmet need for therapies that can restore vaginal tissue function. We hypothesize that human pSMCs can restore vaginal function in a vaginal-injury rat model. Methods : Female immune-compromised RNU rats were divided into 5 groups: intact controls (n=12), VSHAM (surgery + saline injection, n=33), and cell-injection group (surgery + cell injection using three patient pSMCs lines, n=14/cell line). The surgery, similar to what is done in vaginal prolapse surgery, involved ovariectomy, urethrolysis, and vagina injury. The vagina, urethra, bladder dome and trigone were harvested 10 weeks after surgery (5 weeks after injection). Organ bath myography was performed to evaluate the contractile function of vagina, and smooth muscle thickness was examined by tissue immunohistochemistry. Collagen I, collagen III, and elastin mRNA and protein expressions in tissues were assessed. Results : When compared to the VSHAM group, cell-injection groups showed significantly increased vaginal smooth muscle contractions induced by carbachol (groups A and C) and by KCl (group C), and significantly higher collagen I protein expression in the vagina (groups A and B). Elastin mRNA and protein expressions in the vagina did not correlate with injection group. In the urethra, mRNA expressions of collagen I, collagen III, and elastin were all significantly higher in the cell-injection groups compared to the VSHAM group. Collagen I protein expression of the urethra was also higher in the cell-injection group compared to the VSHAM group. Elastin protein expression in the urethra did not correlate with injection group. Conclusions : Human iPSC-derived pSMCs improved contractile function of the post-surgery vagina. Additionally, pSMC injection modulated collagen I, collagen III and elastin mRNA and protein expressions in the vagina and urethra. These findings suggest that pSMCs may be a possible therapy for vaginal prolapse recurrence after surgical intervention.

To sling or not to sling at time of abdominal sacrocolpopexy: a cost-effectiveness analysis.

PURPOSE: We compare the cost-effectiveness of 3 strategies for the use of a mid urethral sling to prevent occult stress urinary incontinence in patients undergoing abdominal sacrocolpopexy. MATERIALS AND METHODS: Using decision analysis modeling we compared cost-effectiveness during a 1-year postoperative period of 3 treatment approaches including 1) abdominal sacrocolpopexy alone with deferred option for mid urethral sling, 2) abdominal sacrocolpopexy with universal concomitant mid urethral sling and 3) preoperative urodynamic study for selective mid urethral sling. Using published data we modeled probabilities of stress urinary incontinence after abdominal sacrocolpopexy with or without mid urethral sling, the predictive value of urodynamic study to detect occult stress urinary incontinence and the likelihood of complications after mid urethral sling. Costs were derived from Medicare 2010 reimbursement rates. The main outcome modeled was incremental cost-effectiveness ratio per quality adjusted life-years gained. In addition to base case analysis, 1-way sensitivity analyses were performed. RESULTS: In our model, universally performing mid urethral sling at abdominal sacrocolpopexy was the most cost-effective approach with an incremental cost per quality adjusted life-year gained of $2,867 compared to abdominal sacrocolpopexy alone. Preoperative urodynamic study was more costly and less effective than universally performing intraoperative mid urethral sling. The cost-effectiveness of abdominal sacrocolpopexy plus mid urethral sling was robust to sensitivity analysis with a cost-effectiveness ratio consistently below $20,000 per quality adjusted life-year. CONCLUSIONS: Universal concomitant mid urethral sling is the most cost-effective prophylaxis strategy for occult stress urinary incontinence in women undergoing abdominal sacrocolpopexy. The use of preoperative urodynamic study to guide mid urethral sling placement at abdominal sacrocolpopexy is not cost-effective.

The predictive value of a cystocele for concomitant vaginal apical prolapse.

PURPOSE: Recent studies showing a correlation between descent of the anterior and apical vaginal compartments suggest that cystoceles may recur if associated apical prolapse is not corrected. However, to date the anatomical relationship of apical prolapse with respect to cystocele has been incompletely reported. We present the predictive value of a cystocele for clinically significant vaginal apical prolapse. MATERIALS AND METHODS: We retrospectively reviewed the records of all new patient visits to a urogynecology clinic in a 30-month period. Women with a point Ba value of -1 or greater (stage 2 cystocele and above) were included in analysis. Predictive values of clinically significant apical prolapse, defined as point C -3 or greater, were calculated and stratified by cystocele stage. RESULTS: A total of 385 women were included in study. Point Ba was the leading edge of prolapse in 83.9% of cases. The position of Ba strongly correlated with that of the vaginal apex (Spearman ρ = 0.769, p <0.001). Overall 59.7% of patients had a point C of -3 or greater. The finding of clinically significant apical prolapse increased significantly with increasing Ba values. Of patients with stage 2, 3 and 4 cystocele point C was -3 or greater in 42%, 85% and 100%, respectively. CONCLUSIONS: The finding of stage 2 or greater cystocele is highly suggestive of clinically significant apical vaginal descent to -3 or greater. Furthermore, as cystocele stage increases, the predictive value of apical prolapse also increases. Surgeons contemplating cystocele repair should have high suspicion for vaginal apical prolapse and consider concomitant repair.

Improving the accuracy of prolapse and incontinence procedure epidemiology by utilizing both inpatient and outpatient data.

INTRODUCTION AND HYPOTHESIS: The epidemiologic description of pelvic organ prolapse (POP) and stress urinary incontinence (SUI) procedures is documented in several large studies using national database cohorts. These studies, however, may underestimate the number of procedures performed because they only capture procedures performed in either the inpatient or outpatient settings alone. We present a complete annual description of all inpatient and outpatient surgeries for POP and SUI in California. METHODS: We reviewed a record of all inpatient and outpatient POP and SUI surgeries performed in California in 2008 using data from the Office of Statewide Health Planning (OSHPD). RESULTS: In 2008, 20,004 and 20,330 women in California underwent POP and SUI procedures, respectively. Of these, 3,134 (15.6%) and 9,016 (44.3%) were performed in an outpatient setting. The age-adjusted rates of POP and SUI were 1.20 and 1.20 per 1,000 US females, respectively. This correlates to 186,000 POP and 186,000 SUI procedures per year nationally. Vaginal apical suspensions were more common in those undergoing surgery as an inpatient (45.1 vs 19.4%). The use of mesh to augment prolapse repairs was similar (22.3% inpatient vs 19.3% outpatient). SUI procedures performed in the outpatient setting were more likely to be performed as stand-alone procedures (82.9 vs 18.8%, respectively). CONCLUSIONS: In California, 16% of POP and 44% of SUI procedures were performed in an outpatient surgical setting in 2008. Epidemiologic studies of POP and SUI should account for the fact that a substantial number of repairs are performed in the outpatient setting in order to achieve accuracy.

Long-term effects of vaginal surgery and endogenous ovarian hormones on the vagina and bladder.

Background: Surgery is a common treatment for pelvic organ prolapse (POP); however, risk of recurrence and reoperation is high, resulting in a negative impact on quality of life and sexual function. Aim: To examine the long-term effects of POP surgery and endogenous circulating ovarian hormones on the vagina and bladder. Methods: Our animal model simulated surgical injury of the vagina and bladder during POP surgery. Female Rowett nude rats were divided into 4 groups: intact control (IC), vaginal surgery only (V), ovariectomy only (O), and ovariectomy + vaginal surgery (OV). Rats were euthanized 10 weeks postsurgery. Proximal vagina and bladder dome/trigone underwent (1) organ bath myography to assess smooth muscle contractility; (2) real-time quantitative polymerase chain reaction to quantify mRNA expression of elastin, collagen I and III, and PGP9.5 (protein gene product 9.5); (3) enzyme-linked immunosorbent assay for protein quantification of elastin and collagen I and III; and (4) hematoxylin-eosin/immunohistochemistry staining. Outcomes: The primary outcome was tissue contractility as measured by organ bath myography. Secondary outcomes included gene and protein expression of collagen I and III and elastin. Results: O and OV showed reduced vaginal wall contractility vs IC and V (P < .002). Bladder dome and trigone displayed different contractile patterns, with significant differences between O and OV (P < .05), suggesting a negative effect from surgery rather than ovariectomy. OV demonstrated consistent reductions in contractility and elastin/collagen protein expression for the vagina and bladder vs IC. V had similar contractility and increased collagen I expression vs IC, suggesting a protective effect of ovarian hormones. Vaginal epithelium thinning was confirmed in the ovariectomized groups (P = .001), although there was no statistical significance in muscularis thinning with surgery or ovariectomy. O, V, and OV showed significant downregulation of PGP9.5 mRNA expression vs IC. Clinical Translation: These data allow researchers to gain insights into the long-term effects of surgery and deprivation of ovarian hormones. Future studies can use this animal model to investigate other mechanisms that may affect long-term tissue changes due to surgical intervention. Strengths and Limitations: Major strengths are long-term data on the effects of POP surgery and development of an animal model for future studies. However, the animal model limits our ability to extrapolate to humans, where tissue healing is modulated by many factors. Conclusion: Our animal model provides evidence that ovarian hormone deprivation and POP surgery result in negative long-term effects on tissue function and extracellular matrix.

Biomechanical properties and associated collagen composition in vaginal tissue of women with pelvic organ prolapse.

PURPOSE: The pelvic tissue of women with pelvic organ prolapse is stiffer than that of controls but there are scant data on the collagen composition that corresponds to these mechanical properties. We evaluated human vaginal wall stiffness using the novel scanning haptic microscope and correlated these measurements to collagen expression in women with and without pelvic organ prolapse. In this simultaneous biomechanical and biochemical assessment we evaluated the usefulness of this measurement technology for pelvic floor disorder research and confirmed an association between mechanical properties and composition. MATERIALS AND METHODS: The elastic constant (a measure of stiffness) of vaginal wall tissue was measured with the scanning haptic microscope. Protein expression of collagen types I and III of the same tissues were determined by Western blot. The Student t test was used for comparisons between groups. RESULTS: The anterior and posterior vaginal walls of premenopausal and postmenopausal women with pelvic organ prolapse were significantly stiffer than those of controls (p <0.05). Collagen III protein expression in the anterior vaginal wall in the control group was higher than in menopausal women. Collagen I expression was not significantly different between controls and cases. CONCLUSIONS: The scanning haptic microscope produced reliable mechanical measurements in small tissue samples without tissue destruction. Vaginal wall tissues are stiffer in women with pelvic organ prolapse than in controls. This vaginal wall stiffness was associated with lower protein expression of collagen III in the vaginal wall compared to that in asymptomatic controls.

Robot-assisted versus open sacrocolpopexy: a cost-minimization analysis.

PURPOSE: Abdominal sacrocolpopexy is considered a standard of care operation for apical vaginal vault prolapse repair. Using outcomes at our center we evaluated whether the robotic approach to sacrocolpopexy is as cost-effective as the open approach. MATERIALS AND METHODS: After obtaining institutional review board approval we performed cost-minimization analysis in a retrospective cohort of patients who underwent sacrocolpopexy at our institution between 2006 and 2010. Threshold values, that is model variable values at which the most cost effective approach crosses over to an alternative approach, were determined by testing model variables over realistic ranges using sensitivity analysis. Hospital billing data were also evaluated to confirm our findings. RESULTS: Operative time was similar for robotic and open surgery (226 vs 221 minutes) but postoperative length of stay differed significantly (1.0 vs 3.3 days, p <0.001). Base case analysis revealed an overall 10% cost savings for robot-assisted vs open sacrocolpopexy ($10,178 vs $11,307). Tornado analysis suggested that the number of institutional robotic cases done annually, length of stay and cost per hospitalization day in the postoperative period were the largest drivers of cost. Analysis of our hospital billing data showed a similar trend with robotic surgery costing 4.2% less than open surgery. CONCLUSIONS: A robot-assisted approach to sacrocolpopexy can be equally or less costly than an open approach. This depends on a sufficient institutional robotic case volume and a shorter postoperative stay for patients who undergo the robot-assisted procedure.

The effect of raloxifene, a SERM, on extracellular matrix protein expression of pelvic fibroblasts.

INTRODUCTION AND HYPOTHESIS: We hypothesize that the abnormal extracellular matrix (ECM) turnover in pelvic tissues of women with prolapse may be attenuated by raloxifene. We examine the effect of raloxifene on ECM protein expression in pelvic fibroblasts. METHODS: Pelvic fibroblasts were isolated from cases (N = 6) and controls (N = 3). Cells were treated with raloxifene. Dose-response analyses were performed by ANOVA. mRNA and protein expression of collagen I, III, MMPs, and TIMPs were determined by RT-PCR and Western blot. MMP activity was analyzed by zymography. RESULTS: The mRNA expression of TIMP-3 and protein expression of TIMP-1 and TIMP-3 were significantly increased by raloxifene in fibroblasts from both cases and controls (P < 0.05). Collagen I, III, and MMP mRNA and protein expressions were not affected. CONCLUSIONS: Raloxifene selectively attenuates abnormal matrix degradation by increasing inhibitors of proteases, TIMPs, in pelvic fibroblasts. This opens the possibility for SERMs to be used as preventive therapy for pelvic floor disorders.