Perioperative Behavioral Therapy and Pelvic Muscle Strengthening Do Not Enhance Quality of Life After Pelvic Surgery: Secondary Report of a Randomized Controlled Trial

Abstract

Background

There is significant need for trials evaluating the long-term effectiveness of a rigorous program of perioperative behavioral therapy with pelvic floor muscle training (BPMT) in women undergoing transvaginal reconstructive surgery for prolapse.

Objective

The purpose of this study was to evaluate the effect of perioperative BPMT on health-related quality of life (HRQOL) and sexual function following vaginal surgery for pelvic organ prolapse (POP) and stress urinary incontinence (SUI).

Design

This study is a secondary report of a 2 × 2 factorial randomized controlled trial.

Setting

This study was a multicenter trial.

Participants

Participants were adult women with stage 2–4 POP and SUI.

Intervention

Perioperative BPMT versus usual care and sacrospinous ligament fixation (SSLF) versus uterosacral ligament suspension (ULS) were provided.

Measurements

Participants undergoing transvaginal surgery (SSLF or ULS for POP and a midurethral sling for SUI) received usual care or five perioperative BPMT visits. The primary outcome was change in body image and in Pelvic Floor Impact Questionnaire (PFIQ) short-form subscale, 36-item Short-Form Health Survey (SF-36), Pelvic Organ Prolapse-Urinary Incontinence Sexual Questionnaire short form (PISQ-12), Patient Global Impression of Improvement (PGII), and Brink scores.

Results

The 374 participants were randomized to BPMT (n = 186) and usual care (n = 188). Outcomes were available for 137 (74%) of BPMT participants and 146 (78%) of the usual care participants at 24 months. There were no statistically significant differences between groups in PFIQ, SF-36, PGII, PISQ-12, or body image scale measures.

Limitations

The clinicians providing BPMT had variable expertise. Findings might not apply to vaginal prolapse procedures without slings or abdominal apical prolapse procedures.

Conclusions

Perioperative BPMT performed as an adjunct to vaginal surgery for POP and SUI provided no additional improvement in QOL or sexual function compared with usual care.

Conservative therapy including pelvic floor muscle exercises, biofeedback, and lifestyle/behavioral interventions are effective for many pelvic symptoms, including urinary incontinence and mild to moderate prolapse.^1–4 However, pelvic surgeons do not routinely offer perioperative pelvic floor muscle training to women undergoing surgery to correct pelvic organ prolapse and/or stress urinary incontinence (SUI) due to lack of robust clinical data supporting the practice.⁵ Evidence is similarly limited for men, as two recent systematic reviews were either unable to show a sustained benefit of physical therapy to prevent postprostatectomy urinary incontinence⁶ or were unable to conclude whether physical therapy helped with prevention or treatment.⁷ In women, a 2011 Cochrane review² as well as a review by Li et al¹ in 2016 concluded that while physical therapy improved both prolapse symptoms and physical examinations, findings regarding physical therapy in the context of surgery were inconclusive because of variability in outcome measures¹ and limited data in large, well-designed prospective trials.² In particular, Hagen and Stark² noted that trials were particularly needed to evaluate the potential long-term effectiveness of a rigorous program of perioperative behavioral therapy with pelvic floor muscle training (BPMT) at the time of prolapse repair surgery.

The purpose of this report is to evaluate the effect of perioperative BPMT on health-related quality of life (HRQOL) and sexual function over 24 months after prolapse and incontinence surgery in women undergoing surgery as part of the Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) trial. The primary outcomes of this factorial randomized trial in 374 women have been previously reported.⁸ Briefly, (1) 2 years after surgery, prolapse and incontinence outcomes were similar for uterosacral and sacrospinous ligament vaginal vault suspension procedures and (2) perioperative BPMT did not improve urinary outcomes at 6 months or prolapse outcomes at 2 years. Interest remains, however, in other measures of quality of life (QOL) after prolapse surgery, such as body image and sexual function. A single-center randomized trial in 57 women comparing pelvic floor physical therapy to no treatment following vaginal reconstructive surgery showed improved muscle function in the women receiving the additional therapy but failed to show improvements in pelvic floor QOL or sexual function beyond that realized after surgery alone.⁹ We sought to investigate these measures in a larger population. Our hypothesis for this report is that rigorous perioperative BPMT will improve QOL and satisfaction, body image, and sexual function outcomes in women undergoing vaginal surgery for prolapse and SUI.

Methods

Design Overview

The details of the methods of the OPTIMAL trial have been published previously.¹⁰ Briefly, this was a multicenter, randomized clinical trial of women with pelvic organ prolapse (POP) and SUI with a 2 × 2 factorial design comparing two vaginal prolapse surgical procedures, sacrospinous ligament fixation (SSLF) and uterosacral ligament suspension (ULS), and assessing the effect of perioperative BPMT versus usual care.

Setting and Participants

This trial was conducted between January 2008 and May 2013 at nine sites of the National Institutes of Health (NIH)–sponsored Pelvic Floor Disorders Network. Institutional review boards at each network site provided protocol approval and each participant provided informed consent to participate. Women 18 years of age and older planning vaginal surgery for POP and SUI were recruited to the study. To be eligible for the trial, a woman was required to have (1) vaginal bulge symptom and SUI symptoms reported on the Pelvic Floor Distress Inventory (PFDI),^11,12 (2) Pelvic Organ Prolapse Quantification (POPQ)¹² stage 2–4 prolapse (vaginal or uterine descent 1 cm proximal to the hymen or beyond), (3) descent of the vaginal apex at least halfway into the vagina per the POPQ, and (4) confirmation of SUI by examination or urodynamic stress test in the previous 12 months.

Randomization and Interventions

Each participant underwent two separate randomizations: (1) perioperative BPMT or usual perioperative care (stratified by clinical site) and (2) SSLF or ULS (stratified by surgeon and concomitant hysterectomy). Participants were assigned to one of the two groups for each intervention with equal probability using a random permuted block design generated by the Data Coordinating Center (DCC). The DCC provided the randomization allocation in two sequentially numbered, sealed, opaque envelopes: (1) preoperative randomization to BPMT or usual care and (2) randomization in the operating room to SSLF or ULS.

Details of the surgical interventions have been described previously.^8,10 Participants underwent transvaginal prolapse surgery with either SSLF or ULS for suspension of the vaginal apex. Participants also underwent placement of a midurethral sling (Tension-Free Vaginal Tape [TVT], Ethicon Women's Health and Urology, Somerville, NJ)] to treat SUI. The BPMT intervention was standardized via a centralized training program for clinicians. This required program included didactic lectures, problem-oriented case discussions, and certification in the conduct of participant visits by direct observations of structured role-play. The clinician group comprised one-third physical therapists and two-thirds certified advance practice nurses, all with 5–25 years of experience in urogynecology or female pelvic floor practice. These centrally trained BPMT clinicians were masked to surgical randomization. The BPMT intervention consisted of five in-person visits in the office setting, including one preoperative visit 2–4 weeks prior to surgery and 4 postoperative visits (2, 4–6, 8, and 12 weeks after surgery) with pelvic floor muscle examination and training, individualized progressive pelvic floor muscle exercise, and education on behavioral strategies to reduce urinary and colorectal symptoms. These behavioral strategies included one-on-one in-person instructions on ways to prevent or reduce urinary incontinence, obstructed defecation or voiding dysfunction such as proper toileting posture and muscular relaxation during defecations, etc. Usual perioperative care included the routine perioperative instructions used at each clinical site (instructions such as diet, postoperative pain medications, and lifting restrictions), and all participants received these instructions. Education on the above behavioral strategies and pelvic floor muscle exercises for POP or urinary incontinence was not included in usual perioperative care.

Adherence to the program was assessed at each postoperative visit, when participants completed an exercise and behavioral adherence questionnaire to determine the number of exercises participants performed daily and whether they encountered any barriers that interfered with exercise and implementation of behavioral strategies. At all but the 2-week postoperative visit, the clinician performed vaginal palpation to confirm correct contraction. The clinician then used this information to guide treatment progression. At the 2-, 4- to 6-, and 8-week postoperative visits the clinician adjusted the participant's exercise regimen by gradually increasing the number (maximum 45–60 per day) and intensity (maximum 10 seconds) of each contraction. At the 3-month postoperative visit, the clinician provided the participant with a maintenance program of 15 contractions per day at the maximum contraction duration achieved during the study period. To promote adherence during the 24-month follow-up period, the clinician mailed a quarterly flyer to the BPMT participants detailing the exercise regimen and encouraging exercise and behavioral strategy adherence. Data collection occurred in person, as well via telephone calls from an interviewing center to assess QOL, at regular intervals up to 24 months postoperatively, with POPQ evaluations and symptom assessments occurring at 6, 12, and 24 months.¹⁰ Further information can be found online.¹³

Outcomes and Follow-up

The primary outcomes of the OPTIMAL trial were previously published.⁸ This report is a planned secondary analysis described in detail in that report, focusing on the impact of BPMT compared to usual perioperative care on Brink scores, HRQOL, and sexual function over the short- and long-term postoperative period. For this analysis we assessed participant-reported outcomes prior to surgery and again at 6, 12, and 24 months postoperatively and compared participants undergoing BPMT to those assigned to usual perioperative care. Change scores were calculated as (postoperative − baseline) scores. Validated questionnaires included both generic (36-item Short-Form Health Survey [SF-36])¹⁴ and condition-specific (Pelvic Floor Impact Questionnaire [PFIQ] subscales for urinary [UIQ], prolapse [POPIQ], and colorectal [CRAIQ] impact)¹² HRQOL, sexual function (Pelvic Organ Prolapse Urinary Incontinence Sexual Questionnaire [PISQ-12]),¹⁵ and normalized body image questionnaires.^16,17 Patient Global Impression of Improvement (PGII) was assessed.^18,19 We measured the Brink score at baseline and the change from baseline. The Brink score is assessed during digital pelvic examination and measures a 4-point scale in each of three categories: contraction pressure, vertical displacement of the examiner's fingers, and duration of contraction, for a total score of 0–12.²⁰ We also assessed adherence to the BPMT program, as described above, and dyspareunia and associated treatment. Dyspareunia after surgery was assessed using the question: “Have you undergone any treatment for painful or difficult intercourse because your vagina was too narrow or too tight?”

Statistical Analysis

Statistical analysis was performed for all participants who underwent randomization for both the BPMT intervention and the surgical intervention, and participants were analyzed in the groups to which they were randomized. All statistical analyses were conducted using SAS version 9.3 (SAS Institute, Cary, NC). Baseline characteristics were compared between BPMT treatment groups using general linear models for continuous outcomes and generalized linear models for categorical outcomes. Baseline models included variables for surgical group, BPMT treatment assignment, and their interaction. Continuous outcomes were compared between BPMT groups using general linear models that included terms for BPMT treatment assignment, surgical group, and their interaction, as well as the stratification factor of clinical site. Statistical significance was determined using a P value of less than .05 and clinically meaningful difference was defined as exceeding published minimum important differences of 2 to 3 for SF-36, 16 for UIQ, 18 for CRAIQ, and 6 for PISQ-12.^14,21–23 As there are no published minimum important differences for the POPIQ or body image scale, clinically meaningful changes in these scores were assessed using half the baseline standard deviation as a conservative estimate of minimum important difference (34.3 for POPDI, 48.4 for POPIQ, and 13.0 for body image).²⁴ Categorical outcomes were analyzed using analogous generalized linear models. For outcomes for which data were available at multiple time points, a longitudinal extension to the models that included terms for time as a categorical variable was used and tests comparing the BPMT groups at each time point were conducted. Longitudinal models additionally included interactions between the BPMT and surgical treatments and time. When the P value for the treatment interaction was less than .05, BPMT groups were compared within each surgical group; otherwise, marginal effects of the BPMT treatment groups were compared.

Results

From March 2008 to March 2011, 418 eligible women were enrolled in the OPTIMAL trial. A total of 408 were randomized to BPMT (200) or usual care (208); 374 participants were later randomized to ULS or SSLF (186 participants in the BPMT group and 188 in the usual care group). After randomization, similar numbers withdrew from the study in the BPMT group (18%) and in the usual care group (13%) during the 24-month follow-up period (P = .15; Fig. 1). There were no significant differences between groups regarding subjects who withdrew after randomization. The full CONSORT diagram for the OPTIMAL study has been previously published.⁸ The proportions of participants with completed questionnaires and POPQ outcomes at 24 months were similar between the two groups (137 [74%] BPMT, 146 [78%] usual care; Fig. 1).

Figure 1.

Disposition by treatment group. POP-Q = Pelvic Organ Prolapse Quantification System, QOL = quality of life, RCT = randomized controlled trial. ^aP = .22. ^bP = .15. ^sP = .35.

Demographic and baseline characteristics did not differ between randomized groups. The majority of participants were White/Caucasian (84%) and postmenopausal (66%) with a mean age of 57 years. Twenty-seven percent had a previous hysterectomy and 7% had a prior surgery for POP. On preoperative physical examination most participants had POPQ Stage III (57%) or Stage II (39%). Preoperatively 22% of participants reported that they regularly performed pelvic muscle exercises (PMEs) while 4% reported participating in a supervised PME program.⁸

An equal number of participants were assigned to each surgical group: ULS (49.7%) or SSLF (49.7%). All but two participants received an apical suspension (99.5%). Concomitant surgical procedures were TVT (99%), hysterectomy (72%), anterior repair (60%) and posterior repair (51%). Surgical procedures were similar between the randomized groups. As shown in Figure 2, no statistically significant UIQ, POPIQ, or CRAIQ differences were noted between the BPMT and usual care groups at all time points, despite clinically meaningful improvements in those QOL measures at 6 months postoperatively that were generally sustained over baseline at 24 months. Similarly, normalized body image scores were not significantly different between groups throughout the study time points. These patterns were also noted for other QOL scales. As shown in Figure 3, there were no differences in PISQ-12 sexual function scores between groups at any point throughout the study, despite clinically and statistically significant improvements at 6 months that were maintained through 24 months compared with baseline. General QOL as measured by SF-36 summary measures of Physical Component Summary and Mental Component Summary also was not significantly different between the BPMT and usual care groups (Fig. 3). PGII scores remained high, again with no differences between treatment groups. At 6 months after surgery, 64.5% of participants in the BPMT group rated themselves as “very much better” or “much better” versus 63.8% in the usual care group (P = .8). Results were similar at 24 months (55.4% versus 55.1%, respectively; P = .65)

Figure 2.

Results summary: no significant differences were shown between the BPMT and UC groups at any time point to 24 months. Figures (a)–(d) denote scales with negative change indicating improvement. BI = body image, BPMT = perioperative behavioral therapy with pelvic floor muscle training, CRAIQ = Colorectal-Anal Impact Questionnaire, POPIQ = Pelvic Organ Prolapse Incontinence Questionnaire, UC = usual care, UIQ = Urinary Incontinence Questionnaire.

Figure 3.

Results summary: no significant differences were shown between the BPMT and UC groups at any time point to 24 months. Figures (a)–(c) denote scales with positive change indicating improvement. BPMT = perioperative behavioral therapy with pelvic floor muscle training, MCS = Mental Component Summary, PCS = Physical Component Summary, PISQ = Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, UC = usual care.

Several participant-reported outcomes had statistically significant interactions between the BPMT and surgical interventions groups, but these observations were isolated, did not conform to any pattern, and did not suggest any difference between the BPMT and usual care groups at 24 months (data not shown).

Self-reported adherence to exercise in the BPMT group was good at 12 (86%) and 24 months (81%). Nonetheless, Brink scores at baseline did not differ between groups (8.0 [1.7] for BPMT vs. 7.9 [2.2] for usual care; P = nonsignificant) and did not change meaningfully over the course of the study.

Treatment for dyspareunia was infrequent and did not differ by treatment group (5 [3%] BPMT, 5 [3%] usual care; P = .69). Adverse and serious adverse events were not different between the two treatment groups and none were related to the BPMT intervention.⁸

Discussion

The primary analysis of this trial concluded that a multicomponent, perioperative BPMT program did not enhance urinary or prolapse outcomes (either anatomic or symptomatic) in women treated surgically for both prolapse and SUI using a vaginal approach. This secondary analysis suggests that perioperative intervention via BPMT also does not improve generic and condition-specific QOL, sexual function, or body image more than usual care. These results suggest that the addition of a perioperative BPMT program may have little additional benefit in women undergoing vaginal surgery for stage 2–4 POP and SUI and therefore our findings do not support routine perioperative BPMT. Surgery for POP and SUI by itself substantially improves incontinence and prolapse symptoms and their impact on HRQOL. The high efficacy rates of surgery (demonstrated in the primary OPTIMAL report⁸ as well as a related article detailing QOL improvements after surgery in this trial²⁵) may overwhelm any additional benefit derived from BPMT.

The findings of our study can be compared with four smaller studies that evaluated pre- and postoperative physiotherapy-supervised pelvic floor muscle training prior to vaginal surgery for POP and incontinence.^9,26,27 In one pilot study (n = 51), Frawley et al²⁶ found no significant effects of pelvic floor muscle training for women undergoing vaginal surgery for prolapse or hysterectomy at 12 months. Similarly, Pauls et al⁹ demonstrated significant improvement in HRQOL in women undergoing POP surgery, with initial benefit of perioperative pelvic muscle exercises at 3 months but no additional benefit at 6 months after surgery. In another recent pilot study (n = 57), McClurg et al²⁷ found statistically significant improvements in POP symptoms with pre- and postoperative pelvic floor muscle training as compared with usual care in women undergoing vaginal surgery for prolapse at 12 months, but it is unclear if these improvements reached a level that is clinically significant. Jarvis et al²⁸ reported that perioperative physiotherapy improved outcomes 3 months after surgery for prolapse and/or incontinence, with significant group differences in urinary symptoms, QOL, pelvic floor muscle strength, and voiding frequency. One potential difference that may impact outcomes in these smaller trials is the training of BPMT clinicians. The McClurg et al and Jarvis et al interventions were implemented by established physical therapists, whereas our trial provided centralized training for clinicians with varying degrees of BPMT experience. However, in our current study, only those certified based on rigorous in-person testing were allowed to participate as BPMT clinicians. This may in fact increase the generalizability of our findings, as highly experienced pelvic floor physical therapists may not be widely geographically available. Furthermore, the duration of follow-up after a surgical intervention may be important, as while some initial perception of benefit may occur over the immediate postoperative period, our study is consistent with most of the above referenced studies. Of the four studies cited, all four noted significant improvements in prolapse symptoms after surgical repair while three of the four found no significant benefit for their programs of pelvic floor muscle training at 6 months postoperatively.

The strengths of the current study include the randomized controlled design, multisite approach, centralized training for the BPMT intervention, good self-reported adherence rates to the intervention, no differences in dropout rates for the two groups at 12 and 24 months, and validated outcome measures obtained by study personnel masked to treatment assignment. In addition, the BPMT intervention was individualized according to a standard protocol and consisted of multiple components, including strategies for stress and urge incontinence, recommendations for normal voiding and defecation techniques, healthy bladder and bowel habits, and ongoing reinforcement of functional bracing (pelvic floor contraction during lifting and physical activity) to protect the surgical repair and the pelvic floor long term. Our findings may be limited by the numbers of highly experienced BPMT clinicians with various levels of clinical expertise at each participating clinical site and any variability in BPMT practice between sites over the course of the study. We do think these limitations were minimized by the generally high level of urogynecologic clinical experience, rigorous initial certification, and subsequent regular telephone conferencing among the clinician team. Finally, our findings may not apply to women undergoing vaginal prolapse surgery without concomitant urinary incontinence surgery or those undergoing abdominal prolapse surgeries such as sacrocolpopexy.

Our findings do not support a routine practice of perioperative BPMT for women undergoing vaginal surgery for stage 2–4 POP and SUI to improve symptoms or QOL. However, it is important to assess symptoms and their impact on QOL in the postoperative period and offer individualized treatment, including behavioral or physical therapy, to women who report new or unresolved symptoms following surgery.

Author Contributions and Acknowledgments

Concept/idea/research design: M.D. Barber, M.G. Gantz, A. Markland, and S. Meikle

Writing: M.D. Barber, K.Y. Dyer, M.G. Gantz, A. Markland, S. Meikle, E.R. Mueller, D.D. Rahn, L.K. Warren, and A.C. Weidner

Data collection: M.D. Barber, M.G. Gantz, S. Meikle, D.D. Rahn, and A.C. Weidner

Data analysis: A. Markland, M.G. Gantz, S. Meikle, E.R. Mueller, L.K. Warren, and A.C. Weidner

Project management: M.D. Barber, S. Meikle, and A.C. Weidner

Fund procurement: S. Meikle

Providing participants: K.Y. Dyer, Y. Hsu, S. Jakus-Waldman, A. Markland, E.R. Mueller, D.D. Rahn, and A.C. Weidner

Providing facilities/equipment: E.R. Mueller and A.C. Weidner

Providing institutional liaisons: Y. Hsu, S. Meikle, E.R. Mueller, and A.C. Weidner

Consultation (including review of the manuscript before submitting): S. Jakus-Waldman, A. Markland, S. Meikle, E.R. Mueller, and A.C. Weidner

The Eunice Kennedy Shriver National Institute of Child Health and Human Development project scientist for the Pelvic Floor Disorders Network, Anne Weber, MD, had a role in the study design. S. Meikle became the project scientist just as the study was initiated and had a role in the conduct of the study; the collection, analysis, and interpretation of the data; and the preparation, review, and approval of the manuscript.

In addition to the authors, the following members of the Pelvic Floor Disorders Network (PFDN) participated in the Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) trial:

RTI International, Research Triangle Park, North Carolina (PFDN Data Coordinating Center, July 1, 2011–present): Dennis Wallace, Kevin A. Wilson, Daryl Matthews, Tamara L. Terry, Jutta Thornberry, Amanda Youmans-Weisbuch, Ryan E. Whitworth, and Michael P. Hieronymus.

University of Michigan, Ann Arbor, Michigan (PFDN Data Coordinating Center, until July 1, 2011): Morton Brown, Nancy Janz, John Wei, Xiao Xu, Beverley Marchant, Donna DiFranco, Yang Casher, Kristina Slusser, and Zhen Chen.

Cleveland Clinic, Cleveland, Ohio: Mark D. Walters, J. Eric Jelovsek, Marie F. R. Paraiso, Beri M. Ridgeway, Ly Pung, Cheryl Williams, Linda McElrath, Betsy O’Dougherty, Megan Edgehouse, Gouri Diwadkar, and Anna Frick.

Loyola University, Chicago, Illinois: Linda Brubaker, Mary Tulke, Kimberly Kenton, Kathleen Jesse.

University of California, San Diego, Health Systems: Charles W. Nager, Michael E. Albo, Cara Grimes, Heidi W. Brown, Anna C. Kirby, Leah Merrin, JoAnn Columbo, and Nehal Mehta.

Southern California Kaiser Permanente, Downey, California: Mercedes Cardona and Eudocia Zapata.

Southern California Kaiser Permanente, San Diego, California: Shawn Menefee, Emily L. Whitcomb, Karl M. Luber, Jasmine Tan-Kim, Gouri B. Diwadkar, Lynn M. Hall, Linda M. Mackinnon, and Gisselle Zazueta-Damian.

University of Utah, Salt Lake City, Utah: Peggy Norton, Yvonne Hsu, Jan Baker, Linda Freedman, Linda Griffin, Maria Masters, Amy Orr, and Kristina Heintz.

University of Alabama, Birmingham, Alabama: Holly Richter, R. Edward Varner, Robert Holley, William J. Greer, L. Keith Lloyd, Tracy S. Wilson, Jonathan L. Gleason, Alicia Ballard, Candace Parker-Autry, Lisa Pair, Velria Willis, Nancy Saxon, Lachele Ward, Kathy Carter, and Julie Burge.

Duke University Medical Center, Durham, North Carolina: Anthony G. Visco, Cindy L. Amundsen, Nazema Y. Siddiqui, Jennifer M. Wu, Mary Raynor, Mary McGuire, and Ingrid Harm-Ernandes.

University of Texas Southwestern Medical Center, Dallas, Texas: Joe Shaffer, Marlene Corton, Clifford Wai, Kelly Moore, Shanna Atnip, Pam Martinez, and Deborah Lawson.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland: Anne Weber (formerly).

PFDN Steering Committee Chair: Katherine Hartmann.

Ethics Approval

Institutional review boards at each network site provided protocol approval and each participant provided informed consent to participate.

Funding

This study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institutes of Health (NIH) Office of Research on Women's Health (U01 HD41249, U10 HD41250, U10 HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10 HD54215, U01 HD069031, and U10 HD54241); S. Meikle was affiliated with the funding source for this study.

Clinical Trial Registration

The trial was registered at ClinicalTrials.gov (registration no. NCT00597935) (http://clinicaltrials.gov/ct2/show/NCT00597935?term=optimal&rank=2).

Disclosure and Presentations

The authors completed the ICJME Form for Disclosure of Potential Conflicts of Interest. M.D. Barber reported having received a research grant from the Foundation for Female Health Awareness and royalties from Up-to-Date and Elsevier. K.Y. Dyer reported having received a research grant from Pelvalon (Sunnyvale, California). No other disclosures were reported.

Portions of this paper were presented at the International Urogynecological Association Annual Meeting, June 12, 2015, in Nice, France, and at the American Urogynecologic Society Annual Meeting, October 13–17, 2015, in Seattle, Washington.