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Success and failure are dynamic, recurrent event states after surgical treatment for pelvic organ prolapse

Published:October 07, 2020DOI:https://doi.org/10.1016/j.ajog.2020.10.009

      Background

      The ideal measure of success after surgery for pelvic organ prolapse has long been debated. Historically, strict definitions based on anatomic perfection have dominated the literature. However, the importance of patient-centered perception of outcomes is equally or more important when comparing the success of various prolapse surgeries. Understanding the limitations of existing outcome definitions will guide surgical outcome reporting and comparisons of pelvic organ prolapse surgeries.

      Objective

      This study aimed to describe the relationships and overlap among the participants who met the anatomic, subjective, and retreatment definitions of success or failure after pelvic organ prolapse surgery; demonstrate rates of transition between success and failure over time; and compare scores from the Pelvic Organ Prolapse Distress Inventory, Short-Form Six-Dimension health index, and quality-adjusted life years among these definitions.

      Study Design

      Definitions of surgical success were evaluated at 3 or 6, 12, 24, 36, 48, and 60 months after surgery for ≥stage II pelvic organ prolapse in a cohort of women (N=1250) from 4 randomized clinical trials conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Surgical failure was defined by a composite measure requiring 1 or more of (1) anatomic failure (Pelvic Organ Prolapse Quantification point Ba, Bp, or C of >0), (2) subjective failure (presence of bothersome vaginal bulge symptoms), or (3) pessary or surgical retreatment for pelvic organ prolapse. Pelvic Organ Prolapse Distress Inventory, Short-Form Six-Dimension health index, and quality-adjusted life years were compared among participants who met a variety of definitions of success and failure including novel “intermittent” success and failure over time.

      Results

      Among the 433 of 1250 women (34.6%) who had surgical failure outcomes at ≥1 time point, 85.5% (370 of 433) met only 1 component of the composite outcome at the assessment of initial failure (anatomic failure, 46.7% [202 of 433]; subjective failure, 36.7% [159 of 433]; retreatment, 2.1% [9 of 433]). Only 12.9% (56 of 433) met the criteria for both for anatomic and subjective failure. Despite meeting the criteria for failure in primary study reporting, 24.2% of these (105 of 433) transitioned between success and failure during follow-up, of whom 83.8% (88 of 105) met the criteria for success at their last follow-up. There were associations between success or failure classification and the 1- and 2-year quality-adjusted life years and a time-varying group effect on Pelvic Organ Prolapse Distress Inventory and Short-Form Six-Dimension health index scores.

      Conclusion

      True failure rates after prolapse surgery may be overestimated in the current literature. Only 13% of clinical trial subjects initially met both subjective and objective criteria for failure. Approximately one-quarter of failures were intermittent and transitioned between success and failure over time, with most intermittent failures being in a state of “surgical success” at their last follow-up. Current composite definitions of success or failure may result in the overestimation of surgical failure rates, potentially explaining, in part, the discordance with low retreatment rates after pelvic organ prolapse surgery.

      Key words

      Introduction

      There is a tremendous variation in reported rates of success after pelvic organ prolapse (POP) surgery.
      • Chmielewski L.
      • Walters M.D.
      • Weber A.M.
      • Barber M.D.
      Reanalysis of a randomized trial of 3 techniques of anterior colporrhaphy using clinically relevant definitions of success.
      • Barber M.D.
      • Brubaker L.
      • Nygaard I.
      • et al.
      Defining success after surgery for pelvic organ prolapse.
      • Kowalski J.T.
      • Mehr A.
      • Cohen E.
      • Bradley C.S.
      Systematic review of definitions for success in pelvic organ prolapse surgery.
      • Meister M.R.
      • Sutcliffe S.
      • Lowder J.L.
      Definitions of apical vaginal support loss: a systematic review.
      This variation results, in part, from the use of multiple definitions and inconsistent guidance from outcomes researchers and professional societies.
      • Kowalski J.T.
      • Mehr A.
      • Cohen E.
      • Bradley C.S.
      Systematic review of definitions for success in pelvic organ prolapse surgery.
      Current recommendations for defining success after POP surgery include reporting subjective and anatomic outcomes and retreatment.
      • Barber M.D.
      • Brubaker L.
      • Nygaard I.
      • et al.
      Defining success after surgery for pelvic organ prolapse.
      ,
      • Kowalski J.T.
      • Mehr A.
      • Cohen E.
      • Bradley C.S.
      Systematic review of definitions for success in pelvic organ prolapse surgery.
      These recommendations emerged from an analysis of 18 different definitions in a single cohort of 322 participants after abdominal sacrocolpopexy using variations of anatomic, symptomatic, or retreatment outcomes.
      • Barber M.D.
      • Brubaker L.
      • Nygaard I.
      • et al.
      Defining success after surgery for pelvic organ prolapse.
      A definition that used the absence of postoperative vaginal bulge symptoms was significantly associated with a patient’s assessment of overall improvement whereas anatomic success alone was not.
      • Barber M.D.
      • Brubaker L.
      • Nygaard I.
      • et al.
      Defining success after surgery for pelvic organ prolapse.
      Although these findings provided useful guidance, the study was limited by small numbers, a single procedure, lack of consideration to the duration women perceived their surgery as successful, and the fact that success after POP surgery may be dynamic over time.

      Why was this study conducted?

      Understanding whether anatomic and subjective outcomes after pelvic organ prolapse surgery are concordant and whether “failure” as a dynamic state should guide future surgical outcome definitions and analyses

      Key findings

      Most initial failures after prolapse surgery meet only one component of a composite definition and one-quarter of “failures” transition during follow-up, with most being in a state of success at their last visit. Women with “intermittent” outcomes report symptoms and quality of life scores in between women with persistent success and persistent failure outcome states.

      What does this add to what is known?

      Composite success definitions and time-to-event analysis methods after prolapse repair may overestimate failure rates and impede true understanding of a woman’s long-term perception of success.
      The first aim of this study was to describe the relationships and overlap among participants who met the anatomic, subjective, and retreatment definitions of success or failure after POP surgery using a larger, more diverse cohort. The second aim was to examine these outcomes longitudinally to determine whether participants transition between success and failure over time. We hypothesized that success after prolapse surgery is a dynamic state: whereas some women achieve and persist in a state of success throughout the duration of follow-up, other women transition between success and failure (“intermittent” success and failure) leading them to be falsely classified as failures in time-to-event analysis methods. A third aim was to compare symptoms and quality of life in patients with “intermittent” success and failure states with those with persistent success or failure.

      Material and Methods

      This was a retrospective analysis of women enrolled in 4 prospective randomized surgical trials for symptomatic stage II to IV POP conducted across 17 centers engaged in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. The design and results of the 4 trials have been published.
      • Nager C.W.
      • Visco A.G.
      • Richter H.E.
      • et al.
      Effect of vaginal mesh hysteropexy vs vaginal hysterectomy With uterosacral ligament suspension on treatment failure in women With uterovaginal prolapse: a randomized clinical trial.
      • Brubaker L.
      • Cundiff G.W.
      • Fine P.
      • et al.
      Abdominal sacrocolpopexy with Burch colposuspension to reduce urinary stress incontinence.
      • Nygaard I.
      • Brubaker L.
      • Zyczynski H.M.
      • et al.
      Long-term outcomes following abdominal sacrocolpopexy for pelvic organ prolapse.
      • Wei J.T.
      • Nygaard I.
      • Richter H.E.
      • et al.
      A midurethral sling to reduce incontinence after vaginal prolapse repair.
      • Barber M.D.
      • Brubaker L.
      • Menefee S.
      • et al.
      Operations and pelvic muscle training in the management of apical support loss (OPTIMAL) trial: design and methods.
      • Jelovsek J.E.
      • Barber M.D.
      • Brubaker L.
      • et al.
      Effect of uterosacral ligament suspension vs sacrospinous ligament fixation with or without perioperative behavioral therapy for pelvic organ vaginal prolapse on surgical outcomes and prolapse symptoms at 5 years in the OPTIMAL randomized clinical trial.
      The Colpopexy and Urinary Reduction Efforts (CARE) trial evaluated the effectiveness of prophylactic Burch cystourethropexy in reducing postoperative de novo stress urinary incontinence in stress-continent women undergoing abdominal sacrocolpopexy between March 2002 and February 2005.
      • Brubaker L.
      • Cundiff G.W.
      • Fine P.
      • et al.
      Abdominal sacrocolpopexy with Burch colposuspension to reduce urinary stress incontinence.
      Those participants who completed a 2-year follow-up were offered enrollment in the extended CARE (e-CARE) study with a follow-up for up to 9 years after surgery.
      • Nygaard I.
      • Brubaker L.
      • Zyczynski H.M.
      • et al.
      Long-term outcomes following abdominal sacrocolpopexy for pelvic organ prolapse.
      The Outcomes Following Vaginal Prolapse Repair and Midurethral Sling (OPUS) trial evaluated the effectiveness of a prophylactic retropubic midurethral sling vs sham in reducing de novo stress urinary incontinence 1 year after surgery in stress-continent women undergoing vaginal prolapse surgery between May 2007 and October 2009.
      • Wei J.T.
      • Nygaard I.
      • Richter H.E.
      • et al.
      A midurethral sling to reduce incontinence after vaginal prolapse repair.
      The OPUS trial also included women who declined to undergo randomization but participated in a patient-preference cohort. The Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) trial evaluated 2-year outcomes in women undergoing native tissue vaginal apical suspension with midurethral sling for symptomatic prolapse and stress urinary incontinence between January 2008 and March 2011.
      • Barber M.D.
      • Brubaker L.
      • Menefee S.
      • et al.
      Operations and pelvic muscle training in the management of apical support loss (OPTIMAL) trial: design and methods.
      Participants were randomized in a 2×2 factorial design to (1) perioperative behavioral therapy with pelvic floor muscle training vs usual care and (2) uterosacral ligament suspension vs sacrospinous ligament suspension. At 2 years, participants were invited to enroll in the extended trial for up to 5 years of follow-up.
      • Jelovsek J.E.
      • Barber M.D.
      • Brubaker L.
      • et al.
      Effect of uterosacral ligament suspension vs sacrospinous ligament fixation with or without perioperative behavioral therapy for pelvic organ vaginal prolapse on surgical outcomes and prolapse symptoms at 5 years in the OPTIMAL randomized clinical trial.
      The Study of Uterine Prolapse Procedures Randomized Trial (SUPeR) compared the efficacy and adverse events of women undergoing vaginal hysterectomy with uterosacral ligament suspension vs transvaginal mesh hysteropexy between April 2013 and February 2015.
      • Nager C.W.
      • Visco A.G.
      • Richter H.E.
      • et al.
      Effect of vaginal mesh hysteropexy vs vaginal hysterectomy With uterosacral ligament suspension on treatment failure in women With uterovaginal prolapse: a randomized clinical trial.
      The primary endpoint was 3 years after the last randomization, and participants were followed up for up to 5 years. All studies received institutional review board approval at each site, and all participants signed a written informed consent.
      The primary outcome for our analyses was surgical success defined as a single composite measure requiring anatomic success, subjective success, and absence of retreatment for POP.
      • Barber M.D.
      • Brubaker L.
      • Nygaard I.
      • et al.
      Defining success after surgery for pelvic organ prolapse.
      Surgical failure was defined as the occurrence of at least 1 of the following: anatomic failure, subjective failure, or retreatment for POP. Anatomic failure was defined as prolapse beyond the hymen (Pelvic Organ Prolapse Quantification [POPQ] point Ba, Bp, or C of >0). Subjective failure was defined as the presence of a bothersome bulge as indicated by an affirmative response to either of the Pelvic Floor Distress Inventory (PFDI or 20-item PFDI [PFDI-20]) questions “Do you usually have a sensation of bulging or protrusion from the vaginal area?” or “Do you usually have a bulge or something falling out that you can see or feel in the vaginal area?” with any degree of bother more than “not at all.” Retreatment included either surgery or pessary. Subjective and anatomic failures could be transient across the visits, but retreatment failure was considered a permanent state of failure. Notably, the composite outcome measure in this analysis slightly differs from those used in the original reports of the OPTIMAL, OPUS, and CARE trials.
      Success and failure outcome definitions were evaluated in this analysis at 3 or 6, 12, 24, 36, 48, and 60 months after surgery as available. Notably, 4 groups were defined based on surgical success and failure states over time. The “persistent success” group met the definition of success at all time points for which the participant had data available, the “persistent failure” group met the definition of failure and their outcomes remained failures at all subsequent visits, and the “intermittent success and failure” group fluctuated between success and failure over time. Participants in the intermittent success and failure group that met the definition of success at their last follow-up were further classified as “terminal success,” and those who met the definition of failure at their last follow-up were labeled “terminal failure.”
      Secondary outcomes included POPQ examinations, Pelvic Organ Prolapse Distress Inventory (POPDI) subscale scores from the PFDI or PFDI-20, and Short-Form Six-Dimension (SF-6D) health index scores. Quality-adjusted life years (QALYs) were calculated using an area under the curve approach following the trapezoidal rule from each subject’s SF-6D index score reported at baseline, 3 or 6 months, 12 months, and 24 months.
      • Glick H.
      • Doshi J.A.
      • Sonnad S.S.
      • Polsky D.
      Economic evaluation in clinical trials.
      • Brazier J.E.
      • Roberts J.
      The estimation of a preference-based measure of health from the SF-12.
      • Brazier J.
      • Roberts J.
      • Deverill M.
      The estimation of a preference-based measure of health from the SF-36.
      POPDI subscale scores, SF-6D scores, and QALYs were compared among participants who met each of the definitions of success and failure over time. Adjusted means, standard errors, and P values for repeated measures outcomes were obtained from general linear mixed models with fixed effects for surgical failure group, visit, and their interaction, and modeling within-subject correlation across visits with an unstructured correlation structure. These modeling methods assumed that missing data were missing at random. This was considered reasonable, particularly because most missing data were caused by differing prespecified lengths of follow-up for the various studies, which was not expected to bias the results. Preoperative risk factors were compared between surgical failure groups using Kruskal-Wallis test for continuous measures and Fisher exact test for categorical measures.

      Results

      Participant flow for the 4 trials is depicted in Figure 1. In summary, 93% of eligible and enrolled participants (1250 of 1337) were included in our analysis: 311 of 322 CARE/e-CARE participants, 414 of 466 OPUS participants, 352 of 374 OPTIMAL/extended OPTIMAL participants, and 173 of 175 SUPeR participants.
      Figure thumbnail gr1
      Figure 1STROBE participant flow
      STROBE, Strengthening the Reporting of Observational studies in Epidemiology.
      Jelovsek et al. Pelvic organ prolapse surgical success and failure states are dynamic. Am J Obstet Gynecol 2021.
      Surgical outcomes and overlap of different definitions of success among all participants at first failure are demonstrated in Figure 2. Among the 433 of 1250 of participants (34.6%) who met the failure criteria at least once during follow-up, at the initial time of failure, 12.9% of participants (56 of 433) met the criteria for both anatomic and subjective failure, and 85.5% (370 of 433) met only 1 component of the composite failure outcome (anatomic failure, 202 of 433 [46.7%]; subjective failure, 159 of 433 [36.7%]; retreatment, 9 of 433 [2.1%]).
      Figure thumbnail gr2
      Figure 2Overlap of surgical outcome definitions at time of initial failure (N=433)
      Jelovsek et al. Pelvic organ prolapse surgical success and failure states are dynamic. Am J Obstet Gynecol 2021.
      Longitudinal patterns of success and failure using the recommended composite definition are demonstrated in Figure 3. Most participants (817 of 1250; 65.4%) met the definition of success at all time points and were classified into the “persistent success” group. Participants that met criteria for failure and stayed in a state of failure, the “persistent failure” group, included 328 of 1250 participants (26.2%). The median time to failure in this group was 1.0 year (interquartile range [IQR], 0.5–2.0 years). The 328 women in the persistent failure group met the criteria for surgical failure at 617 visits as follows: subjective failure only, 199 of 617 (32.3%); anatomic failure only, 234 of 617 (37.9%); and anatomic and subjective failure, 123 of 617 (19.9%). POP retreatment with surgery or pessary occurred in 61 of 328 women (18.6%) in the persistent failure group.
      Figure thumbnail gr3
      Figure 3Dynamic success and failure outcomes after pelvic organ prolapse surgery
      A state of success is indicated by a black circle, state of failure indicated by a red X, and retreatment for pelvic organ prolapse indicated by a blue circle. The top group are the “persistent success” participants who meet the definition of success at all time points. The bottom group are “persistent failures” designated by red X at all follow-up visits. The middle group are participants that move back and forth between success and failure states over the follow-up period.
      Jelovsek et al. Pelvic organ prolapse surgical success and failure states are dynamic. Am J Obstet Gynecol 2021.
      The longitudinal patterns of the “intermittent” success and failures are demonstrated in Figure 4. Despite being considered failures in the primary study analyses using time-to-event methods, 24.2% of participants (105 of 433) who met the criteria for failure transitioned between success and failure during follow-up and 83.8% of these (88 of 105) were successes at their last follow-up (ie, “terminal successes”) whereas 17 of 105 (16.2%) were “terminal failures.” The median time to initial failure for “terminal failures” was 1.0 year (IQR, 0.5–1.0 years), and the median time to initial failure for “terminal successes” was 1.0 year (IQR, 0.5–2.0 years). The intermittent success and failure group had a total of 175 visits with surgical failure as follows: subjective failure only, 97 of 175 (55.4%); anatomic failure only, 69 of 175 (39.4%); and anatomic and subjective failure, 8 of 175 (4.6%). Only 1 of the 105 women in the terminal failure group underwent POP retreatment.
      Figure thumbnail gr4
      Figure 4Intermittent success and failure outcomes after pelvic organ prolapse surgery
      A state of success is indicated by a black circle, state of failure indicated by a red X, and retreatment for pelvic organ prolapse indicated by a blue circle. The top group are the “terminal success” participants who meet the definition of success at the last follow-up visit. The bottom group are “terminal failures” who meet the definition of failure at their last follow-up visit.
      Jelovsek et al. Pelvic organ prolapse surgical success and failure states are dynamic. Am J Obstet Gynecol 2021.
      The characteristics of participants who met the definitions of persistent success, persistent failure, and intermittent failure and success are presented in Table 1. Compared with the persistent success group, women in the intermittent success and failure group were more likely to be obese and to have had any cesarean delivery. They were less likely to be non-Hispanic white, and they had worse baseline POPDI total score and SF-6D index scores. The intermittent success and failure group was also less likely to have undergone abdominal sacral colpopexy.
      Table 1Baseline characteristics of study participants by surgical outcome group
      Odds ratio or location shift and 95% CI (reference=persistent success)
      For categorical measures, odds ratios, 95% CIs, and P values were obtained from Fisher exact test. For continuous measures, P values were obtained using Kruskal-Wallis test and location shift, and 95% CIs were obtained using Wilcoxon rank-sum test with a Hodges-Lehmann estimation of location shift. All tests were conducted at a significance level of .05 and no adjustments for multiple comparisons were made
      CharacteristicPersistent failure (n=328)Intermittent failure and success (n=105)Persistent success (n=817)P value
      For categorical measures, odds ratios, 95% CIs, and P values were obtained from Fisher exact test. For continuous measures, P values were obtained using Kruskal-Wallis test and location shift, and 95% CIs were obtained using Wilcoxon rank-sum test with a Hodges-Lehmann estimation of location shift. All tests were conducted at a significance level of .05 and no adjustments for multiple comparisons were made
      Persistent failureIntermittent failure and success
      Baseline characteristics
      Age, y61 (54, 69)60 (54, 70)62 (55, 68).723−0.6 (−1.9 to 0.8)−0.3 (−2.5 to 2.0)
      BMI, kg/m228 (25, 31)29 (26, 33)27 (24, 30)<.0010.8 (0.2–1.4)1.7 (0.8–2.7)
      Obese (BMI of ≥30 kg/m2)101/327 (30.9)44/105 (41.9)220/817 (26.9).0061.2 (0.9–1.6)2.0 (1.3–3.0)
      Non-Hispanic white234/327 (71.6)70/105 (66.7)689/813 (84.7)<.0010.5 (0.3–0.6)0.4 (0.2–0.6)
      Some college or higher179/310 (57.7)53/98 (54.1)485/799 (60.7).3580.9 (0.7–1.2)0.8 (0.5–1.2)
      Married199/311 (64.0)69/99 (69.7)584/798 (73.2).0110.7 (0.5–0.9)0.8 (0.5–1.4)
      Nulliparous3/327 (0.9)3/105 (2.9)13/816 (1.6).3170.6 (0.1–2.1)1.8 (0.3–6.8)
      Any cesarean delivery21/326 (6.4)15/105 (14.3)50/814 (6.1).0151.1 (0.6–1.8)2.5 (1.3–4.8)
      Any vaginal delivery320/327 (97.9)100/105 (95.2)801/816 (98.2).1410.9 (0.3–2.5)0.4 (0.1–1.3)
      Postmenopausal278/328 (84.8)87/105 (82.9)697/817 (85.3).7681.0 (0.7–1.4)0.8 (0.5–1.5)
      Currently using vaginal estrogen82/327 (25.1)29/105 (27.6)237/817 (29.0).4150.8 (0.6–1.1)0.9 (0.6–1.5)
      Previous urinary incontinence surgery13/327 (4.0)8/105 (7.6)33/817 (4.0).2351.0 (0.5–1.9)2.0 (0.8–4.5)
      Previous prolapse surgery46/327 (14.1)19/105 (18.1)143/817 (17.5).3430.8 (0.5–1.1)1.0 (0.6–1.8)
      Previous hysterectomy109/327 (33.3)38/105 (36.2)319/817 (39.0).1910.8 (0.6–1.0)0.9 (0.6–1.4)
      Current smoker24/327 (7.3)5/105 (4.8)49/817 (6.0).5921.2 (0.7–2.1)0.8 (0.2–2.0)
      Diabetes mellitus37/325 (11.4)13/102 (12.7)93/810 (11.5).9191.0 (0.6–1.5)1.1 (0.6–2.1)
      Connective tissue disease6/321 (1.9)1/103 (1.0)6/812 (0.7).2342.6 (0.7–9.6)1.3 (0.0–11.0)
      POPQ measurements
      POPQ Ba3.0 (1.0, 4.0)2.0 (1.0, 4.0)2.0 (1.0, 4.0).0070.5 (0.0–1.0)0.0 (0.0–1.0)
      POPQ Bp−1.0 (−2.0, 1.5)−1.0 (−2.0, 1.0)−1.0 (−2.0, 1.0).6530.0 (0.0–0.0)0.0 (0.0–0.5)
      POPQ C0.0 (−3.0, 4.0)−2.0 (−4.0, 2.5)−1.0 (−4.0, 3.0).0151.0 (0.0–1.0)0.0 (−1.0–0.0)
      POPQ stage 3 or 4
      POPQ stages: stage 2, the vagina is prolapsed between 1 cm above the hymen and 1 cm below the hymen; stage 3, the vagina is prolapsed more than 1 cm beyond the hymen but is less than totally everted; stage 4, the vagina is everted to within 2 cm of its length
      256/328 (78.0)76/105 (72.4)578/817 (70.7).0411.5 (1.1–2.0)1.1 (0.7–1.8)
      Anatomic POP beyond hymen or POP symptoms
      Anatomic POP beyond the hymen is defined as a POPQ point Ba, Bp, or C of >0. POP symptoms is defined as the presence of a bothersome bulge (ie, a positive response to 46-item PFDI 4 and 5 and 20-item PFDI 3 with a degree of bother indicated).
      325/327 (99.4)103/104 (99.0)794/814 (97.5).0854.1 (1.0–36.3)2.6 (0.4–108.6)
      Anatomic POP beyond hymen
      Anatomic POP beyond the hymen is defined as a POPQ point Ba, Bp, or C of >0. POP symptoms is defined as the presence of a bothersome bulge (ie, a positive response to 46-item PFDI 4 and 5 and 20-item PFDI 3 with a degree of bother indicated).
      294/328 (89.6)97/105 (92.4)715/817 (87.5).2821.2 (0.8–1.9)1.7 (0.8–4.2)
      POP symptoms
      Anatomic POP beyond the hymen is defined as a POPQ point Ba, Bp, or C of >0. POP symptoms is defined as the presence of a bothersome bulge (ie, a positive response to 46-item PFDI 4 and 5 and 20-item PFDI 3 with a degree of bother indicated).
      295/313 (94.2)94/99 (94.9)733/797 (92.0)0.3311.4 (0.8–2.6)1.6 (0.6–5.4)
      Surgical repairs
      AAR<.001
       AAR native tissue250/328 (76.2)79/105 (75.2)475/817 (58.1)ReferenceReference
       AAR (mesh or graft)24/328 (7.3)8/105 (7.6)103/817 (12.6)0.4 (0.3–0.7)0.5 (0.2–1.0)
       Abdominal sacral colpopexy (mesh or graft)54/328 (16.5)18/105 (17.1)239/817 (29.3)0.4 (0.3–0.6)0.5 (0.2–0.8)
      PR.257
       Not performed178/327 (54.4)55/105 (52.4)395/816 (48.4)1.3 (1.0–1.7)1.1 (0.7–1.7)
       PR (native tissue)143/327 (43.7)50/105 (47.6)408/816 (50.0)ReferenceReference
       PR (mesh or graft)6/327 (1.8)0/105 (0.0)13/816 (1.6)1.3 (0.4–3.8)0.0 (0.0–2.2)
      Concomitant urinary incontinence surgery (MUS)222/267 (83.1)82/101 (81.2)483/672 (71.9)<.0011.9 (1.3–2.8)1.7 (1.0–3.0)
      Concomitant hysterectomy203/328 (61.9)61/105 (58.1)425/817 (52.0).0081.5 (1.1–2.0)1.3 (0.8–2.0)
      Patient-reported outcomes (baseline)
      SF-6D index score0.7 (0.6, 0.8)0.6 (0.6, 0.8)0.7 (0.6, 0.8).001−0.0 (−0.0 to 0.0)−0.1 (−0.1 to −0.0)
      SF-6D physical function score2.0 (2.0, 3.0)3.0 (2.0, 4.0)2.0 (2.0, 3.0).0040.0 (0.0–0.0)0.0 (0.0–1.0)
      SF-6D role limitation score2.0 (1.0, 4.0)3.0 (2.0, 4.0)2.0 (1.0, 4.0).0310.0 (0.0–0.0)0.0 (0.0–0.0)
      SF-6D social function score2.0 (1.0, 3.0)2.0 (1.0, 3.0)1.0 (1.0, 2.0)<.0010.0 (0.0–0.0)0.0 (0.0–0.0)
      SF-6D pain score3.0 (2.0, 4.0)3.0 (2.0, 4.0)3.0 (2.0, 4.0).0250.0 (0.0–0.0)0.0 (0.0–1.0)
      SF-6D mental health score2.0 (2.0, 3.0)2.0 (2.0, 3.0)2.0 (1.0, 3.0).0040.0 (0.0–0.0)0.0 (0.0–1.0)
      SF-6D vitality score3.0 (2.0, 3.0)3.0 (2.0, 4.0)3.0 (2.0, 3.0).1060.0 (0.0–0.0)0.0 (0.0–0.0)
      POPDI total score92.9 (56.5, 153.0)105.4 (54.2, 152.4)80.4 (45.2, 131.5)0.00211.9 (3.6–19.6)17.3 (4.8–30.4)
      Data are presented as median (P25, P75) for continuous measures and n/N (percentage) for categorical measures unless otherwise specified.
      AAR, anteroapical pelvic organ prolapse repair; BMI, body mass index; CI, confidence interval; MUS, midurethral sling; P25, 25th percentile; P75, 75th percentile; PFDI, Pelvic Floor Distress Inventory; POP, pelvic organ prolapse; POPDI, Pelvic Organ Prolapse Distress Inventory; POPQ, Pelvic Organ Prolapse Quantification; PR, posterior pelvic organ prolapse repair; SF-6D, Short-Form Six-Dimension.
      Jelovsek et al. Pelvic organ prolapse surgical success and failure states are dynamic. Am J Obstet Gynecol 2021.
      a For categorical measures, odds ratios, 95% CIs, and P values were obtained from Fisher exact test. For continuous measures, P values were obtained using Kruskal-Wallis test and location shift, and 95% CIs were obtained using Wilcoxon rank-sum test with a Hodges-Lehmann estimation of location shift. All tests were conducted at a significance level of .05 and no adjustments for multiple comparisons were made
      b POPQ stages: stage 2, the vagina is prolapsed between 1 cm above the hymen and 1 cm below the hymen; stage 3, the vagina is prolapsed more than 1 cm beyond the hymen but is less than totally everted; stage 4, the vagina is everted to within 2 cm of its length
      c Anatomic POP beyond the hymen is defined as a POPQ point Ba, Bp, or C of >0. POP symptoms is defined as the presence of a bothersome bulge (ie, a positive response to 46-item PFDI 4 and 5 and 20-item PFDI 3 with a degree of bother indicated).
      Adjusted associations between success or failure group and patient-reported outcomes by year of follow-up are presented in Table 2. There were associations between success or failure group and the 1- and 2-year QALYs and a time-varying group effect on POPDI, SF-6D index, and each of the subscales except social function and mental health. Women with intermittent success and failure had mean POPDI scores in between those meeting persistent failure and persistent success definitions at each year of follow-up.
      Table 2Adjusted analyses of quality of life outcomes by surgical outcome group
      Outcome measuresPersistent failure (n=328)Intermittent success and failure (n=105)Persistent success (n=817)P value
      Adjusted means, standard errors, and P values for repeated measures outcomes were obtained from general linear models adjusting for surgical outcome group, visitb, and interaction between surgical outcome group and visit while controlling for within-subject correlation across visits with an unstructured working correlation structure. Adjusted means, standard errors, and P values for all other outcomes were obtained from general linear models adjusting for surgical outcome group. All tests were conducted at a significance level of.05
      POPDI score
       3/6 mo
      3-month visit for subjects in OPUS and CARE studies and 6-month visit for subjects in OPTIMAL and SUPeR studies
      38.72 (310, 2.30)45.35 (97, 4.08)22.76 (759, 1.46)<.001
       1 y45.47 (287, 2.28)42.63 (99, 3.93)19.55 (733, 1.43)<.001
       2 y60.39 (159, 3.28)51.24 (89, 4.89)21.64 (431, 2.02)<.001
       3 y64.48 (104, 3.73)50.39 (75, 5.07)22.06 (325, 2.20)<.001
       4 y77.70 (56, 5.02)59.87 (47, 6.18)21.51 (173, 2.93)<.001
       5 y82.08 (59, 5.50)51.94 (52, 6.33)23.85 (170, 3.26)<.001
      SF-6D physical function score
       3/6 mo
      3-month visit for subjects in OPUS and CARE studies and 6-month visit for subjects in OPTIMAL and SUPeR studies
      2.31 (303, 0.07)2.38 (98, 0.12)2.27 (743, 0.04).664
       1 y2.28 (288, 0.07)2.45 (99, 0.11)2.00 (717, 0.04)<.001
       2 y2.29 (160, 0.08)2.46 (85, 0.12)1.97 (415, 0.05)<.001
       3 y2.43 (102, 0.09)2.44 (73, 0.12)2.02 (317, 0.05)<.001
       4 y2.51 (57, 0.13)2.28 (48, 0.15)2.15 (170, 0.08).059
       5 y2.59 (59, 0.13)2.54 (52, 0.14)2.14 (168, 0.08).002
      SF-6D role limitation score
       3/6 mo
      3-month visit for subjects in OPUS and CARE studies and 6-month visit for subjects in OPTIMAL and SUPeR studies
      2.25 (305, 0.07)2.49 (98, 0.12)2.23 (756, 0.04).135
       1 y2.21 (289, 0.07)2.40 (99, 0.12)1.83 (729, 0.04)<.001
       2 y2.20 (162, 0.09)2.31 (89, 0.13)1.98 (423, 0.06).018
       3 y2.50 (103, 0.11)2.53 (74, 0.14)2.09 (324, 0.06)<.001
       4 y2.73 (57, 0.15)2.66 (48, 0.17)2.06 (175, 0.08)<.001
       5 y2.70 (58, 0.14)2.63 (53, 0.16)2.28 (169, 0.09).017
      SF-6D social function score
       3/6 mo
      3-month visit for subjects in OPUS and CARE studies and 6-month visit for subjects in OPTIMAL and SUPeR studies
      1.70 (307, 0.06)1.80 (99, 0.10)1.59 (758, 0.04).052
       1 y1.73 (290, 0.05)1.79 (99, 0.09)1.49 (733, 0.03)<.001
       2 y1.86 (162, 0.07)1.81 (89, 0.11)1.55 (429, 0.05)<.001
       3 y1.86 (104, 0.09)1.81 (75, 0.11)1.58 (324, 0.05).011
       4 y1.80 (57, 0.11)1.96 (48, 0.12)1.52 (175, 0.06).002
       5 y2.01 (59, 0.12)1.91 (53, 0.13)1.62 (169, 0.07).010
      SF-6D pain score
       3/6 mo
      3-month visit for subjects in OPUS and CARE studies and 6-month visit for subjects in OPTIMAL and SUPeR studies
      2.38 (307, 0.07)2.49 (98, 0.13)2.30 (756, 0.05).341
       1 y2.37 (289, 0.08)2.56 (99, 0.13)2.18 (732, 0.05).007
       2 y2.61 (162, 0.09)2.56 (89, 0.13)2.20 (427, 0.06)<.001
       3 y2.79 (104, 0.11)2.75 (75, 0.15)2.30 (323, 0.07)<.001
       4 y2.94 (57, 0.14)3.02 (48, 0.17)2.38 (175, 0.08)<.001
       5 y2.90 (59, 0.14)3.06 (53, 0.16)2.31 (170, 0.08)<.001
      SF-6D mental health score
       3/6 mo
      3-month visit for subjects in OPUS and CARE studies and 6-month visit for subjects in OPTIMAL and SUPeR studies
      2.08 (307, 0.06)2.23 (98, 0.10)1.94 (757, 0.04).007
       1 y2.05 (290, 0.06)2.21 (99, 0.10)1.92 (733, 0.04).009
       2 y2.16 (162, 0.08)2.22 (89, 0.11)1.94 (426, 0.05).007
       3 y2.06 (104, 0.08)2.12 (75, 0.11)1.89 (324, 0.05).060
       4 y1.90 (57, 0.11)2.28 (48, 0.12)1.91 (175, 0.06).020
       5 y2.12 (59, 0.11)2.22 (53, 0.13)1.89 (170, 0.07).030
      SF-6D vitality score
       3/6 mo
      3-month visit for subjects in OPUS and CARE studies and 6-month visit for subjects in OPTIMAL and SUPeR studies
      2.70 (307, 0.05)2.75 (99, 0.10)2.54 (756, 0.03).014
       1 y2.60 (289, 0.06)2.56 (99, 0.10)2.51 (732, 0.04).407
       2 y2.73 (162, 0.07)2.68 (89, 0.09)2.54 (429, 0.04).034
       3 y2.80 (104, 0.08)2.71 (75, 0.10)2.51 (324, 0.05).004
       4 y2.76 (57, 0.10)2.80 (48, 0.11)2.47 (174, 0.06).004
       5 y3.15 (59, 0.10)2.77 (53, 0.12)2.57 (170, 0.06)<.001
      SF-6D index score
       3/6 mo
      3-month visit for subjects in OPUS and CARE studies and 6-month visit for subjects in OPTIMAL and SUPeR studies
      0.75 (301, 0.01)0.73 (96, 0.01)0.76 (737, 0.00).021
       1 y0.75 (285, 0.01)0.74 (99, 0.01)0.79 (713, 0.00)<.001
       2 y0.73 (160, 0.01)0.74 (85, 0.01)0.78 (405, 0.01)<.001
       3 y0.73 (101, 0.01)0.73 (72, 0.01)0.78 (316, 0.01)<.001
       4 y0.73 (57, 0.01)0.71 (48, 0.02)0.77 (169, 0.01)<.001
       5 y0.70 (58, 0.01)0.71 (52, 0.01)0.76 (166, 0.01)<.001
      1-y QALY
      QALYs are calculated using an area under the curve approach following the trapezoidal rule from each subject’s SF-6D index score reported at baseline, 3/6 months, 12 months, and 24 months. Each subject must have at least an SF-6D index score reported at baseline and 12 months for a 1-year QALY to be calculated. Each subject must have at least an SF-6D index score reported at baseline and either at 12 or 24 months for a 2-year QALY to be calculated. If the SF-6D index score is missing at 24 months, it was assumed to be the same as at 12 months.
      0.75 (272, 0.01)0.72 (94, 0.01)0.76 (678, 0.00)<.001
      2-y QALY
      QALYs are calculated using an area under the curve approach following the trapezoidal rule from each subject’s SF-6D index score reported at baseline, 3/6 months, 12 months, and 24 months. Each subject must have at least an SF-6D index score reported at baseline and 12 months for a 1-year QALY to be calculated. Each subject must have at least an SF-6D index score reported at baseline and either at 12 or 24 months for a 2-year QALY to be calculated. If the SF-6D index score is missing at 24 months, it was assumed to be the same as at 12 months.
      0.75 (289, 0.01)0.72 (100, 0.01)0.78 (708, 0.00)<.001
      Data are adjusted mean (number, standard error).
      CARE, Colpopexy and Urinary Reduction Efforts; OPTIMAL, Operations and Pelvic Muscle Training in the Management of Apical Support Loss; OPUS, Outcomes Following Vaginal Prolapse Repair and Midurethral Sling; POPDI, Pelvic Organ Prolapse Distress Inventory; SF-6D, Short-Form Six-Dimension; SUPeR, Study of Uterine Prolapse Procedures Randomized Trial; QALY, quality-adjusted life year.
      Jelovsek et al. Pelvic organ prolapse surgical success and failure states are dynamic. Am J Obstet Gynecol 2021.
      a Adjusted means, standard errors, and P values for repeated measures outcomes were obtained from general linear models adjusting for surgical outcome group, visit
      3-month visit for subjects in OPUS and CARE studies and 6-month visit for subjects in OPTIMAL and SUPeR studies
      , and interaction between surgical outcome group and visit while controlling for within-subject correlation across visits with an unstructured working correlation structure. Adjusted means, standard errors, and P values for all other outcomes were obtained from general linear models adjusting for surgical outcome group. All tests were conducted at a significance level of.05
      b 3-month visit for subjects in OPUS and CARE studies and 6-month visit for subjects in OPTIMAL and SUPeR studies
      c QALYs are calculated using an area under the curve approach following the trapezoidal rule from each subject’s SF-6D index score reported at baseline, 3/6 months, 12 months, and 24 months. Each subject must have at least an SF-6D index score reported at baseline and 12 months for a 1-year QALY to be calculated. Each subject must have at least an SF-6D index score reported at baseline and either at 12 or 24 months for a 2-year QALY to be calculated. If the SF-6D index score is missing at 24 months, it was assumed to be the same as at 12 months.

      Structured Discussion

      Principal findings

      Outcomes after surgery for prolapse have largely been evaluated, analyzed, and interpreted as dichotomous: success or failure. This analysis of a large, diverse cohort from data collected within 4 rigorously conducted surgical trials suggests that outcomes after surgery for POP are considerably more nuanced and complex. Although most participants in these trials had successful surgery or had initial success that failed over time, a proportion demonstrated dynamic outcomes: Their vaginal support and POP symptoms transitioned back and forth between success and failure outcomes at various time points without treatment.

      Results

      More than 80% of those who fluctuated (intermittent success and failure) met all criteria for success at their last outcome assessment (terminal success). Those with “intermittent success and failure” also report intermediate subjective outcomes among those who met persistent success or failure definitions. These findings have important implications for how we understand, measure, and analyze outcomes after POP surgery.
      Another area of complexity in POP surgery outcomes highlighted in this analysis is the discordance between anatomic and subjective outcomes. Most women included in this analysis who met the criteria for failure met only 1 of 3 components of the composite failure definition at the initial assessment of failure (85.5%) with only 12.9% reporting both symptomatic and anatomic failure and <3% having undergone retreatment. This discordance is even greater than that seen in the original analysis of the CARE study population where 64% of patients with prolapse beyond the hymen at 2 years postoperatively also had vaginal bulge symptoms.
      • Barber M.D.
      • Brubaker L.
      • Nygaard I.
      • et al.
      Defining success after surgery for pelvic organ prolapse.
      Understanding both rates of anatomic and subjective recurrence after POP surgery is important in understanding the effectiveness and mechanisms of failure of these procedures.
      The substantial discordance between symptoms and vaginal anatomy seen in our analysis and others suggests that it may be more valuable to evaluate these outcomes independently, rather than as a composite outcome for POP surgery, because a single composite outcome may muddle our understanding of a patient’s experience. Moreover, our data suggest that single composite outcomes likely overestimate failure relative to the entirety of the patient’s postoperative experience. This discordance also highlights the need for future research about what outcomes matter most to patients—the available data suggest it is subjective outcomes.
      • Dunivan G.C.
      • Sussman A.L.
      • Jelovsek J.E.
      • et al.
      Gaining the patient perspective on pelvic floor disorders’ surgical adverse events.
      In prospective studies of POP repair, surgical outcomes can be assessed either at discrete time points (irrespective of outcomes at earlier time points) or over time using the “once a failure, always a failure” approach that is common to survival analyses. Our data suggest that the latter approach may not truly reflect the patients’ experience for the assessment of the long-term outcomes of POP procedures. Reports on the natural history of prolapse in women suggest that the majority of prolapse does not progress with time and even 3% may demonstrate ≥2 cm of regression in the absence of treatment.
      • Pizarro-Berdichevsky J.
      • Borazjani A.
      • Pattillo A.
      • Arellano M.
      • Li J.
      • Goldman H.B.
      Natural history of pelvic organ prolapse in symptomatic patients actively seeking treatment.
      • Bradley C.S.
      • Zimmerman M.B.
      • Qi Y.
      • Nygaard I.E.
      Natural history of pelvic organ prolapse in postmenopausal women.
      • Handa V.L.
      • Garrett E.
      • Hendrix S.
      • Gold E.
      • Robbins J.
      Progression and remission of pelvic organ prolapse: a longitudinal study of menopausal women.
      Although anatomic regression represents a minority, others have reported improved symptoms of POP in 64% with only 6% worsening over 5 years.
      • Miedel A.
      • Ek M.
      • Tegerstedt G.
      • Mæhle-Schmidt M.
      • Nyrén O.
      • Hammarström M.
      Short-term natural history in women with symptoms indicative of pelvic organ prolapse.
      Our data are consistent with these reports and support that prolapse may be a “recurrent event” even after surgical intervention. Our data make a strong argument that traditional time to (first) event analysis methods are not ideal for evaluating POP surgeries; analytical techniques that account for different outcome states in a single individual over time may provide more valid comparisons.

      Clinical implications

      Our data also support that the intermittent success and failure states matter to participants. Women whose outcomes are in these “intermittent” failure states report different quality of life and satisfaction rates compared with those who are persistently in a state of success or failure over time. Women with anatomic failures, but no symptoms, are commonly seen in the clinical setting and considered “satisfied failures” because they do not request additional retreatment. Possible explanations for the phenomenon may be the perception that, although not perfect, the degree of prolapse is significantly improved compared with preoperatively. They may also have had other symptoms resolved with the repair (such as incontinence or retention) that improved their quality of life despite not having a perfect anatomic result. Alternately, the fear of disappointing their surgeon or denial regarding the success of the operation may prompt a participant to deny symptoms in the setting of prolapse beyond the hymen. Women who are labeled “failures” in the absence of anatomic prolapse beyond the hymen may have reported symptoms of pressure and bulge at 1 time point owing to other conditions, such as constipation or urinary tract infection. Finally, although questions related to prolapse symptoms are highly specific with reports ranging from 79% to 99% ruling “in” the diagnosis, the sensitivity can be low particularly in populations with low prevalence making the absence of prolapse based on questionnaire alone likely overestimated.
      • Barber M.D.
      • Neubauer N.L.
      • Klein-Olarte V.
      Can we screen for pelvic organ prolapse without a physical examination in epidemiologic studies?.
      • Tehrani F.R.
      • Hashemi S.
      • Simbar M.
      • Shiva N.
      Screening of the pelvic organ prolapse without a physical examination; (a community based study).
      • Tegerstedt G.
      • Miedel A.
      • Maehle-Schmidt M.
      • Nyren O.
      • Hammarström M.
      A short-form questionnaire identified genital organ prolapse.
      The characteristics of the questionnaires themselves may contribute to the “intermittent” success and failure based on symptoms alone. Similarly, the measurement error inherent in the POPQ, including a patient’s Valsalva effort, or body mass index may account for intermittent anatomic success and failure over time.

      Research implications

      Implications of this study are that the currently accepted methods likely underestimate success rates after prolapse surgery when using single composite definitions and time-to-event approaches. This may result in the overestimation of surgical failure rates and potentially, in part, explain low retreatment rates. Future research considerations include the need to characterize failure types over time and to update recommendations on defining success and failure that report anatomic, subjective, and retreatment outcomes separately and to follow up over a minimum amount of time with multiple measures to account for the dynamic nature of POP. Researchers may consider reanalyzing pivotal trials using these new recommendations to guide clinicians in estimating average treatment effects over time for common procedures in the field. Qualitative research into the discordance between subjective and objective outcomes may help inform which outcomes to use when comparing optimal surgical treatment approaches. Finally, additional research should be performed to identify women who may experience intermittent failed outcomes because it could be useful to counsel these women preoperatively and potentially alter treatment recommendations.

      Strengths and limitations

      The strengths of this study include the use of randomized controlled trials, consistently implemented surgical techniques, standardized collection of objective and subjective outcome measures across multiple sites, and masked examiners and interviewers. Limitations to this work include the fact that multiple trials were analyzed in aggregate potentially resulting in biases owing to varying study designs and differing missing values. In addition, 2 of the 4 trials were not designed to compare outcomes of POP surgery itself but rather urinary symptoms after POP surgery, and there were varying follow-up time points for each trial with 1 only having a 1-year follow-up.
      • Brubaker L.
      • Cundiff G.W.
      • Fine P.
      • et al.
      Abdominal sacrocolpopexy with Burch colposuspension to reduce urinary stress incontinence.
      Finally, the long time span during which these trials were conducted does not account for evolving practice patterns.

      Conclusions

      True failure rates after prolapse surgery may be overestimated in the current literature. In this population, approximately, 1 in 4 failures were intermittent and fluctuated between success and failure over time. Only 13% initially met failure definitions by both subjective and objective criteria. Most intermittent failures were in a state of “surgical success” at their last follow-up. Both anatomic and subjective outcomes after POP surgery seem to be dynamic in nature and traditional survival analyses where “once a failure, always a failure” may not be ideal.

      References

        • Chmielewski L.
        • Walters M.D.
        • Weber A.M.
        • Barber M.D.
        Reanalysis of a randomized trial of 3 techniques of anterior colporrhaphy using clinically relevant definitions of success.
        Am J Obstet Gynecol. 2011; 205: 69.e1-69.e8
        • Barber M.D.
        • Brubaker L.
        • Nygaard I.
        • et al.
        Defining success after surgery for pelvic organ prolapse.
        Obstet Gynecol. 2009; 114: 600-609
        • Kowalski J.T.
        • Mehr A.
        • Cohen E.
        • Bradley C.S.
        Systematic review of definitions for success in pelvic organ prolapse surgery.
        Int Urogynecol J. 2018; 29: 1697-1704
        • Meister M.R.
        • Sutcliffe S.
        • Lowder J.L.
        Definitions of apical vaginal support loss: a systematic review.
        Am J Obstet Gynecol. 2017; 216: 232.e1-232.e14
        • Brubaker L.
        • Cundiff G.W.
        • Fine P.
        • et al.
        Abdominal sacrocolpopexy with Burch colposuspension to reduce urinary stress incontinence.
        N Engl J Med. 2006; 354: 1557-1566
        • Nygaard I.
        • Brubaker L.
        • Zyczynski H.M.
        • et al.
        Long-term outcomes following abdominal sacrocolpopexy for pelvic organ prolapse.
        JAMA. 2013; 309: 2016-2024
        • Wei J.T.
        • Nygaard I.
        • Richter H.E.
        • et al.
        A midurethral sling to reduce incontinence after vaginal prolapse repair.
        N Engl J Med. 2012; 366: 2358-2367
        • Barber M.D.
        • Brubaker L.
        • Menefee S.
        • et al.
        Operations and pelvic muscle training in the management of apical support loss (OPTIMAL) trial: design and methods.
        Contemp Clin Trials. 2009; 30: 178-189
        • Jelovsek J.E.
        • Barber M.D.
        • Brubaker L.
        • et al.
        Effect of uterosacral ligament suspension vs sacrospinous ligament fixation with or without perioperative behavioral therapy for pelvic organ vaginal prolapse on surgical outcomes and prolapse symptoms at 5 years in the OPTIMAL randomized clinical trial.
        JAMA. 2018; 319: 1554-1565
        • Nager C.W.
        • Visco A.G.
        • Richter H.E.
        • et al.
        Effect of vaginal mesh hysteropexy vs vaginal hysterectomy With uterosacral ligament suspension on treatment failure in women With uterovaginal prolapse: a randomized clinical trial.
        JAMA. 2019; 322: 1054-1065
        • Glick H.
        • Doshi J.A.
        • Sonnad S.S.
        • Polsky D.
        Economic evaluation in clinical trials.
        Oxford University Press, Oxford, England2007
        • Brazier J.E.
        • Roberts J.
        The estimation of a preference-based measure of health from the SF-12.
        Med Care. 2004; 42: 851-859
        • Brazier J.
        • Roberts J.
        • Deverill M.
        The estimation of a preference-based measure of health from the SF-36.
        J Health Econ. 2002; 21: 271-292
        • Dunivan G.C.
        • Sussman A.L.
        • Jelovsek J.E.
        • et al.
        Gaining the patient perspective on pelvic floor disorders’ surgical adverse events.
        Am J Obstet Gynecol. 2019; 220: 185.e1-185.e10
        • Pizarro-Berdichevsky J.
        • Borazjani A.
        • Pattillo A.
        • Arellano M.
        • Li J.
        • Goldman H.B.
        Natural history of pelvic organ prolapse in symptomatic patients actively seeking treatment.
        Int Urogynecol J. 2018; 29: 873-880
        • Bradley C.S.
        • Zimmerman M.B.
        • Qi Y.
        • Nygaard I.E.
        Natural history of pelvic organ prolapse in postmenopausal women.
        Obstet Gynecol. 2007; 109: 848-854
        • Handa V.L.
        • Garrett E.
        • Hendrix S.
        • Gold E.
        • Robbins J.
        Progression and remission of pelvic organ prolapse: a longitudinal study of menopausal women.
        Am J Obstet Gynecol. 2004; 190: 27-32
        • Miedel A.
        • Ek M.
        • Tegerstedt G.
        • Mæhle-Schmidt M.
        • Nyrén O.
        • Hammarström M.
        Short-term natural history in women with symptoms indicative of pelvic organ prolapse.
        Int Urogynecol J. 2011; 22: 461-468
        • Barber M.D.
        • Neubauer N.L.
        • Klein-Olarte V.
        Can we screen for pelvic organ prolapse without a physical examination in epidemiologic studies?.
        Am J Obstet Gynecol. 2006; 195: 942-948
        • Tehrani F.R.
        • Hashemi S.
        • Simbar M.
        • Shiva N.
        Screening of the pelvic organ prolapse without a physical examination; (a community based study).
        BMC Womens Health. 2011; 11: 48
        • Tegerstedt G.
        • Miedel A.
        • Maehle-Schmidt M.
        • Nyren O.
        • Hammarström M.
        A short-form questionnaire identified genital organ prolapse.
        J Clin Epidemiol. 2005; 58: 41-46