Characterizing the phenotype of advanced pelvic organ prolapse.

OBJECTIVE: Genetic studies require a clearly defined phenotype to reach valid conclusions. Our aim was to characterize the phenotype of advanced prolapse by comparing women with stage III to IV prolapse with controls without prolapse. METHODS: Based on the pelvic organ prolapse quantification examination, women with stage 0 to stage I prolapse (controls) and those with stage III to stage IV prolapse (cases) were prospectively recruited as part of a genetic epidemiologic study. Data regarding sociodemographics; medical, obstetric, and surgical history; family history; and body mass index were obtained by a questionnaire administered by a trained coordinator and abstracted from electronic medical records. RESULTS: There were 275 case patients with advanced prolapse and 206 controls with stage 0 to stage I prolapse. Based on our recruitment strategy, the women were younger than the controls (64.7 ± 10.1 vs 68.6 ± 10.4 years; P<0.001); cases were also more likely to have had one or more vaginal deliveries (96.0% vs 82.0%; P<0.001). There were no differences in race, body mass index, and constipation. Regarding family history, cases were more likely to report that either their mother and/or sister(s) had prolapse (44.8% vs 16.9%, P<0.001). In a logistic regression model, vaginal parity (odds ratio, 4.05; 95% confidence interval, 1.67-9.85) and family history of prolapse (odds ratio, 3.74; 95% confidence interval, 2.16-6.46) remained significantly associated with advanced prolapse. CONCLUSIONS: Vaginal parity and a family history of prolapse are more common in women with advanced prolapse compared to those without prolapse. These characteristics are important in phenotyping advanced prolapse, suggesting that these data should be collected in future genetic epidemiologic studies.

Matrix metalloproteinase-9 genetic polymorphisms and the risk for advanced pelvic organ prolapse.

OBJECTIVE: Matrix metalloproteinase-9 (MMP9) is a protease associated with degradation of collagen and elastin. Because increased MMP9 activity in vaginal tissue has been associated with pelvic organ prolapse (POP), we sought to comprehensively estimate MMP9 genetic variants and the risk for advanced prolapse. METHODS: This is a candidate gene association study of women with stage III-IV prolapse (case group, n=239) and women with stage 0-1 prolapse (control group, n=197). We attempted to oversample "extreme" phenotypes, including younger women with severe prolapse and older women without prolapse, in an attempt to concentrate the genetic effect. We used a linkage disequilibrium tagged approach to identify single nucleotide polymorphisms in MMP9 to evaluate in our study. To minimize potential confounding by race, our analysis focused on non-Hispanic white women. We performed multivariable logistic regression to estimate the association between MMP9 single nucleotide polymorphisms and case-control status, adjusting for age and vaginal parity. RESULTS: Women with advanced prolapse were slightly younger (64.8 ± 10.3 compared with 69.0 ± 10.2 years, P<.001) and more likely to have had one or more vaginal deliveries (96.6% compared with 82.2%, P<.001) when compared with control participants. Eight single nucleotide polymorphisms were assessed, which represented 93% coverage of the MMP9 gene. Of these, two were associated with advanced prolapse: 1) rs3918253 (adjusted odds ratio [OR] 0.64, 95% confidence interval [CI] 0.41-1.0, P=.05); and 2) rs3918256 (adjusted OR 0.64, 95% CI 0.41-1.01, P=.05). CONCLUSION: MMP9 is a biologically plausible candidate gene for POP given our results.

Sexual function after vaginal versus nonvaginal prolapse surgery.

OBJECTIVES: To compare sexual function based on the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ) in women who underwent vaginal versus nonvaginal surgery for prolapse. METHODS: This was a prospective cohort study of women who underwent vaginal versus nonvaginal (abdominal or robotic) surgery for stage II to stage IV pelvic organ prolapse. We compared 2 groups: those who received vaginal prolapse surgery (defined as any surgical procedure for prolapse requiring incisions in the vaginal wall) and those who received nonvaginal (ie, exclusively abdominal or robotic) prolapse surgery. Women completed the PISQ and additional pelvic floor symptom questionnaires at baseline and 6 months after surgery. Our primary outcome was change in PISQ score from baseline to 6 months. RESULTS: Of the 80 women in our study population, 58 participants completed 6-month follow-up. Baseline PISQ and pelvic floor symptom questionnaire scores were similar between the vaginal and nonvaginal surgery groups. There were significant overall improvements in sexual function based on the PISQ but no differences in scores between vaginal and nonvaginal surgery groups (mean PISQ change score 6.4±9.2 vs 6.1±14.8; P=0.92). In a linear regression model adjusting for potential confounders, there were still no differences in 6-month PISQ scores between the groups. CONCLUSIONS: In women with prolapse, sexual function is likely to improve after reconstructive surgery, regardless of the route.

Comprehensive analysis of LAMC1 genetic variants in advanced pelvic organ prolapse.

OBJECTIVE: We sought to comprehensively evaluate the association of laminin gamma-1 (LAMC1) and advance pelvic organ prolapse. STUDY DESIGN: We conducted a candidate gene association of patients (n = 239) with stages III-IV prolapse and controls (n = 197) with stages 0-I prolapse. We used a linkage disequilibrium (LD)-tagged approach to identify single-nucleotide polymorphisms (SNPs) in LAMC1 and focused on non-Hispanic white women to minimize population stratification. Additive and dominant multivariable logistic regression models were used to test for association between individual SNPs and advanced prolapse. RESULTS: Fourteen SNPs representing 99% coverage of LAMC1 were genotyped. There was no association between SNP rs10911193 and advanced prolapse (P = .34). However, there was a trend toward significance for SNPs rs1413390 (P = .11), rs20563 (P = .11), and rs20558 (P = .12). CONCLUSION: Although we found that the previously reported LAMC1 SNP rs10911193 was not associated with nonfamilial prolapse, our results support further investigation of this candidate gene in the pathophysiology of prolapse.

Trends in inpatient urinary incontinence surgery in the USA, 1998-2007.

INTRODUCTION AND HYPOTHESIS: This study was conducted to assess national rates in stress urinary incontinence (SUI) surgery in the USA from 1998 to 2007. METHODS: We utilized the 1998-2007 Nationwide Inpatient Sample and assessed women aged 20 years and older who underwent SUI surgery based on the International Classification of Diseases, 9th Revision (ICD-9) procedure and diagnosis codes. RESULTS: The total number of SUI surgeries performed during this 10-year period was 759,821. The annual number of procedures increased from 37,953 in 1998 to 94,910 in 2007. The type of SUI surgery performed also changed (p < 0.001). In 1998, retropubic suspensions represented 52.3%, decreasing to 13.8% in 2007. "Other repair of SUI" (ICD-9 59.79) comprised 22.4% in 1998, increasing to 75.2% in 2007, likely representing midurethral slings. CONCLUSIONS: The total number and incidence rates of SUI surgeries have increased from 1998 to 2007. The type of SUI surgery performed has also changed significantly, likely secondary to adoption of midurethral slings.

Patient preferences for different severities of and treatments for overactive bladder.

OBJECTIVE: : Symptoms of overactive bladder (OAB) can have profound effects on women's quality of life. However, quantitative data on how women value these symptoms and their treatments are limited. We sought to assess women's preferences, which are referred to as utilities, for different severities of and treatment options for OAB. METHODS: : Eighty women-40 with OAB symptoms and 40 without OAB-were recruited from urogynecology and urology practices at an academic institution from April to November 2009. A single, trained interviewer administered a computerized preference elicitation tool to measure preferences for 4 OAB severity levels (urgency/frequency and mild, moderate, and severe urge incontinence), as well as 3 OAB treatments with and without adverse effects or complications, which included (1) anticholinergic medications, (2) botulinum toxin injection, and (3) sacral neuromodulation. Preferences were assessed using the time trade-off (TTO) method. RESULTS: : Median TTO scores for OAB decreased as severity increased (urgency/frequency, 0.88; mild, 0.92; moderate, 0.85; severe, 0.73). Median TTO scores assigned to anticholinergic medications were higher (0.93) than those for botulinum (0.88) and sacral neuromodulation (0.85), and adverse effects or complications lowered the utilities for each treatment (anticholinergics, 0.88; botulinum, 0.75; and sacral neuromodulation, 0.78). CONCLUSIONS: : Women view symptoms of OAB, particularly moderate or severe symptoms, as being quite burdensome. The degree of invasiveness and the number of adverse effect/complications are important contributors to the utilities that women assign to the various treatment options.

Forecasting the prevalence of pelvic floor disorders in U.S. Women: 2010 to 2050.

OBJECTIVES: To estimate the number of women who will have symptomatic pelvic floor disorders in the United States from 2010 to 2050. METHODS: We used population projections from the U.S. Census Bureau from 2010 to 2050 and published age-specific prevalence estimates for bothersome, symptomatic pelvic floor disorders (urinary incontinence [UI], fecal incontinence, and pelvic organ prolapse [POP]) from the 2005 National Health and Nutrition Examination Survey. We abstracted data regarding the number of women aged 20 years or older in 20-year age groups. We assumed that the age-specific prevalences for these disorders and the population distribution of risk factors remained unchanged thru 2050. We also conducted sensitivity analyses that varied both the prevalence estimates and the population projections. RESULTS: The number of American women with at least one pelvic floor disorder will increase from 28.1 million in 2010 to 43.8 million in 2050. During this time period, the number of women with UI will increase 55% from 18.3 million to 28.4 million. For fecal incontinence, the number of affected women will increase 59% from 10.6 to 16.8 million, and the number of women with POP will increase 46% from 3.3 to 4.9 million. The highest projections for 2050 estimate that 58.2 million women will have at least one pelvic floor disorder, with 41.3 million with UI, 25.3 million with fecal incontinence, and 9.2 million with POP. CONCLUSION: The prevalence of pelvic floor disorders will increase substantially given the changing demographics in the United States. This increase has important implications for public health and the field of gynecology. LEVEL OF EVIDENCE: III.