International Urogynecological Consultation (IUC): pathophysiology of pelvic organ prolapse (POP).

INTRODUCTION AND HYPOTHESIS: This manuscript is the International Urogynecology Consultation (IUC) on pelvic organ prolapse (POP) chapter one, committee three, on the Pathophysiology of Pelvic Organ Prolapse assessing genetics, pregnancy, labor and delivery, age and menopause and animal models. MATERIALS AND METHODS: An international group of urogynecologists and basic scientists performed comprehensive literature searches using pre-specified terms in selected biomedical databases to summarize the current knowledge on the pathophysiology of the development of POP, exploring specifically factors including (1) genetics, (2) pregnancy, labor and delivery, (3) age and menopause and (4) non-genetic animal models. This manuscript represents the summary of three systematic reviews with meta-analyses and one narrative review, to which a basic scientific comment on the current understanding of pathophysiologic mechanisms was added. RESULTS: The original searches revealed over 15,000 manuscripts and abstracts which were screened, resulting in 202 manuscripts that were ultimately used. In the area of genetics the DNA polymorphisms rs2228480 at the ESR1 gene, rs12589592 at the FBLN5 gene, rs1036819 at the PGR gene and rs1800215 at the COL1A1 gene are significantly associated to POP. In the area of pregnancy, labor and delivery, the analysis confirmed a strong etiologic link between vaginal birth and symptoms of POP, with the first vaginal delivery (OR: 2.65; 95% CI: 1.81-3.88) and forceps delivery (OR: 2.51; 95% CI: 1.24-3.83) being the main determinants. Regarding age and menopause, only age was identified as a risk factor (OR : 1.102; 95% CI: 1.02-1.19) but current data do not identify postmenopausal status as being statistically associated with POP. In several animal models, there are measurable effects of pregnancy, delivery and iatrogenic menopause on the structure/function of vaginal support components, though not on the development of POP. CONCLUSIONS: Genetics, vaginal birth and age all have a strong etiologic link to the development of POP, to which other factors may add or protect against the risk.

Age and/or postmenopausal status as risk factors for pelvic organ prolapse development: systematic review with meta-analysis.

INTRODUCTION AND HYPOTHESIS: Age is named as a risk factor for pelvic organ prolapse (POP), despite not being the primary outcome for many observational studies. Postmenopausal status is another associated factor but has many confounders. We aimed to systematically review the role of age and/or postmenopausal status in POP development. METHODS: Systematic review addressing age and hormones, more specifically by postmenopausal status, from inception to March 2020 in four databases (PubMed, Embase, WOS, Cochrane Library). Quality of evidence was classified by the ROBINS-I classification for non-randomized studies. Experimental studies, animal studies, studies linking age with recurrent POP and case series were excluded. Effect estimates were collected from adjusted odds ratio plus 95% confidence intervals. Significance level was 5%. A discussion exploring mechanistic factors was also included. RESULTS: Nineteen studies (11 cross sectional, 6 cohort and 2 case control) were included for quantitative analysis. Only two studies presented a low overall risk of bias for age; most of the domains were of moderate risk. Every additional year was responsible for a 10% increase in the risk to develop POP (OR = 1.102 [1.021-1.190]; i2 = 80%, random analysis, p = 0.012). This trend was confirmed when age was dichotomized into a cutoff of 35 (p = 0.035) and 50 (p < 0.001) years. Although an increase in the risk for POP was noted in postmenopausal women, this did not reach statistical significance (OR = 2.080 [0.927-4.668], i2 = 0%, p = 0.076). CONCLUSION: Age is a risk factor for POP; postmenopausal status was not statistically associated with POP, prompting the need for further studies addressing this factor.

Animal models for pelvic organ prolapse: systematic review.

INTRODUCTION AND HYPOTHESIS: We aimed to summarize the knowledge on the pathogenesis of pelvic organ prolapse (POP) generated in animal models. METHODS: We searched MEDLINE, Embase, Cochrane and the Web of Science to establish what animal models are used in the study of suggested risk factors for the development of POP, including pregnancy, labor, delivery, parity, aging and menopause. Lack of methodologic uniformity precluded meta-analysis; hence, results are presented as a narrative review. RESULTS: A total of 7426 studies were identified, of which 51 were included in the analysis. Pregnancy has a measurable and consistent effect across species. In rats, simulated vaginal delivery induces structural changes in the pelvic floor, without complete recovery of the vaginal muscular layer and its microvasculature, though it does not induce POP. In sheep, first vaginal delivery has a measurable effect on vaginal compliance; measured effects of additional deliveries are inconsistent. Squirrel monkeys can develop POP. Denervation of their levator ani muscle facilitates this process in animals that delivered vaginally. The models used do not develop spontaneous menopause, so it is induced by ovariectomy. Effects of menopause depend on the age at ovariectomy and the interval to measurement. In several species menopause is associated with an increase in collagen content in the longer term. In rodents there were no measurable effects of age apart of elastin changes. We found no usable data for other species. CONCLUSION: In several species there are measurable effects of pregnancy, delivery and iatrogenic menopause. Squirrel monkeys can develop spontaneous prolapse.

Two-years results of native tissue versus vaginal mesh repair in the treatment of anterior prolapse according to different success criteria: A randomized controlled trial.

AIMS: To compare efficacy and safety of the traditional colporraphy and transvaginal polypropylene mesh for the treatment of advanced anterior vaginal prolapse according to different success criteria in two-year follow-up. METHODS: In this randomized controlled trial, women with anterior prolapse stage II or greater, with Ba point ≥ +1 (POP-Q quantification), were randomly assigned to have either anterior colporraphy (n = 43) or transvaginal mesh repair (n = 43). The primary outcome was to compare objective success rate under two success definitions: prolapse stage I (Ba < -1) and stage II (Ba < 0). Secondary outcomes included complications and prolapse symptoms, satisfaction and quality of life (QoL). Intention to treat was used for the primary endpoint and per protocol analysis for the secondary outcomes. RESULTS: The groups presented similar preoperative data. Thirty three patients from the colporraphy and 37 from the mesh groups completed two-year follow-up. Under Ba < -1 definition, success rate was 39.53% for both groups (P = 1.00). Considering success as Ba < 0, analysis favored the mesh group by 23% (51.16% and 74.42%; 95% CI for difference: 3-43%; P = 0.022). Patients from the mesh group were more satisfied after two years (81.8% and 97.3% for colporraphy and mesh, respectively, 15.5% difference; 95% CI for difference 1-29%; P = 0.032). Both procedures similarly improved women's symptoms and QoL. Some complications were observed, one being a 13.5% mesh exposure rate. CONCLUSIONS: Transvaginal synthetic mesh repair for advanced anterior vaginal prolapse provided higher anatomical success and satisfaction rates compared with traditional colporraphy. Both procedures equally improved quality of life. Neurourol. Urodynam. 35:509-514, 2016. © 2015 Wiley Periodicals, Inc.

Neural control of lower urinary tract and targets for pharmacological therapy.

Studies on the physiology and pharmacology of the lower urinary tract have brought new information and concepts about the complex neural control of micturition. There are many mechanisms, some proven and others not yet completely understood, in which pharmacological agents may act facilitating the filling, storage, and emptying of the bladder. This review describes the peripheral innervation and the main pathways involved in lower urinary tract control. It also presents potential targets for the treatment of voiding dysfunctions.

Randomized controlled trial comparing TVT-O and TVT-S for the treatment of stress urinary incontinence: 2-year results.

INTRODUCTION AND HYPOTHESIS: The aim was to compare the efficacy and safety of single-incision sling TVT-Secur (TVT-S) and transobturator midurethral sling (TVT-O) for the treatment of stress urinary incontinence (SUI) over 2 years' follow-up. METHODS: This is a randomized controlled trial in which women with SUI were randomly assigned to have either TVT-O (n = 56) or TVT-S (n = 66). Exclusion criteria included: voiding dysfunction, detrusor overactivity, and pelvic organ prolapse beyond the hymen. The primary outcomes were objective and subjective cure rates at a follow-up visit at 24 months, defined as a negative stress test and pad test as well as absence of self-reported SUI symptoms. Secondary endpoints included quality of life assessment using the King's Health Questionnaire (KHQ), and complication and reoperation rates. Analysis was performed using intention to treat, and statistical significance was fixed at 5% (p < 0.05). Statistical methods used were Mann-Whitney, Student's t, Chi-squared, Fisher's, ANOVA, and McNemar's tests. RESULTS: The groups were similar regarding demographic and clinical preoperative parameters. Objective cure rates for TVT-S and TVT-O groups were 77.3% and 83.6%, while subjective cure rates were 75.7% and 80.3% respectively, with no statistically significant differences between the techniques. There was a significant improvement in all KHQ domains in both groups (p < 0.001). A few complications were observed in our study. The most common perioperative complication was thigh pain associated with TVT-O, while the long-term one was tape exposure observed in 5.3% of TVT-O and in 7.5% of TVT-S cases. CONCLUSION: The efficacy of the TVT-S was similar to that of the TVT-O after 2 years' assessment. This cohort will continue to be followed in order to maintain commitment to contributing data on long-term results.

The use of transvaginal synthetic mesh for anterior vaginal wall prolapse repair: a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: The aim of the study was to compare the efficacy and safety of transvaginal trocar-guided polypropylene mesh insertion with traditional colporrhaphy for treatment of anterior vaginal wall prolapse. METHODS: This is a randomized controlled trial in which women with advanced anterior vaginal wall prolapse, at least stage II with Ba ≥ +1 cm according to the Pelvic Organ Prolapse Quantification (POP-Q) classification, were randomly assigned to have either anterior colporrhaphy (n = 39) or repair using trocar-guided transvaginal mesh (n = 40). The primary outcome was objective cure rate of the anterior compartment (point Ba) assessed at the 12-month follow-up visit, with stages 0 and I defined as anatomical success. Secondary outcomes included quantification of other vaginal compartments (POP-Q points), comparison of quality of life by the prolapse quality of life (P-QOL) questionnaire, and complication rate between the groups after 1 year. Study power was fixed as 80% with 5% cutoff point (p < 0.05) for statistical significance. RESULTS: The groups were similar regarding demographic and clinical preoperative parameters. Anatomical success rates for colporrhaphy and repair with mesh placement groups were 56.4 vs 82.5% (95% confidence interval 0.068-0.54), respectively, and the difference between the groups was statistically significant (p = 0.018). Similar total complication rates were observed in both groups, with tape exposure observed in 5% of the patients. There was a significant improvement in all P-QOL domains as a result of both procedures (p < 0.001), but they were not distinct between groups (p > 0.05). CONCLUSIONS: Trocar-guided transvaginal synthetic mesh for advanced anterior POP repair is associated with a higher anatomical success rate for the anterior compartment compared with traditional colporrhaphy. Quality of life equally improved after both techniques. However, the trial failed to detect differences in P-QOL scores and complication rates between the groups.

Single-incision sling compared with transobturator sling for treating stress urinary incontinence: a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: We tested the hypothesis that the single-incision sling, TVT-Secur (TVT-S), placed in U position is not inferior to transobturator midurethral sling (TVT-O) for treating stress urinary incontinence (SUI). METHODS: This was a noninferiority, prospective, randomized controlled trial in which women with SUI, confirmed by physical and urodynamic evaluation, were randomly assigned to receive either TVT-O (n = 56) or TVT-S (n = 66). Exclusion criteria were voiding dysfunction, detrusor overactivity (DO), and pelvic organ prolapse (POP) beyond the hymen. The primary outcomes were objective and subjective cure rates, which were assessed at the 12-month follow-up visit, defined as negative stress, pad, and urodynamic tests and absence of self-reported SUI symptoms. Secondary outcomes were quality of life (QoL) by King's Health Questionnaire (KHQ) validated for Portuguese language, postoperative pain, and complication rate. The power of the study was 80 % to test the hypothesis that TVT-S is not inferior to TVT-O by >15 %. Statistical significance was fixed at 5 % (p < 0.05). RESULTS: Groups were similar regarding demographic and clinical preoperative parameters. Objective cure rates for TVT-S and TVT-O groups were 84.1 % vs 87 % [90 % confidence interbal (CI) -15 to 9.8], and subjective cure rates were 92.1 % vs 90.7 % (95 % CI -11.4 to 6.7), respectively. TVT-S resulted in less postoperative general and thigh pain (p < 0.001). A few, but not statistically significant different complications, were observed in both groups: vaginal mucosa perforation, urinary retention, urinary infection, tape exposure, and de novo urgency. There was a significant improvement in all KHQ domains in both groups (p < 0.001). CONCLUSION: TVT-S was not inferior to TVT-O for treating SUI at 12-month follow-up.