Vaginal smooth muscle cell apoptosis is increased in women with pelvic organ prolapse

To compare the smooth muscle content and apoptosis of the vagina in women with and without anterior vaginal wall prolapse. Vaginal tissues were sampled in women with (n = 6) or without (n = 6) anterior vaginal wall prolapse undergoing hysterectomy. Smooth muscle of the vagina was studied by immunohistochemistry. Digital image analysis was used to determine the fractional area of smooth muscle in the histologic cross-sections. Apoptosis was assessed by TUNEL assay. The fractional area of non-vascular smooth muscle in the vagina of women with anterior vaginal wall prolapse was significantly decreased compared to women without prolapse (0.36 ± 0.12 vs. 0.16 ± 0.12 P = 0.021) and the apoptotic index was significantly higher compared to women without prolapse (0.04 ± 0.01 vs. 0.02 ± 0.03, P = 0.041). The fraction of smooth muscle in the vagina is significantly decreased and the rate of apoptosis is higher in women with anterior vaginal wall prolapse compared to women without prolapse.     

Caldesmon expression is decreased in women with anterior vaginal wall prolapse: a pilot study

Introduction and hypothesis  The purpose of this study is to compare vaginal caldesmon expression in women with and without anterior vaginal wall prolapse. Methods  Vaginal tissues were sampled in women with (n = 11) or without (n = 11) vaginal wall prolapse. Caldesmon messenger RNA (mRNA) expression was assessed by quantitative real-time polymerase chain reaction. Immunohistochemistry and digital image analysis were used to determine caldesmon protein expression in the histologic sections. Results  There were no significant differences in demographic data between the two groups. Caldesmon mRNA expression was significantly decreased in the vaginal tissue from women with anterior vaginal wall prolapse compared to women without prolapse [(caldesmon mean ± SD mRNA expression in relative units) 0.03 ± 0.03 vs 0.17 ± 0.17, P = 0.02]. The fractional area of nonvascular caldesmon staining in the vagina of women with anterior vaginal wall prolapse was significantly decreased compared to women without prolapse [mean ± SD (0.09 ± 0.04 vs 0.16 ± 0.09, P = 0.03)]. Conclusions  Vaginal caldesmon expression is significantly decreased in women with anterior vaginal wall prolapse compared to normal subjects.     

Fibulin-5 expression is decreased in women with anterior vaginal wall prolapse

The aim of this study was to compare fibulin-5 expression in women with and without anterior vaginal wall prolapse. Vaginal tissues were sampled in a standardized fashion from women with (n = 12) or without (n = 10) anterior vaginal wall prolapse. Quantitative real-time polymerase chain reaction was performed to measure mRNA levels of fibulin-5 (FIB-5). FIB-5 protein expression was assessed by immunohistochemistry. There were no significant differences in demographic data between the two groups. FIB-5 mRNA expression was significantly decreased in women with anterior vaginal wall prolapse compared to women without prolapse [(FIB-5 mean ± SD mRNA expression in relative units) 0.01 ± 0.01 vs. 0.09 ± 0.14, P = 0.04]. Fibulin-5 staining intensity was diminished in women with prolapse compared to women without prolapse [intensity score, median (range), 1 (1–2) vs. 3 (2–3), P = 0.04]. Fibulin-5 expression is decreased in vaginal biopsies from women with prolapse. Changes in fibulin expression may play a role in the development of pelvic organ prolapse.     

LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse

Introduction and Hypothesis  

The extracellular matrix proteins collagen and elastin provide tissue strength and resilience, whereas lysyl oxidase enzymes play a major role in their stabilization. This study examines the expression and tissue localization of lysyl oxidase family proteins in the anterior vaginal wall of premenopausal women with advanced pelvic organ prolapse (POP, n = 15) and asymptomatic controls (n = 11). All women were in the proliferative phase of menstrual cycle.     

Anterior vaginal wall length and degree of anterior compartment prolapse seen on dynamic MRI

The objective of the study was to determine the relationship between midsagittal vaginal wall geometric parameters and the degree of anterior vaginal prolapse. We have previously presented data indicating that about half of anterior wall descent can be explained by the degree of apical descent present (Summers et al., Am J Obstet Gynecol, 194:1438–1443, 2006). This led us to examine whether other midsagittal vaginal geometric parameters are associated with anterior wall descent. Magnetic resonance (MR) scans of 145 women from the prior study were suitable for analysis after eight were excluded because of inadequate visibility of the anterior vaginal wall. Subjects had been selected from a study of pelvic organ prolapse that included women with and without prolapse. All patients underwent supine dynamic MR scans in the midsagittal plane. Anterior vaginal wall length, location of distal vaginal wall point, and the area under the midsagittal profile of the anterior vaginal wall were measured during maximal Valsalva. A linear regression model was used to examine how much of the variance in cystocele size could be explained by these vaginal parameters. When both apical descent and vaginal length were considered in the linear regression model, 77% (R ² = 0.77, p < 0.001) of the variation in anterior wall descent was explained. Distal vaginal point and a measure anterior wall shape, the area under the profile of the anterior vaginal wall, added little to the model. Increasing vaginal length was positively correlated with greater degrees of anterior vaginal prolapse during maximal Valsalva (R ² = 0.30, p < 0.01) determining 30% of the variation in anterior wall decent. Greater degrees of anterior vaginal prolapse are associated with a longer vaginal wall. Linear regression modeling suggests that 77% of anterior wall descent can be explained by apical descent and midsagittal anterior vaginal wall length.     

Changes in elastin density in different locations of the vaginal wall in women with pelvic organ prolapse

Introduction and hypothesis

The purpose of this study was to analyze the histomorphometric properties of the vaginal wall in women with pelvic organ prolapse (POP).

Methods

In 15 women undergoing surgery for POP, full-thickness biopsies were collected at two different sites of location from the anterior and/or posterior vaginal wall. Properties of the precervical area (POP-Q point C/D) were compared with the most distal portion of the vaginal wall (POP-Q point Ba/Bp) using histological staining and immunohistochemistry. The densities of total collagen fibers, elastic fibers, smooth muscle cells, and blood vessels were determined by combining high-resolution virtual imaging and computer-assisted digital image analysis.

Results

The mean elastin density was significantly decreased in the lamina propria and muscularis layer of the vaginal wall from the most distal portion of the prolapsed vaginal wall compared with the precervical area. This difference was statistically significant in the lamina propria for both anterior (8.4?±?1.2 and 12.1?±?2.0, p?=?0.048) and posterior (6.8?±?0.5 and 10.1?±?1.4, p?=?0.040) locations, and in the muscularis for the anterior (5.2?±?0.4 and 8.4?±?1.2, p?=?0.009) vaginal wall. There were no statistically significant differences in the mean densities of collagen fibers, smooth muscle cells or blood vessels between the two locations.

Conclusions

In this study, we observed changes in elastin density in two different locations of the vaginal wall from women with POP. The histomorphometric properties of the vaginal wall can be variable from one place to another in the same patient. This result supports the existence of most vulnerable locations within the vaginal wall and the potential benefit of site-specific prolapse surgery.     

Complications of transvaginal monofilament polypropylene mesh in pelvic organ prolapse repair

Introduction and hypothesis  This study aimed to document intraoperative and postoperative complications associated with the use of transvaginal polypropylene mesh in the repair of pelvic organ prolapse (POP). Methods  This is a retrospective review of 127 cases of transvaginal repair of POP using synthetic mesh. Results  Mean postoperative value (±SD) for pelvic organ prolapse quantification (POPQ) measurements Aa, Ap, and C were: −2.4 ± 1.1 (cm), −2.4 ± 0.9 (cm), and −7.7 ± 1.2 (cm), respectively. The difference between preoperative and postoperative values of these points was significant (p < 0.0001). Mesh erosion rate was 13/127 (10.2%) with significant correlation between mesh erosion and concurrent vaginal hysterectomy (p = 0.008). Combined anterior and posterior vaginal mesh surgery increased the risk of intraoperative bleeding and blood transfusion (p < 0.05). Conclusions  Concurrent vaginal hysterectomy is associated with increased risk of vaginal mesh erosion. Combined anterior and posterior vaginal mesh repair is an increased risk factor for intraoperative bleeding and blood transfusion.     

The role of smooth muscle in the pathogenesis of pelvic organ prolapse—an immunohistochemical and morphometric analysis of the cervical third of the uterosacral ligament

The uterosacral ligament (USL) is part of the pelvic floor connecting the uterus to the dorsal body wall and stabilizing it. In samples obtained from hysterectomy patients, the smooth muscle component of the cervical third of the USL was studied by smooth muscle actin (SMA) immunohistochemistry as indicator for structural abnormalities and by morphometric determination of nuclear size as measure for the functional state. From a total of 40 patients, 18 were matched according to age, parity, and premenopausal status. Immunohistochemistry showed a granular patchy distribution of SMA in the pelvic organ prolapse (POP) group. In patients with POP, the size of smooth muscle cell nuclei was significantly reduced in comparison to patients without POP (25.45 ± 1.92 μm² vs 28.87 ± 2.92 μm², p < 0.05). We conclude that the smooth muscle component of the USL is impaired in POP patients, indicating a possible role of smooth muscle in the pathogenesis of POP. Christl Reisenauer and Thomas Shiozawa contributed equally to this publication.     

COL1A1 Sp1-binding site polymorphism as a risk factor for genital prolapse

The objective of this study was to verify the possible association between the Sp1-binding site polymorphism and genital prolapse. A case–control study was conducted in 107 patients with stages III and IV genital prolapse. The control group included 209 women with stages 0 and I. The polymorphism of type I collagen Sp1-binding site was identified by amplification of the first intron of the COL1A1 gene. We did not find differences in the prevalence of the GT and TT genotypes between the groups (p = 0.34), even when we grouped patients with at least one polymorphic allele (GT and TT) and compared them with patients without the polymorphic allele (GG; p = 0.17) The presence of at least one vaginal delivery, family history for prolapse, and macrosomatic fetus were independent risk factors for prolapse. In conclusion, the COL1A1 Sp1-binding site was not significantly associated with genital prolapse among our study subjects.     

Comparison of the main body of the external anal sphincter muscle cross-sectional area between women with and without prolapse

The aim of the study was to compare the main body of the external anal sphincter (EAS) cross-sectional area (CSA) of women with and without pelvic organ prolapse. Pelvic magnetic resonance imaging (MRI) scans of 40 women were selected for analysis. Of these women, 20 had pelvic organ prolapse and 20 had normal support. Of the women with normal support, 10 had known major levator ani (LA) muscle defects and 10 had normal LA muscles. The same was true for the women with pelvic prolapse: half had major LA defects and half had no LA defects. All patients had previously completed pelvic MRI in the supine position. 3-D models of the EAS were made and CSA of the EAS perpendicular to the fiber direction were measured circumferentially at 30° intervals. Univariable and multivariable analyses were performed. The mean CSA did not significantly differ between women with prolapse and normal support regardless of LA defect status (normal/−LA defect = 1.13 cm², prolapse/−LA defect = 0.86 cm², p = 0.065; normal/+LA defect = 1.08 cm², prolapse/+LA defect = 1.28 cm², p = 0.28). Women with prolapse and LA defects had a 49% larger mean muscle CSA compared to prolapse patients without LA defects (p = 0.01). This difference associated with defect status in prolapse patients was not seen in women with normal support. Women with prolapse alone had external anal sphincter CSAs that were comparable to women with normal support. However, women with both prolapse and a major levator ani defect had larger external anal sphincter CSAs compared to prolapse patients without levator ani defects.     

Do overactive bladder symptoms improve after repair of anterior vaginal wall prolapse?

This study aims to evaluate the changes of overactive bladder symptoms to anterior vaginal wall prolapse repair. Ninety-three consecutive women with symptomatic anterior vaginal wall prolapse ≥ stage II and coexistent overactive bladder symptoms were prospectively studied using a urinalysis, urodynamics, King’s Health Questionnaire (KHQ), Prolapse Quality of Life (P-QOL) questionnaire and pelvic organ prolapse quantification (POP-Q) system before and 1 year after surgery. All women underwent a standard fascial anterior repair. Postoperatively, urinary frequency, urgency and urge incontinence disappeared in 60, 70 and 82% of women respectively (p value < 0.001). The vaginal examination findings as well as the quality of life of the women assessed using KHQ and P-QOL significantly improved after surgery (p value < 0.001). This study has demonstrated that anterior vaginal repair does produce significant improvement in overactive bladder symptoms. A larger longer-term study is required to assess if these changes persist over time.     

Self-perceived natural history of pelvic organ prolapse described by women presenting for treatment

Introduction and hypothesis  This study aimed to describe the self-perceived natural history of pelvic organ prolapse (POP) in women seeking care. Methods  Women presenting to a university-based urogynecology clinic for POP (n = 107) completed a questionnaire including questions about how and when their prolapse was discovered. A urogynecologic examination including the pelvic organ prolapse quantification (POP-Q) was also performed. Results  Forty-eight percent of these women sought medical attention “immediately” after discovering a bulge. The median time to seek care was 4 months (range from 1 month to 45 years). Twenty-six percent associated their prolapse with a specific event (e.g., moving furniture or pushing a car). POP was self-discovered by 76% (81/107) of women. Self-discovered prolapses were larger than those diagnosed by physicians (Ba +1.3 vs 0.1 cm, P = .03, respectively). Conclusions  Women seek medical advice within months of discovering their prolapse. Self-discovery is associated with higher stage prolapse than prolapse diagnosed by health care providers.     

A Retrospective Comparison of Abdominal Sacrocolpopexy with Burch Colposuspension versus Sacrospinous Fixation with Transvaginal Needle Suspension for the Management of Vaginal Vault Prolapse and Coexisting Stress Incontinence

The objective of this study was to compare the surgical outcome of abdominal sacrocolpopexy and Burch colposuspension with sacrospinous fixation and transvaginal needle suspension in the management of vaginal vault prolapse and coexisting stress incontinence. One hundred and seventeen women with vaginal vault prolapse and coexisting stress incontinence were surgically managed over a 7-year period. The first 61 consecutive women who underwent sacrospinous fixation and transvaginal needle suspension comprised the vaginal group, and the following 56 consecutive women who underwent abdominal sacrocolpopexy and Burch colposuspension comprised the abdominal group. Office records were reviewed to assess the presence of recurrent prolapse and urinary incontinence during postoperative follow-up. Objective follow-up was available for 101 women. Mean duration of follow-up was 24.0 ± 15 months for the vaginal group, and 23.1 ± 12.6 months for the abdominal group. The incidence of recurrent prolapse to or beyond the hymen (33% vs. 19%, P = 0.0505) and lower urinary tract symptoms (26% vs. 13%, P = 0.0506) were significantly higher in the vaginal group than in the abdominal group. Our data suggest that the combined abdominal approach has a lower incidence of recurrent prolapse and lower urinary tract symptoms than the combined vaginal approach in managing vaginal vault prolapse and coexisting stress incontinence.     

Assessment of sexual function in women with pelvic floor dysfunction

Forty-seven women participated in a pilot study for a multi-centre randomized controlled trial of the effectiveness of pelvic floor muscle training (PFMT) for women with prolapse. Women with symptomatic stage I or II prolapse [measured by Pelvic Organ Prolapse Quantification (POP-Q)] were randomized to a 16-week physiotherapy intervention (PFMT and lifestyle advice; n = 23) or a control group receiving a lifestyle advice sheet (n = 24). Symptom severity and quality of life were measured via postal questionnaires. Blinded POP-Q was performed at baseline and follow-up. Intervention women had significantly greater improvement than controls in prolapse symptoms (mean score decrease 3.5 versus 0.1, p = 0.021), were significantly more likely to have an improved prolapse stage (45% versus 0%, p = 0.038) and were significantly more likely to say their prolapse was better (63% versus 24%, p = 0.012). The data support the feasibility of a substantive trial of PFMT for prolapse. A multi-centre trial is underway.     

Effect of anatomic urethral length on the correlation between the Q-tip test and descent at point Aa of the POP-Q system

The objective of this study is to evaluate the effect of anatomic urethral length on the relationship between descent at point Aa of the pelvic organ prolapse quantification (POP-Q) system and the Q-tip straining angle. The records of 323 patients who were evaluated for urinary incontinence were reviewed. Prolapse staging was performed using the POP-Q system. Urethrovesical junction hypermobility defined as a maximal straining angle ≥30° was assessed with the Q-tip test. Urethral length was measured with a urethral profilometer. A substantial correlation was found between descent at point Aa and the straining Q-tip angle (r = 0.65, p < 0.0001). There was no correlation between the anatomic urethral length and straining Q-tip angle (r = −0.01, p = 0.8). Urethral length does not affect the straining Q-tip angle. Point Aa is a strong predictor of an abnormal straining Q-tip angle in women with stage I anterior vaginal wall prolapse or greater.     

Uterosacral ligament in postmenopausal women with or without pelvic organ prolapse

The uterosacral ligaments are thought to contribute to pelvic support. The objective of this study was to compare the structural components of these ligaments in women with and without pelvic organ prolapse (POP). We characterized uterosacral ligaments of 25 postmenopausal women with POP and 16 controls histomorphologically and immunohistochemically by quantifying their content of collagen I, III, and smooth muscle using a computerized image analysis. In 84% the uterosacral ligaments were composed of more than 20% of smooth muscle cells. There was no difference in collagen I expression and smooth muscle cell amount between women with POP and those without. In contrast, the collagen III expression was significantly related to the presence of POP (p<0.001) rather than age or parity. Our findings suggest that the higher collagen III expression might be a typical characteristic of POP patients connective tissue. The considerable amount of smooth muscle cells in uterosacral ligaments may provide pelvic support.     

Sexual function following surgery for urodynamic stress incontinence

The objective of this study was to compare sexual function in women before and after surgery for urodynamic stress incontinence in the absence of pelvic organ prolapse. This was a prospective questionnaire survey. Fifty-four women undergoing surgery (tension-free vaginal tape/tension-free vaginal tape-obturator) for urodynamic stress incontinence with no evidence of detrusor overactivity or concomitant prolapse were assessed preoperatively and 6 months post operatively. Assessment was based on the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ), the International Consultation on Incontinence Questionnaire (ICIQ) and the Patient Global Impression of Improvement. Paired t-tests were used for comparing pre- and post-op scores and unpaired t-tests for comparing observations between groups. Spearman’s rank correlation was used for testing whether two numerically scored items were related, and McNemar test was used to compare pre- and postoperative responses to individual questions. ICIQ scores showed significant improvement after surgery (p < 0.001). Women completing PISQ were significantly younger (mean = 54) than those who did not (mean = 65; p < 0.001). The total PISQ score was better postoperatively (preoperative = 87.2, postoperative = 92.7; p < 0.001), with improvements in both the physical (preoperative = 31.0, postoperative = 35.2; p < 0.001) and partner-related domains (preoperative = 18.8, postoperative = 19.9; p = 0.002) but no improvement in behaviour emotive domains (preoperative = 37.3, postoperative = 37.6; p = 0.70). There was a reduction in episodes of coital incontinence postoperatively (preoperatively = 16/54, postoperatively = 39/54; p < 0.002). Previous vaginal surgery, oestrogen status of respondents and hysterectomy status did not affect the PISQ. Surgical correction of stress incontinence is associated with an improvement in sexual function.     

The prevalence of pelvic organ prolapse symptoms and signs and their relation with bladder and bowel disorders in a general female population

Introduction and hypothesis  In selected populations, pelvic organ prolapse (POP) was associated with bladder/bowel symptoms, but data on the general female population are lacking. Our aim was to obtain normative data on the prevalence of POP and pelvic floor dysfunction (PFD) symptoms and signs and to identify associations. Methods  Validated questionnaires on POP and PFD (urogenital distress inventory, (UDI) and defaecation distress inventory (DDI)) were sent to a general population of 2,979 women (aged 45–85 years). Data were analysed using the Kruskal–Wallis test, chi square test and Spearman’s rank correlation coefficient. Results  Response rate was 62.7%. Associations between POP stage and parity (0.002) and vaginal bulging (<0.001) are significant. Anatomical locations of POP and PFD symptoms correlated significantly with incontinence of flatus, feeling anal prolapse, manual evacuation of stool, vaginal bulging, constipation and pain during faecal urge (p ≤ 0.005). Conclusions  Strategies should be developed to alleviate obstructive bowel disorders associated with POP. Summary  POP was strongly associated with obstructive bowel disorders. Therefore, preventive strategies should be developed.     

Follow-up of prolapse surgery in rural Nepal

Pelvic organ prolapse (POP) is a significant problem in Nepal. Surgical treatment is scarcely available and little is known of the results of POP surgery on women living under burdensome circumstances. The aim of our study was to set up a follow-up program in rural Nepal and evaluate POP surgery. In 2004 and 2006, 74 women with a POP from remote areas around Dhulikhel Hospital underwent prolapse surgery. Together with local contacts men, a plan was made to implement a follow-up program. All the operated patients were invited to a follow-up visit in March 2007. Thirty-three (45%) patients attended the follow-up: 85% (n = 28) found the effect of the procedure an improvement. A satisfactory anatomic outcome was found in 93% (n = 32). A remarkable finding was the reduction in physical labour after the surgical procedure in 50% of the follow-up cases. Some adjustments in the follow-up program may contribute to a higher participation.