Perioperative outcomes following pelvic floor reconstruction in women with hereditary disorders of connective tissue: a retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: Women with hereditary disorders of connective tissue (HDCT) are at increased risk of pelvic organ prolapse (POP) and stress urinary incontinence (SUI). We hypothesized that patients would have increased incidence and severity of perioperative complications up to 6 weeks after surgeries for POP/SUI. Secondary objectives were to compare pre- and post-operative pelvic floor symptoms and anatomical support as well as pelvic floor disorder recurrence. METHODS: In this multi-center retrospective cohort study, we identified patients with HDCTs by patient history and ICD-9 codes over an 11-year period. Controls without HDCTs were matched 2:1 to the primary POP or SUI procedure and surgeon. Demographic characteristics, perioperative pelvic floor information and complications were collected. A sample size of 65 HDCT patients and 130 controls was calculated to detect a 20% difference in complications with 80% power and alpha of 0.05. RESULTS: We identified 59 HDCT patients and 118 controls. Of the women with HDCTs, 49% had Ehlers-Danlos, 22% joint hypermobility syndrome, 15% Marfan syndrome, and 14% had others. Compared with controls, HDCT patients had more total perioperative complications (46% vs 22%, p = 0.002); an age-adjusted relative risk of complications was 1.4 (CI 0.7-2.6). HDCT patients had more Clavien-Dindo grades I and II complications (p = 0.02, 0.03) and more hospital readmissions (14% vs 3%, p = 0.01) than controls. There was no difference in the incidence of specific complications nor was there a difference in recurrence of POP (10%) or SUI (11%) between groups. CONCLUSIONS: Patients with HDCTs had more Clavien-Dindo grade I and II complications following pelvic floor reconstructive surgery and more readmissions.

Sexual function after pelvic organ prolapse surgery: a systematic review comparing different approaches to pelvic floor repair.

OBJECTIVE: Women consider preservation of sexual activity and improvement of sexual function as important goals after pelvic organ prolapse surgery. This systematic review aimed to compare sexual activity and function before and after prolapse surgery among specific approaches to pelvic organ prolapse surgery including native tissue repairs, transvaginal synthetic mesh, biologic grafts, and sacrocolpopexy. DATA SOURCES: MEDLINE, Embase, and ClinicalTrials.gov databases were searched from inception to March 2021. STUDY ELIGIBILITY CRITERIA: Prospective comparative cohort and randomized studies of pelvic organ prolapse surgeries were included that reported the following specific sexual function outcomes: baseline and postoperative sexual activity, dyspareunia, and validated sexual function questionnaire scores. Notably, the following 4 comparisons were made: transvaginal synthetic mesh vs native tissue repairs, sacrocolpopexy vs native tissue repairs, transvaginal synthetic mesh vs sacrocolpopexy, and biologic graft vs native tissue repairs. METHODS: Studies were double screened for inclusion and extracted for population characteristics, sexual function outcomes, and methodological quality. Evidence profiles were generated for each surgery comparison by grading quality of evidence for each outcome across studies using a modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Screening of 3651 abstracts was performed and identified 77 original studies. The overall quality of evidence was moderate to high. There were 26 studies comparing transvaginal synthetic mesh with native tissue repairs, 5 comparing sacrocolpopexy with native tissue repairs, 5 comparing transvaginal synthetic mesh with sacrocolpopexy, and 7 comparing biologic graft with native tissue repairs. For transvaginal synthetic mesh vs native tissue repairs, no statistical differences were found in baseline or postoperative sexual activity, baseline or postoperative total dyspareunia, persistent dyspareunia, and de novo dyspareunia. Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form change scores were not different between transvaginal synthetic mesh and native tissue repairs (net difference, -0.3; 95% confidence interval, -1.4 to 0.8). For sacrocolpopexy vs native tissue repairs, baseline or postoperative sexual activity, baseline or postoperative total dyspareunia, de novo dyspareunia, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form score differences were not different. For biologic graft vs native tissue repairs, baseline or postoperative sexual activity, baseline or postoperative total dyspareunia, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form changes were also not different. For transvaginal synthetic mesh vs sacrocolpopexy, there was no difference in sexual activity and sexual function score change. Based on 2 studies, postoperative total dyspareunia was more common in transvaginal synthetic mesh than sacrocolpopexy (27.5% vs 12.2%; odds ratio, 2.72; 95% confidence interval, 1.33-5.58). The prevalence of postoperative dyspareunia was lower than preoperative dyspareunia after all surgery types. CONCLUSION: Sexual function comparisons are most robust between transvaginal synthetic mesh and native tissue repairs and show similar prevalence of sexual activity, de novo dyspareunia, and sexual function scores. Total dyspareunia is higher after transvaginal synthetic mesh than sacrocolpopexy. Although sexual function data are sparse in the other comparisons, no other differences in sexual activity, dyspareunia, and sexual function score change were found.

Risk factors predicting the loss of functional independence after obliterative procedures for pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: To determine the risk factors associated with loss of functional independence after obliterative procedures for pelvic organ prolapse (POP). METHODS: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database was used to collect data on women who underwent obliterative vaginal procedures from 2011 to 2016, using current procedural terminology (CPT) codes for LeFort colpocleisis (57120) and vaginectomy (57110). The criterion for loss of functional independence was a transition from a functionally independent status to a dependent status (discharge to a post-care facility) or death within the 30-day postoperative period. Multivariate regression analysis was utilized to determine factors associated with loss of functional independence. RESULTS: A total of 1847 women were included in the analysis. A loss of functional independence was noted in 50 of the 1847 women (2.6%). The women who suffered loss of functional independence were older than those who were independent postoperatively (mean age 79.3 years, SD 7.47 vs. 76.7 years, SD 8.1, respectively). On multiple logistic regression analysis, age ≥ 80 years (OR 2.8, 95% CI 1.4-5.5), American Society of Anesthesiologists (ASA) classification ≥ 3 (OR 2.3, CI 1.1-4.7) and length of stay ≥ 5 days (OR 15.2, 95% CI 6.2-37.1) remained significantly associated with an increased risk of loss of functional independence. CONCLUSIONS: Age ≥ 80 years, ASA classification ≥ 3 and longer length of stay are associated with an increased risk of loss of functional independence after an obliterative procedure for pelvic organ prolapse. Consideration of these factors during the preoperative decision-making process may help improve outcomes in this cohort.

Thermosensitive hydrogels deliver bioactive protein to the vaginal wall.

The pathophysiology and natural history of pelvic organ prolapse (POP) are poorly understood. Consequently, our approaches to treatment of POP are limited. Alterations in the extracellular matrix components of pelvic support ligaments and vaginal tissue, including collagen and elastin, have been associated with the development of POP in animals and women. Prior studies have shown the protease MMP-9, a key player of ECM degradation, is upregulated in vaginal tissues from both mice and women with POP. On the other hand, fibulin-5, an elastogenic organizer, has been found to inhibit MMP-9 in the vaginal wall. Hence, we hypothesized that prolonged release of fibulin-5 may delay progression of POP. To test the hypothesis, oligo (ethylene glycol)-based thermosensitive hydrogels were fabricated, characterized and then used to deliver fibulin-5 to the vaginal wall and inhibit MMP-9 activity. The results indicate that hydrogels are cell and tissue compatible. The hydrogels also prolong the ½ life of fibulin-5 in cultured vaginal fibroblasts and in the vaginal wall in vivo. Finally, fibulin-5-containing hydrogels resulted in incorporation of fibulin-5 into the vaginal matrix and inhibition of MMP-9 for several weeks after injection. These results support the idea of fibulin-5 releasing hydrogel being developed as a new treatment for POP.

Predictors of early postoperative voiding dysfunction and other complications following a midurethral sling.

BACKGROUND: The rates reported for postoperative urinary retention following midurethral sling procedures are highly variable. Determining which patients have a higher likelihood of failing a voiding trial will help with preoperative counseling prior to a midurethral sling. OBJECTIVE: The objective of the study was to identify preoperative predictors for failed voiding trial following an isolated midurethral sling. STUDY DESIGN: A retrospective, multicenter, case-control study was performed by including all isolated midurethral sling procedures performed between Jan. 1, 2010 to June 30, 2015, at 6 academic centers. We collected demographics, medical and surgical histories, voiding symptoms, urodynamic evaluation, and intraoperative data from the medical record. We excluded patients not eligible for attempted voiding trial after surgery (eg, bladder perforation requiring catheterization). Cases failed a postoperative voiding trial and were discharged with an indwelling catheter or taught intermittent self-catheterization; controls passed a voiding trial. We also recorded any adverse events such as urinary tract infection or voiding dysfunction up to 6 weeks after surgery. Bivariate analyses were completed using Mann-Whitney and Pearson χ2 tests as appropriate. Multivariable stepwise logistic regression was used to determine predictors of failing a voiding trial. RESULTS: A total of 464 patients had an isolated sling (70.9% retropubic, 28.4% transobturator, 0.6% single incision); 101 (21.8%) failed the initial voiding trial. At follow-up visits, 90.4% passed a second voiding trial, and 38.5% of the remainder passed on the third attempt. For the bivariate analyses, prior prolapse or incontinence surgery was similar in cases vs controls (31% vs 28%, P = .610) as were age, race, body mass index, and operative time. Significantly more of the cases (32%) than controls (22%) had a Charlson comorbidity index score of 1 or greater (P = .039). Overactive bladder symptoms of urgency, frequency, and urgency incontinence were similar in both groups as was detrusor overactivity in those with a urodynamic evaluation (29% vs 22%, P = .136), but nocturia was reported more in the cases (50% vs 38%, P = .046). Mean (SD) bladder capacity was similar in both groups (406 [148] mL vs 388 [122] mL, P = .542) as was maximum flow rate with uroflowmetry and pressure flow studies. Cases were significantly more likely to have a voiding type other than detrusor contraction: 37% vs 25%, P = .027, odds ratio, 1.79 (95% confidence interval, 1.07-3.00). There was no difference in voiding trial failures between retropubic and transobturator routes (23.1% vs 18.9%, P = .329). Within 6 weeks of surgery, the frequency of urinary tract infection in cases was greater than controls (20% vs 6%, P < .001; odds ratio, 3.51 [95% confidence interval, 1.82-6.75]). After passing a repeat voiding trial, cases were more likely to present with acute urinary retention (10% vs 3%, P = .003; odds ratio, 4.00 [95% confidence interval, 1.61-9.92]). For multivariable analyses, increasing Charlson comorbidity index increased the risk of a voiding trial failure; apart from this, we did not identify other demographic information among the patients who did not undergo urodynamic evaluation that reliably forecasted a voiding trial failure. CONCLUSION: The majority of women will pass a voiding trial on the first attempt after an isolated midurethral sling. Current medical comorbidities are predictive of a voiding trial failure, whereas other demographic/examination findings are not. Patients failing the initial voiding trial are at an increased risk of postoperative urinary tract infection or developing acute retention after passing a subsequent voiding trial.

Effects of preoperative local estrogen in postmenopausal women with prolapse: a randomized trial.

CONTEXT: Pelvic organ prolapse (POP) increases in prevalence with age; recurrence after surgical repair is common. OBJECTIVE: The objective of the study was to determine the effects of local estrogen treatment on connective tissue synthesis and breakdown in the vaginal wall of postmenopausal women planning surgical repair of POP. DESIGN: This was a randomized trial. SETTING: The study was conducted at an academic tertiary medical center. PATIENTS OR OTHER PARTICIPANTS: Postmenopausal women with a uterus and symptomatic anterior and/or apical prolapse at stage 2 or greater participated in the study. INTERVENTION: Estrogen (Premarin) or placebo cream for 6 weeks preoperatively was the intervention. MAIN OUTCOME MEASURES: Full-thickness anterior apical vaginal wall biopsies were obtained at the time of hysterectomy and analyzed for mucosa and muscularis thickness, connective tissue synthesis, and degradation. Serum levels of estrone and 17ß-estradiol were analyzed at baseline and the day of surgery using highly sensitive liquid chromatography-tandem mass spectrometry. RESULTS: Fifteen women per group (n = 30 total) were randomized; 13 per group underwent surgery. Among drug-adherent participants (n = 8 estrogen, n = 13 placebo), epithelial and muscularis thickness was increased 1.8- and 2.7-fold (P = .002 and P =.088, respectively) by estrogen. Collagen types 1α1 and 1α2 mRNA increased 6.0- and 1.8-fold in the vaginal muscularis (P < .05 for both); collagen type Ia protein increased 9-fold in the muscularis (P = .012), whereas collagen III was not changed significantly. MMP-12 (human macrophage elastase) mRNA was suppressed in the vaginal mucosa from estrogen-treated participants (P = .011), and matrix metalloprotease-9 activity was decreased 6-fold in the mucosa and 4-fold in the muscularis (P = .02). Consistent with menopausal norms, serum estrone and 17ß-estradiol were low and did not differ among the two groups. CONCLUSIONS: Vaginal estrogen application for 6 weeks preoperatively increased synthesis of mature collagen, decreased degradative enzyme activity, and increased thickness of the vaginal wall, suggesting this intervention improves both the substrate for suture placement at the time of surgical repair and maintenance of connective tissue integrity of the pelvic floor.

Patient preferences for uterine preservation and hysterectomy in women with pelvic organ prolapse.

OBJECTIVE: The purpose of this study was to describe patient preferences for uterine preservation and hysterectomy in women with pelvic organ prolapse symptoms and to describe predictors of preference for uterine preservation. STUDY DESIGN: This multicenter, cross-sectional study evaluated patient preferences for uterine preservation vs hysterectomy in women with prolapse symptoms who were being examined for initial urogynecologic evaluation. Before meeting the physician, the women completed a questionnaire that asked them to indicate their prolapse treatment preference (uterine preservation vs hysterectomy) for scenarios in which the efficacy of treatment varied. Patient characteristics that were associated with preferences were determined, and predictors for uterine preservation preference were identified with multivariable logistic regression. RESULTS: Two hundred thirteen women participated. Assuming outcomes were equal between hysterectomy and uterine preservation, 36% of the women preferred uterine preservation; 20% of the women preferred hysterectomy, and 44% of the women had no strong preference. If uterine preservation was superior, 46% of the women preferred uterine preservation, and 11% of the women preferred hysterectomy. If hysterectomy was superior, 21% of the women still preferred uterine preservation, despite inferior efficacy. On multivariable logistic regression, women in the South had decreased odds of preferring uterine preservation compared with women in the Northeast (odds ratio [OR], 0.17; 95% CI, 0.05-0.66). Women with at least some college education (OR, 2.87; 95% CI, 1.08-7.62) and those who believed that the uterus is important for their sense of self (OR, 28.2; 95% CI, 5.00-158.7) had increased odds for preferring uterine preservation. CONCLUSION: A higher proportion of women with prolapse symptoms who were examined for urogynecologic evaluation preferred uterine preservation, compared with hysterectomy. Geographic region, education level, and belief that the uterus is important for a sense of self were predictors of preference for uterine preservation.

Prolapse-related knowledge and attitudes toward the uterus in women with pelvic organ prolapse symptoms.

OBJECTIVE: The objective of the study was to describe the basic knowledge about prolapse and attitudes regarding the uterus in women seeking care for prolapse symptoms. STUDY DESIGN: This was a cross-sectional study of English-speaking women presenting with prolapse symptoms. Patients completed a self-administered questionnaire that included 5 prolapse-related knowledge items and 6 benefit-of-uterus attitude items; higher scores indicated greater knowledge or more positive perception of the uterus. The data were analyzed using descriptive statistics and multiple linear regression. RESULTS: A total of 213 women were included. The overall mean knowledge score was 2.2 ± 1.1 (range, 0-5); 44% of the items were answered correctly. Participants correctly responded that surgery (79.8%), pessary (55.4%), and pelvic muscle exercises (34.3%) were prolapse treatment options. Prior evaluation by a female pelvic medicine and reconstructive surgery specialist (beta = 0.57, P = .001) and higher education (beta = 0.3, P = .07) was associated with a higher mean knowledge score. For attitude items, the overall mean score was 15.1 (4.7; range, 6-30). A total of 47.4% disagreed with the statement that the uterus is important for sex. The majority disagreed with the statement that the uterus is important for a sense of self (60.1%); that hysterectomy would make me feel less feminine (63.9%); and that hysterectomy would make me feel less whole (66.7%). Previous consultation with a female pelvic medicine and reconstructive surgery specialist was associated with a higher mean benefit of uterus score (beta = 1.82, P = .01). CONCLUSION: Prolapse-related knowledge is low in women seeking care for prolapse symptoms. The majority do not believe the uterus is important for body image or sexuality and do not believe that hysterectomy will negatively affect their sex lives.

Vascular and ureteral anatomy relative to the midsacral promontory.

OBJECTIVE: The objective of the study was to further characterize the vascular and ureteral anatomy relative to the midsacral promontory, a landmark often used during sacrocolpopexy, and suggest strategies to avoid complications. STUDY DESIGN: Distances between the right ureter, aortic bifurcation, and iliac vessels to the midsacral promontory were examined in 25 unembalmed female cadavers and 100 computed tomography (CT) studies. Data were analyzed using Pearson χ(2), unpaired Student t test, and analysis of covariance. RESULTS: The average distance between the midsacral promontory and right ureter was 2.7 cm (range, 1.6-3.8 cm) in cadavers and 2.9 cm (range, 1.7-5.0 cm) on CT (P = .209). The closest cephalad vessel to the promontory was the left common iliac vein, the average distance being 2.7 cm (range, 0.95-4.75 cm) in cadavers and 3.0 cm (range, 1.0-6.1 cm) on CT (P = .289). The closest vessel to the right of the promontory was the internal iliac artery, with the average distance of 2.5 cm (range, 1.4-3.9 cm) in cadavers and 2.2 cm (range, 1.2-3.9 cm) on CT (P = .015). The average distance from the promontory to the aortic bifurcation was 5.3 cm (range, 2.8-9.7 cm) in cadavers and 6.6 cm (range, 3.1-10.1 cm) on CT (P < .001). The average distance from the aortic bifurcation to the inferior margin of the left common iliac vein was 2.3 cm (range, 1.2-3.9 cm) in cadavers and 3.5 cm (range, 1.7-5.6 cm) on CT (P < .001). CONCLUSION: The right ureter, right common iliac artery, and left common iliac vein are found within 3 cm from the midsacral promontory. A thorough understanding of the extensive variability in vascular and ureteral anatomy relative to the midsacral promontory should help avoid serious intraoperative complications during sacrocolpopexy.

Lowest colpopexy sacral fixation point alters vaginal axis and cul-de-sac depth.

OBJECTIVE: To determine the variation in vaginal axis and posterior cul-de-sac depth when the lowest suture used to attach the sacrocolpopexy mesh to the anterior longitudinal ligament is anchored at different levels. STUDY DESIGN: At five lumbosacral mesh attachment sites, the anterior vaginal wall axis angle was measured relative to a line between the lowest border of the pubic symphysis and fourth sacral (S4) foramen in 9 unembalmed cadavers. The vertical distance from S4 to the posterior mesh was measured as a surrogate of cul-de-sac depth. RESULTS: From a mesh fixation point at the lower border of S2 to a point at the lower border of L5, there was a 3-fold increase in both vaginal axis angle (13.04 ± 3.19 vs 42.88 ± 4.16 cm) and distance from S4 to the posterior mesh (2.50 ± 0.61 vs 7.38 ± 1.30 cm) between these points. CONCLUSION: During sacrocolpopexy, progressively cephalad sacral attachment increases vaginal axis angle and cul-de-sac depth.

Preventing L5-S1 discitis associated with sacrocolpopexy.

OBJECTIVE: To further characterize the anatomy of the fifth lumbar to first sacral (L5-S1) disc space and to provide anatomic landmarks that can be used to predict the locations of the disc, sacral promontory, and surrounding structures during sacrocolpopexy. METHODS: The lumbosacral anatomy was examined in 25 female cadavers and 100 computed tomography (CT) studies. Measurements were obtained using the midpoint of the sacral promontory as a reference. Data were analyzed using Pearson χ, unpaired Student's t test, and analysis of covariance. RESULTS: The average height of the L5-S1 disc was 1.8±0.3 cm (range 1.3-2.8 cm) in cadavers and 1.4±0.4 cm (0.3-2.3) on CT (P<.001). The average angle of descent between the anterior surfaces of L5 and S1 was 60.5±9 degrees (39.5-80.5 degrees) in cadavers and 65.3±8 degrees (42.6-88.6 degrees) on CT (P=.016). The average shortest distance between the S1 foramina was 3.4±0.4 cm in cadavers and 3.0±0.4 cm on CT (P<.001). The average height of the first sacral vertebra (S1) was 3.0±0.2 cm in cadavers and 3.0±0.3 on CT (P=.269). CONCLUSION: In the supine position, the most prominent structure in the presacral space is the L5-S1 disc, which extends approximately 1.5 cm cephalad to the "true" sacral promontory. During sacrocolpopexy, awareness of a 60-degree average drop between the anterior surfaces of L5 and S1 vertebra should assist with intraoperative localization of the sacral promontory and avoidance of the L5-S1 disc. The first sacral nerve can be expected approximately 3 cm from the upper surface of the sacrum and 1.5 cm from the midline. LEVEL OF EVIDENCE: II.

Surgical knot integrity: effect of suture type and caliber, and level of residency training.

OBJECTIVE: To evaluate if suture type and caliber or level of residency training affects strength and mode of failure of surgical knots. DESIGN: All residents in an obstetrics and gynecology training program were invited to tie knots on a bench model using 2 calibers (0 and 3-0) of 2 types of surgical suture (polyglactin 910 and polydioxanone). The failure load, mode of failure, and loop lengths of the knots were determined. SETTING: University of Texas Southwestern Medical Center, Dallas, Texas. PARTICIPANTS: Physicians enrolled in the University of Texas Southwestern Medical Center Obstetrics and Gynecology residency training program. RESULTS: Seventy-one of 73 residents participated. Knots tied with 0-caliber sutures had a higher mean failure load than those tied with 3-0 caliber sutures. For each type and caliber of suture, there were no differences in failure load between each level of residency training. However, senior residents tied knots with shorter loop lengths and had a lower proportion of knots that unraveled or slipped. CONCLUSIONS: Even though there were no differences in failure loads, senior residents tied tighter and more secure knots than their junior counterparts.

Methamphetamine use during pregnancy: maternal and neonatal implications.

OBJECTIVE: To report the demographic characteristics and clinical morbidity of methamphetamine-exposed pregnancies compared with control patients in a tertiary care, urban, academic medical center. METHODS: A single-site chart review from 2000 to 2006 was conducted. International Classification of Diseases, 9th Revision code 648.3x was used to identify potential study participants. Specific inclusion criteria required either a positive urine drug screen for methamphetamine use or by patient statement of methamphetamine use during pregnancy. Data from 276 identified patients were then compared with the 34,055 in the general obstetric population during the same period for various demographic factors and perinatal outcomes. RESULTS: Two hundred seventy-six patients responsible for 273 live births were identified between 2000 and 2006. Factors that were significantly associated with methamphetamine use were age younger than 20 years (9% methamphetamine compared with 16% control patients), non-Hispanic white ethnicity (55% compared with 71%), married (12% compared with 46%), preterm delivery (52% compared with 17%), low Apgar scores (6% compared with 1-2%), cesarean delivery (29% compared with 23%), and neonatal mortality (4% compared with 1%). Additionally, the maternal demographic characteristics suggested that these women were more likely to be unemployed, use other abusive substances, and have higher rates of domestic violence and adoption when compared with the control population. CONCLUSION: Methamphetamine use in pregnancy is complicated by more morbid maternal and neonatal outcomes when compared with the general obstetric population. Because the patients in this study were in a variety of ways demographically distinct, attempts to identify these patients early and intervene in an effort to improve pregnancy-related outcomes appears possible and warranted. LEVEL OF EVIDENCE: II.