Preoperative prolapse phenotype is predictive of surgical outcome with minimally invasive sacrocolpopexy.

BACKGROUND: The gold-standard treatment for advanced pelvic organ prolapse is sacrocolpopexy. However, the preoperative features of prolapse that predict optimal outcomes are unknown. OBJECTIVE: This study aimed to develop a clinical prediction model that uses preoperative scores on the Pelvic Organ Prolapse Quantification examination to predict outcomes after minimally invasive sacrocolpopexy for stages 2, 3, and 4 uterovaginal prolapse and vaginal vault prolapse. STUDY DESIGN: A 2-institution database of pre- and postoperative variables from 881 cases of minimally invasive sacrocolpopexy was analyzed. Data from patients were analyzed in the following 4 groups: stage 2 uterovaginal prolapse, stage 3 to 4 uterovaginal prolapse, stage 2 vaginal vault prolapse, and stage 3 to 4 vaginal vault prolapse. Unsupervised machine learning was used to identify clusters and investigate associations between clusters and outcome. The k-means clustering analysis was performed with preoperative Pelvic Organ Prolapse Quantification points and stratified by previous hysterectomy status. The "optimal" surgical outcome was defined as postoperative Pelvic Organ Prolapse Quantification stage <2. Demographic variables were compared by cluster with Student t and chi-square tests. Odds ratios were calculated to determine whether clusters could predict the outcome. Age at surgery, body mass index, and previous prolapse surgery were used for adjusted odds ratios. RESULTS: Five statistically distinct prolapse clusters (phenotypes C, A, A>P, P, and P>A) were found. These phenotypes reflected the predominant region of prolapse (apical, anterior, or posterior) and whether support was preserved in the nonpredominant region. Phenotype A (anterior compartment prolapse predominant, posterior support preserved) was found in all 4 groups of patients and was considered the reference in the analysis. In 111 patients with stage 2 uterovaginal prolapse, phenotypes A and A>P (greater anterior prolapse than posterior prolapse) were found, and patients with phenotype A were more likely than those with phenotype A>P to have an optimal surgical outcome. In 401 patients with stage 3 to 4 uterovaginal prolapse, phenotypes C (apical compartment predominant, prolapse in all compartments), A, and A>P were found, and patients with phenotype A>P were more likely than those with phenotype A to have ideal surgical outcome. In 72 patients with stage 2 vaginal vault prolapse, phenotypes A, A>P, and P (posterior compartment predominant, anterior support preserved) were found, and those with phenotype A>P were less likely to have an ideal outcome than patients with phenotype A. In 297 patients with stage 3 to 4 vaginal vault prolapse, phenotypes C, A, and P>A (prolapse greater in posterior than in anterior compartment) were found, but there were no significant differences in rate of ideal outcome between phenotypes. CONCLUSION: Five anatomic phenotypes based on preoperative Pelvic Organ Prolapse Quantification scores were present in patients with stages 2 and 3 to 4 uterovaginal prolapse and vaginal vault prolapse. These phenotypes are predictive of surgical outcome after minimally invasive sacrocolpopexy. Further work needs to confirm the presence and predictive nature of these phenotypes. In addition, whether the phenotypes represent a progression of prolapse or discrete prolapse presentations resulting from different anatomic and life course risk profiles is unknown. These phenotypes may be useful in surgical counseling and planning.

Vaginal morphology and position associated with prolapse recurrence after vaginal surgery: A secondary analysis of the DEMAND study.

OBJECTIVE: To identify vaginal morphology and position factors associated with prolapse recurrence following vaginal surgery. DESIGN: Secondary analysis of magnetic resonance images (MRI) of the Defining Mechanisms of Anterior Vaginal Wall Descent cross-sectional study. SETTING: Eight clinical sites in the US Pelvic Floor Disorders Network. POPULATION OR SAMPLE: Women who underwent vaginal mesh hysteropexy (hysteropexy) with sacrospinous fixation or vaginal hysterectomy with uterosacral ligament suspension (hysterectomy) for uterovaginal prolapse between April 2013 and February 2015. METHODS: The MRI (rest, strain) obtained 30-42 months after surgery, or earlier for participants with recurrence who desired reoperation before 30 months, were analysed. MRI-based prolapse recurrence was defined as prolapse beyond the hymen at strain on MRI. Vaginal segmentations (at rest) were used to create three-dimensional models placed in a morphometry algorithm to quantify and compare vaginal morphology (angulation, dimensions) and position. MAIN OUTCOME MEASURES: Vaginal angulation (upper, lower and upper-lower vaginal angles in the sagittal and coronal plane), dimensions (length, maximum transverse width, surface area, volume) and position (apex, mid-vagina) at rest. RESULTS: Of the 82 women analysed, 12/41 (29%) in the hysteropexy group and 22/41 (54%) in the hysterectomy group had prolapse recurrence. After hysteropexy, women with recurrence had a more laterally deviated upper vagina (p = 0.02) at rest than women with successful surgery. After hysterectomy, women with recurrence had a more inferiorly (lower) positioned vaginal apex (p = 0.01) and mid-vagina (p = 0.01) at rest than women with successful surgery. CONCLUSIONS: Vaginal angulation and position were associated with prolapse recurrence and suggestive of vaginal support mechanisms related to surgical technique and potential unaddressed anatomical defects. Future prospective studies in women before and after prolapse surgery may distinguish these two factors.

Pubococcygeal Line Versus H-line as MR Defecography Reference for Bladder Descent.

INTRODUCTION AND HYPOTHESIS: Magnetic resonance defecography imaging techniques have been used widely to study pelvic floor function and diagnose pelvic organ prolapse (POP). The aim of this study was to investigate the diagnostic accuracy of the H-line to detect bladder descent compared with the current landmark, the pubococcygeal line (PCL). METHODS: In this retrospective cohort study, patients who underwent MR defecography in our medical center and were diagnosed with moderate to severe cystocele by radiological measurements were recruited. One rest image and one maximum evacuation image for each subject were used for the following measurements: bladder base perpendicular distance from the genital hiatus (GH), indicative of clinically significant bladder descent, PCL as the current radiological reference line, and the H-line, or minimal levator hiatus line, indicative of pelvic floor muscle and connective tissue support. Subjects were categorized as having clinically significant cystocele if the "bladder base" reached within 1 cm or lower of the GH (stage II or higher cystocele). A comparison was performed to assess differences and predictive capabilities of the reference lines relative to the GH measure. RESULTS: Seventy subjects were included, 30 with clinically significant bladder descent based on distance to GH. Women with bladder descent were older (64.0 ± 11.8 vs 51.2 ± 15.6, p < 0.001), had increased parity (3 [1-7] vs 2 [0-5], p = 0.009), and had a bladder that descended lower than the H-line at rest (1.9 ± 0.5 vs 2.2 ± 0.4, p = 0.003) and evacuation (-2.4 ± 1.6 vs -0.7 ± 1.1, p < 0.001). Multivariate regression analysis confirmed that age, length of the H-line at evacuation, the perpendicular distances between the H-line and the lowest bladder point at rest, and the PCL to the lowest bladder point at evacuation significantly correlated with bladder descent. Receiver operating characteristic analysis was used to identify a measurement threshold to diagnose clinically significant cystocele for both measurements, bladder base to the H-line: -1.2 (80.0, 72.5) area under the curve (AUC) 0.82, and bladder base PCL: -3.3 (77.8, 79.5) AUC 0.86. CONCLUSION: Our data support the application of using the minimal levator hiatus plane and specifically the H-line as a reliable landmark to diagnose bladder descent using MR defecography imaging.

Multimodal measurements of levator bowl volume in nulligravid asymptomatic women: endovaginal ultrasound versus MRI.

INTRODUCTION AND HYPOTHESIS: Measurements of levator bowl volume using advanced imaging, may be predictive of pelvic floor muscle function. The aim of this study was to compare the volume of the levator bowl using both magnetic resonance imaging (MRI) and endovaginal ultrasound (EVU) of healthy asymptomatic women. METHODS: All participants underwent a comprehensive interview including completion of the Pelvic Floor Distress Inventory Questionnaire-20 questionnaire, pelvic examination with a pelvic organ prolapse quantification evaluation, MRI, and EVU. The pelvic floor was segmented using Slicer and the MRI segmentations were trimmed using two methods: soft-tissue landmarks and the field of view (FOV) of the ultrasound volume. The levator bowl volume of the 3D segmented shapes was measured using Blender's 3D printing toolkit. Normality was tested using the Shapiro-Wilks test and comparisons were made using self-paired t tests. RESULTS: The final analysis included 19 patients. Levator bowl volume measured via MRI was larger than that measured in EVU (46.1 ± 7.9 cm3 vs 27.4 ± 5.9 cm3, p<0.001). Reducing the FOV of the MRI to that of EVU caused the MRI volume to be much closer to the EVU volume (35.5 ± 3.3 cm3 vs 27.4 ± 5.9 cm3, p<0.001); however, it remained significantly larger. CONCLUSION: Levator bowl volume measured using MRI was larger than that measured using EVU no matter the method of delineation of the levator muscles. Although EVU is safe, cheap, and easy to perform, it captures a smaller volume of levator bowel than MRI.

Quantifying the effect of an endo-vaginal probe on position of the pelvic floor viscera and muscles.

INTRODUCTION AND HYPOTHESIS: Endovaginal ultrasound has long been hypothesized to have a significant effect on locations of what it visualizes. However, little work has directly quantified its effect. This study aimed to quantify it. METHODS: This cross-sectional study consisted of 20 healthy asymptomatic volunteers who underwent both endovaginal ultrasound and MRI. The urethra, vagina, rectum, pelvic floor, and pubic bone were segmented in both ultrasound and MRI using 3DSlicer. Then, using 3DSlicer's transform tool the volumes were rigidly aligned based on the posterior curvature of the pubic bone. The organs were then split into thirds along their long axis to compare their distal, middle, and proximal sections. Using Houdini, we compared the location of the centroid of each of the urethra, vagina, and rectum and the surface-to-surface difference of the urethra and rectum. The anterior curvature of the pelvic floor was also compared. Normality of all variables was assessed by Shapiro-Wilk test. RESULTS: The largest amount of surface-to-surface distance was observed in the proximal region for the urethra and rectum. Across all three organs, the majority of the deviation was in the anterior direction for geometries obtained from ultrasound versus those from MRI. For each subject, the trace defining the midline of the levator plate was more anterior for ultrasound compared to MRI. CONCLUSIONS: While it has often been assumed that placing a probe in the vagina probably distorts the anatomy, this study quantified the distortion and displacement of the pelvic viscera. This allows for better interpretation of clinical and research findings based on this modality.

Quantifying the physiologic motions of the pelvic viscera during evacuation in nulligravid asymptomatic women.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) is often diagnosed during an in-office examination, which looks for motion of the vaginal wall while performing a strain maneuver. It is believed that the pelvic organs in adequately supported women are relatively stationary. This study was aimed at investigating the physiological displacements of pelvic organs using MR defecography. METHODS: This prospective cohort study included 19 volunteers. Midsagittal slices representing rest and the maximum movement of the posterior vaginal fornix during three maneuvers were identified. Normalized axes for analysis were defined as the x' (line connecting the inferior-posterior-most point on the pubic symphysis to the anterior edge of the sacrococcygeal joint) and the y' (line orthogonal to the x axis that passed through the sacral promontory). The positions of the posterior vaginal fornix, mid-vagina, bladder neck, anorectal junction, and hymen were recorded. These subjects were then analyzed using the current radiological grading system of POP to determine any overlap between asymptomatic subjects and diagnostic ranges of POP. RESULTS: Evacuation caused the most motion in the landmarks. The majority of the motion of the landmarks was along the y axis. The posterior vaginal fornix experienced significant descent (125% of the initial distance) without much anterior-posterior translation (7% of the initial distance) during defecation. All landmarks experienced similar trends. CONCLUSIONS: We have shown that there is significant rotational motion of the pelvic organs around the pubic bone in adequately supported women. This motion when described using radiological grading is likely to be considered mild or moderate prolapse, which may contribute to overdiagnosis of POP.

A Computational Procedure to Derive the Curve of Carus for Childbirth Computational Modeling.

Computational modeling serves an important role in childbirth-related research. Prescribed fetal descent trajectory is a key characteristic in childbirth simulations. Two major types of fully prescribed fetal descent trajectories can be identified in the literature: straight descent trajectories and curve of Carus. The straight descent trajectory has the advantage of being simpler and can serve as a reasonable approximation for relatively small fetal movements during labor, but it cannot be used to simulate the entire childbirth process. The curve of Carus is the well-recognized fetal descent trajectory with physiological significance. However, no detailed procedure to geometrically define the curve of Carus can be found in existing computational studies. This status of curve of Carus simulation in the literature hinders the direct comparison of results across different studies and the advancement of computational techniques built upon previous research. The goals of this study are: (1) propose a universal approach to derive the curve of Carus for the second stage of labor, from the point when the fetal head engages the pelvis to the point when the fetal head is fully delivered; and (2) demonstrate its utility when considering various fetal head sizes. The current study provides a detailed formulation of the curve of Carus, considering geometries of both the mother and the fetus. The maternal geometries were obtained from MRI data, and the fetal head geometries were based on laser scanning of a replica of a real fetal head.

Urethral support in female urinary continence part 1: dynamic measurements of urethral shape and motion.

INTRODUCTION AND HYPOTHESIS: Urethral closure mechanism dysfunction in female stress urinary incontinence (SUI) is poorly understood. We aimed to quantify these mechanisms through changes in urethral shape and position during squeeze (voluntary closure) and Valsalva (passive closure) via endovaginal ultrasound in women with varying SUI severity. METHODS: In this prospective cohort study, 76 women who presented to our tertiary center for urodynamic testing as preoperative assessment were recruited. Urodynamics were performed according to International Continence Society criteria. Urethral pressures were obtained during serial Valsalva maneuvers. Urethral lengths, thicknesses, and angles were measured in the midsagittal plane via dynamic anterior compartment ultrasound. Statistical shape modeling was carried out by a principal component analysis on aligned urethra shapes. RESULTS: Age, parity, and BMI did not vary by SUI group. Ultrasound detected a larger retropubic angle, urethral knee-pubic bone angle (a novel measure developed for this study), and infrapubic urethral length measurements at Valsalva in women with severe SUI (p = 0.016, 0.015, and 0.010). Shape analysis defined increased "c" shape concavity and distal wall pinching during squeeze and increased "s" shape concavity and distal wall thickening during Valsalva (p < 0.001). It also described significant urethral shape differences across SUI severity groups (p < 0.001). CONCLUSIONS: Dynamic endovaginal ultrasound can visualize and allow for quantification of voluntary and passive urethral closure and variations with SUI severity. In women with severe SUI, excessive bladder neck and distal urethra swinging during Valsalva longitudinally compressed the urethra, resulting in a proportionally thicker wall at the mid-urethra and urethral knee.

Urethral support in female urinary continence part 2: a computational, biomechanical analysis of Valsalva.

INTRODUCTION AND HYPOTHESIS: In Part 1, we observed urethral mechanics during Valsalva that oppose current continence theories. In this study, we utilize a finite element model to elucidate the role of supportive tissues on the urethra during Valsalva. By determining the sensitivity of urethral motion and deformations to variations in tissue stiffnesses, we formulate new hypotheses regarding mechanisms of urethral passive closure. METHODS: Anatomy was segmented from a nulliparous, continent woman at rest. The model was tuned such that urethral motion during Valsalva matched that observed in that patient. Urethra and surrounding tissue material properties were varied using Latin hypercube sampling to perform a sensitivity analysis. As in Part 1, urethral length, proximal and distal swinging, and shape parameters were measured at peak Valsalva for 50 simulations, and partial rank correlation coefficients were calculated between all model inputs and outputs. Cumulative influence factors determined which tissue properties were meaningfully influential (≥ 0.5). RESULTS: The material properties of the urethra, perineal membrane, bladder, and paraurethral connective tissues meaningfully influenced urethral motion, deformation, and shape. Reduction of the urethral stiffness and/or the perineal membrane soft constraint resulted in simulated urethral motions and shapes associated with stress urinary incontinence in Part 1. CONCLUSIONS: The data from Parts 1 and 2 suggest that connective tissues guide the controlled swinging motion and deformation of the urethra needed for passive closure during Valsalva. The swinging and kinking quantified in Part 1 and simulated in Part 2 are inconsistent with current continence theories.

3D quantitative analysis of normal clitoral anatomy in nulliparous women by MRI.

INTRODUCTION AND HYPOTHESIS: We present a 3D computational approach for automated clitoral measurements. We hypothesized that computationally derived measurements would be comparable and less variable than reported manual measures. METHODS: In this retrospective study, MRIs of 22 nulliparous women age 20-49 years with normal vaginal and clitoral anatomy were collected. Manual segmentations were performed to reconstruct 3D models of the whole clitoris (glans, body, crura, and bulbs) and vagina. The length, width, and volume of the clitoral structures and the distance between the vagina and clitoral structures were calculated. Computed clitoral morphometrics (length, width) were compared to median [range] values from a previously published cadaver study (N = 22) using the median test and Moses extreme reaction test. Calculated distances were compared to mean (± SD) reported by a 2D MRI study (N = 20) using independent t-test and Levene's test. RESULTS: Overall, computed clitoral morphometrics were similar to manual cadaver measurements, where the majority of length and width measures had ~1-2 mm difference and had less variability (smaller range). All calculated distances were significantly smaller and had smaller SDs than manual 2D MRI values, with two-fold differences in the means and SDs. Large variation was observed in clitoral volumetric measures in our cohort. CONCLUSIONS: The proposed 3D computational method improves the standardization and consistency of clitoral measurements compared to traditional manual approaches. The use of this approach in radiographic studies will give better insight into how clitoral anatomy relates to sexual function and how both are impacted by gynecologic surgery, where outcomes can assist treatment planning.

A soft elastomer alternative to polypropylene for pelvic organ prolapse repair: a preliminary study.

INTRODUCTION AND HYPOTHESIS: We compared the impact of a mesh manufactured from the soft elastomer polydimethylsiloxane (PDMS) to that of a widely used lightweight polypropylene (PP) mesh. To achieve a similar overall device stiffness between meshes, the PDMS mesh was made with more material and therefore was heavier and less porous. We hypothesized that the soft polymer PDMS mesh, despite having more material, would have a similar impact on the vagina as the PP mesh. METHODS: PDMS and PP meshes were implanted onto the vaginas of 20 rabbits via colpopexy. Ten rabbits served as sham. At 12 weeks, mesh-vagina complexes were explanted and assessed for contractile function, histomorphology, total collagen, and glycosaminoglycan content. Outcome measures were compared using one-way ANOVA and Kruskal-Wallis testing with appropriate post-hoc testing. RESULTS: Relative to sham, vaginal contractility was reduced following the implantation of PP (p = 0.035) but not the softer PDMS (p = 0.495). PP had an overall greater negative impact on total collagen and glycosaminoglycan content, decreasing by 53% (p < 0.001) and 54% (p < 0.001) compared to reductions of 35% (p = 0.004 and p < 0.001) with PDMS. However, there were no significant differences in the contractility, collagen fiber thickness, total collagen, and glycosaminoglycan content between the two meshes. CONCLUSIONS: Despite having a substantially higher weight, PDMS had a similar impact on the vagina compared to a low-weight PP mesh, implicating soft polymers as potential alternatives to PP. The notion that heavyweight meshes are associated with a worse host response is not applicable when comparing across materials.

Comparison of 2 single incision slings on the vagina in an ovine model.

BACKGROUND: Stress urinary incontinence carries a significant healthcare burden for women worldwide. Single incision slings are minimally invasive mesh devices designed to treat stress urinary incontinence. For prolapse repair, meshes with higher porosity and lower structural stiffness have been associated with improved outcomes. OBJECTIVE: In this study, we compared the higher stiffness, lower porosity Altis sling with the lower stiffness, higher porosity Solyx sling in an ovine model. We hypothesized that SIS-B would have a negative impact on the host response. STUDY DESIGN: A total of Altis and Solyx single incision slings were implanted suburethrally into sheep according to the manufacturer's instructions on minimal tension. The mesh-urethral-vaginal complex and adjacent ungrafted vagina (no mesh control) were harvested en bloc at 3 months. Masson's trichrome and picrosirius red staining of 6 µm thin sections was performed to measure interfiber distance and tissue integration. Smooth muscle contractility to a 120 mM KCl stimulus was performed in an organ bath to measure myofiber-driven contractions. Standard biochemical assays were used to quantify glycosaminoglycan, total collagen, and elastin content, and collagen subtypes. Bending stiffness was performed in response to a uniaxial force to define susceptibility to folding/buckling. Statistical analysis was performed using Mann-Whitney, Gabriel's pairwise post hoc, Wilcoxon matched-pairs, and chi-square tests. RESULTS: The animals had similar ages (3-5 years), parity (multiparous), and weights (45-72 kg). Trichrome cross sections showed that the Altis sling buckled in a "C" or "S" shape in most samples (8 of 11), whereas buckling after Solyx sling implantation was observed in only a single sample (1 of 13; P=.004). Tissue integration, as measured by the presence of collagen or smooth muscle between the mesh fibers on trichrome 4× imaging, was increased in samples implanted with the Solyx sling compared with the Altis sling (P<.05). Total collagen content decreased significantly with both products when compared with the ungrafted vagina consistent with stress shielding. There was no difference in the 2 groups with regard to glycosaminoglycan or elastin content. The Altis sling mesh tissue complex demonstrated significantly higher amounts of both collagen types I and III than the Solyx sling-implanted tissue and the ungrafted control. Smooth muscle contractility in response to 120 mM KCl was decreased after implantation of both slings compared with the sham (P=.011 and P<.01), with no difference between mesh types (P=.099). Bending stiffness in the Altis sling was more than 4 times lower than in the Solyx, indicating an increased propensity to buckle (0.0186 vs 0.0883). CONCLUSION: The structurally stiffer Altis sling had decreased tissue integration and increased propensity to buckle after implantation. Increased collagen types I and III after the implantation of this device suggests that these changes may be associated with a fibrotic response. In contrast, the Solyx sling largely maintained a flat configuration and had improved tissue integration. The deformation of the Altis sling is not an intended effect and is likely caused by its lower bending stiffness. Both meshes induced a decrease in collagen content and smooth muscle contractility similar to previous findings for prolapse meshes and consistent with stress shielding. The long-term impact of buckling warrants further investigation.

Defining mechanisms of recurrence following apical prolapse repair based on imaging criteria.

BACKGROUND: Prolapse recurrence after transvaginal surgical repair is common; however, its mechanisms are ill-defined. A thorough understanding of how and why prolapse repairs fail is needed to address their high rate of anatomic recurrence and to develop novel therapies to overcome defined deficiencies. OBJECTIVE: This study aimed to identify mechanisms and contributors of anatomic recurrence after vaginal hysterectomy with uterosacral ligament suspension (native tissue repair) vs transvaginal mesh (VM) hysteropexy surgery for uterovaginal prolapse. STUDY DESIGN: This multicenter study was conducted in a subset of participants in a randomized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Overall, 94 women with uterovaginal prolapse treated via native tissue repair (n=48) or VM hysteropexy (n=46) underwent pelvic magnetic resonance imaging at rest, maximal strain, and poststrain rest (recovery) 30 to 42 months after surgery. Participants who desired reoperation before 30 to 42 months were imaged earlier to assess the impact of the index surgery. Using a novel 3-dimensional pelvic coordinate system, coregistered midsagittal images were obtained to assess study outcomes. Magnetic resonance imaging-based anatomic recurrence (failure) was defined as prolapse beyond the hymen. The primary outcome was the mechanism of failure (apical descent vs anterior vaginal wall elongation), including the frequency and site of failure. Secondary outcomes included displacement of the vaginal apex and perineal body and change in the length of the anterior wall, posterior wall, vaginal perimeter, and introitus of the vagina from rest to strain and rest to recovery. Group differences in the mechanism, frequency, and site of failure were assessed using the Fisher exact tests, and secondary outcomes were compared using Wilcoxon rank-sum tests. RESULTS: Of the 88 participants analyzed, 37 (42%) had recurrent prolapse (VM hysteropexy, 13 of 45 [29%]; native tissue repair, 24 of 43 [56%]). The most common site of failure was the anterior compartment (VM hysteropexy, 38%; native tissue repair, 92%). The primary mechanism of recurrence was apical descent (VM hysteropexy, 85%; native tissue repair, 67%). From rest to strain, failures (vs successes) had greater inferior displacement of the vaginal apex (difference, -12 mm; 95% confidence interval, -19 to -6) and perineal body (difference, -7 mm; 95% confidence interval, -11 to -4) and elongation of the anterior vaginal wall (difference, 12 mm; 95% confidence interval, 8-16) and vaginal introitus (difference, 11 mm; 95% confidence interval, 7-15). CONCLUSION: The primary mechanism of prolapse recurrence following vaginal hysterectomy with uterosacral ligament suspension or VM hysteropexy was apical descent. In addition, greater inferior descent of the vaginal apex and perineal body, lengthening of the anterior vaginal wall, and increased size of the vaginal introitus with strain were associated with anatomic failure. Further studies are needed to provide additional insight into the mechanism by which these factors contribute to anatomic failure.

Transvaginal sacrospinous ligament suture rectopexy for obstructed defecation symptoms: 1-year outcomes.

INTRODUCTION AND HYPOTHESIS: The current study was aimed at investigating the safety, efficiency, and durability of transvaginal sacrospinous ligament suture rectopexy in women with obstructed defecation symptoms (ODS) and significant rectal hypermobility/folding. METHODS: This was a prospective case series study performed during December 2018 to July 2020. Women presenting to our center with pelvic organ prolapse electing for surgical treatment were screened for ODS utilizing the PFDI-20 questionnaire. Patients were eligible for inclusion if they reported OD symptoms accompanying >50% of bowel movements (BMs), BM frequency ≥3 per week, stool type 3 or 4 based on the Bristol stool chart, absence of dyssynergic Valsalva, and dynamic ultrasound indicating a rectal compression ratio >25%. Patients underwent transvaginal sacrospinous ligament rectopexy and were followed up at 2 and 12 months postoperatively. RESULTS: A total of 20 patients underwent the procedure and completed the follow-up. Statistically significant improvements were observed in all OD symptoms and subjective improvement (94.7% ± 13.4 and 90.6% ± 18) at 2 and 12 months after the surgery respectively. Mean rectal compression ratio, detected via ultrasound, improved from 45.5% ± 18.4 preoperatively to 9.2% ± 13.7 at 2 months (p < 0.0001) and 19.6% ± 14.4 at 12 months (p < 0.0012). Surgical failure, defined as combined subjective (ODS >50% of bowel movements) and anatomical failure (rectal compression ratio >25%), occurred in 2 patients. CONCLUSION: Transvaginal sacrospinous ligament suture rectopexy was safe, feasible, and effectively treated ODS within this cohort of women undergoing POP surgery with rectal hypermobility confirmed by dynamic ultrasound.

Methods for the defining mechanisms of anterior vaginal wall descent (DEMAND) study.

INTRODUCTION AND HYPOTHESIS: The protocol and analysis methods for the Defining Mechanisms of Anterior Vaginal Wall Descent (DEMAND) study are presented. DEMAND was designed to identify mechanisms and contributors of prolapse recurrence after two transvaginal apical suspension procedures for uterovaginal prolapse. METHODS: DEMAND is a supplementary cohort study of a clinical trial in which women with uterovaginal prolapse randomized to (1) vaginal hysterectomy with uterosacral ligament suspension or (2) vaginal mesh hysteropexy underwent pelvic magnetic resonance imaging (MRI) at 30-42 months post-surgery. Standardized protocols have been developed to systematize MRI examinations across multiple sites and to improve reliability of MRI measurements. Anatomical failure, based on MRI, is defined as prolapse beyond the hymen. Anatomic measures from co-registered rest, maximal strain, and post-strain rest (recovery) sequences are obtained from the "true mid-sagittal" plane defined by a 3D pelvic coordinate system. The primary outcome is the mechanism of failure (apical descent versus anterior vaginal wall elongation). Secondary outcomes include displacement of the vaginal apex and perineal body and elongation of the anterior wall, posterior wall, perimeter, and introitus of the vagina between (1) rest and strain and (2) rest and recovery. RESULTS: Recruitment and MRI trials of 94 participants were completed by May 2018. CONCLUSIONS: Methods papers which detail studies designed to evaluate anatomic outcomes of prolapse surgeries are few. We describe a systematic, standardized approach to define and quantitatively assess mechanisms of anatomic failure following prolapse repair. This study will provide a better understanding of how apical prolapse repairs fail anatomically.

Descent and hypermobility of the rectum in women with obstructed defecation symptoms.

INTRODUCTION AND HYPOTHESIS: Obstructed defecation symptoms (ODS) are common in women; however, the key underlying anatomic factors remain poorly understood. We investigated rectal mobility and support defects in women with and without ODS using pelvic floor ultrasound and MR defecography. METHODS: This prospective case-control study categorized subjects based on questions 7, 8 and 14 on the PFDI-20, which asks about obstructed defecation symptoms. All subjects underwent an interview, examination and pelvic floor ultrasound, and a subset of 16 subjects underwent MR defecography. The cul de sac-to-anorectal junction distance at rest and during maximum strain was measured on ultrasound and MRI images. The 'compression ratio' was calculated by dividing the change in rectovaginal septum length by its rest length to quantify rectal folding and hypermobility during dynamic imaging and to correlate with ODS. RESULTS: Sixty-two women were recruited, 32 cases and 30 controls. There were no statistically significant differences in age, parity, BMI or stage of rectocele between groups. A threshold analysis indicated the risk of ODS was 32 times greater (OR 32.5, 95% CI 4.8-217.1, p = 0.0003) among women with a high compression ratio (≥ 14) compared with those with a low compression ratio (< 14) after controlling for age, BMI, parity, stool type and BM frequency. CONCLUSIONS: Female ODS are associated with distinct alterations in rectal mobility and support that can be clearly observed on dynamic ultrasound. The defects in rectal support were quantifiable using a compression ratio metric, and these defects strongly predicted the likelihood of symptoms; interestingly, the presence or degree of rectocele defects played no role. These findings may provide new insight into the anatomic factors underlying female ODS.

Motion of the vaginal apex during strain and defecation.

INTRODUCTION AND HYPOTHESIS: Although the main function of the suspensory ligaments of the vaginal apex is to prevent its descent toward the vaginal introitus, there remains limited information regarding its normal physiological motion. This study was aimed at quantifying the motion of the non-prolapsed vaginal apex during strain and defecation maneuvers. METHODS: This study represents a sub-analysis of a parent study that was aimed at evaluating rectal mobility with regard to obstructed defecation symptoms. Patients with normal apical vaginal support who had undergone MR defecography were entered into the study. For each patient, midsagittal images at rest, maximum strain, and maximum evacuation were utilized. The location of the cervicovaginal junction, S4-S5 intervertebral disc, sacral promontory, and hymen were identified. Vectors were calculated from each of these landmarks to the vaginal apex to compare vector angles and magnitudes across subjects. RESULTS: Twelve patients were included in this study. At rest, the vagina extends from the hymen, which is inferior and posterior to the inferior symphysis pubis, to the vaginal apex at an angle of 45.2° ± 14.5° relative to the pubococcygeal line. This angle became more acute with strain and even more so during maximum evacuation (14.1° ± 9.0°, p < 0.001). Differences in the vector magnitude, although not statistically significant, showed a trend indicating shorter lengths with maximum evacuation. CONCLUSIONS: The vaginal apex is a highly mobile structure demonstrating significantly more mobility during defecation compared with strain. The data obtained contradict the general perception that the vaginal apex is relatively fixed within the pelvis of normally supported women.

The role of conventional pelvic floor reconstructive surgeries in obstructed defecation symptoms change: CARE and OPTIMAL trials sub-analysis of 2-year follow-up data.

INTRODUCTION AND HYPOTHESIS: The current study was aimed at addressing two questions: first, is any conventional vaginal prolapse repair effective in curing obstructed defecation symptoms, and second, is there evidence to suggest that a sacrocolpopexy will increase the risk of worsening or new-onset obstructed defecation symptoms? METHODS: This is a sub-analysis of two major clinical trials performed by the Pelvic Floor Disorders Network: the Colpopexy and Urinary Reduction Efforts (CARE) trial and the Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) trial. Two-year follow-up data were included. Demographics, pelvic organ prolapse quantification examination, and symptoms were compared between first, two surgical arms in the OPTIMAL study and second, CARE and OPTIMAL datasets using Chi-squared test for categorical variables and Student's t test or Mann-Whitney U test for continuous variables. RESULTS: A total of 353 subjects form the OPTIMAL study and 279 subjects from the CARE study met the inclusion criteria. Regardless of trial, obstructed defecation symptoms were present in more than half of the patients at the initial visit before the surgical intervention, and interestingly, about one third of the patients were symptomatic at the 24-month follow-up in all surgical groups. CONCLUSION: The conventional vaginal prolapse surgeries, with or without posterior vaginal wall repair, improved obstructed defecation symptoms by 50%, but about 35% of patients were suffering from at least one of the aspects of obstructed defecation at the 24-month follow-up. It is also important to note that about a quarter of the patients experienced persisting or worsening of their obstructed defecation symptoms in the absence of anatomical failure.

New Zealand white rabbit: a novel model for prolapse mesh implantation via a lumbar colpopexy.

INTRODUCTION AND HYPOTHESIS: New Zealand white rabbits are an inexpensive large-animal model. This study explored the rabbit as a model for mesh-augmented colpopexy using the intra-abdominal vagina. We hypothesized that polypropylene mesh would negatively impact rabbit vaginal smooth muscle (VSM) morphology and contractile function, similar to the nonhuman primate (NHP)-the established model for prolapse mesh evaluation. METHODS: Restorelle was implanted onto the vagina of ten rabbits via lumbar colpopexy after a hysterectomy. Ten rabbits served as sham. Twelve weeks post-implantation, the vagina was excised and VSM morphology and vaginal contractility were assessed. Outcome measures were compared using independent samples t and Mann-Whitney U tests with a Bonferroni correction, where appropriate. Results from the rabbits were compared with published NHP data. RESULTS: Animals had similar age, parity and BMI. VSM was 18% thinner after Restorelle implantation, P = 0.027. Vaginal contractility was 43% decreased in response to 120 mM KCl (P = 0.003), similar to the 46% reduction observed in the NHP vagina implanted with Restorelle (P = 0.027). Three meshes wrinkled in vivo, resulting in dramatic thinning of the underlying vagina in the area of the mesh causing a mesh exposure. CONCLUSIONS: Polypropylene mesh negatively impacts VSM morphology and vaginal contractility in the rabbit, similar to the NHP, suggesting that the rabbit may serve as an alternative large-animal model. The vaginal thinning and appearance of a mesh exposure in the area of a mesh wrinkle suggest the rabbit may also serve as a model for understanding the pathophysiology of mesh exposure.

Impact of polypropylene prolapse mesh on vaginal smooth muscle in rhesus macaque.

BACKGROUND: The use of polypropylene prolapse mesh to treat pelvic organ prolapse has been limited by mesh-related complications. Gynemesh PS mesh, implanted via sacrocolpopexy in rhesus macaques, had a negative impact on the vagina with thinning of vaginal muscularis and decreased vaginal smooth muscle contractility. The negative effect was attenuated when a bioscaffold derived from urinary bladder extracellular matrix was used as a composite with Gynemesh PS. OBJECTIVE: The objective of the study was to further elucidate the impact of Gynemesh PS polypropylene mesh and MatriStem extracellular matrix bioscaffolds on the vaginal smooth muscle in terms of micromorphology of vaginal smooth muscle (muscle bundles and individual myocytes), innervation, and nerve-mediated contractile function following their implantations in a rhesus macaque model via sacrocolpopexy. STUDY DESIGN: Thirty-two middle-aged rhesus macaques were randomized to undergo either a sham surgery (sham, n = 8), or the implantation of Gynemesh PS alone (n = 8) vs composite mesh comprised of Gynemesh PS plus 2-ply MatriStem (n = 8) vs 6-ply MatriStem alone (n = 8) via sacrocolpopexy. The graft-vagina complexes were harvested 3 months later. Histomorphometrics of smooth muscle bundles and myocytes were performed by immunofluorescent labeling of alpha smooth muscle actin, caveolin-3 (membrane protein), and cell nuclei followed by confocal imaging. The cross-sectional diameters of smooth muscle bundles and individual myocytes were quantified using images randomly taken in at least 5 areas of each section of sample. Contractile proteins alpha smooth muscle actin and smoothelin were quantified by Western immunoblotting. Nerve density was measured by immunohistochemical labeling of a pan-neuron marker, PGP9.5. Nerve-mediated smooth muscle contractility was quantified using electrical field stimulation. One-way analysis of variance and appropriate post hoc tests were used for statistical comparisons. RESULTS: Compared with sham, the implantation of Gynemesh PS alone resulted in a disorganized smooth muscle morphology with the number of small muscle bundles (cross-sectional diameter less than 20 µm) increased 67% (P = .004) and the myocyte diameter decreased 22% (P < .001). Levels of contractile proteins were all decreased vs sham with alpha smooth muscle actin decreased by 68% (P = .009), low-molecular-weight smoothelin by 51% (P = .014), and high-molecular-weight smoothelin by 40% (P = .015). Nerve density was decreased by 48% (P = .03 vs sham) paralleled by a 63% decrease of nerve-mediated contractility (P = .02). Following the implantation of composite mesh, the results of measurements were similar to sham (all P > .05), with a 39% increase in the myocyte diameter (P < .001) and a 2-fold increase in the level of alpha smooth muscle actin relative to Gynemesh (P = .045). Following the implantation of MatriStem alone, the number of small muscle bundles were increased 54% vs sham (P = .002), while the other parameters were not significantly different from sham (all P > .05). CONCLUSION: The implantation of Gynemesh PS had a negative impact on the structural and functional integrity of vaginal smooth muscle evidenced by atrophic macro- and microscopic muscle morphology, decreased innervation, and impaired contractile property, consistent with a maladaptive remodeling response. The extracellular matrix bioscaffold (MatriStem), when used with Gynemesh PS as a composite (2 ply), attenuated the negative impact of Gynemesh PS; when used alone (6 ply), it induced adaptive remodeling as evidenced by an increased fraction of small smooth muscle bundles with normal contractility.