Patient perspectives in adverse event reporting after vaginal apical prolapse surgery.

BACKGROUND: Many clinical trials use systematic methodology to monitor adverse events (AE) and determine grade (severity), expectedness, and relatedness to treatments as determined by clinicians. However, patient perspective in the process remains lacking. OBJECTIVES: To compare clinician versus patient grading of AE severity in a urogynecologic surgical trial. Secondary objectives were to estimate the association between patient grading of AEs with decision-making and quality of life outcomes and to determine if patient perspective changes over time. STUDY DESIGN: This was a planned supplementary study, "Patient-Perspectives in Adverse Event Reporting" (PPAR), to a randomized trial comparing 3 surgical approaches to vaginal apical prolapse. In the parent trial, AEs experienced by patients were collected per a standardized protocol every 6 months where clinicians graded AE severity (mild, moderate, severe/life threatening). In this sub-study, we obtained additional longitudinal patient perspectives for 19 predetermined "PPAR AEs". Patients provided their own severity grading (mild, moderate, severe/very severe/ life threatening) at initial assessment and at 12 and 36 months postoperatively. Clinicians and patients were masked to each other's reporting. The primary outcome was the interrater agreement (kappa statistic, κ) for AE severity between the initial clinician and patient assessment, combining patient grades of mild and moderate. Association between AE severity and the Decision-Regret Scale (DRS), Satisfaction with Decision Scale (SDS), the Short-Form Health Survey-12 (SF-12), and Patient-Global Impression of Improvement (PGI-I) scores were assessed utilizing Spearman's correlation coefficient (ρ) for continuous scales, Mantel-Haenszel chi-squared test for PGI-I, and T-tests or chi-squared tests comparing assessments of severe vs other grades. To describe patient perspective changes over time, the intra-observer agreement was estimated for AE severity grade over time using weighted kappa-coefficients. RESULTS: Of 360 patients randomized, 219 (61%) experienced a total of 527 PPAR AEs (91% moderate and 9% severe/life threatening by clinician grading). Mean patient age was 67 years, 87% were White, and 12% Hispanic. Of patients reporting any PPAR event, the most common were urinary tract infection (61%), de novo urgency urinary incontinence (35%), stress urinary incontinence (22%), and fecal incontinence (13%). Overall agreement between clinician and participant grading of severity was poor (κ=0.24 (95%CI 0.14, 0.34). Of 414 AEs clinicians graded as moderate, patients graded 120 (29%) mild, and 80 (19%) severe. Of 39 AEs graded severe by clinicians, patients graded 15 (38%) mild or moderate. Initial patient grading of the most severe reported AE was mildly correlated with worse DRS (ρ=0.2, p=0.01), SF-12 (ρ=-0.24, p<0.01) and PGI-I (p<0.01). There was no association between AE severity and SDS. Patients with an initial grading of "severe" had more regret, lower quality of life, and poorer global impressions of health than those whose worst severity grade was mild (p<0.05). Agreement between the patients' initial severity and later timepoints was fair at 12 months (κ=0.48 (95% CI 0.39, 0.58)) and 36 months (κ=0.45 (95% CI 0.37, 0.53)). CONCLUSIONS: Clinician and patient perceptions of AE severity are discordant. Worse severity from the patient perspective was associated with patient-centered outcomes. Including the patient perspective provides additional information for evaluating surgical procedures.

Regenerative Medicine in Gynecology.

The female reproductive tract undergoes dynamic changes across the life span. Congenital abnormalities, life events, and medical interventions can negatively affect the structure and function of reproductive tract organs, resulting in lifelong sequelae. The objective of regenerative gynecology is to discover and promote endogenous mechanisms by which a healthy tissue maintains overall tissue integrity after injury, after disease, or with age. In this review, we discuss some of the key state-of-the-art cell-based and scaffolding therapies that have been applied to regenerate gynecologic tissues and organs primarily in animal and tissue culture models. We further discuss the limitations of current technologies, problems of implementation and scalability, and future outlook of the field.

Dysregulated inflammatory response to urogynecologic meshes in women with diabetes and its implications.

BACKGROUND: Diabetes is an independent risk factor for mesh complications in women undergoing mesh-augmented surgical repairs of stress urinary incontinence and/or pelvic organ prolapse. The underlying mechanism remains unclear. OBJECTIVE: This study aimed to define the diabetes-associated alterations in the host inflammatory response to mesh and correlate them with perioperative glucose management. STUDY DESIGN: Deidentified demographics and medical records of patients who underwent mesh removal and participated in a mesh biorepository study were reviewed (n=200). In patients with diagnosed diabetes (n=25), blood glucose management before initial mesh implantation and before and after mesh removal was assessed by blood glucose and hemoglobin A1c levels. Age- and body mass index-matched tissue samples excised from patients with and without diabetes were examined. Transcriptomic profiles of immune cell markers, immune mediators, key inflammatory regulators, cell senescence, and epigenetic enzymes were determined by multiplex transcriptomic assays (NanoString). Ratios of apoptotic cells to CD68+ macrophages were examined with immunofluorescence. Protein profiles of 12 molecules involved in apoptotic cell clearance were examined with a multiplex protein assay (Luminex). RESULTS: Demographic and clinical characteristics, including duration between mesh implantation and removal, reason for removal, and type of mesh, etc., were comparable between patients with and without diabetes, except for 11.6% higher body mass index in the former (P=.005). In patients with diabetes, suboptimal management of blood glucose following mesh implantation was observed, with 59% of the patients having loosely or poorly controlled glucose before and after the mesh removal. Ongoing chronic inflammatory response was observed in the excised mesh-tissue complexes in both groups, whereas markers for M2 macrophages (Mrc1 [mannose receptor C-type 1]) and helper T cells (Cd4 [CD4 molecule]) were increasingly expressed in the diabetic vs nondiabetic group (P=.023 and .047, respectively). Furthermore, the gene expressions of proinflammatory Ccl24 (C-C motif chemokine ligand 24) and Ccl13 (C-C motif chemokine ligand 13) were upregulated by 1.5- and 1.8-fold (P=.035 and .027, respectively), whereas that of Il1a (interleukin 1 alpha) was paradoxically downregulated by 2.2-fold (P=.037) in the diabetic vs nondiabetic group. Interestingly, strong positive correlations were found between the expression of Ccl13, Setdb2 (SET domain bifurcated histone lysine methyltransferase 2), and M2 macrophage markers, and between the expression of Il1a, Fosl1 (activator protein-1 transcription factor subunit), and dendritic cell markers, suggesting the involvement of macrophages and dendritic cells in the diabetes-dysregulated proinflammatory response. Supportively, apoptotic cell clearance, which is an important function of macrophages, appeared to be impaired in the diabetic group, with a significantly increased protein level of CALR (calreticulin), an "eat-me" signal on the surface of apoptotic cells (P=.031), along with an increase of AXL (AXL receptor tyrosine kinase) (P=.030), which mediates apoptotic cell clearance. CONCLUSION: Diabetes was associated with altered long-term inflammatory response in complicated mesh implantation, particularly involving innate immune cell dysfunction. Suboptimal blood glycemic control following mesh implantation may contribute to this immune dysregulation, necessitating further mechanistic studies.

Management of mixed urinary incontinence: IUGA committee opinion.

INTRODUCTION AND HYPOTHESIS: Mixed urinary incontinence (MUI) is defined by the International Urogynecology Association (IUGA) and International Continence Society as the complaint of involuntary leakage of urine associated with urgency and also with exertion, effort, sneezing or coughing. It therefore implies the coexistence of both stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). MUI is a heterogeneous diagnosis that requires an assessment of its individual components of SUI and UUI. Management requires an individualised approach to the symptom components. The aim of this review is to identify the assessment/investigations and management options for MUI. METHODS: A working subcommittee from the IUGA Research & Development (R&D) Committee was created and volunteers invited from the IUGA membership. A literature review was performed to provide guidance focused on the recommended assessment and management of MUI. The document was then evaluated by the entire IUGA R&D Committee and IUGA Board of Directors and revisions made. The final document represents the IUGA R&D Committee Opinion. RESULTS: The R&D Committee MUI opinion paper provides guidance on the assessment and management of women with MUI and summarises the evidence-based recommendations. CONCLUSIONS: Mixed urinary incontinence is a complex problem and successful management requires alleviation of both the stress and urge components. Care should be individualised based on patient preferences. Further research is needed to guide patients in setting goals and to determine which component of MUI to treat first. The evidence for many of the surgical/procedural treatment options for MUI are limited and needs to be explored in more detail.

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.

The Use of Disposable Supplies: Measuring Suburethral Sling Surgical Waste by Cost and Weight.

IMPORTANCE: The health care industry is a leading contributor to solid waste in the United States, and two thirds of a hospital's regulated medical waste is produced from surgery. OBJECTIVE: The primary objective was to assess the utilization of single-use disposable supplies during suburethral sling cases. STUDY DESIGN: We observed suburethral sling plus cystoscopy procedures at an academic medical center. Cases with concomitant procedures were excluded. Our primary outcome was the quantity of wasted supplies, defined as disposable supplies that were opened at the start of the procedure and were unused. Secondarily, we quantified those supplies in both weight and United States dollars. In a subset of cases, we obtained the weight of the total amount of trash generated from the procedure. RESULTS: A total of 20 cases were observed. Most frequently wasted items included an emesis basin, large ring basin, and rectangle plastic tray. Redundant supplies wasted included a 1-L sterile water bottle and, on average, 2.73 (SD, 2.34) blue towels. The sum of the weight of the wasted items among cases was 1.33 lb, associated with $9.50. The average total amount of trash produced from 11 cases was 14.13 lb (SD, 2.27). Removal of the most frequently wasted items would achieve a 9.4% reduction in solid waste produced by the case. CONCLUSIONS: A large waste burden per surgical case was produced by a minor procedure. Removal of frequently wasted items, a reduced number of towels, and smaller cystoscopy fluid bags are simple strategies that would decrease overall waste production.

Sacrum and Coccyx Shape Changes During Pregnancy and After Delivery.

Remodeling of the sacrum and coccyx to accommodate pregnancy and delivery has been hypothesized but not directly quantified. This study aimed to quantify the remodeling of the sacrum and coccyx by comparing midsagittal lengths, angles, curvature, and shape between nulliparous, pregnant, and parous women using both 2 and 3 dimensional measures. Ninety pelvic magnetic resonance images of the pelvis were retrospectively collected and segmented. Twelve length, angle, and curvature measurements were made using definitions from previous literature on the midsagittal plane to define the sacrum, coccyx, and combined sacrum-coccyx shape. These measures were followed by a statistical shape analysis, which returned modes of variation and principal component scores. A separate MANCOVA analysis was conducted for both the 2D and 3D measures. The 2D and 3D analyses agreed that pregnant women had a significantly straighter coccyx and combined sacrum/coccyx than nulliparous (9.1% and 5.6%, respectively) and parous (7.5% and 2.7%, respectively) subjects. All comparisons showed that, on average, a pregnant woman's sacrum and coccyx were significantly straighter than their nulliparous counterparts. Then after delivery, the sacrum/coccyx returned, but not completely back to a more curved configuration.

Dysregulated wound healing in the pathogenesis of urogynecologic mesh complications.

To test the hypothesis that dysregulated wound healing is associated with Urogynecologic mesh complications, we collected vaginal cell secretions using vaginal swabs after polypropylene mesh implantation in patients with (N = 39) and without (N = 40) complication. A customized multiplex immunoassay measured markers of inflammation (MCP-1, IGFBP-1, IL-2, IL-10, IL-17, PDGF-BB, bFGF, IL-1b, IL-6, IL-12p70, TNF-α), neuroinflammation (IL-1RA, TGF-ß, IL-15, IL-18, IL-3, M-CSF), angiogenesis (VEGF), and matrix proteins (fibronectin, tenasin c, thrombospondin-2, lumican) between groups. Patients with complications were younger, heavier, implanted with mesh longer, and more likely to be ever smokers. A 5 kg/m2 BMI increase and ever-smoking were associated with a 2.4-fold and sixfold increased risk of complication, respectively. Patients with the highest tertile of bFGF, fibronectin, thrombospondin-2, TNF-ß, or VEGF had an odds ratio (OR) of 11.8 for having a mesh complication while ≥ 3 elevated had an OR of 237 while controlling for age, BMI, and smoking. The highest tertile of bFGF, thrombospondin-2, and fibronectin together perfectly indicated a complication (P < 0.0001). A receiver-operator curve for high bFGF, thrombospondin-2, and fibronectin showed excellent discrimination between complications and controls (AUC 0.87). These data provide evidence of dysregulated wound healing in mesh complications. Modifiable factors provide potential targets for patient counseling and interventions.

Twelve Month Outcomes of Pelvic Organ Prolapse Surgery in Patients With Uterovaginal or Posthysterectomy Vaginal Prolapse Enrolled in the Multicenter Pelvic Floor Disorders Registry.

OBJECTIVE: The aim of the study was to compare 12-month subjective and objective outcomes between 3 approaches to apical pelvic organ prolapse (POP) surgery in patients presenting with uterovaginal or posthysterectomy vaginal prolapse enrolled in the Pelvic Floor Disorders Registry for Research. STUDY DESIGN: This was an analysis of a multicenter, prospective registry that collected both patient- and physician-reported data for up to 3 years after conservative (pessary) and surgical treatment for POP. Twelve-month subjective and anatomic outcomes for patients who underwent surgical treatment were extracted from the registry for analysis. Pelvic organ prolapse recurrence was defined as a composite outcome and compared between the 3 apical surgery groups (native tissue repair, sacrocolpopexy, colpocleisis) as well as the 2 reconstructive surgery groups (native tissue repair and sacrocolpopexy). RESULTS: A total of 1,153 women were enrolled in the registry and 777 (67%) opted for surgical treatment, of whom 641 underwent apical repair and were included in this analysis (404 native tissue repair, 187 sacrocolpopexy, and 50 colpocleisis). The overall incidence of recurrence was as follows: subjective 6.5%, anatomic 4.7%, retreatment 7.2%, and composite 13.6%. The incidence of recurrence was not different between the 3 surgical groups. When baseline patient characteristics were controlled for, composite POP recurrence between the native tissue and sacrocolpopexy groups remained statistically nonsignificant. Concurrent perineorrhaphy with any type of apical POP surgery was associated with a lower risk of recurrence (adjusted odds ratio, 0.43; 95% confidence interval, 0.25-0.74; P = 0.002) and prior hysterectomy was associated with a higher risk (adjusted odds ratio, 1.77, 95% confidence interval, 1.04-3.03; P = 0.036). CONCLUSION: Pelvic Floor Disorders Registry for Research participants undergoing native tissue apical POP repair, sacrocolpopexy, and colpocleisis surgery had similar rates of POP recurrence 12 months after surgery.

Deformation and Durability of Soft Three-Dimensional-Printed Polycarbonate Urethane Porous Membranes for Potential Use in Pelvic Organ Prolapse.

Pelvic organ prolapse (POP) is the herniation of the pelvic organs into the vaginal space, resulting in the feeling of a bulge and organ dysfunction. Treatment of POP often involves repositioning the organs using a polypropylene mesh, which has recently been found to have relatively high rates of complications. Complications have been shown to be related to stiffness mismatches between the vagina and polypropylene, and unstable knit patterns resulting in mesh deformations with mechanical loading. To overcome these limitations, we have three-dimensional (3D)-printed a porous, monofilament membrane composed of relatively soft polycarbonate-urethane (PCU) with a stable geometry. PCU was chosen for its tunable properties as it is comprised of both hard and soft segments. The bulk mechanical properties of PCU were first characterized by testing dogbone samples, demonstrating the dependence of PCU mechanical properties on its measurement environment and the effect of print pathing. The pore dimensions and load-relative elongation response of the 3D-printed PCU membranes under monotonic tensile loading were then characterized. Finally, a fatigue study was performed on the 3D-printed membrane to evaluate durability, showing a similar fatigue resistance with a commercial synthetic mesh and hence its potential as a replacement.

Going green in gynecology: a call to action.

The climate change crisis poses a central threat to public health. The health outcomes of this crisis are well known, but lesser known to medical professionals is the role that healthcare delivery plays in worsening this crisis. The United States healthcare system is responsible for producing 10% of the total greenhouse gases. The adverse health outcomes caused by the overall healthcare system emissions in the United States is estimated to be 470,000 disability-adjusted life years lost, which is commensurate with the 44,000 to 98,000 people who die in hospitals each year in the United States as a consequence of preventable medical errors. Factors that contribute to healthcare greenhouse gas emissions include emissions from our facilities and from the purchase, transport, and use of supplies and waste. In the purview of obstetrics and gynecology, providers should minimize their use of disposable supplies, replace single-use specula with stainless steel specula, and educate themselves and operating room staff about best waste disposal practices. In addition, they can use their individual and collective voice to advocate for sustainable energy and supply practices. A transformation in the way we supply and power our hospitals is needed, and providers should be early adopters of this transformational change. Physician buy-in is essential to decrease the carbon footprint of our care. This narrative is a call to action for obstetricians and gynecologists to reduce our carbon footprint as a public health measure to uphold the quality of care we provide to women.

Morphological Variation in the Pelvic Floor Muscle Complex of Nulliparous, Pregnant, and Parous Women.

Specific levator ani muscle imaging measures change with pregnancy and vaginal parity, though entire pelvic floor muscle complex (PFMC) shape variation related to pregnancy-induced and postpartum remodeling has never been quantified. We used statistical shape modeling to compute the 3D variation in PFMC morphology of reproductive-aged nulliparous, late pregnant, and parous women. Pelvic magnetic resonance images were collected retrospectively and PFMCs were segmented. Modes of variation and principal component scores, generated via statistical shape modeling, defined significant morphological variation. Nulliparous (have never given birth), late pregnant (3rd trimester), and parous (have given birth and not currently pregnant) PFMCs were compared via MANCOVA. The overall PFMC shape, mode 2, and mode 3 significantly differed across patient groups (p < 0.001, = 0.002, = 0.001, respectively). This statistical shape analysis described greater perineal and external anal sphincter descent, increased iliococcygeus concavity, and a proportionally wider mid-posterior levator hiatus in late pregnant compared to nulliparous and parous women. The late pregnant group was the most divergent, highlighting differences that likely reduce the mechanical burden of vaginal childbirth. This robust quantification of PFMC shape provides insight to pregnancy and postpartum remodeling and allows for generation of representative non-patient-specific PFMCs that can be used in biomechanical simulations.

Reducing pelvic floor injury by induction of labor.

INTRODUCTION AND HYPOTHESIS: We hypothesized that elective induction of labor (eIOL) at 39 weeks is protective of levator ani muscle injury (LAMI) and is associated with decreased pelvic symptoms at 6 weeks postpartum compared to expectant management of labor. METHODS: Prospective cohort pilot study of uncomplicated, primiparous women with a singleton, vertex gestation enrolled immediately post-vaginal delivery (VD). Subjects were dichotomized into two groups based on labor management: eIOL without complication defined by the ARRIVE trial versus spontaneous VD between 39 weeks0/7 and 42 weeks5/7 or no indication for IOL prior to 40 weeks5/7. The primary outcome was LAMI at 6 weeks postpartum as evidenced by any of the following ultrasound measures: (1) increased levator hiatal area (LHA) > 2500 mm2, (2) increased elasticity index (EI, > 75th quartile) or (3) levator enthesis avulsion. RESULTS: Analysis represents 45/102 consented women from July 2019-October 2020 (eIOL n = 22 and spontaneous VD, n = 23). Neither maternal, clinical, sociodemographic characteristics nor pelvic symptoms differed between groups. Fewer women had LAMI as defined by the primary outcome with eIOL (n = 5, 23.8%) compared to spontaneous VD (n = 15, 65.2%), p = 0.008. Levator enthesis was more deformable (increased EI) with spontaneous VD as compared to the eIOL [10.66 (8.99) vs. 5.68 (2.93), p = 0.046]. On univariate logistic regression women undergoing spontaneous VD had unadjusted OR of 6.0 (1.6-22.5, p = 0.008) of sustaining LAMI compared to those undergoing eIOL. CONCLUSIONS: Composite measures of LAMI though not pelvic floor symptoms were markedly increased in women undergoing spontaneous VD compared to those undergoing eIOL at 39 weeks.

Mesh deformation: A mechanism underlying polypropylene prolapse mesh complications in vivo.

Polypropylene meshes used in pelvic organ prolapse (POP) repair are hampered by complications. Most POP meshes are highly unstable after tensioning ex vivo, as evidenced by marked deformations (pore collapse and wrinkling) that result in altered structural properties and material burden. By intentionally introducing collapsed pores and wrinkles into a mesh that normally has open pores and remains relatively flat after implantation, we reproduce mesh complications in vivo. To do this, meshes were implanted onto the vagina of rhesus macaques in nondeformed (flat) vs deformed (pore collapse +/- wrinkles) configurations and placed on tension. Twelve weeks later, animals with deformed meshes had two complications, (1) mesh exposure through the vaginal epithelium, and (2) myofibroblast proliferation with fibrosis - a mechanism of pain. The overarching response to deformed mesh was vaginal thinning associated with accelerated apoptosis, reduced collagen content, increased proteolysis, deterioration of mechanical integrity, and loss of contractile function consistent with stress shielding - a precursor to mesh exposure. Regional differences were observed, however, with some areas demonstrating myofibroblast proliferation and matrix deposition. Variable mechanical cues imposed by deformed meshes likely induce these two disparate responses. Utilizing meshes associated with uniform stresses on the vagina by remaining flat with open pores after tensioning is critical to improving outcomes. STATEMENT OF SIGNIFICANCE: Pain and exposure are the two most reported complications associated with the use of polypropylene mesh in urogynecologic procedures. Most meshes have unstable geometries as evidenced by pore collapse and wrinkling after tensioning ex vivo, recapitulating what is observed in meshes excised from women with complications in vivo. We demonstrate that collapsed pores and wrinkling result in two distinct responses (1) mesh exposure associated with tissue degradation and atrophy and (2) myofibroblast proliferation and matrix deposition consistent with fibrosis, a tissue response associated with pain. In conclusion, mesh deformation leads to areas of tissue degradation and myofibroblast proliferation, the likely mechanisms of mesh exposure and pain, respectively. These data corroborate that mesh implantation in a flat configuration with open pores is a critical factor for reducing complications in mesh-augmented surgeries.

Complications Reported to the Food and Drug Administration: A Cross-sectional Comparison of Urogynecologic Meshes.

IMPORTANCE: The U.S. Food and Drug Administration uses the Manufacturer and User Facility Device Experience database to evaluate the safety of urogynecologic meshes; however, reports on individual meshes have not been characterized. OBJECTIVE: The aim of the study was to compare complications among available urogynecologic meshes reported to the Manufacturer and User Facility Device Experience database. STUDY DESIGN: This study is a cross-sectional analysis of medical device reports (MDRs) of urogynecologic mesh from January 2004 to March 2019, using the Reed Tech Navigator (LexisNexis), which codes MDRs. The percentage of reports containing specific complaints (not an adverse event rate) were compared with χ 2 tests with Dunn-Sidak correction. Correlations with time on market, mesh weight, stiffness, and porosity were determined. RESULTS: The 34,485 reports examined included 6 transvaginal meshes, 4 sacrocolpopexy meshes, and 10 midurethral slings. Most reported events were pain, erosion, and infection. For transvaginal prolapse, less than 10% of Uphold Lite (Boston Scientific) reports contained pain or erosion versus greater than 90% of Prolift/Prolift+M (Ethicon, P < 0.001). For sacrocolpopexy mesh, greater than 90% of Gynemesh (Ethicon; Prolift in vaginal form) reports included erosion and pain versus less than 60% for Artisyn (Ethicon), Restorelle (Colpoplast), and Upsylon (Boston Scientific, P < 0.0001). For slings, Gynecare TVT Obturator had the highest proportion of erosion and pain complaints. Heavier sling meshes had more reports. When Ascend (Caldera Medical), an outlier with only 5 reports, was excluded, transvaginal mesh stiffness correlated strongly with number of reports. For transvaginal meshes, number of reports correlated with time on market (ρ = 0.8, P = 0.04). CONCLUSIONS: Individual meshes have different properties with different complication profiles, which should inform mesh development and use. Gynemesh MDRs included pain and erosion more frequently than others. Comprehensive registries are needed.

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.

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

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