Structural Changes in Brain White Matter Tracts Associated with Overactive Bladder Revealed by Diffusion Tensor MRI: Findings from a LURN Cross-Sectional Case-Control Study.

PURPOSE: To investigate structural changes in brain white matter tracts using diffusion tensor magnetic resonance imaging (DTI) in patients with overactive bladder (OAB). MATERIALS AND METHODS: Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control Symptoms of Lower Urinary Tract Dysfunction Research Network Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity (MD). OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form (OAB-q) and International Consultation on Incontinence Questionnaire-UI. The Lower Urinary Tract Symptoms (LUTS) Tool UUI questions and responses were correlated with FA values. RESULTS: Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency [UU]-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased MD, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and para-hippocampal region. Among participants with OAB, higher OAB-q scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the UU-only (OAB-dry) but not the UUI (OAB-wet) subgroup. CONCLUSIONS: Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB.

Pelvic floor injury during vaginal birth is life-altering and preventable: what can we do about it?

Pelvic floor disorders after childbirth have distressing lifelong consequences for women, requiring more than 300,000 women to have surgery annually. This represents approximately 10% of the 3 million women who give birth vaginally each year. Vaginal birth is the largest modifiable risk factor for prolapse, the pelvic floor disorder most strongly associated with birth, and is an important contributor to stress incontinence. These disorders require 10 times as many operations as anal sphincter injuries. Imaging shows that injuries of the levator ani muscle, perineal body, and membrane occur in up to 19% of primiparous women. During birth, the levator muscle and birth canal tissues must stretch to more than 3 times their original length; it is this overstretching that is responsible for the muscle tear visible on imaging rather than compression or neuropathy. The injury is present in 55% of women with prolapse later in life, with an odds ratio of 7.3, compared with women with normal support. In addition, levator damage can affect other aspects of hiatal closure, such as the perineal body and membrane. These injuries are associated with an enlarged urogenital hiatus, now known as antedate prolapse, and with prolapse surgery failure. Risk factors for levator injury are multifactorial and include forceps delivery, occiput posterior birth, older maternal age, long second stage of labor, and birthweight of >4000 g. Delivery with a vacuum device is associated with reduced levator damage. Other steps that might logically reduce injuries include manual rotation from occiput posterior to occiput anterior, slow gradual delivery, perineal massage or compresses, and early induction of labor, but these require study to document protection. In addition, teaching women to avoid pushing against a contracted levator muscle would likely decrease injury risk by decreasing tension on the vulnerable muscle origin. Providing care for women who have experienced difficult deliveries can be enhanced with early recognition, physical therapy, and attention to recovery. It is only right that women be made aware of these risks during pregnancy. Educating women on the long-term pelvic floor sequelae of childbirth should be performed antenatally so that they can be empowered to make informed decisions about management decisions during labor.

Dynamic analysis of the individual patterns of intakes, voids, and bladder sensations reported in bladder diaries collected in the LURN study.

The goal of this study was to develop the novel analytical approach and to perform an in-depth dynamic analysis of individual bladder diaries to inform which behavioral modifications would best reduce lower urinary tract symptoms, such as frequency and urgency. Three-day bladder diaries containing data on timing, volumes, and types of fluid intake, as well as timing, volumes, and bladder sensation at voids were analyzed for 197 participants with lower urinary tract symptoms. A novel dynamic analytic approach to bladder diary time series data was proposed and developed, including intra-subject correlations between time-varying variables: rates of intake, bladder filling rate, and urge growth rate. Grey-box models of bladder filling rate and multivariable linear regression models of urge growth rate were developed for individual diaries. These models revealed that bladder filling rate, rather than urine volume, was the primary determinant of urinary frequency and urgency growth rate in the majority of participants. Simulations performed with the developed models predicted that the most beneficial behavioral modifications to reduce the number of urgency episodes are those that smooth profiles of bladder filling rate, which might include behaviors such as exclusion of caffeine and alcohol and/or other measures, e.g., increasing number and decreasing volumes of intakes.

Dynamic analysis of the individual patterns of intakes, voids, and bladder sensations reported in bladder diaries collected in the LURN study.

The goal of this study was to perform an in-depth dynamic analysis of individual bladder diaries to inform which behavioral modifications would best reduce lower urinary tract symptoms, such as frequency and urgency. Three-day bladder diaries containing data on timing, volumes, and types of fluid intake, as well as timing, volumes, and bladder sensation at voids were analyzed for 197 participants with lower urinary tract symptoms. A novel dynamic analytic approach to bladder diary time series data was proposed and developed, including intra-subject correlations between time-varying variables: rates of intake, bladder filling rate, and urge growth rate. Grey-box models of bladder filling rate and multivariable linear regression models of urge growth rate were developed for individual diaries. These models revealed that bladder filling rate, rather than urine volume, was the primary determinant of urinary frequency and urgency growth rate in the majority of participants. Simulations performed with the developed models predicted that the most beneficial behavioral modifications to reduce the number of urgency episodes are those that smooth profiles of bladder filling rate, which might include behaviors such as exclusion of caffeine and alcohol and/or other measures, e.g., increasing number and decreasing volumes of intakes.

Electrochemical Sensing of Urinary Chloride Ion Concentration for Near Real-Time Monitoring.

Urinary chloride concentration is a valuable health metric that can aid in the early detection of serious conditions, such as acid base disorders, acute heart failure, and incidences of acute renal failure in the intensive care unit. Physiologically, urinary chloride levels frequently change and are difficult to measure, involving time-consuming and inconvenient lab testing. Thus, near real-time simple sensors are needed to quickly provide actionable data to inform diagnostic and treatment decisions that affect health outcomes. Here, we introduce a chronopotentiometric sensor that utilizes commercially available screen-printed electrodes to accurately quantify clinically relevant chloride concentrations (5-250 mM) in seconds, with no added reagents or electrode surface modification. Initially, the sensor's performance was optimized through the proper selection of current density at a specific chloride concentration, using electrical response data in conjunction with scanning electron microscopy. We developed a unique swept current density algorithm to resolve the entire clinically relevant chloride concentration range, and the chloride sensors can be reliably reused for chloride concentrations less than 50 mM. Lastly, we explored the impact of pH, temperature, conductivity, and additional ions (i.e., artificial urine) on the sensor signal, in order to determine sensor feasibility in complex biological samples. This study provides a path for further development of a portable, near real-time sensor for the quantification of urinary chloride.

Hiatal failure: effects of pregnancy, delivery, and pelvic floor disorders on level III factors.

INTRODUCTION AND HYPOTHESIS: The failure of the levator hiatus (LH) and urogenital hiatus (UGH) to remain closed is not only associated with pelvic floor disorders, but also contributes to recurrence after surgical repair. Pregnancy and vaginal birth are key events affecting this closure. An understanding of normal and failed hiatal closure is necessary to understand, manage, and prevent pelvic floor disorders. METHODS: This narrative review was conducted by applying the keywords "levator hiatus" OR "genital hiatus" OR "urogenital hiatus" in PubMed. Articles that reported hiatal size related to pelvic floor disorders and pregnancy were chosen. Weighted averages for hiatal size were calculated for each clinical situation. RESULTS: Women with prolapse have a 22% and 30% larger LH area measured by ultrasound at rest and during Valsalva than parous women with normal support. Women with persistently enlarged UGH have 2-3 times higher postoperative failure rates after surgery for prolapse. During pregnancy, the LH area at Valsalva increases by 29% from the first to the third trimester in preparation for childbirth. The enlarged postpartum hiatus recovers over time, but does not return to nulliparous size after vaginal birth. Levator muscle injury during vaginal birth, especially forceps-assisted, is associated with increases in hiatal size; however, it only explains a portion of hiatus variation-the rest can be explained by pelvic muscle function and possibly injury to other level III structures. CONCLUSIONS: Failed hiatal closure is strongly related to pelvic floor disorders. Vaginal birth and levator injury are primary factors affecting this important mechanism.

Comparison of in vivo visco-hyperelastic properties of uterine suspensory tissue in women with and without pelvic organ prolapse.

The uterine suspensory tissue (UST) complex includes the cardinal (CL) and uterosacral "ligaments" (USL), which are mesentery-like structures that play a role in resisting pelvic organ prolapse (POP). Since there is no information on the time-dependent material properties of the whole structure in situ and in vivo, we developed and tested an intraoperative technique to quantify in vivo whether there is a significant difference in visco-hyperelastic behavior of the CL and USL between women with and without POP. Thirteen women with POP (cases) and four controls scheduled for surgery were selected from an ongoing POP study. Immediately prior to surgery, a computer-controlled linear servo-actuator with a series force transducer applied a continuous, caudally directed traction force while simultaneously recording the resulting cervical displacement in the same direction. After applying an initial 1.1 N preload, a ramp rate of 4 mm/s was used to apply a maximum force of 17.8 N in three "ramp-and-hold" test trials. A simplified bilateral four-cable biomechanical model was used to identify the material behavior of each ligament. For this, the initial cross-section areas of the CL and USL were measured on 3-T magnetic resonance image-based 3D models from each subject. The time-dependent strain energy function of CL/USL was defined with a three-parameter hyperelastic Mooney-Rivlin material model and a two-term Prony series in relaxation form. When cases were compared with controls, the estimated time-dependent material constants of CL and USL did not differ significantly. These are the first measurements that compare the in vivo and in situ visco-hyperelastic response of the tissues comprising the CL and USL to loading in women with and without prolapse. Larger sample sizes would help improve the precision of intergroup differences.

Natural history of lower urinary tract symptoms in treatment-seeking women with pelvic organ prolapse; the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

BACKGROUND: The association of pelvic organ prolapse with overactive bladder and other lower urinary tract symptoms, and the natural history of those symptoms are not well characterized. Previous cross-sectional studies demonstrated conflicting relationships between prolapse and lower urinary tract symptoms. OBJECTIVE: This study primarily aimed to determine the baseline association between lower urinary tract symptoms and prolapse and to assess longitudinal differences in symptoms over 12 months in women with and without prolapse. Secondary aims were to explore associations between lower urinary tract symptoms and prolapse treatment. We hypothesized that: (1) prolapse is associated with the presence of lower urinary tract symptoms, (2) lower urinary tract symptoms are stable over time in patients with and without prolapse, and (3) prolapse treatment is associated with lower urinary tract symptom improvement. STUDY DESIGN: Women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network Observational Cohort Study with adequate 12-month follow-up data were included. Prolapse and lower urinary tract symptom treatment during follow-up was guided by standard of care. Outcome measures included the Lower Urinary Tract Symptoms Tool total severity score (in addition to overactive bladder, obstructive, and stress urinary incontinence subscales) and Urogenital Distress Inventory-6 Short Form. Prolapse (yes or no) was defined primarily when Pelvic Organ Prolapse Quantification System points Ba, C or Bp were >0 (beyond the hymen). Mixed-effects models with random effects for patient slopes and intercepts were fitted for each lower urinary tract symptom outcome and prolapse predictor, adjusted for other covariates. The study had >90% power to detect differences as small as 0.4 standard deviation for less prevalent group comparisons (eg, prolapse vs not). RESULTS: A total of 371 women were analyzed, including 313 (84%) with no prolapse and 58 (16%) with prolapse. Women with prolapse were older (64.6±8.8 vs 55.3±14.1 years; P<.001) and more likely to have prolapse surgery (28% vs 1%; P<.001) and pessary treatment (26% vs 4%; P<.001) during the study. Average baseline Lower Urinary Tract Symptoms Tool total severity scores were lower (fewer symptoms) for participants with prolapse compared with those without (38.9±14.0 vs 43.2±14.0; P=.036), but there were no differences in average scores between prolapse groups for other scales. For all urinary outcomes, average scores were significantly lower (improved) at 3 and 12 months compared with baseline (all P<.05). In mixed-effects models, there were no statistically significant interactions between pelvic organ prolapse measurement and visit and time-dependent prolapse treatment groups (P>.05 for all regression interaction coefficients). The Lower Urinary Tract Symptoms Tool obstructive severity score had a statistically significant positive association with Pelvic Organ Prolapse Quantification System Ba, Bp, and point of maximum vaginal descent. The Lower Urinary Tract Symptoms Tool total severity scale had a statistically significant negative association with Pelvic Organ Prolapse Quantification System Ba and point of maximum vaginal descent. No other associations between prolapse and lower urinary tract symptoms were significant (P>.05 for all regression coefficients). Symptom differences between prolapse groups were small: all regression coefficients (interpretable as additive percentage change in each score) were between -5 and 5 (standard deviation of outcomes ranged from 14.0-32.4). CONCLUSION: Among treatment-seeking women with urinary symptoms, obstructive symptoms were positively associated with prolapse, and overall lower urinary tract symptom severity was negatively associated with prolapse. Lower Urinary Tract Symptoms Tool scores improved over 12 months regardless of prolapse status, including in those with treated prolapse, untreated prolapse, and without prolapse.

Pelvic inclination correction system for magnetic resonance imaging analysis of pelvic organ prolapse in upright position.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse quantification by means of upright magnetic resonance imaging (MRI) is a promising research field. This study determines the angle for the pelvic inclination correction system (PICS) for upright patient position, which is hypothesized to deviate from the supine PICS angle. The necessity of different PICS angles for various patient positions will also be discussed. METHODS: Magnetic resonance scans of 113 women, acquired in an upright patient position, were used to determine the upright PICS angle, defined as the angle between the sacrococcygeal-inferior pubic point (SCIPP) line and the horizontal line. The difference and correlation between the upright and supine PICS angles were calculated using the paired Student's t-test and the Pearson's correlation coefficient (r) respectively. The effect of the difference between the upright and supine PICS angle on the measured pelvic organ extent was calculated using goniometry. RESULTS: The mean (interquartile range) PICS angles were 29° (26-35°) for the upright and 33° (30-37°) for the supine patient position. They were significantly different (p<0.001) and very strongly correlated (r = 0.914, p<0.001). The 4° difference between the average upright and supine PICS angle results in an average underestimation of the measured cervix height of approximately 0.5 cm for patients scanned in upright position. CONCLUSIONS: The PICS angle for the upright patient position is 29°. The use of a dedicated PICS angle for different patient positions allows for more accurate pelvic organ extent analysis in patients with prolapse.

Subtyping of common complex diseases and disorders by integrating heterogeneous data. Identifying clusters among women with lower urinary tract symptoms in the LURN study.

We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data types (continuous and categorical) required novel methodology using a weighted Tanimoto indices approach. Data domains only available on a subset of the cohort were integrated using a semi-supervised clustering approach. Novel contrast criterion for determination of the optimal number of clusters in consensus clustering was introduced and compared with existing criteria. Distinctiveness of the clusters was confirmed by using multiple criteria for cluster quality, and by testing for significantly different variables in pairwise comparisons of the clusters. Cluster dynamics were explored by analyzing longitudinal data at 3- and 12-month follow-up. Five clusters of women with LUTS were identified using the developed methodology. None of the clusters could be characterized by a single symptom, but rather by a distinct combination of symptoms with various levels of severity. Targeted proteomics of serum samples demonstrated that differentially abundant proteins and affected pathways are different across the clusters. The clinical relevance of the identified clusters is discussed and compared with the current conventional approaches to the evaluation of LUTS patients. The rationale and thought process are described for the selection of procedures for data preprocessing, clustering, and cluster evaluation. Suggestions are provided for minimum reporting requirements in publications utilizing clustering methodology with multiple heterogeneous data domains.

Lies, damned lies, and pelvic floor illustration: Confused about pelvic floor anatomy? You are not alone.

Dissection reveals elegant simplicity in pelvic floor structure. So, why are so many of us confused about the pelvic floor? The pelvic floor is in an invisible region between what we see from above and below, so our experience does not help. It is confusing because there is conflict between existing illustrations, so we do not know which are false and which are true. To resolve conflicts in pelvic anatomy we must: recognize the Vesalian principle that truth lies in the body, not necessarily in books; commit to focusing on structures rather than words; and overcome "theory-induced blindness," the psychological principle that discounts what is seen when it contradicts a theory we believe. We should revive century-old standards that require accuracy in anatomical illustration analogous to the p value in statistics. Committing to anatomical accuracy will ensure that we no longer navigate in surgery and research using a flawed map.

Multi-label classification of pelvic organ prolapse using stress magnetic resonance imaging with deep learning.

INTRODUCTION AND HYPOTHESIS: We aimed to develop a deep learning-based multi-label classification model to simultaneously diagnose three types of pelvic organ prolapse using stress magnetic resonance imaging (MRI). METHODS: Our dataset consisted of 213 midsagittal labeled MR images at maximum Valsalva. For each MR image, the two endpoints of the sacrococcygeal inferior-pubic point line were auto-localized. Based on this line, a region of interest was automatically selected as input to a modified deep learning model, ResNet-50, for diagnosis. An unlabeled MRI dataset, a public dataset, and a synthetic dataset were used along with the labeled image dataset to train the model through a novel training strategy. We conducted a fivefold cross-validation and evaluated the classification results using precision, recall, F1 score, and area under the curve (AUC). RESULTS: The average precision, recall, F1 score, and AUC of our proposed multi-label classification model for the three types of prolapse were 0.84, 0.72, 0.77, and 0.91 respectively, which were improved from 0.64, 0.53, 0.57, and 0.83 from the original ResNet-50. Classification took 0.18 s to diagnose one patient. CONCLUSIONS: The proposed deep learning-based model were demonstrated feasible and fast in simultaneously diagnosing three types of prolapse based on pelvic floor stress MRI, which could facilitate computer-aided prolapse diagnosis and treatment planning.

Changes in cardinal ligament length and curvature with parity and prolapse and their relation to level III hiatus measures.

INTRODUCTION AND HYPOTHESIS: Test the hypotheses that (1) cardinal ligament (CL) straightening and lengthening occur with parity and prolapse, (2) CL straightening occurs before lengthening, and (3) CL length is correlated with level III measures. METHODS: We performed a secondary analysis of MRIs from women in three groups: (1) nulliparous with normal support, (2) parous with normal support, and (3) uterine prolapse (POP-Q point C > - 4 and Ba > 1 cm). The 3D stress MRI images at rest and maximal Valsalva were analyzed. CLs were traced from their origin to cervico-vaginal insertions. Curvature ratio was calculated as curved length/straight length. Level III measures included urogenital hiatus (UGH), levator hiatus (LH), and levator bowl volume (LBV), and their correlations with CL length were calculated. RESULTS: Ten women were included in each group. Compared to the nulliparous group, CL length was 18% longer in parous controls (p = .04) and 59% longer with prolapse (p < .01) at rest, while at Valsalva, CL length was 10% longer in parous controls (p = .21) and 49% longer with prolapse (p < .01). Curvature ratios showed 18% more straightening in women with prolapse compared to parous controls (p < .01). Curved CL length and level III measures were moderately to strongly correlated: UGH (rest: R = 0.68, p < .01; Valsalva: R =0.80, p < .01), LH (rest: R = 0.60, p < .01; Valsalva: R = 0.78, p < .01), and LBV (rest: R = 0.71, p < .01; Valsalva: R =0.89, p < .01). CONCLUSION: Our findings suggest that the CLs undergo three times as much lengthening with prolapse as with parity; however, straightening only occurs with prolapse. Strong correlations exist between level I and level III support.

Pelvic floor muscle injury during a difficult labor. Can tissue fatigue damage play a role?

Pubovisceral muscle (PVM) injury during a difficult vaginal delivery leads to pelvic organ prolapse later in life. If one could address how and why the muscle injury originates, one might be able to better prevent these injuries in the future. In a recent review we concluded that many atraumatic injuries of the muscle-tendon unit are consistent with it being weakened by an accumulation of passive tissue damage during repetitive loading. While the PVM can tear due to a single overstretch at the end of the second stage of labor we hypothesize that it can also be weakened by an accumulation of microdamage and then tear after a series of submaximal loading cycles. We conclude that there is strong indirect evidence that low cycle fatigue of PVM passive tissue is a possible mechanism of its proximal failure. This has implications for finding new ways to better prevent PVM injury in the future.

Three-dimensional self super-resolution for pelvic floor MRI using a convolutional neural network with multi-orientation data training.

PURPOSE: High-resolution pelvic magnetic resonance (MR) imaging is important for the high-resolution and high-precision evaluation of pelvic floor disorders (PFDs), but the data acquisition time is long. Because high-resolution three-dimensional (3D) MR data of the pelvic floor are difficult to obtain, MR images are usually obtained in three orthogonal planes: axial, sagittal, and coronal. The in-plane resolution of the MR data in each plane is high, but the through-plane resolution is low. Thus, we aimed to achieve 3D super-resolution using a convolutional neural network (CNN) approach to capture the intrinsic similarity of low-resolution 3D MR data from three orientations. METHODS: We used a two-dimensional (2D) super-resolution CNN model to solve the 3D super-resolution problem. The residual-in-residual dense block network (RRDBNet) was used as our CNN backbone. For a given set of low through-plane resolution pelvic floor MR data in the axial or coronal or sagittal scan plane, we applied the RRDBNet sequentially to perform super-resolution on its two projected low-resolution views. Three datasets were used in the experiments, including two private datasets and one public dataset. In the first dataset (dataset 1), MR data acquired from 34 subjects in three planes were used to train our super-resolution model, and low-resolution MR data from nine subjects were used for testing. The second dataset (dataset 2) included a sequence of relatively high-resolution MR data acquired in the coronal plane. The public MR dataset (dataset 3) was used to demonstrate the generalization ability of our model. To show the effectiveness of RRDBNet, we used datasets 1 and 2 to compare RRDBNet with interpolation and enhanced deep super-resolution (EDSR) methods in terms of peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) index. As 3D MR data from one view have two projected low-resolution views, different super-resolution orders were compared in terms of PSNR and SSIM. Finally, to demonstrate the impact of super-resolution on the image analysis task, we used datasets 2 and 3 to compare the performance of our method with interpolation on the 3D geometric model reconstruction of the urinary bladder. RESULTS: A CNN-based method was used to learn the intrinsic similarity among MR acquisitions from different scan planes. Through-plane super-resolution for pelvic MR images was achieved without using high-resolution 3D data, which is useful for the analysis of PFDs.

Urethral function and failure: A review of current knowledge of urethral closure mechanisms, how they vary, and how they are affected by life events.

INTRODUCTION: A critical appraisal of the literature regarding female urethral function and dysfunction is needed in light of recent evidence showing the urethra's role in causing stress and urge urinary incontinence. METHODS: An evidence assessment was conducted using selected articles from the literature that contained mechanistic data on factors affecting urethral function and failure. RESULTS: Maximal urethral closure pressure (MUCP) is 40% lower in stress urinary incontinence (SUI) than normal controls. Evidence from five women shows relatively equal contributions to MUCP from striated/smooth muscle, vascular-plexus, connective tissue. MUCP varies twofold in individuals of similar age and declines 15% per decade even in nulliparous women. Age explains 57% of the variance in MUCP. This parallels with striated/smooth muscle loss and reduced nerve density. Factors influencing pressure variation minute-to-minute and decade-to-decade are poorly understood. Connective tissue changes have not been investigated. MUCP in de novo SUI persisting 9-months postpartum is 25% less than in age and parity-matched controls. Longitudinal studies do not show significant changes in urethral function after vaginal birth suggesting that changes in urethral support from birth may unmask pre-existing sphincter weakness and precipitate SUI. Mechanisms of interaction between support injury, pre-existing urethral weakness, and neuropathy are unclear. CONCLUSION: Urethral failure is the predominant cause of SUI and a contributing factor for UUI; potentially explaining why mixed symptoms predominate in epidemiological studies. Age-related striated muscle loss and differences between women of similar age are prominent features of poor urethral closure. Yet, connective tissue changes, vasculature function, and complex interactions among factors are poorly understood.