Harnessing the power within: engineering the microbiome for enhanced gynecologic health.

Abstract: Although numerous studies have demonstrated the impact of microbiome manipulation on human health, research on the microbiome's influence on female health remains relatively limited despite substantial disease burden. In light of this, we present a selected review of clinical trials and preclinical studies targeting both the vaginal and gut microbiomes for the prevention or treatment of various gynecologic conditions. Specifically, we explore studies that leverage microbiota transplants, probiotics, prebiotics, diet modifications, and engineered microbial strains. A healthy vaginal microbiome for females of reproductive age consists of lactic acid-producing bacteria predominantly of the Lactobacillus genus, which serves as a protective barrier against pathogens and maintains a balanced ecosystem. The gut microbiota's production of short-chain fatty acids, metabolism of primary bile acids, and modulation of sex steroid levels have significant implications for the interplay between host and microbes throughout the body, ultimately impacting reproductive health. By harnessing interventions that modulate both the vaginal and gut microbiomes, it becomes possible to not only maintain homeostasis but also mitigate pathological conditions. While the field is still working toward making broad clinical recommendations, the current studies demonstrate that manipulating the microbiome holds great potential for addressing diverse gynecologic conditions. Lay summary: Manipulating the microbiome has recently entered popular culture, with various diets thought to aid the microbes that live within us. These microbes live in different locations of our body and accordingly help us digest food, modulate our immune system, and influence reproductive health. The role of the microbes living in and influencing the female reproductive tract remains understudied despite known roles in common conditions such as vulvovaginal candidiasis (affecting 75% of females in their lifetime), bacterial vaginosis (25% of females in their lifetime), cervical HPV infection (80% of females in their lifetime), endometriosis (6-10% of females of reproductive age), and polycystic ovary syndrome (10-12% of females of reproductive age). Here, we review four different approaches used to manipulate the female reproductive tract and gastrointestinal system microbiomes: microbiota transplants, probiotics, prebiotics, and dietary interventions, and the use of engineered microbial strains. In doing so, we aim to stimulate discussion on new ways to understand and treat female reproductive health conditions.

Detection of Bacteria in Bladder Mucosa of Adult Females.

PURPOSE: Interstitial cystitis/bladder pain syndrome is a chronic urological condition diagnosed in nearly 8 million females in the United States. Whether urinary microbiota play an etiological role remains controversial. Most studies assessed the microbiota of interstitial cystitis/bladder pain syndrome patients with voided or catheterized urine as a proxy for bladder urothelium; however, urine may not be a true reflection of the bladder microbiota. Bladder biopsy tissue may provide a more accurate, and thus more clinically relevant, picture of bladder microbiota. MATERIALS AND METHODS: Bladder biopsy tissues were obtained from: (1) 30 females with interstitial cystitis/bladder pain syndrome (18-80 years old) via cystoscopically guided cold-cup biopsy following therapeutic bladder hydrodistention, and (2) 10 non-interstitial cystitis/bladder pain syndrome females undergoing pelvic organ prolapse repair. To detect bacteria, technical duplicates of each RNAlater-preserved biopsy were subjected to 16S rRNA gene sequencing. To visualize bacteria, paraformaldehyde-fixed, paraffin-embedded biopsies were subjected to a combined multiplexed fluorescence in situ hybridization and fluorescence immunohistochemistry assay and confocal microscopy. RESULTS: Bacteria were detected by 16S rRNA gene sequencing in at least 1 technical duplicate of most biopsies. The most abundant genus was Staphylococcus, followed by Lactobacillus; Escherichia was common but not abundant. There was no significant difference between interstitial cystitis/bladder pain syndrome patients and controls (P > .05). Combined fluorescence in situ hybridization and immunohistochemistry reproducibly detected 16S rRNA in epithelial cells and shed cells in the urothelium and lesioned areas and capillary walls in the lamina propria of human bladder biopsy tissue. CONCLUSIONS: We conclude that urothelial and urinary microbiota are similar but not identical in adult females.

Urinary Tract Infections After Urogynecologic Surgery: Risk Factors, Timeline, and Uropathogens.

IMPORTANCE: Urinary tract infection (UTI) is a common and potentially avoidable postoperative (PO) adverse event after urogynecologic surgery. Understanding pathophysiology will help prevent the associated morbidity of the disease and treatment of PO-UTI. OBJECTIVE: The objective of this study is to determine the following: (1) risk factors for both PO-UTI and PO recurrent UTI (RUTI) after urogynecologic surgery, (2) temporal distribution of UTI, and (3) uropathogen identification. STUDY DESIGN: Women undergoing urogynecologic surgery were retrospectively reviewed. Urinary tract infection was defined by culture or antibiotic prescription for symptoms. Recurrent UTI was defined as occurring outside a 6-week perioperative period. The χ 2 test or Fischer exact and Student t tests or Mann-Whitney U test were used as appropriate. Individual odds ratio (OR), 95% confidence interval [CI], and sequential multivariable logistic regression were calculated. Statistical significance was set at P < 0.05. RESULTS: The 6-week PO-UTI rate after 33,626 procedures was 12.9%. Recurrent UTI increased from 3.7% preoperatively to 4.4% postoperatively ( P < 0.001). A 6-week preoperative UTI and RUTI increased the risk of 6-week PO-UTI (OR, 1.65; 95% CI < 1.26-2.16; P = 0.001 and OR, 2.19; 95% CI, 1.84-2.62; P < 0.001, respectively) and PO-RUTI (OR, 2.95; 95% CI, 2.11-4.11; P < 0.001 and OR, 6.79; 95% CI, 5.61-8.23; P < 0.001, respectively). Compared with pelvic organ prolapse (POP) surgery only, stress urinary incontinence (SUI) surgery (OR 1.57[1.30-1.89]), and combined POP/SUI surgery (OR, 1.36; 95% CI, 1.13-1.63]) increased the risk of PO-RUTI ( P < 0.001). Urinary tract infection within 1 week preoperatively was protective against 6-week PO-UTI (OR, 0.68; 95% CI, 0.48-0.97; P = 0.035). No perioperative factors were protective of PO-RUTI. CONCLUSIONS: The PO-RUTI rate in the first year after urogynecologic surgery is low; however, SUI procedures may increase PO-RUTI risk. Potentially, modifiable risk factors for both PO-UTI and PO-RUTI include UTI diagnosis within 6 weeks preoperatively or preoperative RUTI diagnosis. Retesting women the week before surgery to ensure adequate treatment of preoperative UTI may reduce 6-week PO-UTI.

Importance of internal vaginal pelvic floor muscle exams for women with external lumbar/hip/pelvic girdle pain.

INTRODUCTION AND HYPOTHESIS: The relationship between external lumbar, hip, and/or pelvic girdle pain and internal vaginal pelvic floor myofascial pain is not well described. We assessed this relationship in a cohort of adult women. METHODS: The cohort included women ≥ 18 years old who received care for external lumbar, hip, and/or pelvic girdle pain (reported or elicited on physical examination) who then underwent internal vaginal myofascial levator ani pain assessments, in a tertiary care Female Pelvic Medicine and Reconstructive Surgery pelvic pain clinic over a 2-year period (2013 and 2014). RESULTS: The cohort of 177 women had an average age of 44.9±16.0 years, an average body mass index of 27.2±7.0 kg/m2, and the majority (79.2%) were white. Most patients presented with a chief complaint of pelvic (51.4%), vulvovaginal (18.6%), and/or lumbar (15.3%) pain. Women who reported symptoms of lumbar, hip, or pelvic girdle pain were more likely to have pain on vaginal pelvic floor muscle examination than women without this history (OR, 7.24; 95% CI, 1.95-26.93, p=0.003). The majority (85.9%) of women had bilateral internal vaginal pelvic floor myofascial pain on examination. CONCLUSIONS: Although participants did not describe "vaginal pelvic floor myofascial pain," the high detection rate for internal vaginal pelvic floor myofascial pain on clinical examination highlights an opportunity to improve treatment planning. These findings suggest that the vaginal pelvic floor muscle examination should be part of the assessment of all women with lumbar, hip, and/or pelvic girdle pain. The relationship between this finding and clinical outcomes following directed treatment warrants additional study.

Effects of Variation in Urine Sample Storage Conditions on 16S Urogenital Microbiome Analyses.

Replicability is a well-established challenge in microbiome research with a variety of contributing factors at all stages, from sample collection to code execution. Here, we focus on voided urine sample storage conditions for urogenital microbiome analysis. Using urine samples collected from 10 adult females, we investigated the microbiome preservation efficacy of AssayAssure Genelock (Genelock), compared with no preservative, under different temperature conditions. We varied temperature over 48 h in order to examine the impact of conditions samples may experience with home voided urine collection and shipping to a central biorepository. The following common lab and shipping conditions were investigated: -20°C, ambient temperature, 4°C, freeze-thaw cycle, and heat cycle. At 48 h, all samples were stored at -80°C until processing. After generating 16S rRNA gene amplicon sequencing data using the highly sensitive KatharoSeq protocol, we observed individual variation in both alpha and beta diversity metrics below interhuman differences, corroborating reports of individual microbiome variability in other specimen types. While there was no significant difference in beta diversity when comparing Genelock versus no preservative, we did observe a higher concordance with Genelock samples shipped at colder temperatures (-20°C and 4°C) when compared with the samples shipped at -20°C without preservative. Our results indicate that Genelock does not introduce a significant amount of microbial bias when used on a range of temperatures and is most effective at colder temperatures. IMPORTANCE The urogenital microbiome is an understudied yet important human microbiome niche. Research has been stimulated by the relatively recent discovery that urine is not sterile; urinary tract microbes have been linked to health problems, including urinary infections, incontinence, and cancer. The quality of life and economic impact of UTIs and urgency incontinence alone are enormous, with $3.5 billion and $82.6 billion, respectively, spent in the United States. annually. Given the low biomass of urine, novelty of the field, and limited reproducibility evidence, it is critical to study urine sample storage conditions to optimize scientific rigor. Efficient and reliable preservation methods inform methods for home self-sample collection and shipping, increasing the potential use in larger-scale studies. Here, we examined both buffer and temperature variation effects on 16S rRNA gene amplicon sequencing results from urogenital samples, providing data on the consequences of common storage methods on urogenital microbiome results.

Intraoperative Gentamicin Intravesical Instillation for Prevention of Urinary Tract Infection After Urogynecologic Surgery: A Randomized Controlled Trial.

IMPORTANCE: Currently available evidence for efficacy of postoperative antibiotics to prevent postoperative urinary tract infection (UTI) conflicts. Oral antibiotics rely on patient adherence and can cause unwanted systemic effects. Gentamicin is a broad-spectrum antibiotic with rapid bactericidal activity and, when administered intravesically, has no systemic absorption through intact urothelium. OBJECTIVE: We aimed to determine whether a single intravesical instillation of gentamicin at the conclusion of urogynecologic surgery would reduce the proportion of women treated for UTI within 6 weeks postoperatively compared with sham instillation. STUDY DESIGN: This was a multicenter, randomized (stratified by study site, route of prolapse repair ±suburethral sling, with balanced 1:1 randomization), participant-masked, sham-controlled, study. The primary outcome was the proportion of participants treated with antibiotics for UTI within 6 weeks postoperatively. An adjusted multivariable logistic regression model was constructed to determine predictors of postoperative UTI treatment. RESULTS: Three hundred seventy participants were randomized (gentamicin, 185; sham, 185), and data from 363 participants were analyzed (gentamicin, 183; sham, 180). Nineteen women in the gentamicin group and 20 women in the sham group were treated for UTI within 6 weeks postoperatively (10.4% vs 11.1%, P = 0.87). There were no adverse events related to the instillations. Increasing age (odds ratio, 1.028 [1.000-1.057]) and number of intraoperative transurethral instrumentations (odds ratio, 1.342 [1.080-1.668]) were independent predictors of postoperative UTI treatment. CONCLUSIONS: In women undergoing urogynecologic surgery, postoperative intravesical gentamicin did not reduce the incidence of postoperative UTI. The number of intraoperative transurethral instrumentations is an important, potentially modifiable risk factor for postoperative UTI treatment.

The Urobiomes of Adult Women With Various Lower Urinary Tract Symptoms Status Differ: A Re-Analysis.

The discovery of the urinary microbiome (urobiome) has created opportunities for urinary health researchers who study a wide variety of human health conditions. This manuscript describes an analysis of catheterized urine samples obtained from 1,004 urobiome study participants with the goal of identifying the most abundant and/or prevalent (common) taxa in five clinically relevant cohorts: unaffected adult women (n=346, 34.6%), urgency urinary incontinence (UUI) (n=255, 25.5%), stress urinary incontinence (SUI) (n=50, 5.0%), urinary tract infection (UTI) (n=304, 30.4%), and interstitial cystitis/painful bladder syndrome (IC/PBS) (n=49, 4.9%). Urine was collected via transurethral catheter and assessed for microbes with the Expanded Quantitative Urine Culture (EQUC) technique. For this combined analytic cohort, the mean age was 59 ± 16; most were Caucasian (n=704, 70.2%), Black (n=137, 13.7%), or Hispanic (n=130, 13.0%), and the mean BMI was 30.4 ± 7.7. Whereas many control or IC/PBS cohort members were EQUC-negative (42.4% and 39.8%, respectively), members of the other 3 cohorts were extremely likely to have detectable microbes. The detected urobiomes of the controls and IC/PBS did not differ by alpha diversity or genus level composition and differed by only a few species. The other 3 cohorts differed significantly from the controls. As expected, Escherichia was both prevalent and highly abundant in the UTI cohort, but other taxa also were prevalent at more moderate abundances, including members of the genera Lactobacillus, Streptococcus, Staphylococcus, Corynebacterium, Actinomyces, and Aerococcus. Members of these genera were also prevalent and highly abundant in members of the UUI cohort, especially Streptococcus anginosus. Intriguingly, these taxa were also detected in controls but at vastly lower levels of both prevalence and abundance, suggesting the possibility that UUI-associated symptoms could be the result of an overabundance of typical urobiome constituents. Finally, prevalence and abundance of microbes in the SUI cohort were intermediate to those of the UUI and control cohorts. These observations can inform the next decade of urobiome research, with the goal of clarifying the mechanisms of urobiome community composition and function. There is tremendous potential to improve diagnosis, evaluation and treatment for individuals affected with a wide variety of urinary tract disorders.

Symptom improvement with mirabegron treatment is associated with urobiome changes in adult women.

INTRODUCTION AND HYPOTHESIS: Mirabegron, a beta-3 agonist, is prescribed for urgency urinary incontinence (UUI). We assessed the correlation of symptom improvement with urobiome characteristics in adult women participants prescribed mirabegron for UUI treatment. METHODS: We enrolled participants seeking UUI treatment who selected mirabegron and agreed to participate in this 12-week, open label study conducted at the Female Pelvic Medicine and Reconstructive Surgery Center at Loyola University Medical Center. Following eligibility screening and research consent, participants completed the overactive bladder questionnaire (OAB-Q) and provided a catheterized urine sample at baseline, 4, 8, and 12 weeks. The primary outcome, symptom improvement at 12 weeks, was based on the validated Patient Global Symptom Control questionnaire score to dichotomize symptom response (responder vs nonresponder [PGSC score ≤3]). Urine samples were processed by the Expanded Quantitative Urine Culture (EQUC) protocol. RESULTS: Eighty-three participants (mean age 68 years) completed baseline assessment. Of the 47 participants with primary outcome data and samples analysis, there were 16 responders and 31 nonresponders; responder groups were similar demographically. Living microbes were detected in most participants. There were no significant differences in alpha diversity (within sample) at baseline between groups. However, at the 12-week follow-up, the responder urobiome became significantly richer, with a larger number of genera (p = 0.027) and was significantly more diverse than the nonresponders. CONCLUSIONS: Longitudinal urobiome changes are associated with symptom improvement in adult women being treated with mirabegron for UUI. The mechanism for symptoms improvement may relate to the detected changes in the urobiome and warrants further study.

Measuring Bladder Health: Development and Cognitive Evaluation of Items for a Novel Bladder Health Instrument.

PURPOSE: We describe the item development and cognitive evaluation process used in creating the Prevention of Lower Urinary Tract Symptoms Bladder Health Instrument (PLUS-BHI). MATERIALS AND METHODS: Questions assessing bladder health were developed using reviews of published items, expert opinion, and focus groups' transcript review. Candidate items were tested through cognitive interviews with community-dwelling women and an online panel survey. Items were assessed for comprehension, language, and response categories and modified iteratively to create the PLUS-BHI. RESULTS: Existing measures of bladder function (storage, emptying, sensation components) and bladder health impact required modification of time frame and response categories to capture a full range of bladder health. Of the women 167 (18-80 years old) completed individual interviews and 791 women (18-88 years) completed the online panel survey. The term "bladder health" was unfamiliar for most and was conceptualized primarily as absence of severe urinary symptoms, infection, or cancer. Coping mechanisms and self-management strategies were central to bladder health perceptions. The inclusion of prompts and response categories that captured infrequent symptoms increased endorsement of symptoms across bladder function components. CONCLUSIONS: Bladder health measurement is challenged by a lack of awareness of normal function, use of self-management strategies to mitigate impact on activities, and a common tendency to overlook infrequent lower urinary tract symptoms. The PLUS-BHI is designed to characterize the full spectrum of bladder health in women and will be validated for research use.

Risk Factors for Surgical Failure and Worsening Pelvic Floor Symptoms Within 5 Years After Vaginal Prolapse Repair.

OBJECTIVE: To assess independent risk factors for surgical failure and worsening pelvic floor symptoms within 5 years after vaginal prolapse surgery. METHODS: This secondary analysis includes OPTIMAL (Operations and Pelvic Muscle Training in the Management of Apical Support Loss) (n=374) and E-OPTIMAL (Extended) (n=285) trial participants. Surgical failure was defined as apical descent greater than one third of the total vaginal length, anterior or posterior vaginal wall past the hymen, subsequent surgery or bothersome vaginal bulge. Worsening pelvic floor symptoms were defined as increases from baseline as large as the minimally important difference for subscale scores of the Pelvic Floor Distress Inventory: 11 for the Urinary Distress Inventory and Colorectal-Anal Distress Inventory and 34.3 for the Pelvic Organ Prolapse Distress Inventory. Outcomes were measured at 6 months then 1, 2, 3, 4, and 5 years. Chi-square and t test results from bivariate models and clinical relevance were used to inform final models. RESULTS: Baseline risk factors for surgical failure were Hispanic ethnicity (adjusted odds ratio [aOR] 1.92, 95% CI 1.17-3.15), perineal body (aOR 1.34, 95% CI 1.09-1.63), and pretreatment Pelvic Organ Prolapse Distress Inventory score (aOR 1.16, 95% CI 1.05-1.28). Risk factors for worsening of pelvic floor symptoms were pretreatment Pelvic Organ Prolapse Distress Inventory score (aOR 0.75, 95% CI 0.60-0.94) for worsening Pelvic Organ Prolapse Distress Inventory score, vaginal deliveries (aOR 1.26, 95% CI 1.10-1.44) and pretreatment Urinary Distress Inventory score (aOR 0.86, 95% CI 0.80-0.93) for worsening Urinary Distress Inventory score, and age (aOR 1.03, 95% CI 1.01-1.05) and pretreatment Colorectal-Anal Distress Inventory score (aOR 0.95, 95% CI 0.92-0.98) for worsening Colorectal-Anal Distress Inventory score. CONCLUSIONS: Hispanic ethnicity, larger preoperative perineal body, and higher pretreatment Pelvic Organ Prolapse Distress Inventory scores were risk factors for surgical failure up to 5 years after vaginal prolapse repair. Participants with higher baseline Pelvic Floor Distress Inventory scores were less likely to worsen. Risk factors for worsening Urinary Distress Inventory and Colorectal-Anal Distress Inventory scores included more vaginal deliveries and increased age, respectively. CLINICAL TRIAL REGISTRATION: NCT00597935, NCT01166373.

Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder symptoms.

BACKGROUND: Previous work has shown that the vaginal microbiome decreases in Lactobacillus predominance and becomes more diverse after menopause. It has also been shown that estrogen therapy restores Lactobacillus dominance in the vagina and that topical estrogen is associated with overactive bladder symptom improvement. We now know that the bladder contains a unique microbiome and that increased bladder microbiome diversity is associated with overactive bladder. However, there is no understanding of how quickly each pelvic floor microbiome responds to estrogen or if those changes are associated with symptom improvement. OBJECTIVE: This study aimed to determine if estrogen treatment of postmenopausal women with overactive bladder decreases urobiome diversity. STUDY DESIGN: We analyzed data from postmenopausal participants in 2 trials (NCT02524769 and NCT02835846) who chose vaginal estrogen as the primary overactive bladder treatment and used 0.5 g of conjugated estrogen (Premarin cream; Pfizer, New York City, NY) twice weekly for 12 weeks. Baseline and 12-week follow-up data included the Overactive Bladder questionnaire, and participants provided urine samples via catheter, vaginal swabs, perineal swabs, and voided urine samples. Microbes were detected by an enhanced culture protocol. Linear mixed models were used to estimate microbiome changes over time. Urinary antimicrobial peptide activity was assessed by a bacterial growth inhibition assay and correlated with relative abundance of members of the urobiome. RESULTS: In this study, 12 weeks of estrogen treatment resulted in decreased microbial diversity within the vagina (Shannon, P=.047; Richness, P=.043) but not in the other niches. A significant increase in Lactobacillus was detected in the bladder (P=.037) but not in the vagina (P=.33), perineum (P=.56), or voided urine (P=.28). The change in Lactobacillus levels in the bladder was associated with modest changes in urgency incontinence symptoms (P=.02). The relative abundance of the genus Corynebacterium correlated positively with urinary antimicrobial peptide activity after estrogen treatment. CONCLUSION: Estrogen therapy may change the microbiome of different pelvic floor niches. The vagina begins to decrease in diversity, and the bladder experiences a significant increase in Lactobacillus levels; the latter is correlated with a modest improvement in the symptom severity subscale of the Overactive Bladder questionnaire.

Postoperative urinary tract infection after urogynecologic surgery: timing and uropathogens.

INTRODUCTION AND HYPOTHESIS: Although postoperative urinary tract infections (UTIs) after urogynecologic surgery are a common adverse event, there is no standardized postoperative time period used to assess this outcome, and the uropathogens unique to this sub-population of patients have not been well described. Our objective is to describe the timing and uropathogens of postoperative UTI after urogynecologic surgery. METHODS: This retrospective study analyzed postoperative UTI occurring within 90 days following urogynecologic procedures from November 2013 to January 2018 at a single academic institution. Postoperative UTI was defined as any uropathogen growth from standard urine culture. Continuous variables were compared with independent samples t-test and categorical variables with chi-square with Bonferonni corrections as appropriate. RESULTS: One hundred and two of 1085 (9.4%) patients experienced UTI; 63.7% occurred within 6 weeks and 78.4% within 8 weeks; 36.3% of UTIs occurred at a time period of 6 weeks to 90 days. Most commonly isolated uropathogens were Escherichia coli (47.8%) with an additional 11.2% extended-spectrum beta-lactamase (ESBL) Escherichia coli. Other bacteria included Enterococcus faecalis (10.4%), Klebsiella pneumoniae (9%), and one culture each for ESBL Klebsiella pneumoniae and vancomycin-resistant (VRE) Enterococcus faecium. CONCLUSIONS: More than one third of UTIs after urogynecologic surgery occur between 6 weeks and 90 days postoperatively. A plateau of UTI incidence occurs at 8 weeks, a time period at which 78.4% of all UTIs were captured. Escherichia coli was the most commonly isolated uropathogen, and multi-drug-resistant bacteria were implicated in 12.8% of UTIs.

Screening for Microscopic Hematuria in a Urogynecologic Population.

OBJECTIVES: The objectives of this were to determine the correlation of greater than or equal to 3 red blood cells per high-power field (RBCs/HPF) with a positive urine dipstick for blood and to identify clinically relevant factors than can influence this relationship. METHODS: The charts of women with positive blood urine dipsticks were reviewed from August 2012 to August 2013. The cohort of women was divided into 2 groups; those with urine with greater than or equal to 3 RBCs/HPF on microscopy and those without. Relevant clinical and demographic variables were extracted from the electronic medical record. Data analysis was conducted using SAS version 9.4 (SAS Institute, Cary, NC). RESULTS: Most of the 203 patients eligible for analysis were Caucasian, and the total cohort had a mean age of approximately 62.8 years. Microscopy confirmed greater than or equal to 3 RBCs/HPF in 25.6% of the urine samples. A dipstick finding of moderate or large blood was significantly more likely to have greater than or equal to 3 RBCs/HPF on univariate and multivariable analyses (P < 0.001). Factors significantly associated with greater than or equal to 3 RBCs/HPF were increasing age, recurrent urinary tract infections, and urinary specific gravity of greater than 1.010. CONCLUSIONS: Lower urinary specific gravities appear to be associated with underestimating microhematuria, likely owing to the underrepresentation of the true number of red blood cells. Urine dipstick indicators of moderate or large blood increase the likelihood the microscopy samples demonstrated greater than or equal to 3 RBCs/HPF. These findings suggest that clarification of microhematuria detection and evaluation guidelines should be considered, given both important clinical and economic consequences.

Identification and management of urinary incontinence in midlife women.

Urinary incontinence is a common bladder health problem that disproportionately affects women, especially midlife women. In the absence of alarming signs or symptoms, a step-wise evaluation aligned with patient treatment preferences is appropriate. Initial interventions can include simple behavior therapies, lifestyle modifications, and toileting habits. Systemic medication, surgery, and specialty treatment also can be offered.

Recruitment and retention: A randomized controlled trial of video-enhanced versus standard consent processes within the E-OPTIMAL study.

BACKGROUND/AIMS: In this study, we compared two research consent techniques: a standardized video plus usual consent and usual consent alone. METHODS: Individuals who completed 24-month outcomes (completers) in the Operations and Pelvic Muscle Training in the Management of Apical Support Loss study were invited to participate in an extended, longitudinal follow-up study (extended Operations and Pelvic Muscle Training in the Management of Apical Support Loss). Potential participants who were (1) able to provide consent and (2) not in long-term care facilities were randomized 1:1 to a standardized video detailing the importance of long-term follow-up studies of pelvic floor disorders followed by the usual institutional consent process versus the usual consent process alone. Randomization, stratified by site, used randomly permuted blocks. The primary outcome was the proportion of participants who enrolled in the extended study and completed data collection events 5 years after surgery. Secondary outcomes included the proportion enrolled in the extended study, completion of follow-up at each study year, completion of data collection points, completion of in-person visits, and completion of quality of life calls. Motivation and barriers to enrollment (study-level and personal-level) and satisfaction with the study consent process were measured by questionnaire prior to recruitment into extended Operations and Pelvic Muscle Training in the Management of Apical Support Loss. Groups were compared using an intention-to-treat principle, using unadjusted Student's t-test (continuous) and chi-square or Fisher's exact (categorical) test. A sample size of 340 (170/group) was estimated to detect a 15% difference in enrollment and study completion between groups with p < 0.05. RESULTS: Of the 327 Operations and Pelvic Muscle Training in the Management of Apical Support Loss completers, 305 were randomized to the consent process study (153 video vs 152 no video). Groups were similar in demographics, surgical treatment, and outcomes. The overall rate of extended study enrollment was high, without significant differences between groups (video 92.8% vs no video 94.1%, p = 0.65). There were no significant differences in the primary outcome (video 79.1% vs no video 75.7%, p = 0.47) or in any secondary outcomes. Being "very satisfied" overall with study information (97.7% vs 88.5%, p = 0.01); "strong agreement" for feeling informed about the study (81.3% vs 70.8%, p = 0.06), understanding the study purpose (83.6% vs 71.0%, p = 0.02), nature and extent (82.8% vs 70.2%, p = 0.02), and potential societal benefits (82.8% vs 67.9%, p = 0.01); and research coordinator/study nurse relationship being "very important" (72.7% vs 63.4%, p = 0.03) were better in the video compared to the no video consent group. CONCLUSION: The extended study had high enrollment; most participants completed most study tasks during the 3-year observational extension, regardless of the use of video to augment research consent. The video was associated with a higher proportion of participants reporting improved study understanding and relationship with study personnel.

Pain and activity after vaginal reconstructive surgery for pelvic organ prolapse and stress urinary incontinence.

BACKGROUND: Little is known about short- and long-term pain and functional activity after surgery for pelvic organ prolapse. OBJECTIVE: The objectives of the study were to describe postoperative pain and functional activity after transvaginal native tissue reconstructive surgery with apical suspension and retropubic synthetic midurethral sling and to compare these outcomes between patients receiving 2 common transvaginal prolapse repairs, uterosacral ligament, and sacrospinous ligament vaginal vault suspension. STUDY DESIGN: This planned secondary analysis of a 2 × 2 factorial randomized trial included 374 women randomized to receive uterosacral (n = 188) or sacrospinous (n = 186) vaginal vault suspension to treat both stages 2-4 apical vaginal prolapse and stress urinary incontinence between 2008 and 2013 at 9 medical centers. Participants were also randomized to receive perioperative pelvic muscle therapy or usual care. All patients received transvaginal native tissue repairs and a midurethral sling. Participants completed the Surgical Pain Scales (0-10 numeric rating scales; higher scores = greater pain) and Activity Assessment Scale (0-100; higher score = higher activity) prior to surgery and at 2 weeks, 4-6 weeks, and 3 months postoperatively. The MOS 36-item Short-Form Health Survey was completed at baseline and 6, 12, and 24 months after surgery; the bodily pain, physical functioning, and role-physical subscales were used for this analysis (higher scores = less disability). Self-reported pain medication use was also collected. RESULTS: Before surgery, average pain at rest and during normal activity were (adjusted mean ± SE) 2.24 ± 0.23 and 2.76 ± 0.25; both increased slightly from baseline at 2 weeks (+0.65, P = .004, and +0.74, P = .007, respectively) and then decreased below baseline at 3 months (-0.87 and -1.14, respectively, P < .001), with no differences between surgical groups. Pain during exercise/strenuous activity and worst pain decreased below baseline levels at 4-6 weeks (-1.26, P = .014, and -0.95, P = .002) and 3 months (-1.97 and -1.50, P < .001) without differences between surgical groups. Functional activity as measured by the Activity Assessment Scale improved from baseline at 4-6 weeks (+9.24, P < .001) and 3 months (+13.79, P < .001). The MOS 36-item Short-Form Health Survey Bodily Pain, Physical Functioning, and Role-Physical Scales demonstrated significant improvements from baseline at 6, 12, and 24 months (24 months: +5.62, +5.79, and +4.72, respectively, P < .001 for each) with no differences between groups. Use of narcotic pain medications was reported by 14.3% of participants prior to surgery and 53.7% at 2 and 26.1% at 4-6 weeks postoperatively; thereafter use was similar to baseline rates until 24 months when it decreased to 6.8%. Use of nonnarcotic pain medication was reported by 48.1% of participants prior to surgery, 68.7% at 2 weeks, and similar to baseline at 3 months; thereafter use dropped steadily to 26.6% at 2 years. Uterosacral ligament suspension resulted in less new or worsening buttock pain than sacrospinous suspension at 4-6 weeks postoperatively (4.6% vs 10.5%, P = .043) but no difference in groin or thigh pain. CONCLUSION: Pain and functional activity improve for up to 2 years after native tissue reconstructive surgery with uterosacral or sacrospinous vaginal vault suspension and midurethral sling for stages 2-4 pelvic organ prolapse. On average, immediate postoperative pain is low and improves to below baseline levels by 4-6 weeks.