International Urogynecology Consultation Chapter 1 Committee 5: relationship of pelvic organ prolapse to associated pelvic floor dysfunction symptoms: lower urinary tract, bowel, sexual dysfunction and abdominopelvic pain.

INTRODUCTION AND HYPOTHESIS: This article from Chapter 1 of the International Urogynecology Consultation (IUC) on Pelvic Organ Prolapse (POP) establishes the prevalence of lower urinary tract disorders, bowel symptoms, vulvo-vaginal/lower abdominal/back pain and sexual dysfunction in women with POP. METHODS: An international group of nine urogynecologists/urologists and one medical student performed a search of the literature using pre-specified search terms in Ovid, MEDLINE, Embase and CINAHL from January 2000 to March 2019. Publications were eliminated if not relevant or they did not include clear definitions of POP or the symptoms associated with POP. Definitions of POP needed to include both a physical examination finding using a validated examination technique and the complaint of a bothersome vaginal bulge. Symptoms were categorized into symptom groups for ease of evaluation. The Specialist Unit for Review Evidence (SURE) was used to evaluate for quality of the included articles. The resulting list of articles was used to determine the prevalence of various symptoms in women with POP. Cohort studies were used to evaluate for possible causation of POP as either causing or worsening the symptom category. RESULTS: The original search yielded over 12,000 references, of which 50 were used. More than 50% of women with POP report lower urinary tract symptoms. Cohort studies suggest that women with POP have more obstructive lower urinary tract symptoms than women without POP. Pain described in various ways is frequently reported in women with POP, with low back pain being the most common pain symptom reported in 45% of women with POP. In cohort studies those with POP had more pain complaints than those without POP. Sexual dysfunction is reported by over half of women with POP and obstructed intercourse in 37-100% of women with POP. Approximately 40% of women have complaints of bowel symptoms. There was no difference in the median prevalence of bowel symptoms in those with and without POP in cohort studies. CONCLUSIONS: The prevalence of lower urinary tract disorders, bowel symptoms, vulvo-vaginal/lower abdominal/back pain and sexual dysfunction in women with POP are common but inconsistently reported. There are few data on incidence of associated symptoms with POP, and cohort studies evaluating causality are rare or inconsistent. Obstructive voiding, lower abdominal and pelvic pain, and sexual dysfunction are most frequently associated with POP.

Does cystoscopy method affect the investigation of bladder pain syndrome/interstitial cystitis?

INTRODUCTION AND HYPOTHESIS: Cystoscopic investigation to identify associated histological findings of increased mast cells in the detrusor muscle has been recommended by the European Society for the Study of Bladder Pain Syndrome (ESSIC) in the investigation of bladder pain syndrome/interstitial cystitis (BPS/IC). The aim of this study was to identify if the cystoscopy approach impacts the biopsy results when investigating women presenting with symptoms of BPS/IC. METHODS: We performed a single-centre retrospective analysis of 300 bladder biopsy reports from 2015 to 2018 from women undergoing cystoscopy for BPS/IC. Biopsies obtained using closed cup forceps through a flexible (FC) or rigid cystoscope (RC) were compared. RESULTS: Fifty-eight FC biopsies were compared with 242 RC biopsies. FC biopsies had a smaller mean diameter (1.6 mm vs 2.9 mm p < 0.01) and volume (4.1 mm3 vs 9.6 mm3 p < 0.001) compared with RC biopsies. There was no significant difference in the histological depth of sampling to the muscularis propria. A total of 292 samples had CD117 immunohistochemical staining for mast cell count (MCC) analysis. The MCC/mm2 was significantly lower in FC biopsies (p < 0.01). Sixteen percent of FC samples compared with 60% of RC samples had a high MCC >28/mm2 (p < 0.01). There was no significant difference in positive microbiology culture between FC (21%) and RC (28%) sampling. CONCLUSION: Rigid and flexible cystoscopy can be used to investigate BPS/IC as recommended by international societies. However, the biopsy method impacts the mast cell count analysis, which can influence diagnosis and management. Therefore, RC would be the optimal investigation.

Interstitial cystitis/bladder pain syndrome and recurrent urinary tract infection and the potential role of the urinary microbiome.

Interstitial cystitis/bladder pain syndrome and recurrent urinary tract infections carry significant burden for those affected. As women enter the menopause, other factors may influence how these conditions manifest. The urinary microbiome has shown that the urine contains extensive numbers of bacteria. There is some evidence to suggest that it is altered depending on the menopausal state of the individual. It is possible that this alteration may go on to influence how the disease course of interstitial cystitis/bladder pain syndrome and recurrent urinary tract infections runs in the post-menopausal group. The review will explore these two conditions and the potential role of the urinary microbiome.

Does size matter? Perineometer and digital examination of a model levator hiatus.

INTRODUCTION: Evaluation of the female pelvic floor muscles is commonly carried out with digital examination and assigning a modified Oxford scale score or vaginal manometry. Racial differences can influence the size of the levator hiatus (LH) with "black" or African nulliparous women having a significantly larger LH compared to Caucasian women. The aim of this study was to assess the impact of LH size on manometry readings of simulated pelvic floor muscle contractions (PFMCs) using a small and large model LH. METHODS: Small and large LH models were created using published data for size. Inflation of a pressure cuff placed circumferentially in the LH model represented a simulated PFMC. The models were examined in a supine position by three examiners and a perineometer twice each at varying simulated PFMC strength. RESULTS: Positive correlation was found between increasing simulated PFMC strength with a higher Oxford score following digital examination and manometry readings for both the small (rs = .87, rs = .98) and large (rs = .95, rs = .87) models. There was good to excellent inter and intraobserver correlation for digital assessment of both models. The manometry measurements showed a much larger incremental rise from baseline in the small model compared with the large model (P < .05). CONCLUSION: This study demonstrates that perineometer readings are affected by natural variations in LH size and PFMC strength. Therefore improvement to pelvic floor strength cannot be interpreted and measurements cannot be compared with others unless the LH size is known or digital examination is carried out.

The role of bladder instillation in the treatment of bladder pain syndrome: Is intravesical treatment an effective option for patients with bladder pain as well as LUTS?

The aetiology of bladder pain syndrome/interstitial cystitis is still unknown. Numerous mechanisms have been proposed and treatments targeting various aspects of these are used. This review looks at the existing evidence on bladder instillations and whether they could be used in the treatment of lower urinary tract symptoms as well.

Posterior tibial nerve stimulation for overactive bladder-techniques and efficacy.

The ideal treatment for overactive bladder is still elusive. In those where medication fails to improve symptoms options include invasive treatments such as botulinum toxin-A, sacral neural stimulation or posterior tibial nerve stimulation. Scientific professional society guidelines advise percutaneous posterior tibial nerve stimulation as a third line treatment option only after multi-disciplinary team review as well as failure of both conservative and pharmacological management. The aim of this article is to review all techniques for tibial nerve stimulation and their efficacy.

The use of laser in urogynaecology.

INTRODUCTION: The use of lasers in urogynaecology has increased in recent years. Their use has been described in pelvic organ prolapse, urinary incontinence and genito-urinary symptoms of menopause. The aim of this study was to review the published literature on CO2 and erbium:YAG laser use in urogynaecological conditions. METHODS: An extensive search of literature databases (PubMed, EMBASE) was performed for publications (full text and abstracts) written in English up to July 2018. Relevant trials were selected and analysed by an independent reviewer. Twenty-five studies were identified in total. RESULTS: All studies were either prospective cohort or case-control studies. The results of individual studies indicate that both CO2 and erbium lasers are effective in treating urogynaecological conditions. Most studies use a vaginal approach with only two investigations of intraurethral application. CONCLUSION: The use of lasers to treat these conditions may seem appealing; however, the lack of good-quality evidence in the form of multi-centre randomised placebo-controlled trials is concerning. The safety and effectiveness of these laser devices have not been established. Use of lasers may lead to serious adverse events such as vaginal burns, scarring, dyspareunia and chronic pain. Randomised placebo-controlled trials in addition to formal evaluation of the laser devices are required before this treatment modality can be recommended.

Reliability and validity of urinary nerve growth factor measurement in women with lower urinary tract symptoms.

INTRODUCTION AND HYPOTHESIS: The validity and reliability of measurement of urinary NGF as a diagnostic biomarker in women with lower urinary tract dysfunction (LUTD) is uncertain. We aimed to evaluate both the diagnostic and discriminant validity, and the test-retest reliability of urinary NGF measurement in women with LUTD. METHODS: Urinary NGF was measured in women with LUTD (n = 205) and asymptomatic subjects (n = 31). Urinary NGF was assayed using an ELISA method and normalized against urinary creatinine. NGF/creatinine ratios were compared between symptom subgroups using Mann-Whitney U test, and between different urodynamic diagnoses using the Kruskal-Wallis test. Receiver Operator Characteristic (ROC) analysis was employed to evaluate the diagnostic performance of urinary NGF. Test-retest reliability of NGF measurement was assessed using intra-class correlation (ICC). RESULTS: Urinary NGF was significantly but non-specifically increased in symptomatic patients when compared to controls (13.33 vs. 2.05 ng NGF/g Cr, P < 0.001). On multivariate logistic regression NGF was a good predictor of patients having OAB or not, however, the adjusted odds ratio only 1.006. ROC analysis demonstrated poor discriminant ability between different symptomatic groups and urodynamic groups. Using a cut off of 13.0 ng NGF/g creatinine the test provides a sensitivity of 81%, but a specificity of only 39% for overactive bladder. The assays demonstrated good test-retest reliability with ICC of 0.889. CONCLUSIONS: Although urinary NGF can be reliably assayed, and is increased in various LUTDs, it discriminates poorly between these disorders therefore has very limited potential as a biomarker. Neurourol. Urodynam. 35:944-948, 2016. © 2015 Wiley Periodicals, Inc.

Sacral neuromodulation: an effective treatment for lower urinary tract symptoms in multiple sclerosis.

INTRODUCTION AND HYPOTHESIS: Most subjects with multiple sclerosis (MS) suffer from lower urinary tract symptoms (LUTS). Detrusor overactivity, detrusor hypocontractility and detrusor-sphincter dyssynergia are the most common bladder dysfunctions. Management is not straightforward due to the progressive course of the disease. Sacral neuromodulation (SNM) has received increasing attention among new effective treatments for bladder disorders associated with MS. The aim of this study was to review the published literature on the role of SNM in the treatment of LUTS in patients with MS. METHODS: A literature search was carried out up to December 2014, using relevant search terms in MEDLINE and EMBASE databases. The ClinicalTrials.gov and Controlled-trials.com online trial registries and the abstracts from international scientific meetings were searched for English-language studies containing relevant search terms. Relevant reviews and trials and prospective studies were analysed by two independent reviewers. RESULTS: Two prospective studies and four retrospective studies were included. Overall, MS patients represented small series (4 to 25 subjects). The longest follow-up was 7 years and the evaluation of the treatment outcomes was not homogeneous among the studies. The definition of objective cure was often unclear. The subjective cure rate was 45 %, patients' reported satisfaction was 85 % and all the results were stable over time. CONCLUSIONS: SNM seems to be a safe and effective treatment for LUTS in MS patients. Further and larger studies as well as randomized controlled trials are needed to confirm its clinical role in patients with MS.

Mode of delivery after obstetric anal sphincter injury.

OBJECTIVE: To assess the effect of vaginal delivery and caesarean section on faecal symptoms and structure and function of anal sphincter in women who sustained obstetric anal sphincter injuries (OASIS) in their previous pregnancy and were advised about the mode of delivery based on faecal incontinence symptoms, anal manometry and endoanal ultrasound. STUDY DESIGN: It is a descriptive study on a cohort of women who had OASIS from 2006 to 2013. They were assessed after OASIS and during subsequent pregnancy with a questionnaire, endoanal ultrasound and anal manometry. Vaginal delivery was recommended to asymptomatic women with normal investigations. Elective caesarean section was recommended to women with faecal symptoms, anal sphincter defects of more than 30° or low resting or incremental anal pressures. All women were reassessed after subsequent delivery. RESULTS: Fifty women who had pregnancies after OASIS, were seen after OASIS, during subsequent pregnancy and after the second delivery. 15 women had faecal symptoms after OASIS. The external, internal and combined anal sphincter defects were seen in 13, 11 and 9 women respectively. Low resting and incremental pressure were seen in 15 and 11 women respectively. Caesarean section was done in 22 women and 28 women delivered vaginally. Worsening of faecal symptoms and reduction in anal pressures were not observed in planned vaginal delivery or elective caesarean section groups. Faecal symptoms were worse with reduced anal pressures in three women from the planned caesarean section group. One of the women had a vaginal delivery and two women had emergency caesarean section at 7cm and 10cm dilatation. There were no new sphincter defects or recurrent OASIS in any of the women in the study group. CONCLUSION: Decision about the mode of delivery of pregnancy after OASIS based on symptoms, anal manometry and endoanal ultrasound helps in preserving the anal sphincter function and avoiding unnecessary caesarean sections. Further follow-up of these patients is essential to evaluate the long-term effects of this decision.

The pelvic floor muscle hyperalgesia (PFMH) scoring system: a new classification tool to assess women with chronic pelvic pain: multicentre pilot study of validity and reliability.

OBJECTIVE: The contribution of pelvic floor muscle tenderness to chronic pelvic pain (CPP) is well established in the literature. However pelvic floor muscle hyperalgesia (PFMH) is often missed during vaginal examination of women with CPP. To our knowledge criteria for diagnosing PFMH has not been established or validated so far. The aim of this study is to assess the validity and reliability of the PFMH scoring system. STUDY DESIGN: Women with and without PFMH were recruited prospectively. Digital pelvic examination was performed to detect any pain. All women were asked to report of any discomfort or pain evoked by digital palpation of the PFMs and to rate the severity of pain/discomfort as none (grade 0), mild (grade I) moderate (grade II) or severe (grade III). All women were also asked to describe the severity of the pain/discomfort using a visual analogue scale (VAS). Following examination a PFMH score was given according to each patient's reactions. Intra-observer and inter-observer reliability was assessed. Construct and content validity was also determined. RESULTS: 111 (44 symptomatic and 67 controls) were recruited. Intraobserver reliability had ICCs between 0.426 and 0.804. Interobserver reliability had ICCs between 0.724 and 0.917. There was a good correlation between PFMH scores and VAS scores (rho 0.994, p<0.01). Total scores between symptomatic and controls were significantly different (p<0.01 Mann-Whitney U test). CONCLUSION: The PFMH scoring system is a simple, reliable, valid and easy screening tool for in the assessment of women with CPP.

Lack of association of joint hypermobility with urinary incontinence subtypes and pelvic organ prolapse.

OBJECTIVE: To test the hypothesis that joint hypermobility (JHM) is associated with specific urinary incontinence (UI) subtypes and uterovaginal prolapse. PATIENTS AND METHODS: In all, 270 women scheduled to undergo urodynamic investigations were invited to self-complete a validated five-item JHM questionnaire. Women underwent history taking, symptoms assessing via the King's Health Questionnaire and clinical examination using the Pelvic Organ Prolapse Quantification system. Associations between JHM and pelvic floor disorders in univariate and multivariate ordinal regression were reported using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The prevalence of JHM was 31.1%. JHM had a negative association with age (OR 0.98/year, P = 0.04). There was no association between JHM and either urodynamic (P = 0.41), or symptomatic stress UI (P = 0.48). Nor was there association with detrusor overactivity or symptomatic urgency UI. Multivariate ordinal regression of JHM with maximum prolapse stage, adjusting for age, showed a significant relationship (OR 1.26/stage, 95% CI 1.06-1.46, P < 0.05). CONCLUSION: Although JHM is highly prevalent amongst women with lower urinary tract symptoms (LUTS), there is no strong association of JHM with any UI subtype. There is a trend towards higher prolapse staging in women with JHM, which becomes significant only after adjustment for the confounding negative association between age and JHM.

Botulinum neurotoxin type A injection of the pelvic floor muscle in pain due to spasticity: a review of the current literature.

The role of muscle spasm is not a new concept in the genesis of pain. Botulinum neurotoxin type A (BoNTA) has been successfully employed in a variety of muscular and inflammatory conditions. The aim of our study was to review the published literature on the role of BoNTA injection of the pelvic floor muscle in the management of women with chronic pelvic pain (CPP). A systematic search of the literature published up to June 2012 on the use of BoNTA in the treatment of female pelvic floor muscle spasm was carried out using relevant search terms in MEDLINE and EMBASE databases. The results were limited to full-text English language articles. Relevant trials as well as relevant reviews were selected and analyzed by two independent reviewers. Five studies (2 case reports, 1 prospective pilot study, 1 retrospective study and 1 randomised double-blind placebo controlled study) were included in this systematic review. Overall, BoNTA has shown to be beneficial in relieving CPP related to pelvic floor spasm. The role of BoNTA as a treatment of CPP has been recognized for more than 10 years. Although data are still scarce preliminary results are encouraging. BoNTA is an attractive option for refractory CPP related to pelvic floor muscle spasm, but further studies using validated and reproducible outcome measures are needed, to establish its effectiveness, safeness, technique, optimal dosage, and duration of symptom relief.

Biomarkers in overactive bladder.

A biomarker is an indicator of a particular disease. It is generally used to define the presence (diagnostic biomarker), severity, progression (prognostic biomarker) of a condition and/or its response to a specific treatment (predictive biomarker). Biomarkers can be specific cells, enzymes, hormones, genes or gene products, which can be detected and measured in parts of the body such as blood, urine or tissue. Therefore, biomarkers have been suggested to play an important role in both the clinical assessment and the management of patients, as well as in the research setting. Recently, interest has gathered in urinary biomarkers as a tool to assess overactive bladder (OAB), potentially playing a role in the diagnosis, disease progression and monitoring response to treatment. Urinary biomarkers identified so far include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), prostaglandins, cytokines and C-reactive protein. The aim of this review was to review the published literature on biomarkers in OAB. A literature review using Pub Med, clinicaltrials.gov and the controlled trials online registries was performed from 1970 up to June 2012. The search keywords were: the International Continence Society (ICS) definition of "OAB", "nerve growth fac- tor" (NGF), "brain derived growth factor" (BDNF), "prostaglandins," "cytokines," "genetic biomarkers" and "C reactive protein".The results were limited for fully published English-language articles. The search was then subsequently expanded to include urinary biomarkers in interstitial cystitis and bladder pain where relevant. Each of the studies/articles was reviewed, interpreted and discussed to consider the role of urinary biomarkers in OAB. Using the search criteria, a total of 20 studies (animal and human) that investigated the role of urinary biomarkers in OAB were identified. Full text versions of these articles were obtained and reviewed. Studies on NGF suggested that urinary levels were higher in OAB patients and decreased with antimuscarinic and botulinum toxin treatment. BDNF studies have demonstrated raised levels in OAB and also increased levels in situations of acute bladder inflammation. The role of urinary prostaglandins, cytokines and CRP does not appear to be specific to the OAB disease process according to the current available evidence. Based on the evidence so far NGF and BDNF appear to be the most promising biomarkers in OAB. Although still in their infancy these neurotrophic factors could potentially diagnose OAB, replacing urodynamics and aiding in monitoring disease progression and response to treatment in addition to clinical symptoms.

Fesoterodine in randomised clinical trials: an updated systematic clinical review of efficacy and safety.

INTRODUCTION AND HYPOTHESIS: This is a systematic review of clinical data assessing the safety, efficacy and tolerability of fesoterodine in randomised control trials (RCTs) in the treatment of overactive bladder (OAB). METHODS: We performed a MEDLINE literature search of articles published between 2005 and 2010 regarding the efficacy and safety of fesoterodine. The US Food and Drug Administration Web site was also searched for RCTs. RESULTS: Two studies demonstrated significant improvement of OAB symptoms with fesoterodine compared with placebo. Two phase III studies showed both doses of fesoterodine to be more effective than placebo for most symptoms. Another phase III trial confirmed the superiority of 8 mg fesoterodine compared with tolterodine ER 4 mg. Dry mouth was the commonest side effect. CONCLUSIONS: Fesoterodine is effective for treating OAB symptoms. Its once-daily dosing regime and the flexibility to increase the dose are appealing factors.

Use of mirabegron in treating overactive bladder.

The lack of an alternative to antimuscarinics has led to the search for new drug targets for overactive bladder (OAB) symptoms. The presence of ß-3 adrenoreceptors in the bladder has been confirmed, and they are known to have a role in bladder relaxation. Targeting these receptors improves bladder compliance on filling and increases bladder capacity. MEDLINE literature search on efficacy and safety of mirabegron was performed. The US Food and Drug Administration Web site, clinicaltrials.gov, and controlled-trials.com online trial registries were searched for English-language articles containing the term "mirabegron". Finally, abstracts from recent International scientific meetings were searched for randomised controlled trials (RCTs). Studies show that mirabegron reduces the number of micturitions and incontinence episodes in a 24-h period compared with placebo. Dry mouth and gastrointestinal disturbances are the most common side effects, but these have been rated as mild to moderate. A small rise in mean heart rate and blood pressure has been shown. Further investigations are ongoing and results are awaited. Although mirabegron is metabolised by CYP2D6, it is also thought to inhibit the activity of this enzyme. Therefore, potential drug interactions with other CYP2D6 substrates need to be further studied. Mirabegron is a promising alternative to antimuscarinics. Further information on its long-term use in terms of efficacy, safety, and tolerability is awaited.

Mirabegron - a selective ß3-adrenoreceptor agonist for the treatment of overactive bladder.

Overactive bladder is a common condition that significantly impacts overall quality of life. Antimuscarinics are the current main pharmacological option for treatment; however, many patients fail to adhere to therapy due to troublesome side effects. Mirabegron is a new beta-3 adrenoreceptor agonist which causes detrusor smooth muscle relaxation and has been proposed to be effective for treating overactive bladder symptoms. Mirabegron has been shown to be superior to placebo for reducing the mean number of incontinence episodes per 24 hours and the mean number of micturitions per 24 hours. Side effects such as dry mouth were observed at similar or lower rates than those seen for placebo and antimuscarinics. Higher doses of mirabegron were associated with minor increases in pulse rate and mean blood pressure. Mirabegron offers a new alternative for treating overactive bladder in patients for which antimuscarinics are either not tolerated or not appropriate.