The Future of Basic Science: Development of the Next Generation of Mechanistic Researchers in Female Pelvic Medicine.

INTRODUCTION AND HYPOTHESIS: The International Urogynecological Association (IUGA) brought together senior and junior members actively engaged in scholarly and educational activities for a consensus conference centered on developing a strategy for sustainable training of the next generation of mechanistic researchers in female pelvic medicine. METHODS: Four a priori identified major foci were explored in a half-day virtual consensus conference. Participants included representatives from various countries and disciplines with diverse backgrounds-clinicians, physician-scientists, and basic scientists in the fields of urogynecology, biomechanical engineering, and molecular biology. Following a keynote address, each focus area was first tackled by a dedicated breakout group, led by the Chair(s) of the most relevant IUGA committees. The break-out sessions were followed by an iterative discussion among all attendees to identify mitigating strategies to address the shortage of mechanistic researchers in the field of female pelvic medicine. RESULTS: The major focus areas included: research priorities for IUGA basic science scholar program; viable strategies for sustainable basic science mentorship; core competencies in basic science training; and the challenges of conducting complex mechanistic experiments in low-resource countries. Key gaps in knowledge and core competencies that should be incorporated into fellowship/graduate training were identified, and existing training modalities were discussed. Recommendations were made for pragmatic approaches to increasing the exposure of trainees to learning tools to enable sustainable training of the next generation of basic science researchers in female pelvic medicine worldwide. CONCLUSIONS: The attendees presented multiple perspectives to gain consensus regarding critical areas of need for training future generations of mechanistic researchers. Recommendations for a sustainable Basic Science Scholar Program were developed using IUGA as a platform. The overarching goal of such a program is to ensure a successful bench-to-bedside-and-back circuit in Urogynecology and Pelvic Reconstructive Surgery, ultimately improving lives of millions of women worldwide through scientifically rational effective preventative and therapeutic interventions.

A Comparison of Health-Related Quality of Life of Women Awaiting Pelvic Organ Prolapse Surgery versus Hip or Knee Replacement.

OBJECTIVE: Pelvic organ prolapse (POP) can significantly decrease the health-related quality of life (HRQOL) of women. In 2005, provincial and territorial wait time benchmarks were set in areas such as hip and knee replacement, but such efforts were lagging for urogynaecological surgeries. This study aimed to compare wait times and HRQOL scores of females awaiting surgery for POP with those of women awaiting hip or knee replacement. METHODS: This was a prospectively planned study comparing women undergoing surgical repair of POP to women having a hip or knee replacement. All women completed a validated HRQOL questionnaire, the Short Form 36 Health Survey. The date of the decision to operate was recorded and patients were followed up prospectively to determine surgical wait time. RESULTS: Three of four physical health concepts were significantly worse for orthopedic patients compared with urogynaecology patients, including the physical component summary (29.2 vs. 41.5, respectively, P < 0.001). Urogynaecology and orthopedic patients had similar emotional and mental well-being, as demonstrated by similar mental component summaries (41.5 vs. 44.6, respectively, P = 0.09). The mean wait time at our institution for hip or knee replacement was 98 days, which was significantly shorter than the mean wait time of 210 days for POP surgery (P < 0.001). CONCLUSION: Despite less physical and pain impact, urogynaecology patients showed similar emotional distress and mental impact compared with orthopedic patients based on a validated HRQOL questionnaire. Because urogynaecology patients waited more than twice as long for their surgery, resources should be directed to prioritize and improve the surgical wait time for urogynaecology patients.

A Streamlined Surgical Approach to Laparoscopic Sacrocolpopexy for Post-Hysterectomy Vault Prolapse.

OBJECTIVE: To describe a streamlined laparoscopic sacrocolpopexy (LSCP) surgical technique in women with post-hysterectomy vault prolapse and to evaluate the functional outcomes, complication rates, and surgical morbidity within our centre. METHODS: We retrospectively reviewed the charts of 180 patients scheduled for LSCP between November 2002 and May 2013 in a tertiary care centre. Patients were followed-up at six weeks, six months, and yearly after surgery. We reviewed patient demographics, preoperative and postoperative symptoms, and perioperative variables. Objective success of the surgery was defined as having a less than stage 2 vault prolapse, and subjective success was defined as the absence of bulge or prolapse symptoms. Success and complication rates were calculated. RESULTS: Of the 180 patients who underwent surgery, 144 patients underwent the procedure as planned and had at least six months of follow-up. At the last follow-up visit, 133 of these 144 patients (92.4%) were free of prolapse symptoms. Several bladder and bowel symptoms showed significant improvement. Anatomical success of vault support was achieved in 140 of 144 patients (97.2%), and 119 patients (82.6%) had no prolapse beyond the hymen. Early complications (within the first 6 weeks) occurred in 8.3% of 162 patients with limited outcome data, and late complications (after 6 weeks) occurred in 11.5% of the 144 patients with long-term data. There were no cystotomies or mesh exposures. CONCLUSION: At an average of 32 months, this cohort of patients had low prolapse recurrence rates and no reports of cystotomy or mesh erosion. The abridged LSCP technique, as practised in our institution, is safe and effective in the surgical management of post-hysterectomy vault prolapse.

Static Mechanical Loading Influences the Expression of Extracellular Matrix and Cell Adhesion Proteins in Vaginal Cells Derived From Premenopausal Women With Severe Pelvic Organ Prolapse.

INTRODUCTION: Primary human vaginal cells derived from women with severe pelvic organ prolapse (POP-HVCs) demonstrate altered cellular characteristics as compared to cells derived from asymptomatic women (control-HVCs). Using computer-controllable Flexcell stretch unit, we examined whether POP-HVCs react differently to mechanical loading as compared to control-HVCs by the expression of extracellular matrix (ECM) components, cell-ECM adhesion proteins, and ECM degrading and maturating enzymes. METHODS: Vaginal tissue biopsies from premenopausal patients with Pelvic Organ Prolapse Quantification System stage ≥3 (n = 8) and asymptomatic controls (n = 7) were collected during vaginal hysterectomy or repair. Human vaginal cells were isolated by enzymatic digestion, seeded on collagen (COLI)-coated plates, and stretched (24 hours, 25% elongation). Total RNA was extracted, and 84 genes were screened using Human ECM and Adhesion Molecules polymerase chain reaction array; selected genes were verified by quantitative reverse transcription-polymerase chain reaction. Stretch-conditioned media (SCM) were collected and analyzed by protein array, immunoblotting, and zymography. RESULTS: In mechanically stretched control-HVCs, transcript levels of integrins (ITGA1, ITGA4, ITGAV, and ITGB1) and matrix metalloproteinases (MMPs) 2, 8, and 13 were downregulated (P < .05); in POP-HVCs, MMP1, MMP3, and MMP10, ADAMTS8 and 13, tissue inhibitor of metalloproteinases (TIMPs) 1 to 3, ITGA2, ITGA4, ITGA6, ITGB1, contactin (CNTN1), catenins (A1 and B1), and laminins (A3 and C1) were significantly upregulated, whereas COLs (1, 4, 5, 6, 11, and 12) and LOXL1 were downregulated. Human vaginal cells massively secrete MMPs and TIMPs proteins; MMP1, MMP8, MMP9 protein expression and MMP2 gelatinase activity were increased, whereas TIMP2 decreased in SCM from POP-HVCs compared to control-HVCs. CONCLUSIONS: Primary human vaginal cells derived from women with severe pelvic organ prolapse and control-HVCs react differentially to in vitro mechanical stretch. Risk factors that induce stretch may alter ECM composition and cell-ECM interaction in pelvic floor tissue leading to the abatement of pelvic organ support and subsequent POP development.

Comparative Characterization of Vaginal Cells Derived From Premenopausal Women With and Without Severe Pelvic Organ Prolapse.

BACKGROUND: This study tested a hypothesis that primary human vaginal cells derived from tissue of premenopausal women with severe pelvic organ prolapse (POP-HVCs) would display differential functional characteristics as compared to vaginal cells derived from asymptomatic women with normal pelvic floor support (control-HVCs). METHODS: Vaginal tissue biopsies were collected from premenopausal patients with POP (n = 8) and asymptomatic controls (n = 7) during vaginal hysterectomy or repair. Primary vaginal cells were isolated by enzymatic digestion and characterized by immunocytochemistry. Cell attachment and proliferation on different matrices (collagen I, collagen II, collagen IV, fibronectin, laminin, tenascin, and vitronectin) were compared between POP-HVCs and control-HVCs. RNA was extracted, and the expression of 84 genes was screened using Human Extracellular Matrix and Adhesion Molecules RT(2) Profiler PCR array. The expression of selected genes was verified by quantitative reverse transcription-polymerase chain reaction. RESULTS: (1) Control-HVCs attached to collagen IV more efficiently than POP-HVCs; (2) control-HVCs and POP-HVCs show a similar proliferation rate when plated on proNectin and collagen I; (3) when seeded on collagen I, resting POP-HVCs expressed significantly (P < .05) increased transcript levels of collagen VII, multiple matrix metalloproteinases (MMP3, MMP7, MMP10, MMP12, MMP13, and MMP14), integrins (ITGA1, ITGA4, ITGA6, ITGA8, ITGB1, ITGB2, and ITGB3), and cell adhesion molecules as compared to control-HVCs. Collagen XV and tissue inhibitors of MMPs (TIMP1 and TIMP2) as well as genes involved in the biogenesis and maturation of collagen and elastin fibers (LOX, LOXL1-LOXL3, BMP1, and ADAMTS2) were significantly downregulated in POP-HVCs versus control-HVCs (P < .05). CONCLUSIONS: Resting primary POP-HVCs in vitro show altered cellular characteristics as compared to control-HVCs, which may influence their dynamic responses to external mechanical or hormonal stimuli.

Attachment of Primary Vaginal Fibroblasts to Absorbable and Nonabsorbable Implant Materials Coated With Platelet-Rich Plasma: Potential Application in Pelvic Organ Prolapse Surgery.

OBJECTIVES: Pelvic organ prolapse (POP) is a common condition in women. The lifetime risk of undergoing surgery to correct POP is 11%, with 30% recurrence rate. Various types of vaginal implants, absorbable and nonabsorbable, that have been introduced in pelvic floor reconstructive surgeries have numerous serious adverse effects. Platelet-rich plasma (PRP) is an autologous product that accelerates tissue healing and regeneration. We hypothesized that autologous PRP will promote human vaginal fibroblast (HVF) attachment to vaginal implants and increase their healing potential. METHODS: Vaginal tissue biopsies were collected from postmenopausal patients with POP (n = 10) and asymptomatic control subjects (n = 4) during vaginal hysterectomy or repair. Primary cells were isolated and characterized by immunocytochemistry. Cell attachment and proliferation were compared between POP HVFs and control HVFs (n = 4/group). Twelve weeks after the surgery, blood samples were collected from 6 POP patients to obtain autologous PRP. Two meshes, absorbable (Vicryl) and nonabsorbable (Restorelle), were coated in PRP or control media; autologous POP HVFs (n = 6) were seeded on meshes for 2 hours. Cells attached to the meshes were fixed, stained with DAPI (4,6-diamidino-2-phenylindole dihydrochloride), and counted. RESULTS: Pelvic organ prolapse HVFs were similar to control HVFs in attachment to different matrix substrates and in proliferation rate. Attachment of POP HVFs to both meshes was significantly increased after coating with PRP versus Dulbecco modified Eagle medium (Vicryl: 9875 vs. 1006 cells/cm, Restorelle: 3724 vs. 649 cells/cm; P < 0.001 for both). CONCLUSIONS: In vitro, primary POP HVFs show better attachment to implant materials when treated with PRP, which may lead to reduced mesh-related complications in vivo, indicating its great potential for urogynecologic surgeries.

Prevalence of obstructive sleep apnea detected by the Berlin Questionnaire in patients with nocturia attending a urogynecology unit.

INTRODUCTION AND HYPOTHESIS: Nocturia has been associated with several chronic conditions including obstructive sleep apnea (OSA). The pathophysiological link between nocturia and OSA has been well delineated, but the prevalence of this condition in patients with nocturia is unknown. The aim of this study was to determine the prevalence of sleep apnea in patients with nocturia compared with patients without nocturia in a group of women referred to a urogynecology unit. METHODS: After ethics approval, a cross-sectional case control study including 81 cases and 79 controls was conducted. The sample size of 72 patients was required for each arm to detect a 23 % difference in the prevalence of OSA with a 95 % confident interval (CI) and statistical power of 80 %. All patients completed the Nocturia, Nocturia Enuresis and Sleep Interruption Questionnaire (NNES-Q) and the Berlin OSA Questionnaire. The NNES-Q was used to define cases and controls. The Berlin Questionnaire was used to classify patients as being at a high or a low risk of having OSA. Univariate analysis was first performed, followed by logistic regression to assess the association between nocturia and OSA, as well as other possible variables associated with nocturia. RESULTS: Fifty of the cases (61.7 %) were classified as being at a high risk of having OSA compared with only 19 (24.1 %) in the control group (OR 2.9, 95 % CI 1.29-6.52, p = 0.01). Other variables found to be statistically significant by logistic regression were high BMI, overactive bladder, and low bladder capacity (<300 cc). CONCLUSION: Patients with nocturia showed a significantly higher risk of having OSA. Patients with nocturia should be screened for OSA.

Expression of extracellular matrix-remodeling proteins is altered in vaginal tissue of premenopausal women with severe pelvic organ prolapse.

AIM: The molecular etiology of pelvic organ prolapse (POP) is complex and not well understood. We compared the expression/activity of extracellular matrix (ECM)-processing (procollagen I N-proteinase/ a disintegrin and metalloproteinase with thrombospondin motifs [ADAMTS]-2,-3,-14) and ECM-degrading (matrix metalloproteinase [MMP]-1, -2, -7, -8, -9, -12) enzymes and their natural tissue inhibitors (tissue inhibitors of metalloproteinase [TIMP]-1,-2,-3,-4) in vaginal tissues from premenopausal women with advanced POP (POP-Q stage ≥ 3) and asymptomatic controls (POP-Q = 0). STUDY DESIGN: We sampled the anterior vaginal wall of 36 premenopausal women (17 patients with POP and 19 controls) undergoing total hysterectomy. Exclusion criteria include steroid therapy, malignancy, previous pelvic surgery, and connective tissue diseases. Total RNAs and proteins were quantified by real-time polymerase chain reaction, immunoblotting, and Luminex assay; MMPs activity was analyzed by zymography and tissue localization by immunohistochemistry. RESULTS: The MMP-2 gelatinase activity as well as expression of 58-kDa isoform of ADAMTS-2 was upregulated in patients with POP, irrespective of menstrual phase status, secretory or proliferative, when compared to controls (P < .05). The TIMP-1-4 gene and TIMP-1 protein expression were significantly (P < .05) reduced, whereas protein expression of MMP-12 (pro and active forms) was significantly increased in vaginal biopsies of patients with POP in the proliferative phase of the menstrual cycle compared to corresponding controls. Analyses of MMP-12, TIMP-1, and ADAMTS-2 tissue immunostaining indicate similar localization in the vaginal specimens from control and patients with POP. CONCLUSION: Expression of ECM-remodeling proteins is altered in the vagina of premenopausal patients with severe POP. We speculate that dysregulation of MMP/TIMP complexes and ADAMTS-2 proteins may cause connective tissue defects, which result in weakened vaginal wall support and POP development.

Outcome of the laparoscopic two-team sling procedure, tension-free vaginal tape insertion, and transobturator tape insertion in women with recurrent stress urinary incontinence.

OBJECTIVE: Although the surgical treatment of primary stress urinary incontinence (SUI) has been well studied, the optimal treatment of persistent or recurrent SUI represents a significant challenge to the surgeon, and there are limited relevant published data. The aim of this study was to document outcome data for various surgical techniques used at our centre for the treatment of recurrent SUI, and to assess the immediate and long-term complications associated with these procedures. METHODS: This retrospective study assessed the outcome of the laparoscopic two-team sling procedure, tension-free vaginal tape (TVT) insertion, and transobturator tape (TOT) insertion in the treatment of recurrent SUI in women. Data collected included patient demographics, urodynamic data, postoperative subjective cure and objective cure (negative cough stress test), and intraoperative and postoperative complications. RESULTS: Forty-six women with recurrent SUI were included in the study: 24 had had laparoscopic two-team sling procedures, 15 had had TVT insertion, and 7 had had TOT insertion. For each procedure, objective cure rates were 91.7%, 73.3%, and 85.7%, respectively, and subjective cure rates were 79.2%, 60%, and 57.1% respectively. In the laparoscopic two-team sling group, one woman developed an infected hematoma and one required surgery for a small bowel obstruction. CONCLUSION: The laparoscopic two-team sling procedure or TVT or TOT insertion may be used in experienced hands for surgical management of patients with recurrent stress urinary incontinence. We found no statistically significant differences in outcomes between the three groups, possibly because of the small sample size. Larger sample size and longer follow-up within prospective randomized trials are warranted to identify any possible differences.

Objectif : Bien que la prise en charge chirurgicale de l'incontinence urinaire à l'effort primaire (IUE) ait été bien étudiée, la prise en charge optimale de l'IUE persistante ou récurrente constitue un défi considérable pour le chirurgien et les données publiées pertinentes sont limitées. Cette étude avait pour but de documenter les données quant aux issues de diverses techniques chirurgicales utilisées dans notre centre pour la prise en charge de l'IUE récurrente, ainsi que d'évaluer les complications immédiates et à long terme étant associées à ces interventions. Méthodes : Cette étude rétrospective a évalué l'issue de l'intervention laparoscopique de fronde à deux équipes, de l'insertion d'une bandelette vaginale sans tension (TVT) et de l'insertion d'une bandelette transobturatrice (TOT) dans la prise en charge de l'IUE récurrente chez des femmes. Parmi les données recueillies, on trouvait les caractéristiques démographiques des patientes, les données urodynamiques, la guérison postopératoire subjective et la guérison objective (test à la toux négatif), ainsi que les complications peropératoires et postopératoires. Résultats : Quarante-six femmes présentant une IUE récurrente ont été admises à l'étude : 24 d'entre elles ont subi une intervention laparoscopique de fronde à deux équipes, 15 ont subi une insertion de TVT et 7 ont subi une insertion de TOT. Les taux de guérison objective ont été de 91,7 %, de 73,3 % et de 85,7 %, respectivement, tandis que les taux de guérison subjective ont été de 79,2 %, de 60 % et de 57,1 %, respectivement. Au sein du groupe « intervention laparoscopique de fronde à deux équipes ¼, une des participantes en est venue à présenter un hématome infecté, tandis qu'une autre a nécessité une chirurgie en raison d'une occlusion de l'intestin grêle. Conclusion : L'intervention laparoscopique de fronde à deux équipes ou l'insertion d'une TVT ou d'une TOT peuvent être utilisées par des praticiens expérimentés pour assurer la prise en charge chirurgicale des patientes qui présentent une incontinence urinaire à l'effort récurrente. Nous n'avons constaté aucune différence significative sur le plan statistique en matière d'issues entre ces trois groupes, et ce, peut-être en raison de la faible envergure de l'échantillon. La tenue d'essais randomisés prospectifs comptant des échantillons de plus grande envergure et des suivis prolongés s'avère justifiée aux fins de l'identification de toute différence possible.

Obstetric anal sphincter injuries: a survey of clinical practice among Canadian obstetricians.

OBJECTIVE: To describe the current practice, experience, and confidence of Canadian obstetricians in the management of obstetric anal sphincter injuries (OASIS) and to explore the need for national practice guidelines on this topic. METHODS: We conducted a cross-sectional, Internet-based survey between December 2010 and March 2011. The survey was initially tested among a sample population and then distributed electronically to 665 Canadian obstetricians. Data were analyzed descriptively. The main outcome measures were the self-reported confidence and experience of Canadian obstetricians in OASIS management and the frequency of performing specific OASIS management steps. RESULTS: The survey response rate was 28.7%. The majority of the respondents (95%) reported confidence in performing OASIS repairs. In the event of a perineal laceration, 47.9% of respondents routinely performed a rectal examination. Most OASIS repairs were performed in the delivery room (89.4%) under local anaesthesia (60.6%) when regional anaesthesia was not already present. If lacerated, the internal anal sphincter was repaired separately by 63.4% of respondents, and intraoperative antibiotics were ordered by 51.1% of respondents. Most (92%) reported the absence of a local protocol to guide OASIS repair. CONCLUSION: The confidence of Canadian obstetricians who participated in this survey in performing OASIS repairs was high. However, their experience in performing repairs and their use of management steps varied. The need for national guidelines and an increase in awareness is suggested.

Efficacy and safety of tension-free vaginal tape compared with transobturator tape among obese women with stress urinary incontinence: a retrospective cohort study.

OBJECTIVE: To determine the efficacy and safety of tension-free vaginal tape (TVT) compared with transobturator tape (TOT) in obese women with stress urinary incontinence (SUI). METHODS: We performed a retrospective chart review of patients who underwent insertion of TVT or TOT for stress urinary incontinence between January 2003 and October 2009. Women were excluded if they had had previous surgery for SUI or had a diagnosis of intrinsic sphincter deficiency. RESULTS: One hundred eighty obese women (BMI > 30 kg/m²) with SUI and with follow-up for at least one year were identified (90 had TVT and 90 had TOT). The rates of success on the objective criteria were 91% for the TVT group and 88% for the TOT group (P = 0.46) and 87% versus 80% (P = 0.23) on subjective assessment. CONCLUSION: Our retrospective cohort study demonstrated similar rates of cure for obese women with SUI who underwent insertion of TVT and TOT.

Expression of genes encoding smooth muscle contractile proteins in vaginal tissue of women with and without pelvic organ prolapse.

AIMS: We hypothesize that the expression of genes encoding vaginal smooth muscle (SM) contractile proteins is altered in patients with pelvic organ prolapse (POP) and is influenced by age and menopausal status. We aim to analyze the expression of SM-myosin heavy chain (MHY11), caldesmon (CALD1), SM gamma-actin (ACTG2), and tropomyosin (TPM1), in premenopausal and postmenopausal women with advanced POP and asymptomatic controls. METHODS: During total hysterectomy we collected anterior vaginal wall biopsy samples from 55 women, 37 premenopausal (23 patients and 14 controls), and 18 postmenopausal women (13 patients and 5 controls). Total mRNA from the tissues was quantified by real-time RT-PCR. RESULTS: MHY11 gene expression was down-regulated in premenopausal POP patients compared to premenopausal controls (fivefold, P = 0.002). In the postmenopausal groups, we observed a sixfold increase in the CALD1 gene expression in POP patients compared to asymptomatic controls (P = 0.03). The gene expression of CALD1, ACTG2, and TPM1 was significantly down-regulated in vaginal tissue of healthy women after menopause (P < 0.05). CONCLUSION: Dysregulation of the vaginal SM content in POP patients involves alteration of different cellular pathways according to age and menopausal status.

Randomized controlled trial of cystocele plication risks: a pilot study.

OBJECTIVE: We wished to determine the feasibility of a single-centre randomized controlled trial to investigate whether avoiding cystocele plication in women undergoing transvaginal repair of cystocele decreases the need for catheterization beyond the second postoperative day. METHODS: Patients undergoing transvaginal repair of cystocele were randomly assigned to either have or not have plication sutures during their procedure. We assessed the success of recruitment, physician acceptability, and adherence to protocol, and we also assessed the need for catheterization beyond the second postoperative day. RESULTS: Twenty-two women were randomized (a recruitment rate of 85%), and participating surgeons did not feel that one surgical technique was superior to the other. There were no protocol violations after randomization. No cases of postoperative voiding dysfunction were identified. CONCLUSION: A multicentre randomized controlled trial is required to determine the short-term and long-term risks and benefits of avoiding plication sutures in women undergoing transvaginal repair of cystocele. If patients and physicians support the study protocol, conducting such a trial is feasible.

Overactive bladder: the importance of tailoring treatment to the individual patient.

INTRODUCTION: Overactive bladder (OAB) is a prevalent and persistent condition that is often under-diagnosed and under-treated, and which frequently requires tailored treatment for successful management. METHODS: This consensus opinion-based review summarizes the discussions of a group of experts in the field of OAB that were assembled to evaluate the importance of correct diagnosis and appropriate pharmacotherapy in patients with OAB. RESULTS: A thorough diagnostic process is crucial for allowing exclusion of underlying medical issues and differentiation from genitourinary conditions other than OAB. In addition, selecting the most appropriate pharmacotherapy needs to be carefully considered in the context of each patient with OAB. In general, patients with OAB tend to be older with various comorbidities and often receiving multiple concomitant medications. Treatment decisions should take into consideration the differing potential for antimuscarinic medications to alter cognitive and cardiovascular functions, both of which may be compromised in this patient population. CONCLUSION: Tailoring treatment to individual patients by comprehensive patient assessment may lead to more effective management of patients with OAB, especially those receiving polypharmacy for comorbidities.

Expression of Bone Morphogenetic Protein-1 in vaginal tissue of women with severe pelvic organ prolapse.

OBJECTIVES: To analyze the differential gene and protein expression of Bone Morphogenetic Protein-1 in vaginal tissue of women with advanced pelvic organ prolapse and controls. STUDY DESIGN: We sampled the anterior vaginal wall of 39 premenopausal (23 patients and 16 controls), and 18 postmenopausal women (13 patients and 5 controls) during hysterectomy. Total mRNAs and proteins were quantified by real-time RT-PCR and immunoblotting. RESULTS: Bone Morphogenetic Protein-1 gene expression was decreased in pre- and postmenopausal pelvic organ prolapse patients compared with asymptomatic women (P = .01). The expression of 130 kDa, 92.5 kDa, and 82.5 kDa isoforms of Bone Morphogenetic Protein-1 were down-regulated in postmenopausal patients (P = .01), whereas the 130 kDa isoform expression was up-regulated in premenopausal patients (P = .009), when compared with respective controls. CONCLUSION: The Bone Morphogenetic Protein-1 expression in human vagina was altered in patients with severe pelvic organ prolapse and influenced by menopausal status. Dysregulation of Bone Morphogenetic Protein-1 may contribute for a deficient vaginal connective tissue and support.

LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The extracellular matrix proteins collagen and elastin provide tissue strength and resilience, whereas lysyl oxidase enzymes play a major role in their stabilization. This study examines the expression and tissue localization of lysyl oxidase family proteins in the anterior vaginal wall of premenopausal women with advanced pelvic organ prolapse (POP, n = 15) and asymptomatic controls (n = 11). All women were in the proliferative phase of menstrual cycle. METHODS: Total mRNAs and proteins extracted from the vaginal tissue were examined by real-time polymerase chain reaction and immunoblotting, and tissue specimens were analyzed by immunohistochemistry. RESULTS: The expression of LOX, LOXL1, and LOXL3 genes as well as LOX and LOXL3 proteins were significantly reduced in POP patients (P < 0.05). Immunolocalization of LOX family proteins was confirmed in all vaginal specimens. CONCLUSION: We proposed that reduced expression of LOX enzymes may result in defective assembly of pelvic tissues and development of POP.

Tolerability of 5 mg solifenacin once daily versus 5 mg oxybutynin immediate release 3 times daily: results of the VECTOR trial.

PURPOSE: Although antimuscarinic treatment is indicated for overactive bladder, many patients discontinue it because of dry mouth. Of available antimuscarinics oxybutynin is associated with the highest dry mouth rate. We compared the safety and tolerability of 5 mg solifenacin vs 15 mg oxybutynin immediate release. MATERIALS AND METHODS: At 12 Canadian centers a total of 132 patients with overactive bladder symptoms (greater than 1 urgency episode per 24 hours, and 8 or greater micturitions per 24 hours) were randomized to 5 mg solifenacin once daily or 5 mg oxybutynin 3 times daily for 8 weeks. The primary end point was the incidence and severity of dry mouth reported after direct questioning. Efficacy end points (3-day diary documented changes in urgency, frequency, incontinence, nocturia and voided volume), and changes on the Patient Perception of Bladder Condition scale and the Overactive Bladder Questionnaire were evaluated secondarily. RESULTS: Of patients on solifenacin vs oxybutynin immediate release 35% vs 83% reported dry mouth (p <0.0001). Of patients reporting dry mouth severity was graded moderate by 13% and 42% of those on solifenacin and oxybutynin immediate release, and severe by 13% and 28%, respectively (p = 0.001). Patients in each group showed improvements in efficacy end points, and Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire scores from baseline to treatment end. CONCLUSIONS: Significantly fewer patients on 5 mg solifenacin once daily reported dry mouth vs those receiving 5 mg oxybutynin immediate release 3 times daily. Significantly fewer patients on solifenacin reported moderate/severe dry mouth. Significantly fewer patients on solifenacin withdrew from study due to dry mouth and there were significantly fewer overall adverse events. Solifenacin and oxybutynin immediate release were efficacious in decreasing efficacy end points, and improved Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire results from baseline to treatment end.