Effects of mesenchymal stem cells and heparan sulfate mimetics on urethral function and vaginal wall biomechanics in a simulated rat childbirth injury model

Introduction and hypothesis: New treatments are needed for pelvic floor disorders. ReGeneraTing Agent® (RGTA®) is a promising regenerative therapy. Therefore, the objective of this study was to compare regenerative abilities of mesenchymal stem cells (MSCs) and RGTA® on regeneration after simulated childbirth injury in rats. Methods: Rats underwent pudendal nerve crush and vaginal distension (PNC+VD) or sham injury. Rats that underwent PNC+VD were treated intravenously with vehicle, MSCs or RGTA® 1 h, 7 days, and 14 days after surgery. Sham rats received 1 ml vehicle at all time points. After 21 days, urethral function and pudendal nerve function were tested. Vaginal tissues were harvested for biomechanical testing and histology. Biaxial testing was performed to measure tissue stiffness. Results: PNC+VD decreased urethral and pudendal nerve function compared with sham. Vaginal wall stiffness was significantly decreased in longitudinal and transverse tissue axes after PNC+VD compared with sham. MSC or RGTA® did not restore urethral or pudendal nerve function. However, MSC treatment resolved loss in vaginal wall stiffness in both tissue axes and improved collagen content within the vaginal wall. RGTA® treatment increased vaginal wall anisotropy by increasing relative stiffness in the longitudinal direction. PNC+VD (with vehicle or MSCs) enhanced elastogenesis, which was not observed after RGTA® treatment. Conclusions: Treatment with MSCs facilitated recovery of vaginal wall biomechanical properties and connective tissue composition after PNC+VD, whereas treatment with RGTA® resulted in anisotropic biomechanical changes. This indicates that MSCs and RGTA® promote different aspects of vaginal tissue regeneration after simulated childbirth injury

Female Sexual Functioning in Women With a Symptomatic Pelvic Organ Prolapse; A Multicenter Prospective Comparative Study Between Pessary and Surgery

Background: Female pelvic organ prolapse (POP) has a negative effect on female sexual functioning and with an increasing life expectancy female sexual dysfunction caused by POP will be an arising global issue. Aim: Improvement in female sexual functioning, measured with the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire IUGA-Revised (PISQ-IR), 24-months after pessary or surgery, for both sexually active (SA) and sexually inactive women (NSA) presenting with POP. Methods: A multicenter prospective comparative cohort study was conducted in 22 Dutch hospitals. Women referred with moderate to severe POP symptoms and POP stage ≥ 2 were included and chose either pessary therapy or surgical intervention. The PISQ-IR was filled in at baseline and 24-months, the delta of change was calculated and compared between both groups. Multivariate linear regression was performed to adjust for potential confounding factors in the association between the summary score of the PISQ-IR and therapy. Outcomes: Change in PISQ-IR between pessary and surgical intervention. Results: The delta of change at 24-months was calculated for 198 women in the pessary group and 129 women in the surgery group. SA women in the surgery group reported statistically significant more improvement on the condition-specific (-0.19 95%CI -0.35; -0.03, P = .02), and condition-impact (-0.48 95%CI -0.69; -0.28, P < .001) domains as well as on the summary score (-0.15 95%CI -0.23; -0.08, P < .001) as compared to the pessary group. No significant differences between pessary and surgery were found on the domains for NSA women. After controlling for potential baseline confounders, surgery still had a statistically significant effect on the summary score (B = 0.08; 95%CI interval 0.007–0.15, P = .03). Women having surgery had 2.62 times higher odds of changing from NSA to SA than pessary therapy. Clinical implications: SA women who clearly express that POP-related symptoms limit their sexual functioning should be counseled that surgery results in a more remarkable improvement. Strengths & Limitations: Our strengths include the large sample size, long-term follow-up, the use of the PISQ-IR as a validated outcome tool evaluating both SA and NSA women, and this study reflects real-life clinical practice that enhances the external validity of the findings. A limitation of our study is the considerable proportion of non-responders at 24-months follow-up. Conclusion: Sexual function in SA women with POP is superior in case surgery is performed as compared to pessary therapy. van der Vaart LR, Vollebregt A, Pruijssers B, et al. Female Sexual Functioning in Women With a Symptomatic Pelvic Organ Prolapse; A Multicenter Prospective Comparative Study Between Pessary and Surgery. J Sex Med 2022;19:270–279

Mean echogenicity and area of puborectalis muscle in women with stress urinary incontinence during pregnancy and after delivery

INTRODUCTION AND HYPOTHESIS: Pregnancy and childbirth are risk factors for the development of stress urinary incontinence (SUI). Urinary continence depends on normal urethral support, which is provided by normal levator ani muscle function. Our objective was to compare mean echogenicity and the area of the puborectalis muscle between women with and those without SUI during and after their first pregnancy. METHODS: We examined 280 nulliparous women at a gestational age of 12 weeks, 36 weeks, and 6 months after delivery. They filled out the validated Urogenital Distress Inventory and underwent perineal ultrasounds. SUI was considered present if the woman answered positively to the question "do you experience urine leakage related to physical activity, coughing, or sneezing?" Mean echogenicity of the puborectalis muscle (MEP) and puborectalis muscle area (PMA) were calculated. The MEP and PMA during pregnancy and after delivery in women with and without SUI were compared using independent Student's t test. RESULTS: After delivery the MEP was higher in women with SUI if the pelvic floor was at rest or in contraction, with effect sizes of 0.30 and 0.31 respectively. No difference was found in the area of the puborectalis muscle between women with and those without SUI. CONCLUSIONS: Women with SUI after delivery had a statistically significant higher mean echogenicity of the puborectalis muscle compared with non-SUI women when the pelvic floor was at rest and in contraction; the effect sizes were small. This higher MEP is indicative of a relatively higher intramuscular extracellular matrix component and could represent diminished contractile function

Cost-effectiveness of pessary therapy versus surgery for symptomatic pelvic organ prolapse: an economic evaluation alongside a randomised non-inferiority controlled trial

Objective To evaluate the cost-effectiveness of pessary therapy as an initial treatment option compared with surgery for moderate to severe pelvic organ prolapse (POP) symptoms in secondary care from a healthcare and a societal perspective. Design Economic evaluation alongside a multicentre randomised controlled non-inferiority trial with a 24-month follow-up. Setting 21 hospitals in the Netherlands, recruitment conducted between 2015 and 2022. Participants 1605 women referred to secondary care with symptomatic prolapse stage ≥2 were requested to participate. Of them, 440 women gave informed consent and were randomised to pessary therapy (n=218) or to surgery (n=222) in a 1:1 ratio stratified by hospital. Interventions Pessary therapy and surgery. Primary and secondary outcome measures The Patient Global Impression of Improvement (PGI-I), a 7-point scale dichotomised into successful versus unsuccessful, with a non-inferiority margin of −10%; quality-adjusted life-years (QALYs) measured by the EQ-5D-3L; healthcare and societal costs were based on medical records and the institute for Medical Technology Assessment questionnaires. Results For the PGI-I, the mean difference between pessary therapy and surgery was −0.05 (95% CI −0.14; 0.03) and −0.03 (95% CI −0.07; 0.002) for QALYs. In total, 54.1% women randomised to pessary therapy crossed over to surgery, and 3.6% underwent recurrent surgery. Healthcare and societal costs were significantly lower in the pessary therapy (mean difference=−€1807, 95% CI −€2172; −€1446 and mean difference=−€1850, 95% CI −€2349; −€1341, respectively). The probability that pessary therapy is cost-effective compared with surgery was 1 at willingness-to-pay thresholds between €0 and €20 000/QALY gained from both perspectives. Conclusions Non-inferiority of pessary therapy regarding the PGI-I could not be shown and no statistically significant differences in QALYs between interventions were found. Due to significantly lower costs, pessary therapy is likely to be cost-effective compared with surgery as an initial treatment option for women with symptomatic POP treated in secondary care

Transurethral versus suprapubic catheterization to test urethral function in rats

Transurethral and suprapubic catheterization have both been used to test urethral function in rats; however, it is unknown whether these methods affect urethral function or if the order of catheterization affects the results. The aim of this cross-over designed experiment was to compare the effects of catheterization methods and order on leak point pressure (LPP) testing. LPP and simultaneous external urethral sphincter electromyography (EUS EMG) were recorded in anesthetized female virgin Sprague-Dawley rats in a cross-over design to test the effects of transurethral and suprapubic catheterization. There was no significant difference in peak bladder pressure during LPP testing whether measured with a transurethral or suprapubic catheter. There was no significant difference in peak bladder pressure between the first and second catheter insertions. However, peak EMG firing rate, as well as peak EMG amplitude and EMG amplitude difference between peak and baseline were significantly higher after the first catheter insertion compared to the second insertion, regardless of the catheter method. Our results suggest that route of catheterization does not alter urethral function, e.g. create a functional partial outlet obstruction. Either catheterization method could be used for LPP and/or EUS EMG testing in rats

Functional outcome after sacrospinous hysteropexy for uterine descensus

The study aimed to evaluate urogenital symptoms, defecatory symptoms and quality of life before and after a sacrospinous hysteropexy for uterovaginal prolapse. Seventy-two women with symptomatic uterovaginal prolapse were treated with sacrospinous hysteropexy. Before and after surgery, urogenital and defecatory symptoms and quality of life were assessed with a validated questionnaire. Anatomical outcome was assessed by means of pelvic examination before and after surgery. The mean follow-up time was 12.7 months. Scores on all domains of urogenital symptoms and defecatory symptoms, except for the pain and fecal incontinence domain, improved significantly. Also, quality of life improved on all domains. No major complications were encountered

Female Sexual Functioning in Women With a Symptomatic Pelvic Organ Prolapse; A Multicenter Prospective Comparative Study Between Pessary and Surgery

Background: Female pelvic organ prolapse (POP) has a negative effect on female sexual functioning and with an increasing life expectancy female sexual dysfunction caused by POP will be an arising global issue. Aim: Improvement in female sexual functioning, measured with the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire IUGA-Revised (PISQ-IR), 24-months after pessary or surgery, for both sexually active (SA) and sexually inactive women (NSA) presenting with POP. Methods: A multicenter prospective comparative cohort study was conducted in 22 Dutch hospitals. Women referred with moderate to severe POP symptoms and POP stage ≥ 2 were included and chose either pessary therapy or surgical intervention. The PISQ-IR was filled in at baseline and 24-months, the delta of change was calculated and compared between both groups. Multivariate linear regression was performed to adjust for potential confounding factors in the association between the summary score of the PISQ-IR and therapy. Outcomes: Change in PISQ-IR between pessary and surgical intervention. Results: The delta of change at 24-months was calculated for 198 women in the pessary group and 129 women in the surgery group. SA women in the surgery group reported statistically significant more improvement on the condition-specific (-0.19 95%CI -0.35; -0.03, P = .02), and condition-impact (-0.48 95%CI -0.69; -0.28, P < .001) domains as well as on the summary score (-0.15 95%CI -0.23; -0.08, P < .001) as compared to the pessary group. No significant differences between pessary and surgery were found on the domains for NSA women. After controlling for potential baseline confounders, surgery still had a statistically significant effect on the summary score (B = 0.08; 95%CI interval 0.007–0.15, P = .03). Women having surgery had 2.62 times higher odds of changing from NSA to SA than pessary therapy. Clinical implications: SA women who clearly express that POP-related symptoms limit their sexual functioning should be counseled that surgery results in a more remarkable improvement. Strengths & Limitations: Our strengths include the large sample size, long-term follow-up, the use of the PISQ-IR as a validated outcome tool evaluating both SA and NSA women, and this study reflects real-life clinical practice that enhances the external validity of the findings. A limitation of our study is the considerable proportion of non-responders at 24-months follow-up. Conclusion: Sexual function in SA women with POP is superior in case surgery is performed as compared to pessary therapy. van der Vaart LR, Vollebregt A, Pruijssers B, et al. Female Sexual Functioning in Women With a Symptomatic Pelvic Organ Prolapse; A Multicenter Prospective Comparative Study Between Pessary and Surgery. J Sex Med 2021;XX:XXX–XXX