Long-term effects of surgically corrected menstrual outflow obstruction: A case-control study.

OBJECTIVE: To enhance evidence-based knowledge on long-term sequalae in patients with surgically corrected obstructing Müllerian anomalies. METHODS: This long-term case-control study included patients with menstrual outflow obstruction due to congenital anomalies of the uterus or vagina, who were at least 18 years old, and for whom 2 years had elapsed since the first surgery at the start of this study. The control group consisted of women without current gynecological problems. Patients underwent a surgical correction at the Radboud University Medical Center Nijmegen between 1980 and 2013. Of 78 patients approached, 38 (49%) were included in this study. The control group consisted of 54 females. The main outcome measures were pain and health state. The following questionnaires were used: Visual Analogue Scale pain scores, European Quality of Life-5 Dimensions questionnaire (EQ-5D-3L) and the adapted Endometriosis Health Profile questionnaire (EHP-30). RESULTS: Patients had higher actual and maximum abdominal pain scores compared with controls (11 vs 0 [P = 0.007] and 48 vs 21 [P = 0.035], respectively). Based on the EQ-5D-3L scores, patients had more pain and discomfort (P = 0.005), more mood problems (P = 0.023), and a poorer subjective health state (P = 0.002) and self-rated health state (P = 0.031). Based on the EHP-30, patients had a significant poorer self-rated health state on four out of five subscales. CONCLUSION: In this study, following surgically corrected menstrual obstruction, patients had statistically significant higher abdominal pain scores and a poorer self-rated health state compared with controls.

Manchester Procedure vs Sacrospinous Hysteropexy for Treatment of Uterine Descent: A Randomized Clinical Trial.

Importance: In many countries, sacrospinous hysteropexy is the most commonly practiced uterus-preserving technique in women undergoing a first operation for pelvic organ prolapse. However, there are no direct comparisons of outcomes after sacrospinous hysteropexy vs an older technique, the Manchester procedure. Objective: To compare success of sacrospinous hysteropexy vs the Manchester procedure for the surgical treatment of uterine descent. Design, Setting, and Participants: Multicenter, noninferiority randomized clinical trial conducted in 26 hospitals in the Netherlands among 434 adult patients undergoing a first surgical treatment for uterine descent that did not protrude beyond the hymen. Interventions: Participants were randomly assigned to undergo sacrospinous hysteropexy (n = 217) or Manchester procedure (n = 217). Main Outcomes and Measures: The primary outcome was a composite outcome of success, defined as absence of pelvic organ prolapse beyond the hymen in any compartment evaluated by a standardized vaginal support quantification system, absence of bothersome bulge symptoms, and absence of prolapse retreatment (pessary or surgery) within 2 years after the operation. The predefined noninferiority margin was 9%. Secondary outcomes were anatomical and patient-reported outcomes, perioperative parameters, and surgery-related complications. Results: Among 393 participants included in the as-randomized analysis (mean age, 61.7 years [SD, 9.1 years]), 151 of 196 (77.0%) in the sacrospinous hysteropexy group and 172 of 197 (87.3%) in the Manchester procedure group achieved the composite outcome of success. Sacrospinous hysteropexy did not meet the noninferiority criterion of -9% for the lower limit of the CI (risk difference, -10.3%; 95% CI, -17.8% to -2.8%; P = .63 for noninferiority). At 2-year follow-up, perioperative outcomes and patient-reported outcomes did not differ between the 2 groups. Conclusions: Based on the composite outcome of surgical success 2 years after primary uterus-sparing pelvic organ prolapse surgery for uterine descent, these results support a finding that sacrospinous hysteropexy is inferior to the Manchester procedure. Trial Registration: TrialRegister.nl Identifier: NTR 6978.

Progesterone from ovulatory menstrual cycles is an important cause of breast cancer.

Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins.

Laparoscopic sacrocolpopexy versus vaginal sacrospinous fixation for vaginal vault prolapse: a randomised controlled trial and prospective cohort (SALTO-2 trial).

OBJECTIVE: To determine whether laparoscopic sacrocolpopexy (LSC) or vaginal sacrospinous fixation (VSF) is the most optimal surgical treatment in patients with POP-Q stage ≥2 vaginal vault prolapse (VVP). DESIGN: Multicentre randomised controlled trial (RCT) and prospective cohort study alongside. SETTING: Seven non-university teaching hospitals and two university hospitals in the Netherlands. POPULATION: Patients with symptomatic post-hysterectomy vaginal vault prolapse, requiring surgical treatment. METHODS: Randomisation in a 1:1 ratio to LSC or VSF. Evaluation of prolapse was done using the pelvic organ prolapse quantification (POP-Q). All participants were asked to fill in various Dutch validated questionnaires 12 months postoperatively. MAIN OUTCOME MEASURES: Primary outcome was disease-specific quality of life. Secondary outcomes included composite outcome of success and anatomical failure. Furthermore, we examined peri-operative data, complications and sexual function. RESULTS: A total of 179 women, 64 women randomised and 115 women, participated in a prospective cohort. Disease-specific quality of life did not differ after 12 months between the LSC and VSF group in the RCT and the cohort (RCT: P = 0.887; cohort: P = 0.704). The composite outcomes of success for the apical compartment, in the RCT and cohort, were 89.3% and 90.3% in the LSC group and 86.2% and 87.8% in the VSF group, respectively (RCT: P = 0.810; cohort: P = 0.905). There were no differences in number of reinterventions and complications between both groups (reinterventions RCT: P = 0.934; cohort: P = 0.120; complications RCT: P = 0.395; cohort: P = 0.129). CONCLUSIONS: LSC and VSF are both effective treatments for vaginal vault prolapse, after a follow-up period of 12 months.

Subjective outcomes 12 years after transvaginal mesh versus native tissue repair in women with recurrent pelvic organ prolapse; a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: The present study describes an extended follow-up study after 12 years and focusses on subjective outcomes of women who underwent surgery for recurrent pelvic organ prolapse in the randomized index study. METHODS: One hundred and ninety-four (194) women had been randomized in the original study and in the present study, 45 (47%) in the vaginal mesh repair versus 43 (43%) women with conventional vaginal native tissue repair completed the long-term questionnaires. The mesh used was a first-generation non-absorbable mesh kit. All types of conventional vaginal native tissue repairs were allowed, and additional vaginal native tissue repairs were allowed in the mesh group. The questionnaires as applied at baseline were used. The Patient Global Impression of Improvement questionnaire (PGI-I) was the primary outcome. RESULTS: At 12 years, 30 (71%) women in the mesh group versus 23 (59%) women in the native tissue repair group reported to be PGI-I (very) much improved (p=0.24). There were no differences found in any of the questionnaire domains. There was, however, a higher number of women who had had additional operations for recurrent pelvic organ prolapse, stress urinary incontinence, and/or exposure in the mesh group: 18 women (40%) in the mesh group versus 8 women (19%) in the native tissue repair group (p=0.03). CONCLUSIONS: There was no difference in subjective outcome between the groups, but there was a statistically significant higher number of women who had needed further operations. This study confirms that vaginal mesh should not be used in all women with recurrent pelvic organ prolapse.

Patient's preference for sacrospinous hysteropexy or modified Manchester operation: A discrete choice experiment.

OBJECTIVE: To investigate women's preference for modified Manchester (MM) or sacrospinous hysteropexy (SH) as surgery for uterine prolapse. DESIGN: Labelled discrete choice experiment (DCE). SETTING: Eight Dutch hospitals. POPULATION: Women with uterine prolapse, eligible for primary surgery and preference for uterus preservation. METHODS: DCEs are attribute-based surveys. The two treatment options were labelled as MM and SH. Attributes in this survey were treatment success ( levels SH: 84%, 89%, 94%; levels MM: 89%, 93%, 96%), dyspareunia (levels: 0%, 5%, 10%), cervical stenosis (levels: 1%, 6%, 11%) and severe buttock pain (levels: 0%, 1%). A different combination of attribute levels was used in each choice set. Women completed nine choice sets, making a choice based on attribute levels. Data were analysed in multinomial logit models. MAIN OUTCOME MEASURES: Women's preference for MM or SH. RESULTS: 137 DCEs were completed (1233 choice sets). SH was chosen in 49% of the choice sets, MM in 51%. Of all women, 39 (28%) always chose the same surgery. After exclusion of this group, 882 choice sets were analysed, in which women preferred MM, likely associated with a labelling effect, i.e. description of the procedure, rather than the tested attributes. In that group, MM was chosen in 53% of the choice sets and SH in 47%. When choosing MM, next to the label, dyspareunia was relevant for decision-making. For SH, all attributes were relevant for decision-making. CONCLUSIONS: The preference of women for MM or SH seems almost equally divided. The variety in preference supports the importance of individualised healthcare.

Does presence of a VACTERL anomaly predict an associated gynecologic anomaly in females with anorectal malformations?: A Pediatric Colorectal and Pelvic Learning Consortium Study.

BACKGROUND: VACTERL association is defined by the presence of 3 or more anomalies in any of the following systems: vertebral, anorectal, cardiac, trachea-esophageal, renal, or limb. This study hypothesized that the presence of VACTERL association would correlate with an increased risk of gynecologic anomalies in patients with anorectal malformation (ARM). METHODS: This study is a cross-sectional, retrospective analysis from the prospectively collected, multicenter registry of the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC). The 834 female patients with ARM who were enrolled in the registry by January 1, 2020 were included in this study. The relationship of VACTERL association with presence of a gynecologic anomaly was evaluated with Fisher's exact test. The relationship of each VACTERL system with presence of a gynecologic anomaly was assessed in patients with cloaca, rectovestibular fistulas and rectoperineal fistulas. P-values reported were based on a 2-sided alternative and considered significant when less than 0.05. RESULTS: 834 patients with ARM underwent VACTERL screening and gynecologic evaluation with the three most common subtypes being cloaca (n = 215, 25.8%), rectovestibular fistula (n = 191, 22.9%) and rectoperineal fistula (n = 194, 23.3%). A total of 223 (26.7%) patients with ARM had gynecologic anomalies. VACTERL association was seen in 380 (45.6%) of patients with ARM. Gynecologic anomalies were present in 149 (39.1%) vs. 74 (16.3%) of subjects with vs. without VACTERL association (p < 0.001). VACTERL association did not significantly increase the risk of gynecologic anomaly in patients with cloaca and VACTERL (n = 88, 61.5%) vs. cloaca without VACTERL (n = 39, 54.2% p = 0.308). VACTERL association increased the risk of gynecologic anomalies in patients with rectoperineal fistulas (n = 7, 14.9% vs n = 9, 6.1% p = 0.014) and rectovestibular fistulas (n = 19, 31.1% vs. n = 13, 10.0% p<0.001). In patients with ARM who had a VACTERL association, when one of the associated anomalies was renal, there was an even higher risk of having an associated gynecologic anomaly (n = 138, 44.2% vs. n = 85, 16.3% p<0.001). CONCLUSIONS: VACTERL association in patients with rectoperineal and rectovestibular fistulas correlates with an increased risk of gynecologic anomalies. The presence of VACTERL associated findings, especially renal, should prompt a thorough evaluation of the gynecologic system. LEVEL OF EVIDENCE: III. Retrospective comparative study.

Risk factors for primary pelvic organ prolapse and prolapse recurrence: an updated systematic review and meta-analysis.

OBJECTIVE: To update a previously published systematic review and perform a meta-analysis on the risk factors for primary pelvic organ prolapse and prolapse recurrence. DATA SOURCES: PubMed and Embase were systematically searched. We searched from July 1, 2014 until July 5, 2021. The previous search was from inception until August 4, 2014. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials and cross-sectional and cohort studies conducted in the Western developed countries that reported on multivariable analysis of risk factors for primary prolapse or prolapse recurrence were included. The definition of prolapse was based on anatomic references, and prolapse recurrence was defined as anatomic recurrence after native tissue repair. Studies on prolapse recurrence with a median follow-up of ≥1 year after surgery were included. METHODS: Quality assessment was performed with the Newcastle-Ottawa Scale. Data from the previous review and this review were combined into forest plots, and meta-analyses were performed where possible. If the data could not be pooled, "confirmed risk factors" were identified if ≥2 studies reported a significant association in multivariable analysis. RESULTS: After screening, 14 additional studies were selected-8 on the risk factors for primary prolapse and 6 on prolapse recurrence. Combined with the results from the previous review, 27 studies met the inclusion criteria, representing the data of 47,429 women. Not all studies could be pooled because of heterogeneity. Meta-analyses showed that birthweight (n=3, odds ratio, 1.04; 95% confidence interval, 1.02-1.06), age (n=3, odds ratio, 1.34; 95% confidence interval, 1.23-1.47), body mass index (n=2, odds ratio, 1.75; 95% confidence interval, 1.17-2.62), and levator defect (n=2, odds ratio, 3.99; 95% confidence interval, 2.57-6.18) are statistically significant risk factors, and cesarean delivery (n=2, pooled odds ratio, 0.08; 95% confidence interval, 0.03-0.20) and smoking (n=3, odds ratio, 0.59; 95% confidence interval, 0.46-0.75) are protective factors for primary prolapse. Parity, vaginal delivery, and levator hiatal area are identified as "confirmed risk factors." For prolapse recurrence, preoperative prolapse stage (n=5, odds ratio, 2.68; 95% confidence interval, 1.93-3.73) and age (n=2, odds ratio, 3.48; 95% confidence interval, 1.99-6.08) are statistically significant risk factors. CONCLUSION: Vaginal delivery, parity, birthweight, age, body mass index, levator defect, and levator hiatal area are risk factors, and cesarean delivery and smoking are protective factors for primary prolapse. Preoperative prolapse stage and younger age are risk factors for prolapse recurrence after native tissue surgery.

Risk factors for pelvic organ prolapse recurrence after sacrospinous hysteropexy or vaginal hysterectomy with uterosacral ligament suspension.

BACKGROUND: Given that the number of surgeries for pelvic organ prolapse is expected to increase worldwide, knowledge on risk factors for prolapse recurrence is of importance for developing preventive strategies and shared decision-making. OBJECTIVE: To identify risk factors for subjective and objective failure after either sacrospinous hysteropexy or vaginal hysterectomy with uterosacral ligament suspension over a period of 5 years after surgery. STUDY DESIGN: This was a secondary analysis of the 5-year follow-up of the SAVE-U trial. The SAVE-U trial was conducted in 4 Dutch hospitals. A total of 208 women with uterine prolapse stage ≥2 were randomized to sacrospinous hysteropexy or vaginal hysterectomy with uterosacral ligament suspension. For the current analysis, available annual 5-year follow-up data of 207 women were analyzed. Without missing values this analysis would have included 1035 measurements in total over the 5-year follow-up. Recurrences were analyzed as "events" using generalized linear mixed models because recurrences of anatomic failure and bothersome vaginal bulge symptoms fluctuated over time. The primary outcome was the composite outcome of failure defined as prolapse beyond the hymen, bothersome bulge symptoms, repeated surgery, or pessary use for recurrent prolapse. Secondary outcome measures were bothersome vaginal bulge symptoms, overall anatomic failure (Pelvic Organ Prolapse Quantification stage ≥2 in any compartment), apical compartment recurrence (Pelvic Organ Prolapse Quantification stage ≥2), anterior compartment recurrence (Pelvic Organ Prolapse Quantification stage ≥2), and posterior compartment recurrence (Pelvic Organ Prolapse Quantification stage ≥2). RESULTS: For the composite outcome of failure (164 events in 66 different women), statistically significant risk factors were: body mass index (odds ratio, 1.10 [per 1 kg/m2]; 95% confidence interval, 1.02-1.19; P=.02), smoking (odds ratio, 2.88; 95% confidence interval, 1.12-7.40; P=.03), and preoperative Pelvic Organ Prolapse Quantification point Ba (odds ratio, 1.23 [per 1 cm]; 95% confidence interval, 1.01-1.50; P=.04). When analyzing each surgical outcome measure separately, body mass index and Pelvic Organ Prolapse Quantification point Ba were risk factors for overall anatomic failure (462 events in 147 women; odds ratio, 1.15; 95% confidence interval, 1.07-1.25; P<.01 and odds ratio, 1.14; 95% confidence interval, 1.00-1.30; P=.05, respectively) and anterior compartment recurrence (385 events in 128 women; odds ratio, 1.11; 95% confidence interval, 1.02-1.22; P=.02 and odds ratio, 1.17; 95% confidence interval, 1.02-1.34; P=.02, respectively). Vaginal hysterectomy was a risk factor for posterior compartment recurrence when compared with sacrospinous hysteropexy (93 events in 40 women; odds ratio, 5.21; 95% confidence interval, 2.05-13.27; P<.01). Smoking was a risk factor for bothersome vaginal bulge symptoms (70 events in 41 women; odds ratio, 3.80; 95% confidence interval, 1.48-9.75; P=.01), and preoperative Pelvic Organ Prolapse Quantification stage 3 or 4 was significantly protective against bothersome bulge symptoms (odds ratio, 0.32; 95% confidence interval, 0.11-0.89; P=.03). CONCLUSION: Body mass index, smoking, and Pelvic Organ Prolapse Quantification point Ba were statistically significant risk factors for the composite outcome of failure (prolapse beyond the hymen, bothersome bulge symptoms, repeated surgery, or pessary use for recurrent prolapse) in the period of 5 years after surgery.

Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies.

Stress urinary incontinence (SUI) is a common and burdensome condition. Because of the large knowledge gap around the molecular processes involved in its pathophysiology, the aim of this review was to provide a systematic overview of genetic variants, gene and protein expression changes related to SUI in human and animal studies. On 5 January 2021, a systematic search was performed in Pubmed, Embase, Web of Science, and the Cochrane library. The screening process and quality assessment were performed in duplicate, using predefined inclusion criteria and different quality assessment tools for human and animal studies respectively. The extracted data were grouped in themes per outcome measure, according to their functions in cellular processes, and synthesized in a narrative review. Finally, 107 studies were included, of which 35 used animal models (rats and mice). Resulting from the most examined processes, the evidence suggests that SUI is associated with altered extracellular matrix metabolism, estrogen receptors, oxidative stress, apoptosis, inflammation, neurodegenerative processes, and muscle cell differentiation and contractility. Due to heterogeneity in the studies (e.g., in examined tissues), the precise contribution of the associated genes and proteins in relation to SUI pathophysiology remained unclear. Future research should focus on possible contributors to these alterations.

Reconsidering Diagnosis, Treatment, and Postoperative Care in Children with Cloacal Malformations.

Cloacal malformations are among the most complex types of anorectal malformation and are characterized by the urological, genital, and intestinal tracts opening through a single common channel in the perineum. Long-term outcome is affected by multiple factors, which include anatomical variants of the malformation itself, associated anomalies, and the surgical approach. Reconsidering these variables and their influence on "patient important" function might lead to strategies that are more outcome-driven than focused on the creation of normal anatomy. Key outcomes reflect function in each of the involved tracts and the follow-up needed should therefore not only include the classical fields of colorectal surgery and urology but also focus on items such as gynecology, sexuality, family-building, and quality of life as well as other psychological aspects. Involving patients and families in determining optimal treatment strategies and outcome measures could lead to improved outcomes for the individual patient. A strategy to support delivery of personalized care for patients with cloacal malformations by aiming to define the best functional outcomes achievable for any individual, then select the treatment pathway most likely deliver that, with the minimum morbidity and cost, would be attractive. Combining the current therapies with ongoing technological advances such as tissue expansion might be a way to achieve this.

Gynecologists' perspectives on two types of uterus-preserving surgical repair of uterine descent; sacrospinous hysteropexy versus modified Manchester.

INTRODUCTION AND HYPOTHESIS: The modified Manchester (MM) and sacrospinous hysteropexy (SSH) are the most common uterus-preserving surgical procedures for uterine descent. Little is known about gynecologists' preferences regarding the two interventions. The study's aim was to identify which factors influence Dutch (uro)gynecologists when choosing one of these techniques. METHODS: This qualitative study consists of ten semi-structured interviews with Dutch (uro)gynecologists using predetermined, open explorative questions, based on a structured topic list. An inductive content analysis was performed using Atlas.ti. RESULTS: For SSH, the majority (6/10 gynecologists) reported the more dorsal change of direction of the vaginal axis as a disadvantage and expected more cystocele recurrences (7/10). The most reported disadvantage of MM was the risk of cervical stenosis (7/10). Four gynecologists found MM not to be appropriate for patients with higher stage uterine prolapse. The quality of the uterosacral ligaments was related to the chance of recurrence according to five gynecologists. Patient counseling was biased toward one of the uterus-preserving operations (7/10). Four gynecologists stated they make the final decision while two let patient-preference lead the final decision. CONCLUSIONS: Preference for one of the uterus-preserving interventions is mainly based on the gynecologist's own experience and background. The lack of information regarding these two uterus-preserving procedures hampers evidence-based decision making, which explains the practice pattern variation. In conclusion, further research is needed to improve evidence-based counseling and shared decision making regarding the choice of procedure.

Long-term safety, objective and subjective outcomes of laparoscopic sacrocolpopexy without peritoneal closure.

INTRODUCTION AND HYPOTHESIS: The laparoscopic sacrocolpopexy (LSC) is performed to support DeLancey's level I in patients with pelvic organ prolapse (POP). Although several studies have been conducted on the safety, objective and subjective outcomes of LSC, the specific effect of retroperitonealisation of mesh is unknown. This study is aimed at analysing the safety, objective and subjective outcomes of the LSC without peritoneal closure of mesh. METHODS: The patients included have undergone an LSC for POP between 2004 and 2014. Retrospectively, a cohort of n = 178 was identified and asked to participate in a follow-up study. Chart research was performed. When informed consent was obtained, questionnaires were sent and the patients underwent a physical examination, including a POP-Q assessment. Each complication was scored by four reviewers for possibly being related to the non-peritonealisation of mesh. RESULTS: The data on the outcome cohorts were complete for safety n = 178, objective n = 124, and subjective n = 61. The Patient Global Impression of Improvement (PGI-I) score is provided in 106 questionnaires. In this study, 77 complications were observed in 49 different patients. The total success rate (no reoperation, no descent beyond the hymen and no bulging symptoms) is 59.0% with a median follow-up (IQR) of 35 months (18-51). Seventy-six patients (71.7%) described their condition as being (much) improved after LSC. CONCLUSIONS: Three serious complications observed during the 178 LSCs were, by full consensus, thought to be possibly related to the non-peritonealisation of mesh. More than 70% of the patients found their condition to be (much) improved after the procedure.

Sacrospinous hysteropexy versus vaginal hysterectomy with uterosacral ligament suspension in women with uterine prolapse stage 2 or higher: observational follow-up of a multicentre randomised trial.

OBJECTIVE: To evaluate the effectiveness and success of uterus preserving sacrospinous hysteropexy as an alternative to vaginal hysterectomy with uterosacral ligament suspension in the surgical treatment of uterine prolapse five years after surgery. DESIGN: Observational follow-up of SAVE U (sacrospinous fixation versus vaginal hysterectomy in treatment of uterine prolapse ≥2) randomised controlled trial. SETTING: Four non-university teaching hospitals, the Netherlands. PARTICIPANTS: 204 of 208 healthy women in the initial trial (2009-12) with uterine prolapse stage 2 or higher requiring surgery and no history of pelvic floor surgery who had been randomised to sacrospinous hysteropexy or vaginal hysterectomy with uterosacral ligament suspension. The women were followed annually for five years after surgery. This extended trial reports the results at five years. MAIN OUTCOME MEASURES: Prespecified primary outcome evaluated at five year follow-up was recurrent prolapse of the uterus or vaginal vault (apical compartment) stage 2 or higher evaluated by pelvic organ prolapse quantification system in combination with bothersome bulge symptoms or repeat surgery for recurrent apical prolapse. Secondary outcomes were overall anatomical failure (recurrent prolapse stage 2 or higher in apical, anterior, or posterior compartment), composite outcome of success (defined as no prolapse beyond the hymen, no bothersome bulge symptoms, and no repeat surgery or pessary use for recurrent prolapse), functional outcome, quality of life, repeat surgery, and sexual functioning. RESULTS: At five years, surgical failure of the apical compartment with bothersome bulge symptoms or repeat surgery occurred in one woman (1%) after sacrospinous hysteropexy compared with eight women (7.8%) after vaginal hysterectomy with uterosacral ligament suspension (difference-6.7%, 95% confidence interval -12.8% to-0.7%). A statistically significant difference was found in composite outcome of success between sacrospinous hysteropexy and vaginal hysterectomy (89/102 (87%) v 77/102 (76%). The other secondary outcomes did not differ. Time-to-event analysis at five years showed no differences between the interventions. CONCLUSIONS: At five year follow-up significantly less anatomical recurrences of the apical compartment with bothersome bulge symptoms or repeat surgery were found after sacrospinous hysteropexy compared with vaginal hysterectomy with uterosacral ligament suspension. After hysteropexy a higher proportion of women had a composite outcome of success. Time-to-event analysis showed no differences in outcomes between the procedures. TRIAL REGISTRATION: trialregister.nl NTR1866.

Evaluation of two vaginal, uterus sparing operations for pelvic organ prolapse: modified Manchester operation (MM) and sacrospinous hysteropexy (SSH), a study protocol for a multicentre randomized non-inferiority trial (the SAM study).

BACKGROUND: Pelvic organ prolapse (POP) affects up to 40% of parous women which adversely affects the quality of life. During a life time, 20% of all women will undergo an operation. In general the guidelines advise a vaginal operation in case of uterine descent: hysterectomy with uterosacral ligament plication (VH), sacrospinous hysteropexy (SSH) or a modified Manchester operation (MM). In the last decade, renewed interest in uterus sparing techniques has been observed. Previous studies have shown non-inferiority between SSH and VH. Whether or not SSH and MM are comparable concerning anatomical and functional outcome is still unknown. The practical application of both operations is at least in The Netherlands a known cause of practice pattern variation (PPV). To reveal any difference between both techniques the SAM-study was designed. METHODS: The SAM-study is a randomized controlled multicentre non-inferiority study which compares SSH and MM. Women with symptomatic POP in any stage, uterine descent and POP-Quantification (POP-Q) point D at ≤ minus 1 cm are eligible. The primary outcome is the composite outcome at two years of absence of prolapse beyond the hymen in any compartment, the absence of bulge symptoms and absence of reoperation for pelvic organ prolapse. Secondary outcomes are hospital parameters, surgery related morbidity/complications, pain perception, further treatments for prolapse or urinary incontinence, POP-Q anatomy in all compartments, quality-of-life, sexual function, and cost-effectiveness. Follow-up takes place at 6 weeks, 12 and 24 months. Additionally at 12 weeks, 6 and 9 months cost-effectiveness will be assessed. Validated questionnaires will be used and gynaecological examination will be performed. Analysis will be performed following the intention-to-treat and per protocol principle. With a non-inferiority margin of 9% and an expected loss to follow-up of 10%, 424 women will be needed to prove non-inferiority with a confidence interval of 95%. DISCUSSION: This study will evaluate the effectiveness and costs of SSH versus MM in women with primary POP. The evidence will show whether the existing PPV is detrimental and a de-implementation process regarding one of the operations is needed. TRIAL REGISTRATION: Dutch Trial Register (NTR 6978, http://www.trialregister.nl ). Date of registration: 29 January 2018. Prospectively registered.

Partially absorbable mesh or native tissue repair for pelvic organ prolapse: a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: The objective was to compare medium-term efficacy and safety of a partially absorbable mesh kit and native tissue repair in pelvic organ prolapse (POP). MATERIALS AND METHODS: Women with primary POP stage ≥ II were randomized to transvaginal trocar-guided partially absorbable mesh (81 women) or native tissue repair (82 women). Primary outcome was overall anatomical success (POP < stage II) at 24 months. Secondary outcomes were composite success, global improvement, and adverse events. RESULTS: Sixty-nine (85%) of the women allocated to partially absorbable mesh underwent mesh surgery; 8 (10%) crossed over to native tissue repair and 4 women (5%) withdrew from the study. Eighty (98%) of the women allocated to native tissue repair underwent the assigned treatment and 2 (2%) withdrew. Twenty-four months later, 140 surgically treated women (89%) demonstrated an overall anatomical success of 39%; 45% (32 out of 71 women) for mesh, and 32% (22 out of 69) for native tissue repair (RR 1.4, 95% CI 0.92 to 2.2). Composite success was 88 and 73% respectively (RR: 1.1, 95% CI 0.93 to 1.4). There was global improvement in 86% (48 out of 56 women) in the mesh group and in 77% (47 out of 60 women) in the native tissue group (RR: 1.1, 95% CI 0.92 to 1.3). Four women were diagnosed with mesh exposure at 2 years (6%). CONCLUSION: At 24 months, no significant anatomical or composite benefit of partially absorbable mesh over native tissue repair could be demonstrated in women who had been surgically treated for primary POP.

Management of Gonads in Adults with Androgen Insensitivity: An International Survey.

BACKGROUND: Complete and partial androgen insensitivity syndrome (CAIS, PAIS) are associated with an increased risk of gonadal germ cell cancer (GGCC). Recent guidelines recommend gonadectomy in women with CAIS in late adolescence. Nevertheless, many adult women prefer to retain their gonads. AIMS: This study aims to explore attitudes towards gonadectomy in AIS in centres around the world, estimate the proportion of adults with retained gonads and/or who developed GGCC, and explore reasons for declining gonadectomy. METHODS: A survey was performed among health care professionals who use the International DSD Registry (I-DSD). RESULTS: Data were provided from 22 centres in 16 countries on 166 women (CAIS) and 26 men (PAIS). In CAIS, gonadectomy was recommended in early adulthood in 67% of centres; 19/166 (11.4%) women refused gonadectomy. Among 142 women who had gonadectomy, evidence of germ cell neoplasm in situ (GCNIS), the precursor of GGCC, was reported in 2 (1.4%) out of 8 from whom pathology results were formally provided. Nine out of 26 men with PAIS (34.6%) had retained gonads; 11% of centres recommended routine gonadectomy in PAIS. CONCLUSION: Although development of GGCC seems rare, gonadectomy after puberty is broadly recommended in CAIS; in PAIS this is more variable. Overall, our data reflect the need for evidence-based guidelines regarding prophylactic gonadectomy in AIS.

De-implementation of urodynamics in The Netherlands after the VALUE/VUSIS-2 results: a nationwide survey.

INTRODUCTION AND HYPOTHESIS: We aimed to estimate the level of de-implementation of preoperative routine urodynamics (UDS) before stress urinary incontinence (SUI) surgery in The Netherlands and to analyze facilitators and barriers. Routine UDS was performed by 37% of the medical specialists in 2010. We hypothesized that the recommendations from the recent Value of Urodynamics prior to Stress Incontinence Surgery (VUSIS) and Value of Urodynamic Evaluation (ValUE) studies would have been followed by a reduction of routine UDS. METHODS: A national survey was performed among all Dutch gynecologists and urologists dealing with SUI in daily practice. The questionnaire contained two parts: (1) respondents' characteristics and their actual care concerning preoperative UDS, and (2) facilitators and barriers. RESULTS: The response rate was 41% (127/308). Of the respondents, 93% (n = 118) did not perform routine UDS in the preoperative workup for women in this group. Professional characteristics associated with not following the recommendations were profession urologist, academic hospital, and a lower number of midurethral sling (MUS) placed yearly. Facilitators to follow the recommendation not to perform routine UDS were adequate design of the VUSIS-II study and outcome and recommendations from the studies. Barriers not to follow the recommendation were believe in the additional value of UDS, especially the pressure transmission ratio, and the presence of detrusor overactivity. CONCLUSION: According to respondents to this questionnaire, VUSIS-II and ValUE study results are well implemented in The Netherlands. The vast majority of respondents replied as not performing routine preoperative UDS in women with primary, uncomplicated (predominant) SUI. Therefore, there is no need for a further de-implementation strategy.

Long-term outcome of vaginal mesh or native tissue in recurrent prolapse: a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: Our aim was to evaluate clinically relevant long-term outcomes of transvaginal mesh or native tissue repair in women with recurrent pelvic organ prolapse (POP). METHODS: We performed a 7-year follow-up of a randomized controlled trial on trocar-guided mesh placement or native tissue repair in women with recurrent POP. Primary outcome was composite success, defined as absence of POP beyond the hymen, absence of bulge symptoms, and absence of retreatment for POP. Secondary outcomes were adverse events, pain, and dyspareunia. Multiple imputation was used for missing data of composite success and pain; estimates are presented with 95% confidence intervals (CI). RESULTS: Between August 2006 and July 2008, 194 women were randomized; 190 underwent surgery. At 7 years, 142 (75%) were available for analysis, of whom, the primary outcome could be calculated in 127. Composite success was 53% (95% CI 41, 66) for mesh and 54% (95% CI 42, 65) for native tissue. Repeat surgery for POP was 25% for mesh and 16% for native tissue (difference 9%; 95% CI -5, 23) and occurred in untreated compartments in the mesh group and treated compartments in the native tissue group. Mesh exposure rate was 42%; pain with mesh 39% and native tissue 50% (difference - 11%, 95% CI -27, 6); dyspareunia with mesh 20% and native tissue 17% (difference 3%, 95% CI -9, 17). CONCLUSIONS: Seven-year composite success rates appeared similar for mesh and native tissue. Mesh did not reduce long-term repeat surgery rates due to de novo POP in nonmesh-treated vaginal compartments. Mesh exposure rates were high, though significant differences in pain and dyspareunia were not detected. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT00372190.

Dutch women's attitudes towards hysterectomy and uterus preservation in surgical treatment of pelvic organ prolapse.

OBJECTIVE: To investigate Dutch women's attitudes and preferences towards hysterectomy or uterus preservation in surgical treatment of pelvic organ prolapse. STUDY DESIGN: Women's attitude was assessed by a structured questionnaire in one university hospital and one non-university teaching hospital in the Netherlands. Between December 2013 and November 2014, 102 women referred with prolapse complaints, without previous prolapse surgery, responded to the questionnaire received by mail prior to gynaecological consultation. Main outcome was the preference for uterus preserving surgery versus hysterectomy. Furthermore we studied the impact of uterus preservation and hysterectomy on body image and sexual function and the importance of treatment success, risk of urinary incontinence after surgery, complication risk, recovery time, length of hospital stay, costs and the risk of developing endometrial cancer. RESULTS: Assuming that functional and anatomical outcomes after hysterectomy and uterus preserving surgery were equal, more women expressed preference for uterus preservation (43%, 44 out of 102 women) compared to hysterectomy (27%, 27 out of 102 women). The majority of women expected a similar improvement in sexuality and body image after the two treatment modalities. Treatment success, risk for urinary incontinence after surgery and complication risk were the most important factors. Taken the future risk of endometrial cancer into account, 18% of the women preferred hysterectomy because of this risk. CONCLUSIONS: This study demonstrated that women referred with prolapse complaints have a preference for uterus preservation in case outcomes after both interventions are expected to be equal. The majority of women expected that body image and sexual function would equally improve after both interventions.