Septum resection versus expectant management in women with a septate uterus: an international multicentre open-label randomized controlled trial.

STUDY QUESTION: Does septum resection improve reproductive outcomes in women with a septate uterus? SUMMARY ANSWER: Hysteroscopic septum resection does not improve reproductive outcomes in women with a septate uterus. WHAT IS KNOWN ALREADY: A septate uterus is a congenital uterine anomaly. Women with a septate uterus are at increased risk of subfertility, pregnancy loss and preterm birth. Hysteroscopic resection of a septum may improve the chance of a live birth in affected women, but this has never been evaluated in randomized clinical trials. We assessed whether septum resection improves reproductive outcomes in women with a septate uterus, wanting to become pregnant. STUDY DESIGN, SIZE, DURATION: We performed an international, multicentre, open-label, randomized controlled trial in 10 centres in The Netherlands, UK, USA and Iran between October 2010 and September 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with a septate uterus and a history of subfertility, pregnancy loss or preterm birth were randomly allocated to septum resection or expectant management. The primary outcome was conception leading to live birth within 12 months after randomization, defined as the birth of a living foetus beyond 24 weeks of gestational age. We analysed the data on an intention-to-treat basis and calculated relative risks with 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: We randomly assigned 80 women with a septate uterus to septum resection (n = 40) or expectant management (n = 40). We excluded one woman who underwent septum resection from the intention-to-treat analysis, because she withdrew informed consent for the study shortly after randomization. Live birth occurred in 12 of 39 women allocated to septum resection (31%) and in 14 of 40 women allocated to expectant management (35%) (relative risk (RR) 0.88 (95% CI 0.47 to 1.65)). There was one uterine perforation which occurred during surgery (1/39 = 2.6%). LIMITATIONS, REASONS FOR CAUTION: Although this was a major international trial, the sample size was still limited and recruitment took a long period. Since surgical techniques did not fundamentally change over time, we consider the latter of limited clinical significance. WIDER IMPLICATIONS OF THE FINDINGS: The trial generated high-level evidence in addition to evidence from a recently published large cohort study. Both studies unequivocally do not reveal any improvements in reproductive outcomes, thereby questioning any rationale behind surgery. STUDY FUNDING/COMPETING INTEREST(S): There was no study funding. M.H.E. reports a patent on a surgical endoscopic cutting device and process for the removal of tissue from a body cavity licensed to Medtronic, outside the scope of the submitted work. H.A.v.V. reports personal fees from Medtronic, outside the submitted work. B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work. M.G. reports several research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the scope of the submitted work. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER: Dutch trial registry: NTR 1676. TRIAL REGISTRATION DATE: 18 February 2009. DATE OF FIRST PATIENT'S ENROLMENT: 20 October 2010.

Septum resection in women with a septate uterus: a cohort study.

STUDY QUESTION: Does septum resection improve reproductive outcomes in women with a septate uterus? SUMMARY ANSWER: In women with a septate uterus, septum resection does not increase live birth rate nor does it decrease the rates of pregnancy loss or preterm birth, compared with expectant management. WHAT IS KNOWN ALREADY: The septate uterus is the most common uterine anomaly with an estimated prevalence of 0.2-2.3% in women of reproductive age, depending on the classification system. The definition of the septate uterus has been a long-lasting and ongoing subject of debate, and currently two classification systems are used worldwide. Women with a septate uterus may be at increased risk of subfertility, pregnancy loss, preterm birth and foetal malpresentation. Based on low quality evidence, current guidelines recommend removal of the intrauterine septum or, more cautiously, state that the procedure should be evaluated in future studies. STUDY DESIGN, SIZE, DURATION: We performed an international multicentre cohort study in which we identified women mainly retrospectively by searching in electronic patient files, medical records and databases within the time frame of January 2000 until August 2018. Searching of the databases, files and records took place between January 2016 and July 2018. By doing so, we collected data on 257 women with a septate uterus in 21 centres in the Netherlands, USA and UK. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included women with a septate uterus, defined by the treating physician, according to the classification system at that time. The women were ascertained among those with a history of subfertility, pregnancy loss, preterm birth or foetal malpresentation or during a routine diagnostic procedure. Allocation to septum resection or expectant management was dependent on the reproductive history and severity of the disease. We excluded women who did not have a wish to conceive at time of diagnosis. The primary outcome was live birth. Secondary outcomes included pregnancy loss, preterm birth and foetal malpresentation. All conceptions during follow-up were registered but for the comparative analyses, only the first live birth or ongoing pregnancy was included. To evaluate differences in live birth and ongoing pregnancy, we used Cox proportional regression to calculate hazard rates (HRs) and 95% CI. To evaluate differences in pregnancy loss, preterm birth and foetal malpresentation, we used logistic regression to calculate odds ratios (OR) with corresponding 95% CI. We adjusted all reproductive outcomes for possible confounders. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 257 women were included in the cohort. Of these, 151 women underwent a septum resection and 106 women had expectant management. The median follow-up time was 46 months. During this time, live birth occurred in 80 women following a septum resection (53.0%) compared to 76 women following expectant management (71.7%) (HR 0.71 95% CI 0.49-1.02) and ongoing pregnancy occurred in 89 women who underwent septum resection (58.9%), compared to 80 women who had expectant management (75.5%) (HR 0.74 (95% CI 0.52-1.06)). Pregnancy loss occurred in 51 women who underwent septum resection (46.8%) versus 31 women who had expectant management (34.4%) (OR 1.58 (0.81-3.09)), while preterm birth occurred in 26 women who underwent septum resection (29.2%) versus 13 women who had expectant management (16.7%) (OR 1.26 (95% CI 0.52-3.04)) and foetal malpresentation occurred in 17 women who underwent septum resection (19.1%) versus 27 women who had expectant management (34.6%) (OR 0.56 (95% CI 0.24-1.33)). LIMITATIONS, REASONS FOR CAUTION: Our retrospective study has a less robust design compared with a randomized controlled trial. Over the years, the ideas about the definition of the septate uterus has changed, but since the 257 women with a septate uterus included in this study had been diagnosed by their treating physician according to the leading classification system at that time, the data of this study reflect the daily practice of recent decades. Despite correcting for the most relevant patient characteristics, our estimates might not be free of residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that septum resection, a procedure that is widely offered and associated with financial costs for society, healthcare systems or individuals, does not lead to improved reproductive outcomes compared to expectant management for women with a septate uterus. The results of this study need to be confirmed in randomized clinical trials. STUDY FUNDING/COMPETING INTEREST(S): A travel for JFWR to Chicago was supported by the Jo Kolk Studyfund. Otherwise, no specific funding was received for this study. The Department of Obstetrics and Gynaecology, University Medical Centre, Groningen, received an unrestricted educational grant from Ferring Pharmaceutical Company unrelated to the present study. BWM reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck, personal fees from Guerbet, other payment from Guerbet and grants from Merck, outside the submitted work. The other authors declare no conficts of interest. TRIAL REGISTRATION NUMBER: N/A.

Congenital Uterine Malformation by Experts (CUME): diagnostic criteria for T-shaped uterus.

OBJECTIVES: To identify uterine measurements that are reliable and accurate to distinguish between T-shaped and normal/arcuate uterus, and define T-shaped uterus, using Congenital Uterine Malformation by Experts (CUME) methodology, which uses as reference standard the decision made most often by several independent experts. METHODS: This was a prospectively planned multirater reliability/agreement and diagnostic accuracy study, performed between November 2017 and December 2018, using a sample of 100 three-dimensional (3D) datasets of different uteri with lateral uterine cavity indentations, acquired from consecutive women between 2014 and 2016. Fifteen representative experts (five clinicians, five surgeons and five sonologists), blinded to each others' opinions, examined anonymized images of the coronal plane of each uterus and provided their independent opinion as to whether it was T-shaped or normal/arcuate; this formed the basis of the CUME reference standard, with the decision made most often (i.e. that chosen by eight or more of the 15 experts) for each uterus being considered the correct diagnosis for that uterus. Two other experienced observers, also blinded to the opinions of the other experts, then performed independently 15 sonographic measurements, using the original 3D datasets of each uterus. Agreement between the diagnoses made by the 15 experts was assessed using kappa and percent agreement. The interobserver reliability of measurements was assessed using the concordance correlation coefficient (CCC). The diagnostic test accuracy was assessed using the area under the receiver-operating-characteristics curve (AUC) and the best cut-off value was assessed by calculating Youden's index, according to the CUME reference standard. Sensitivity, specificity, negative and positive likelihood ratios (LR- and LR+) and post-test probability were calculated. RESULTS: According to the CUME reference standard, there were 20 T-shaped and 80 normal/arcuate uteri. Individual experts recognized between 5 and 35 (median, 19) T-shaped uteri on subjective judgment. The agreement among experts was 82% (kappa = 0.43). Three of the 15 sonographic measurements were identified as having good diagnostic test accuracy, according to the CUME reference standard: lateral indentation angle (AUC = 0.95), lateral internal indentation depth (AUC = 0.92) and T-angle (AUC = 0.87). Of these, T-angle had the best interobserver reproducibility (CCC = 0.87 vs 0.82 vs 0.62 for T-angle vs lateral indentation depth vs lateral indentation angle). The best cut-off values for these measurements were: lateral indentation angle ≤ 130° (sensitivity, 80%; specificity, 96%; LR+, 21.3; LR-, 0.21), lateral indentation depth ≥ 7 mm (sensitivity, 95%; specificity, 77.5%; LR+, 4.2; LR-, 0.06) and T-angle ≤ 40° (sensitivity, 80%; specificity, 87.5%; LR+, 6.4; LR-, 0.23). Most of the experts diagnosed the uterus as being T-shaped in 0% (0/56) of cases when none of these three criteria was met, in 10% (2/20) of cases when only one criterion was met, in 50% (5/10) of cases when two of the three criteria were met, and in 93% (13/14) of cases when all three criteria were met. CONCLUSIONS: The diagnosis of T-shaped uterus is not easy; the agreement among experts was only moderate and the judgement of individual experts was commonly insufficient for accurate diagnosis. The three sonographic measurements with cut-offs that we identified (lateral internal indentation depth ≥ 7 mm, lateral indentation angle ≤ 130° and T-angle ≤ 40°) had good diagnostic test accuracy and fair-to-moderate reliability and, when applied in combination, they provided high post-test probability for T-shaped uterus. In the absence of other anomalies, we suggest considering a uterus to be normal when none or only one criterion is met, borderline when two criteria are met, and T-shaped when all three criteria are met. These three CUME criteria for defining T-shaped uterus may aid in determination of its prevalence, clinical implications and best management and in the assessment of post-surgical morphologic outcome. The CUME definition of T-shaped uterus may help in the development of interventional randomized controlled trials and observational studies and in the diagnosis of uterine morphology in everyday practice, and could be adopted by guidelines on uterine anomalies to enrich their classification systems. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The pathophysiology of the septate uterus: a systematic review.

BACKGROUND: Little is known about the pathophysiology underlying the increased risk for impaired reproductive outcomes in women with a septate uterus. OBJECTIVES: We explored the available evidence on the pathophysiology of the septate uterus in an attempt to find a biological basis for these effects. SEARCH STRATEGY: We performed a systematic literature search in OVID MEDLINE and OVID EMBASE from inception to January 2018. SELECTION CRITERIA: We selected studies that investigated the pathophysiology of the septate uterus. Case reports or reviews without original data were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated potentially eligible papers. MAIN RESULTS: Thirty-eight studies were included for analysis. The overall findings were that the intrauterine septum consists of endometrium and myometrium similar to the uterine wall. All five imaging studies that evaluated vascularity found that most of the intrauterine septa were vascularised. Histological studies found that the intrauterine septum consisted of myometrium and was covered by endometrium (n = 9). The endometrium covering the septum showed differences in histological composition in four studies and in gene expression in three studies compared with the normal uterine wall. CONCLUSIONS: We found no clear biological basis for the impaired reproductive outcomes in women with a septate uterus. Either the gross anatomy of the septum itself or differences in histology or gene expression of the septum could account for the increased risk of reproductive waste observed after implantation in the septum. TWEETABLE ABSTRACT: In women with a septate uterus differences in histology or gene expression could account for impaired reproductive outcome.

Congenital Uterine Malformation by Experts (CUME): better criteria for distinguishing between normal/arcuate and septate uterus?

OBJECTIVES: To assess the level of agreement between experts in distinguishing between septate and normal/arcuate uterus using their subjective judgment when reviewing the coronal view of the uterus from three-dimensional ultrasound. Another aim was to determine the interobserver reliability and diagnostic test accuracy of three measurements suggested by recent guidelines, using as reference standard the decision made most often by experts (Congenital Uterine Malformation by Experts (CUME)). METHODS: Images of the coronal plane of the uterus from 100 women with suspected fundal internal indentation were anonymized and provided to 15 experts (five clinicians, five surgeons and five sonologists). They were instructed to indicate whether they believed the uterus to be normal/arcuate (defined as normal uterine morphology or not clinically relevant degree of distortion caused by internal indentation) or septate (clinically relevant degree of distortion caused by internal indentation). Two other observers independently measured indentation depth, indentation angle and indentation-to-wall-thickness (I:WT) ratio. The agreement between experts was assessed using kappa, the interobserver reliability was assessed using the concordance correlation coefficient (CCC), the diagnostic test accuracy was assessed using the area under the receiver-operating characteristics curve (AUC) and the best cut-off value was assessed using Youden's index, considering as the reference standard the choice made most often by the experts (CUME). RESULTS: There was good agreement between all experts (kappa, 0.62). There were 18 septate and 82 normal/arcuate uteri according to CUME; European Society of Human Reproduction and Embryology (ESHRE)-European Society for Gynaecological Endoscopy (ESGE) criteria (I:WT ratio > 50%) defined 80 septate and 20 normal/arcuate uteri, while American Society for Reproductive Medicine (ASRM) criteria defined five septate (depth > 15 mm and angle < 90°), 82 normal/arcuate (depth < 10 mm and angle > 90°) and 13 uteri that could not be classified (referred to as the gray-zone). The agreement between ESHRE-ESGE and CUME was 38% (kappa, 0.1); the agreement between ASRM criteria and CUME for septate was 87% (kappa, 0.39), and considering both septate and gray-zone as septate, the agreement was 98% (kappa, 0.93). Among the three measurements, the interobserver reproducibility of indentation depth (CCC, 0.99; 95% CI, 0.98-0.99) was better than both indentation angle (CCC, 0.96; 95% CI, 0.94-0.97) and I:WT ratio (CCC, 0.92; 95% CI, 0.90-0.94). The diagnostic test accuracy of these three measurements using CUME as reference standard was very good, with AUC between 0.96 and 1.00. The best cut-off values for these measurements to define septate uterus were: indentation depth ≥ 10 mm, indentation angle < 140° and I:WT ratio > 110% . CONCLUSIONS: The suggested ESHRE-ESGE cut-off value overestimates the prevalence of septate uterus while that of ASRM underestimates this prevalence, leaving in the gray-zone most of the uteri that experts considered as septate. We recommend considering indentation depth ≥ 10 mm as septate, since the measurement is simple and reliable and this criterion is in agreement with expert opinion. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The randomised uterine septum transsection trial (TRUST): design and protocol.

BACKGROUND: A septate uterus is a uterine anomaly that may affect reproductive outcome, and is associated with an increased risk for miscarriage, subfertility and preterm birth. Resection of the septum is subject of debate. There is no convincing evidence concerning its effectiveness and safety. This study aims to assess whether hysteroscopic septum resection improves reproductive outcome in women with a septate uterus. METHODS/DESIGN: A multi-centre randomised controlled trial comparing hysteroscopic septum resection and expectant management in women with recurrent miscarriage or subfertility and diagnosed with a septate uterus. The primary outcome is live birth, defined as the birth of a living foetus beyond 24 weeks of gestational age. Secondary outcomes are ongoing pregnancy, clinical pregnancy, miscarriage and complications following hysteroscopic septum resection. The analysis will be performed according to the intention to treat principle. Kaplan-Meier curves will be constructed, estimating the cumulative probability of conception leading to live birth rate over time. Based on retrospective studies, we anticipate an improvement of the live birth rate from 35% without surgery to 70% with surgery. To demonstrate this difference, 68 women need to be randomised. DISCUSSION: Hysteroscopic septum resection is worldwide considered as a standard procedure in women with a septate uterus. Solid evidence for this recommendation is lacking and data from randomised trials is urgently needed. TRIAL REGISTRATION: Dutch trial registry ( NTR1676 , 18th of February 2009).

Hysteroscopic proximal tubal occlusion versus laparoscopic salpingectomy as a treatment for hydrosalpinges prior to IVF or ICSI: an RCT.

STUDY QUESTION: Does hysteroscopic proximal tubal occlusion by intratubal devices as a treatment for hydrosalpinges result in comparable ongoing pregnancy rates following IVF/ICSI when compared with laparoscopic salpingectomy? SUMMARY ANSWER: Hysteroscopic proximal tubal occlusion by intratubal devices is inferior to laparoscopic salpingectomy in the treatment of hydrosalpinges in women undergoing IVF/ICSI with respect to ongoing pregnancy rates. WHAT IS KNOWN ALREADY: It is known that women with hydrosalpinges undergoing IVF have poorer pregnancy outcomes compared with women with other forms of tubal infertility. In these women, both laparoscopic salpingectomy and laparoscopic proximal tubal ligation are known to improve IVF outcomes. At present, it is unclear whether a less-invasive hysteroscopic treatment with intratubal devices leads to similar ongoing pregnancy rates following IVF when compared with laparoscopic salpingectomy. STUDY DESIGN, SIZE, DURATION: A two-centre, randomized, controlled, non-inferiority trial. Between October 2009 and December 2014 a total of 85 women were included in this study; of whom, 42 were randomized to hysteroscopic proximal occlusion by intratubal device placement and 43 were randomized to laparoscopic salpingectomy. Randomization was based on a computer-generated randomization list. The study was unblinded. The primary outcome was ongoing pregnancy rate, defined as a fetal heartbeat on ultrasound beyond 10-week gestation following one IVF/ICSI treatment (fresh and frozen-thawed embryo transfers). PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied women aged 18-41 years, with uni- or bilateral ultrasound visible hydrosalpinges who were scheduled for an IVF/ICSI treatment. MAIN RESULTS AND THE ROLE OF CHANCE: The ongoing pregnancy rates per patient according to the intention-to-treat principle were 11/42 (26.2%) after hysteroscopic proximal occlusion by intratubal devices (intervention group) versus 24/43 (55.8%) after laparoscopic salpingectomy (control group) (P = 0.008) [absolute difference: 26.1%; 95% confidence interval (CI): 0.5-51.7, relative risk (RR): 0.56; 95% CI: 0.31-1.03, P = 0.01]. In the per protocol analysis, the ongoing pregnancy rate per patient following hysteroscopic proximal occlusion by intratubal devices was 9/27 (33.3%) compared with 19/32 (59.4%) following laparoscopic salpingectomy (P = 0.067) (absolute difference: 29.6%; 95% CI: 7.1 to 49.1, RR: 0.47; 95% CI: 0.27-0.83, P = 0.062). LIMITATIONS, REASONS FOR CAUTION: Masking participants and investigators would be difficult due to the nature of both interventions. Since we had objective outcome measurements, we withheld sham procedures, leaving the study unblinded. Furthermore, our low sample size resulted in wide CIs. A larger sample size would result in a more accurate treatment effect; however, this was non-feasible for recruitment and inclusion. WIDER IMPLICATIONS OF THE FINDINGS: In the treatment of hydrosalpinges prior to IVF/ICSI, hysteroscopic proximal occlusion by intratubal devices is inferior to laparoscopic salpingectomy. STUDY FUNDING/COMPETING INTERESTS: The intratubal devices were received from Conceptus, Inc., San Carlos, CA, USA, which was acquired by Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA in 2013. Conceptus, Inc./Bayer HealthCare Pharmaceuticals, Inc. had no role in the study design, data collection and analyses, decision to publish or preparation of the manuscript. The study as a whole was funded by the SWOG (foundation for scientific investigation in obstetrics and gynaecology of the VU University Medical Centre, Amsterdam, the Netherlands). P.G.A.H. has received non-financial support from Conceptus, Inc. during the conduct of this study. He has received grants from Ferring B.V., Merck Serono and Abbott outside the submitted work. M.H.E. has received personal fees from Smith and Nephew and IQ Medical Ventures outside the submitted work. TRIAL REGISTRATION NUMBER: The Dutch Trial Register: NTR 2073. TRIAL REGISTRATION DATE: October 21, 2009. DATE OF FIRST PATIENT'S ENROLMENT: October 26, 2009.

Process evaluation of a multidisciplinary care program for patients undergoing gynaecological surgery.

PURPOSE: This study describes the process evaluation of an innovative multidisciplinary care program for patients undergoing benign gynaecologic surgery. This care program aims at improving recovery and preventing delayed return to work and consists of two steps: (1) an interactive e-health intervention for all participants, and (2) integrated clinical and occupational care management for those participants whose sick leave exceeds 10 weeks. METHODS: Eligible for this study were employed women aged between 18-65 years scheduled for a laparoscopic adnexal surgery and/or hysterectomy. Data were collected from patients, their supervisors and their gynaecologists, by means of electronic questionnaires during a 6 month follow-up period and an automatically generated, detailed weblog of the patient web portal ( www.ikherstel.nl ). Investigated process measures included: reach, dose delivered, dose received, and fidelity. In addition, attitudes towards the intervention were explored among all stakeholders. RESULTS: 215 patients enrolled in the study and accounted to a reach of 60.2 % (215/357). All intervention group patients used their account at least once and total time spent on the patient web portal was almost 2 h for each patient (median 118 min, IQR 64-173 min). Most patients visited the website several times (median 11 times, IQR 6-16). Perceived effectiveness among patients was high (74 %). In addition, gynaecologists (76 %) and employers (61 %) were satisfied with the web portal as well. Implementation of the second step of the intervention was suboptimal. Motivating patients to consent to additional guidance and developing an accurate return-to-work-prognosis were two important obstacles. CONCLUSIONS: The results of this study indicate good feasibility for implementation on a broad scale of the e-health intervention for patients undergoing benign gynaecological surgery. To enhance the implementation of the second step of the perioperative care program, adaptations in the integrated care protocol are needed.

Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparison.

STUDY QUESTION: What is the treatment success rate of systemic methotrexate (MTX) compared with expectant management in women with an ectopic pregnancy or a pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations? SUMMARY ANSWER: In women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations, expectant management is an alternative to medical treatment with single-dose systemic MTX. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: MTX is often used in asymptomatic women with an ectopic pregnancy or a PUL with low and plateauing serum hCG concentrations. These pregnancies may be self-limiting and watchful waiting is suggested as an alternative, but evidence from RCTs is lacking. The results of this RCT show that expectant management is an alternative to treatment with systemic MTX in a single-dose regimen in these women. STUDY DESIGN, SIZE, DURATION: A multicentre RCT women were assigned to systemic MTX (single dose) treatment or expectant management, using a web-based randomization program, block randomization with stratification for hospital and serum hCG concentration (<1000 versus 1000-2000 IU/l). The primary outcome measure was an uneventful decline of serum hCG to an undetectable level (<2 IU/l) by the initial intervention strategy. Secondary outcome measures included additional treatment, side effects and serum hCG clearance time. PARTICIPANTS, SETTING, METHODS: From April 2007 to January 2012, we performed a multicentre study in The Netherlands. All haemodynamically stable women >18 years old with both an ectopic pregnancy visible on transvaginal sonography and a plateauing serum hCG concentration <1500 IU/l or with a PUL and a plateauing serum hCG concentration <2000 IU/l were eligible for the trial. MAIN RESULTS: We included 73 women of whom 41 were allocated to single-dose MTX and 32 to expectant management. There was no difference in primary treatment success rate of single-dose MTX versus expectant management, 31/41 (76%) and 19/32 (59%), respectively [relative risk (RR) 1.3 95% confidence interval (CI) 0.9-1.8]. In nine women (22%), additional MTX injections were needed, compared with nine women (28%) in whom systemic MTX was administered after initial expectant management (RR 0.8; 95% CI 0.4-1.7). One woman (2%) from the MTX group underwent surgery compared with four women (13%) in the expectant management group (RR 0.2; 95% CI 0.02-1.7), all after experiencing abdominal pain within the first week of follow-up. In the MTX group, nine women reported side effects versus none in the expectant management group. No serious adverse events were reported. Single-dose systemic MTX does not have a larger treatment effect compared with expectant management in women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations. WIDER IMPLICATIONS OF THE FINDINGS: Sixty percent of women after expectant management had an uneventful clinical course with steadily declining serum hCG levels without any intervention, which means that MTX, a potentially harmful drug, can be withheld in these women. BIAS, LIMITATION AND GENERALISABILITY: A limitation of this RCT is that it was an open (not placebo controlled) trial. Nevertheless, introduction of bias was probably limited by the strict criteria to be fulfilled for treatment with MTX. STUDY FUNDING: This trial is supported by a grant of the Netherlands Organization for Health Research and Development (ZonMw Clinical fellow grant 90700154). TRIAL REGISTRATION: ISRCTN 48210491.

Anterior colporrhaphy does not induce bladder outlet obstruction.

INTRODUCTION AND HYPOTHESIS: We aimed to evaluate if anterior colporrhaphy causes incomplete voiding due to bladder outlet obstruction. METHODS: Women scheduled for anterior colporrhaphy were asked to undergo multichannel urodynamic investigation before surgery and the first postoperative day. Bladder outlet obstruction was assessed using the Blaivas­Groutz voiding nomogram. Maximum flow rate, detrusor pressure and residual volume were compared between pre- and postoperative measurements and between women with and without an abnormal post-void residual volume (PVR; volume exceeding 150 ml). RESULTS: Seventeen women participated. One woman who was unobstructed before surgery was obstructed after surgery. Overall, detrusor pressure and maximum flow rate before and after surgery did not differ. After surgery, six women had an abnormal PVR, one was unable to void, four were mildly obstructed and one moderately obstructed. CONCLUSION: Urodynamic investigation the first day after anterior colporrhaphy did not show that anterior colporrhaphy induces bladder outlet obstruction. The explanation for postoperative urinary retention can therefore also lie in nonanatomical causes such as postoperative pain and psychological factors.

Patient preferences for clean intermittent catheterisation and transurethral indwelling catheterisation for treatment of abnormal post-void residual bladder volume after vaginal prolapse surgery.

OBJECTIVE: To determine patient preferences for clean intermittent catheterisation (CIC) relative to transurethral indwelling catheterisation (TIC) as the treatment of abnormal post-void residual bladder volume (PVR) following vaginal prolapse surgery. DESIGN: Scenario-based preference assessment during face-to-face interview. SETTING: Teaching hospital. POPULATION: A sample of consecutive patients scheduled for vaginal prolapse surgery. METHODS: Preference for CIC relative to TIC was assessed using written treatment scenarios. Initially, treatment duration was set at 3 days and the risk for urinary tract infection (UTI) was 30% for both interventions. Both treatment duration and UTI risk related to TIC were kept constant. Treatment duration and UTI risk after CIC were varied until patients altered their preference. In this way, the duration of catheterisation and level of UTI risk related to CIC at which patients would prefer CIC to TIC could be determined. MAIN OUTCOME MEASURES: Patients' preference for CIC relative to TIC. RESULTS: When both duration of treatment and UTI risk were identical for both interventions, 64% of patients prefer CIC. Ninety-two percent of patients prefer CIC when CIC lasts 3 days but results in a 15% lower risk of UTI. Assuming that CIC results in a 15% risk of UTI, a total of 98 and 99% of patients prefer CIC to TIC when catheterisation with CIC last 2 and 1 day, respectively. CONCLUSIONS: Most patients with abnormal PVR prefer CIC to TIC. The results of a recent randomised controlled trial showed that CIC resulted in a 2 days shorter catheterisation and more than 20% reduced risk of UTI. These conditions correspond to a preference of 99% of patients for CIC.

Comparing clean intermittent catheterisation and transurethral indwelling catheterisation for incomplete voiding after vaginal prolapse surgery: a multicentre randomised trial.

OBJECTIVE: To compare clean intermittent catheterisation with transurethral indwelling catheterisation for the treatment of abnormal post-void residual bladder volume (PVR) following vaginal prolapse surgery. DESIGN: Multicentre randomised controlled trial. SETTING: Five teaching hospitals and one non-teaching hospital in the Netherlands. POPULATION: All patients older than 18 years experiencing abnormal PVR following vaginal prolapse surgery, with or without the use of mesh. Exclusion criteria were: any neurological or anxiety disorder, or the need for combined anti-incontinence surgery. METHODS: All patients were given an indwelling catheter directly after surgery, which was removed on the first postoperative day. Patients with a PVR of more than 150 ml after their first void were randomised for clean intermittent catheterisation (CIC), performed by nursing staff, or for transurethral indwelling catheterisation (TIC) for 3 days. MAIN OUTCOME MEASURE: Bacteriuria rate at end of treatment. RESULTS: A total of 87 patients were included in the study. Compared with the TIC group (n = 42), there was a lower risk of developing bacteriuria (14 versus 38%; P = 0.02) or urinary tract infection (UTI; 12 versus 33%; P = 0.03) in the CIC group (n = 45); moreover, a shorter period of catheterisation was required (18 hours CIC versus 72 hours TIC; P < 0.001). Patient satisfaction was similar in the two groups, and no adverse events occurred. CONCLUSION: Clean intermittent catheterisation is preferable over indwelling catheterisation for 3 days in the treatment of abnormal PVR following vaginal prolapse surgery.

Metroplasty versus expectant management for women with recurrent miscarriage and a septate uterus.

BACKGROUND: The prevalence of recurrent miscarriage in women with a septate uterus has increased. Restoration of the morphology of the uterus can hypothetically increase live birth rate and subsequent pregnancies in women with a septate uterus and recurrent miscarriage. OBJECTIVES: To determine whether hysteroscopic metroplasty in women with a septate uterus and two or more preceding miscarriages improves pregnancy outcomes. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (inception to August 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (inception to August 2010),  MEDLINE (1950 to August 2010), EMBASE (1980 to August 2010). PSYCHINFO (1806 to August 2010). In addition we searched trial registers for ongoing and registered trials, conference abstracts and OpenSigle and sources of Grey literature. SELECTION CRITERIA: Only randomised controlled trials (RCTs) that assess the effect on reproductive outcome of hysteroscopic metroplasty in women with a history of two or more preceding miscarriages and a septate uterus were eligible for inclusion. DATA COLLECTION AND ANALYSIS: If there had been data to include, two authors would have independently assessed trial quality and extracted data. They would have also contacted study authors for additional information. We collected adverse effects information from the trials. MAIN RESULTS: No randomised controlled trials were identified for inclusion. AUTHORS' CONCLUSIONS: Hysteroscopic metroplasty in women with recurrent miscarriage and a septate uterus is being performed in many countries to improve reproductive outcomes in women.This treatment has been assessed in non-controlled studies, which suggested a positive effect on pregnancy outcomes. However, these studies are biased due to the fact that the participants with recurrent miscarriage treated by hysteroscopic metroplasty served as their own controls. Until now, the effectiveness and possible complications of hysteroscopic metroplasty have never been considered in a randomised controlled trial.Taking this into account there is insufficient evidence to support this treatment in these women. A randomised controlled trial is urgently needed and currently underway (www.studies-obsgyn.nl/trust NTR 1676).

Gel instillation sonohysterography (GIS) and saline contrast sonohysterography (SCSH): comparison of two diagnostic techniques.

OBJECTIVE: To compare gel instillation sonohysterography (GIS) with saline contrast sonohysterography (SCSH) as diagnostic methods for the evaluation of the uterine cavity. METHODS: A prospective cohort study was performed at the Department of Obstetrics and Gynecology of the VU University Medical Center, Amsterdam, between September 2007 and April 2008. We included 65 women suspected of having an intrauterine abnormality with an indication for SCSH/GIS. First SCSH and subsequently GIS were performed in all women. Distension of the uterine cavity, image quality, visualization of intrauterine abnormalities and pain experienced on a visual analog scale (VAS score) were recorded for both procedures. RESULTS: The mean distension with GIS was 9.0 mm and with SCSH it was 8.5 mm (P = 0.15). The mean image quality, on a scale from 0 to 5, for SCSH was 4.0 and for GIS it was 3.6 (P = 0.01). No difference was found for the visualization of intrauterine abnormalities, and the VAS scores for pain experienced on SCSH and GIS were 1.5 and 1.6, respectively (P = 0.62). CONCLUSIONS: The image quality of SCSH is slightly better than that of GIS. This difference is likely to be attributable to the presence of air bubbles in the gel. The small difference in uterine cavity distension in favor of GIS and comparable stable distension during at least 4 min make GIS a suitable alternative for SCSH if air bubbles can be prevented.

The clinical relevance of hysteroscopic polypectomy in premenopausal women with abnormal uterine bleeding.

This study assessed the efficacy of hysteroscopic polyp removal in the management of abnormal uterine bleeding (AUB) of premenopausal patients. The monthly menstrual blood loss, measured semi-objectively by the pictorial blood loss assessment chart (PBAC) and patients satisfaction were recorded prospectively preoperatively and postoperatively. Twenty-one patients were included. Median monthly PBAC-score before treatment was 288 (range 142-670) and 6 months after polyp removal 155 (range 39-560). It was concluded that hysteroscopic polyp removal in premenopausal women with AUB reduces the monthly blood loss significantly and has a high satisfaction rate on the short term.

Transcervical hysteroscopic resection of submucous fibroids for abnormal uterine bleeding: results regarding the degree of intramural extension.

OBJECTIVE: To examine the results of transcervical resection of submucous fibroids in relation to the degree of intramural extension. METHODS: A prospective 3-year observational study was performed of transcervical resection of submucous fibroids for abnormal uterine bleeding. The mean follow-up was 20 months (range 10-34). Fifty-one patients with a mean age of 38 years (range 23-55) were treated with transcervical resection after classification according to the degree of intramural extension of the submucous fibroids. The intention was to perform complete resection, established at control hysteroscopy. A repeat procedure was performed in cases of incomplete resection unless the patient denied further hysteroscopic treatment. Outcome measures were control of bleeding, subsequent surgery, number of procedures, number of complete resections, and number of recurrences. RESULTS: Bleeding was controlled in 48 (94.1%) of all patients after final resection. Hysterectomy was performed in three patients (5.9%) because of persistent complaints: in two cases after incomplete resection and in one case after complete resection. Three patients were lost to follow-up. Of the remaining 45 patients (42 with complete and three with incomplete final resection), three (6.7%) had a recurrence (one after complete and two after incomplete final resection). With more extensive intramural involvement, the chance to achieve complete resection decreased and the mean number of procedures to achieve complete resection increased. CONCLUSIONS: Complete resection improves the long-term results of transcervical resection of submucous fibroids for control of abnormal uterine bleeding. Transcervical resection of submucous fibroids with more than 50% intramural extension should be performed only in selected cases, as complete resection usually necessitates repeat procedures.

Long-term results of hysteroscopic myomectomy for abnormal uterine bleeding.

OBJECTIVE: To analyze the efficacy of transcervical resection of submucous myomas and to identify prognostic factors for long-term results. METHODS: Two-hundred eighty-five women were treated with transcervical resection of submucous myomas without endometrial ablation. In case of incomplete resection a repeat procedure was offered. Long-term follow-up was obtained. Recurrence was defined as the need for further surgery. The relation of several variables with the outcome was analyzed using Cox proportional hazard regression analysis. RESULTS: Seventeen cases (6%) were lost to follow-up. The median follow-up was 46 months (range 1-104 months); for cases without recurrence median follow-up was 42 months (range 16-104 months). Forty-one (14.5%) patients had repeat surgery. An independent prognostic value of uterine size (P < .001) and number of submucous myomas (P < .001) for recurrence was noted. Twenty of 41 patients who had repeat surgery subsequently had a hysterectomy. None of the variables investigated predicted the need for hysterectomy. The surgery-free percentage of 165 patients with normal sized uteri and not more than two myomas was 94.3% (standard error +/- 1.8%) at 2 years and 90.3% (+/- 3.0%) at 5 years. CONCLUSION: Transcervical resection of submucous myomas is a safe and effective treatment for patients with a normal sized uterus and not more than two myomas. It is an acceptable alternative for selected other patients. The need for a combined endometrial ablation is questionable. Transcervical resection of submucous myomas will give patients a high chance of averting further surgery and should modify the way patients are counseled.