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

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Introduction and hypothesisThe aim of this study was to identify all treatment decision factors that determined the preference for peri-urethral bulk injection therapy (PBI) or mid-urethral sling (MUS) surgery in patients with primary stress urinary incontinence (SUI). Second, we explored what patients expect from treatment for SUI and whether patients would consider PBI as a primary treatment option.MethodsIn a qualitative design, 20 semi-structured, face-to-face interviews were conducted in women with primary SUI. Exclusion criteria were: previous PBI or MUS surgery; predominating urgency. Interviews were guided by three open-ended questions and a topic list. PBI treatment and MUS surgery were described in detail, and the efficacy was stated as 70% and 90%, respectively. Data saturation was reached when no new treatment decision factors were identified in three consecutive interviews. Interviews were audiotaped and fully transcribed. Thematic analysis by a coding process was done independently by two researchers.ResultsSixteen procedural, personal, professional, social and external treatment decision factors were identified. Regarding expectations about treatment for SUI, women believed ‘becoming dry’ was wishful thinking. The majority of patients accepted a small degree of persistent urinary incontinence after treatment. Regardless of their treatment preference, patients indicated that women should be informed about PBI as a primary treatment option.ConclusionPatients with primary SUI are open to PBI as an alternative treatment option even with lower cure rates compared with MUS surgery performed under general or spinal anesthesia. Patients indicated that women with primary SUI seeking treatment should be informed about PBI as a treatment option.