STUDY QUESTION What is the effect of endometrial scratching in patients with or without prior failed ART cycles on live birth (LBR) and clinical pregnancy rates (CPR)? SUMMARY ANSWER It remains unclear if endometrial scratching improves the chance of pregnancy and, if so, for whom. WHAT IS KNOWN ALREADY Endometrial scratching is hypothesized to improve embryo implantation in ART. Multiple studies have been published, but it remains unclear if endometrial scratching actually improves pregnancy rates and, if so, for which patients. STUDY DESIGN, SIZE, DURATION For this review, a systematic search for published articles on endometrial scratching and ART was performed on 12 February 2018, in Pubmed, Embase and the Cochrane Library. PARTICIPANTS/MATERIALS, SETTING, METHODS Randomized controlled trials (RCTs) that evaluated endometrial scratching in the cycle prior to the stimulation cycle and reported CPR or LBR were included. RCTs investigating the effect of scratching during the stimulation cycle, or prior to cryo-thaw cycles were excluded. Studies were assessed using the Cochrane Risk of Bias tool. The effect of scratching was assessed for three different patient groups: patients with no prior IVF/ICSI treatment (Group 0), patients with one failed full IVF/ICSI cycle, including cryo-thaw cycles (Group 1) and patients with two or more failed full IVF/ICSI cycles (Group 2). A meta-analysis was performed when statistical heterogeneity was low; otherwise, a descriptive analysis was performed. MAIN RESULTS AND THE ROLE OF CHANCE Fourteen RCTs involving 2537 participants were included. Most RCTs contained a high or unclear risk of bias on one or more items. Substantial clinical and statistical heterogeneity was present; therefore meta-analysis for LBR and CPR could only be performed on Group 1. For this group, no differences between scratch and control were found for both LBR (risk ratio (RR) 1.01 [95%CI 0.68–1.51]) and CPR (RR 1.04 [95%CI 0.74–1.45]). For Groups 0 and 2, pooled analysis could not be performed, and for both groups the results of the individual RCTs were negative, neutral and positive. Miscarriage and multiple pregnancy rates were evaluated for the three groups (0, 1 and 2) together. Both outcomes were not significantly different between scratch and control (miscarriage rate RR 0.82 [95%CI 0.57–1.17] and multiple pregnancy rate RR 1.06 [95%CI 0.84–1.35]). Subgroup analysis, excluding trials with a risk of unintentional endometrial injury in the control group, was performed for Group 0 and 2 for LBR and CPR, and for the overall groups for miscarriage rate and multiple pregnancy rate. This reduced the heterogeneity and allowed for pooled analysis in these subgroups. Results of pooled analysis for the subgroups of Group 0 and 2 showed no significant difference for LBR, but CPR was significantly improved after endometrial scratchin...

STUDY QUESTION Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between −0.7% and +9.9%. WHAT IS KNOWN ALREADY Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96–1.59]). These data are consistent with a true difference of between −0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71–2.07) and RR 0.73 (95% CI 0.38–1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between −1.2% and +11.4% (95% CI). LIMITATIONS, REASONS FOR CAUTION This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%. WIDER IMPLICATIONS OF THE FINDINGS The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports ‘other’ from Ferring BV, personal fees from Up to date Hyperthecosis, ‘other’ from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work. TRIAL REGISTRATION NUMBER Registered in the Netherlands Trial Register (NL5193/NTR 5342). TRIAL REGISTRATION DATE 31 July 2015. DATE OF FIRST PATIENT’S ENROLMENT 26 January 2016.

Objectives To determine the association between levator hiatal dimensions, measured using transperineal ultrasound, in

BackgroundSuccess rates of assisted reproductive techniques (ART) are approximately 30%, with the most important limiting factor being embryo implantation. Mechanical endometrial injury, also called ‘scratching’, has been proposed to positively affect the chance of implantation after embryo transfer, but the currently available evidence is not yet conclusive. The primary aim of this study is to determine the effect of endometrial scratching prior to a second fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle on live birth rates in women with a failed first IVF/ICSI cycle.MethodMulticenter randomized controlled trial in Dutch academic and non-academic hospitals. A total of 900 women will be included of whom half will undergo an endometrial scratch in the luteal phase of the cycle prior to controlled ovarian hyperstimulation using an endometrial biopsy catheter. The primary endpoint is the live birth rate after the 2nd fresh IVF/ICSI cycle. Secondary endpoints are costs, cumulative live birth rate (after the full 2nd IVF/ICSI cycle and over 12 months of follow-up); clinical and ongoing pregnancy rate; multiple pregnancy rate; miscarriage rate and endometrial tissue parameters associated with implantation failure.DiscussionMultiple studies have been performed to investigate the effect of endometrial scratching on live birth rates in women undergoing IVF/ICSI cycles. Due to heterogeneity in both the method and population being scratched, it remains unclear which group of women will benefit from the procedure. The SCRaTCH trial proposed here aims to investigate the effect of endometrial scratching prior to controlled ovarian hyperstimulation in a large group of women undergoing a second IVF/ICSI cycle.Trial registrationNTR 5342, registered July 31st, 2015.Protocol versionVersion 4.10, January 4th, 2017.