title: Hysteroscopy in recurrent in-vitro fertilisation failure (TROPHY): a multicentre, randomised controlled trial.
abstract: BACKGROUND
  The success rate of in-vitro fertilisation (IVF) remains low and many women undergo multiple treatment cycles. A previous meta-analysis suggested hysteroscopy could improve outcomes in women who have had recurrent implantation failure; however, studies were of poor quality and a definitive randomised trial was needed. In the TROPHY trial we aimed to assess whether hysteroscopy improves the livebirth rate following IVF treatment in women with recurrent failure of implantation.
  
  
  METHODS
  We did a multicentre, randomised controlled trial in eight hospitals in the UK, Belgium, Italy, and the Czech Republic. We recruited women younger than 38 years who had normal ultrasound of the uterine cavity and history of two to four unsuccessful IVF cycles. We used an independent web-based trial management system to randomly assign (1:1) women to receive outpatient hysteroscopy (hysteroscopy group) or no hysteroscopy (control group) in the month before starting a treatment cycle of IVF (with or without intracytoplasmic sperm injection). A computer-based algorithm minimised for key prognostic variables: age, body-mass index, basal follicle-stimulating hormone concentration, and the number of previous failed IVF cycles. The order of group assignment was masked to the researchers at the time of recruitment and randomisation. Embryologists involved in the embryo transfer were masked to group allocation, but physicians doing the procedure knew of group assignment and had hysteroscopy findings accessible. Participants were not masked to their group assignment. The primary outcome was the livebirth rate (proportion of women who had a live baby beyond 24 weeks of gestation) in the intention-to-treat population. The trial was registered with the ISRCTN Registry, ISRCTN35859078.
  
  
  RESULTS
  Between Jan 1, 2010, and Dec 31, 2013, we randomly assigned 350 women to the hysteroscopy group and 352 women to the control group. 102 (29%) of women in the hysteroscopy group had a livebirth after IVF compared with 102 (29%) women in the control group (risk ratio 1·0, 95% CI 0·79-1·25; p=0·96). No hysteroscopy-related adverse events were reported.
  
  
  CONCLUSIONS
  Outpatient hysteroscopy before IVF in women with a normal ultrasound of the uterine cavity and a history of unsuccessful IVF treatment cycles does not improve the livebirth rate. Further research into the effectiveness of surgical correction of specific uterine cavity abnormalities before IVF is warranted.
  
  
  BACKGROUND
  European Society of Human Reproduction and Embryology, European Society for Gynaecological Endoscopy.
authors.affiliation: Assisted Conception Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK. Electronic address: tarek.el-toukhy@gstt.nhs.uk.
authors.forename: Tarek
authors.initials: T
authors.lastname: El-Toukhy
authors.affiliation: Ziekenhuis Oost Limburg, Assisted Conception Unit, Genk, Belgium.
authors.forename: Rudi
authors.initials: R
authors.lastname: Campo
authors.affiliation: Assisted Conception Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK.
authors.forename: Yacoub
authors.initials: Y
authors.lastname: Khalaf
authors.affiliation: SISMER, Assisted Conception Unit, Bologna, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Tabanelli
authors.affiliation: SISMER, Assisted Conception Unit, Bologna, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Gianaroli
authors.affiliation: Leuven Institute for Fertility and Embryology, Tiensevest, Leuven, Belgium.
authors.forename: Sylvie S
authors.initials: SS
authors.lastname: Gordts
authors.affiliation: Leuven Institute for Fertility and Embryology, Tiensevest, Leuven, Belgium.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gordts
authors.affiliation: Ziekenhuis Oost Limburg, Assisted Conception Unit, Genk, Belgium.
authors.forename: Greet
authors.initials: G
authors.lastname: Mestdagh
authors.affiliation: The Sanatorium Pronatal, Assisted Conception Unit, Prague, Czech Republic.
authors.forename: Tonko
authors.initials: T
authors.lastname: Mardesic
authors.affiliation: The Sanatorium Pronatal, Assisted Conception Unit, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Voboril
authors.affiliation: Obstetrics and Gynaecology Department, University of Turin, Torino, Italy.
authors.forename: Gian L
authors.initials: GL
authors.lastname: Marchino
authors.affiliation: Obstetrics and Gynaecology Department, University of Turin, Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Benedetto
authors.affiliation: Centre for Reproductive Medicine, Barts Health NHS Trust, London, UK.
authors.forename: Talha
authors.initials: T
authors.lastname: Al-Shawaf
authors.affiliation: Centre for Reproductive Medicine, Barts Health NHS Trust, London, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Sabatini
authors.affiliation: Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, St Thomas' Hospital, London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Seed
authors.affiliation: Reproductive Surgery Special Interest Group, European Society of Human Reproduction and Embryology, Brussels, Belgium.
authors.forename: Marco
authors.initials: M
authors.lastname: Gergolet
authors.affiliation: First Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Greece.
authors.forename: Grigoris
authors.initials: G
authors.lastname: Grimbizis
authors.affiliation: Institute of Metabolism and Systems Research and Tommy's National Centre for Miscarriage Care and Research, University of Birmingham, Birmingham, UK.
authors.forename: Hoda
authors.initials: H
authors.lastname: Harb
authors.affiliation: Institute of Metabolism and Systems Research and Tommy's National Centre for Miscarriage Care and Research, University of Birmingham, Birmingham, UK.
authors.forename: Arri
authors.initials: A
authors.lastname: Coomarasamy
mesh_terms: D000328:Adult; D000556:Ambulatory Surgical Procedures; D005060:Europe; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D015907:Hysteroscopy; D007247:Infertility, Female / Q000628:therapy*; D050498:Live Birth; D011247:Pregnancy; D012008:Recurrence; D017211:Treatment Failure