Tarek El-Toukhy1, Rudi Campo2, Yacoub Khalaf3, Carla Tabanelli4, Luca Gianaroli4, Sylvie S Gordts5, Stephan Gordts5, Greet Mestdagh2, Tonko Mardesic6, Jan Voboril6, Gian L Marchino7, Chiara Benedetto7, Talha Al-Shawaf8, Luca Sabatini8, Paul T Seed9, Marco Gergolet10, Grigoris Grimbizis11, Hoda Harb12, Arri Coomarasamy12. 1. Assisted Conception Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK. Electronic address: tarek.el-toukhy@gstt.nhs.uk. 2. Ziekenhuis Oost Limburg, Assisted Conception Unit, Genk, Belgium. 3. Assisted Conception Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK. 4. SISMER, Assisted Conception Unit, Bologna, Italy. 5. Leuven Institute for Fertility and Embryology, Tiensevest, Leuven, Belgium. 6. The Sanatorium Pronatal, Assisted Conception Unit, Prague, Czech Republic. 7. Obstetrics and Gynaecology Department, University of Turin, Torino, Italy. 8. Centre for Reproductive Medicine, Barts Health NHS Trust, London, UK. 9. Division of Women's Health, Women's Health Academic Centre, King's College London and King's Health Partners, St Thomas' Hospital, London, UK. 10. Reproductive Surgery Special Interest Group, European Society of Human Reproduction and Embryology, Brussels, Belgium. 11. First Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Greece. 12. Institute of Metabolism and Systems Research and Tommy's National Centre for Miscarriage Care and Research, University of Birmingham, Birmingham, UK.
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. FINDINGS: 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. INTERPRETATION: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. FUNDING: European Society of Human Reproduction and Embryology, European Society for Gynaecological Endoscopy.
RCT Entities:
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. FINDINGS: 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. INTERPRETATION: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. FUNDING: European Society of Human Reproduction and Embryology, European Society for Gynaecological Endoscopy.
Authors: Mohan S Kamath; Jan Bosteels; Thomas M D'Hooghe; Srividya Seshadri; Steven Weyers; Ben Willem J Mol; Frank J Broekmans; Sesh Kamal Sunkara Journal: Cochrane Database Syst Rev Date: 2019-04-16
Authors: R Campo; F Santangelo; S Gordts; C Di Cesare; H Van Kerrebroeck; M C De Angelis; A Di Spiezio Sardo Journal: Facts Views Vis Obgyn Date: 2018-09