Comparing the cumulative live birth rate of cleavage-stage versus blastocyst-stage embryo transfers between IVF cycles: a study protocol for a multicentre randomised controlled superiority trial (the ToF trial)
Madelon van Wely,
Harold R Verhoeve,
Kathrin Fleischer,
Simone Cornelisse,
Liliana Ramos,
Brigitte Arends,
Janneke J Brink-van der Vlugt,
Jan Peter de Bruin,
Max HJN Curfs,
Josien Derhaag,
Angelique van Dongen,
Jannie van Echten-Arends,
Eva R Groenewoud,
Jacques WM Maas,
Quirine Pieterse,
Evert JP van Santbrink,
Els Slappendel,
Maaike AF Traas,
Jantien Visser,
Carlijn G Vergouw,
Lucette AJ van der Westerlaken,
Yvonne Wurth,
Moniek van der Zanden,
Didi DM Braat,
Sebastiaan Mastenbroek
Affiliations
Madelon van Wely
Amsterdam UMC, location University of Amsterdam, Centre for Reproductive Medicine, Amsterdam, Netherlands
Harold R Verhoeve
Department of Obstetrics and Gynaecology, OLVG Oost, Amsterdam, North Holland, The Netherlands
Kathrin Fleischer
gynaecologist
Simone Cornelisse
Obstetrics and Gynaecology, Radboud University Medical Centre, Nijmegen, The Netherlands
Liliana Ramos
clinical embryologist
Brigitte Arends
clinical embryologist
Janneke J Brink-van der Vlugt
Fertility Clinic, Nij Barrahûs, Wolvega, The Netherlands
Jan Peter de Bruin
Department of Obstetrics and Gynecology, Jeroen Bosch Hospital, s-Hertogenbosch, North Brabant, The Netherlands
Max HJN Curfs
Department of Obstetrics and Gynecology, Isala Fertility Centre, Zwolle, Overijssel, The Netherlands
Josien Derhaag
Department of Reproductive Medicine, Maastricht University Medical Centre, Maastricht, Limburg, The Netherlands
Angelique van Dongen
gynaecologist
Jannie van Echten-Arends
clinical embryologist
Eva R Groenewoud
Department of Obstetrics, Gynaecology and Reproductive Medicine, Northwest Hospital Group, Den Helder, North Holland, The Netherlands
Jacques WM Maas
Department of Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven, North Brabant, The Netherlands
Quirine Pieterse
gynaecologist
Evert JP van Santbrink
Fertility Centre, Reinier de Graaf, Voorburg, South Holland, The Netherlands
Els Slappendel
clinical embryologist
Maaike AF Traas
Department of Gynaecology, Gelre Hospital, Apeldoorn, Gelderland, The Netherlands
Jantien Visser
gynaecologist
Carlijn G Vergouw
Department of Reproductive Medicine, Amsterdam UMC Location VUmc, Amsterdam, North Holland, The Netherlands
Lucette AJ van der Westerlaken
Department of Obstetrics and Gynaecology, Leiden University Medical Center, Leiden, South Holland, The Netherlands
Yvonne Wurth
clinical embryologist
Moniek van der Zanden
Department of Obstetrics and Gynaecology, Haaglanden Medical Centre, the Hague, South Holland, The Netherlands
Didi DM Braat
Obstetrics and Gynaecology, Radboud University Medical Centre, Nijmegen, The Netherlands
Introduction In vitro fertilisation (IVF) has evolved as an intervention of choice to help couples with infertility to conceive. In the last decade, a strategy change in the day of embryo transfer has been developed. Many IVF centres choose nowadays to transfer at later stages of embryo development, for example, transferring embryos at blastocyst stage instead of cleavage stage. However, it still is not known which embryo transfer policy in IVF is more efficient in terms of cumulative live birth rate (cLBR), following a fresh and the subsequent frozen–thawed transfers after one oocyte retrieval. Furthermore, studies reporting on obstetric and neonatal outcomes from both transfer policies are limited.Methods and analysis We have set up a multicentre randomised superiority trial in the Netherlands, named the Three or Fivetrial. We plan to include 1200 women with an indication for IVF with at least four embryos available on day 2 after the oocyte retrieval. Women are randomly allocated to either (1) control group: embryo transfer on day 3 and cryopreservation of supernumerary good-quality embryos on day 3 or 4, or (2) intervention group: embryo transfer on day 5 and cryopreservation of supernumerary good-quality embryos on day 5 or 6. The primary outcome is the cLBR per oocyte retrieval. Secondary outcomes include LBR following fresh transfer, multiple pregnancy rate and time until pregnancy leading a live birth. We will also assess the obstetric and neonatal outcomes, costs and patients’ treatment burden.Ethics and dissemination The study protocol has been approved by the Central Committee on Research involving Human Subjects in the Netherlands in June 2018 (CCMO NL 64060.000.18). The results of this trial will be submitted for publication in international peer-reviewed and in open access journals.Trial registration number Netherlands Trial Register (NL 6857).
