A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer

• Published in: Human Reproduction
• Main Authors: Groenewoud, E. R., Cohlen, B. J., Al-Oraiby, A., Brinkhuis, E. A., Broekmans, F. J. M., de Bruin, J. P., van den Dool, G., Fleisher, K., Friederich, J., Goddijn, M., Hoek, A., Hoozemans, D. A., Kaaijk, E. M., Koks, C. A. M., Laven, J. S. E., van der Linden, P. J. Q., Manger, A. P., Slappendel, E., Spinder, T., Kollen, B. J., Macklon, N. S.
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2016
• Subjects: assisted reproductive techniques; in vitro fertilization; frozen-thawed embryo transfer; modified natural cycle; artificial cycle; REPLACEMENT CYCLES; CLINICAL-OUTCOMES; PREGNANCY RATE; FROZEN; CRYOPRESERVATION; VITRIFICATION; WOMEN; METAANALYSIS; RATES; RCT; Antarc*; Antarctica
• Online Access: https://hdl.handle.net/11370/ce999fe2-471a-4c4d-a361-81e8bf9d914b; https://research.rug.nl/en/publications/ce999fe2-471a-4c4d-a361-81e8bf9d914b; https://doi.org/10.1093/humrep/dew120

STUDY QUESTION: Are live birth rates (LBRs) after artificial cycle frozen-thawed embryo transfer (AC-FET) non-inferior to LBRs after modified natural cycle frozen-thawed embryo transfer (mNC-FET)? SUMMARY ANSWER: AC-FET is non-inferior to mNC-FET with regard to LBRs, clinical and ongoing pregnancy rates (OPRs) but AC-FET does result in higher cancellation rates. WHAT IS ALREADY KNOWN: Pooling prior retrospective studies of AC-FET and mNC-FET results in comparable pregnancy and LBRs. However, these results have not yet been confirmed by a prospective randomized trial. STUDY DESIGN, SIZE AND DURATION: In this non-inferiority prospective randomized controlled trial (acronym 'ANTARCTICA' trial), conducted from February 2009 to April 2014, 1032 patients were included of which 959 were available for analysis. The primary outcome of the study was live birth. Secondary outcomes were clinical and ongoing pregnancy, cycle cancellation and endometrium thickness. A cost-efficiency analysis was performed. PARTICIPANT/MATERIALS, SETTING, METHODS: This study was conducted in both secondary and tertiary fertility centres in the Netherlands. Patients included in this study had to be 18-40 years old, had to have a regular menstruation cycle between 26 and 35 days and frozen-thawed embryos to be transferred had to derive from one of the first three IVF or IVF-ICSI treatment cycles. Patients with a uterine anomaly, a contraindication for one of the prescribed medications in this study or patients undergoing a donor gamete procedure were excluded from participation. Patients were randomized based on a 1: 1 allocation to either one cycle of mNC-FET or AC-FET. All embryos were cryopreserved using a slow-freeze technique. MAIN RESULTS AND THE ROLE OF CHANCE: LBR after mNC-FET was 11.5% (57/495) versus 8.8% in AC-FET (41/464) resulting in an absolute difference in LBR of -0.027 in favour of mNC-FET (95% confidence interval (CI) -0.065-0.012; P = 0.171). Clinical pregnancy occurred in 94/495 (19.0%) patients in mNC-FET versus 75/464 ...