Transfer of fresh or frozen embryos: a randomised controlled trial
Authors: Wong K M , van Wely M , Verhoeve H R , Kaaijk E M , Mol F , van der Veen F , Repping S , Mastenbroek S 
Published: October 2020

Abstract

STUDY QUESTION
Is IVF with frozen-thawed blastocyst transfer (freeze-all strategy) more effective than IVF with fresh and frozen-thawed blastocyst transfer (conventional strategy)?

SUMMARY ANSWER
The freeze-all strategy was inferior to the conventional strategy in terms of cumulative ongoing pregnancy rate per woman.

WHAT IS KNOWN ALREADY
IVF without transfer of fresh embryos, thus with frozen-thawed embryo transfer only (freeze-all strategy), is increasingly being used in clinical practice because of a presumed benefit. It is still unknown whether this new IVF strategy increases IVF efficacy.

STUDY DESIGN, SIZE, DURATION
A single-centre, open label, two arm, parallel group, randomised controlled superiority trial was conducted. The trial was conducted between January 2013 and July 2015 in the Netherlands. The intervention was one IVF cycle with frozen-thawed blastocyst transfer(s) versus one IVF cycle with fresh and frozen-thawed blastocyst transfer(s). The primary outcome was cumulative ongoing pregnancy resulting from one IVF cycle within 12 months after randomisation. Couples were allocated in a 1:1 ratio to the freeze-all strategy or the conventional strategy with an online randomisation programme just before the start of down-regulation.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Participants were subfertile couples with any indication for IVF undergoing their first IVF cycle, with a female age between 18 and 43 years. Differences in cumulative ongoing pregnancy rates were expressed as relative risks (RR) with 95% CI. All outcomes were analysed following the intention-to-treat principle.

MAIN RESULTS AND THE ROLE OF CHANCE
Two-hundred-and-five couples were randomly assigned to the freeze-all strategy (n = 102) or to the conventional strategy (n = 102). The cumulative ongoing pregnancy rate per woman was significantly lower in women allocated to the freeze-all strategy (19/102 (19%)) compared to women allocated to the conventional strategy (32/102 (31%); RR 0.59; 95% CI 0.36–0.98).

LIMITATIONS, REASONS FOR CAUTION
As this was a single-centre study, we were unable to study differences in study protocols and clinic performance. This, and the limited sample size, should make one cautious in using the results as the basis for definitive policy. All patients undergoing IVF, including those with a poor prognosis, were included; therefore, the outcome could differ in women with a good prognosis of IVF treatment success.

WIDER IMPLICATIONS OF THE FINDINGS
Our results indicate that there might be no benefit of a freeze-all strategy in terms of cumulative ongoing pregnancy rates. The efficacy of the freeze-all strategy in subgroups of patients, different stages of embryo development, and different freezing protocols needs to be further established and balanced against potential benefits and harms for mothers and children.

STUDY FUNDING/COMPETING INTEREST(S)
The Netherlands Organisation for Health Research and Development (ZonMW grant 171101007). S.M., F.M. and M.v.W. stated they are authors of the Cochrane review ‘Fresh versus frozen embryo transfers in assisted reproduction’.

TRIAL REGISTRATION NUMBER
Dutch Trial Register, NTR3187

TRIAL REGISTRATION DATE
9 December 2011

DATE OF FIRST PATIENT’S ENROLMENT
8 January 2013