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FREEZE ALL UPDATE

Easy on the ice: SART cohort study finds limited gains from freeze-all strategy

freeze-all

Published 20 September 2018

Only high responders were found to benefit, otherwise freeze-all approach associated with lower live birth rates than fresh transfers

Despite enthusiasm by many clinics - and small-study reports of improved results - the evidence in favour of freezing all embryos before transfer remains patchy - and hotly debated. Now, giving a little more direction, if not conclusion, to the ongoing debate comes a retrospective analysis of almost 83,000 cycles from the SART database (of 2014-2015) in which outcomes from initial fresh non-donor IVF cycles (n = 69,102) were compared with first frozen cycles after a freeze-all IVF stimulation (n = 13,833).(1) For the first time, results were stratified according to high, intermediate and low responders.

But once again, largely as expected, the results give no firm swing of balance in favour of freeze-all. The study found that freeze-all cycles had higher pregnancy rates than fresh transfers only in high responders (61% vs 57.4%). Otherwise freeze-all transfers were not found beneficial, and indeed were associated with lower pregnancy and live birth rates in intermediate and low responders. Specifically, both clinical pregnancy and ;ive birth rates in intermediate responders were higher after fresh embryo transfer than after freeze-all (49.6% vs 44.2%; 41.2 vs 35.3%). And similarly, pregnancy and live birth rates in poor responders were higher after fresh than after freeze-all transfers (33.2% vs 15.9%; 25.9% vs 11.5%). The results, say the investigators, 'thus refute the idea that freeze-all cycles are preferable for all patients'.

A Cochrane review and meta-analysis of 2017 combining four trials of fresh versus frozen transfers found no clear difference between cumulative LBR in the two strategies, although they did find lower rates of OHSS and miscarriage in the frozen cycles.(2) Similarly, two large randomised trials published in the same issue of the New England Journal of Medicine earlier this year failed to find any difference in outcome between the fresh and freeze-all transfers.(3,4) Commenting in response to these two NEJM reports, Christos Coutifaris, President of the ASRM, said that 'to apply the rule to everybody that we should freeze your embryos is probably not correct'.

The SART investigators do note that in their study it was not possible to distinguish between the elective and non-elective freeze-all cycles, which may offer some explanation for the mainly neutral results. 'Perhaps low responders who need FET due to premature luteinization (despite a low number of follicles) represent a poor-prognosis cohort,' they write, suggesting that this might drive the decreased LBRs in freeze-all poor responders. By contrast, they note, some recent studies of elective freeze-all only cycles do show better results.

1. Acharya KS, Acharya CR, Bishop K, et al. Freezing of all embryos in in vitro fertilization is beneficial in high responders, but not intermediate and low responders: an analysis of 82,935 cycles from the Society for Assisted Reproductive Technology registry. Fertil Steril 2018; doi:10.1016/j.fertnstert.2018.05.024
2. Wong KM, van Wely M, Mol F, et al. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev 2017; 3: CD011184.
3. Shi Y, Sun Y, Hao C, et al. Transfer of fresh versus frozen embryos in ovulatory women. N Engl J Med 2018; 378: 126-136.
4. Vuong LN, Dang VQ, Ho TM, et al. IVF transfer of fresh or frozen embryos in women without polycystic ovaries. N Engl J Med 2018; 378: 137-147.