I have read with interest the study of Coates et al, receptlty published in this journal. The authors aim to compare two commonly used protocols (fresh vs. vitrified) used to transfer euploid blastocysts after IVF with preimplantation genetic screening. The authors conclude that either treatment protocol investigated in the present study can be a reasonable option for patients and that their findings suggest a trend toward favoring the freeze-all option as a preferred transfer strategy when using known euploid embryos. In the “Material and methods” section it is descrideb the uterine preparation for the frozen ET cycle : “Estradiol valerate (4 mg/d; Delestrogen, JHP pharmaceuticals) .by IM injection was started 5–7 days after the last OC pill, increasing by 1 mg each injection until dosage of 6 mg twice weekly was reached and the endometrium measured a minimum of 7.5 mm thickness . Then P in oil (Watson) was commenced at a dose of 50 mg/d IM for the initial 2 days and increased to 100 mg/d thereafter. Frozen thawed ET was performed on the seventh day of P injections. I was confused by this treatment schedule. I would appreciate clarification. It is important to describe precisely the uterine preparation used for the ET, as it can have an impact in implantation, endometrial receptivity (1, 2), regardless of transfering euploid embryos. References 1. Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozenthawed embryo transfer in normal responders. Fertil Steril 2011;96:344–8. 2. Evans J, Hannan NJ, Edgell TA, Vollenhoven BJ, Lutjen PJ, Osianlis T, Salamonsen LA, Rombauts LJ. Fresh versus frozen embryo transfer: backing clinical decisions with scientific and clinical evidence. Hum Reprod Update. 2014 Nov-Dec;20(6):808-21. doi: 10.1093/humupd/dmu027. Epub 2014 Jun 10.

Thank you for this very interesting paper. I believe RCT of fresh versus frozen embryos is one of the most pressing questions our field can answer presently. I have one concern with these results. It is not clearly stated anywhere in the paper how many embryos were transferred between the two randomized groups and this could clearly be a large confounder. When looking at table 4 one can calculate that the fresh group had 67 embryos transferred whereas the frozen group had 97 embryos transferred. Both group had a similar number of patients with single embryo transfer, but the frozen group had 1.7 times the number of double embryo transfers. So I question if the results of this paper demonstrate that FET is superior to fresh or simply that transferring more embryos increases live birth rate? Indeed the implantation rates were similar between the two groups (P=0.20) suggesting that the latter explains the difference found in this study. Perhaps it may well turn out that FET is superior to fresh transfer. I think it will take larger studies to adequately investigate this question. If there is a difference there, it is likely smaller than the 22% absolute increase in this study, which I think may be largely explained by the double embryo transfer bias in the frozen group.