Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: a randomized controlled trial
Freezing all embryos allowsfor inclusion of all blastocysts in the cohort of embryos available for transfer,which also results in a higher proportion of patients reaching embryo transfer. These findings suggest a trend toward favoring the freeze-all option as a preferred transfer strategy when using known euploid embryos.
Volume 107, Issue 3, Pages 723–730
Authors:
Alison Coates, B.Sc., Allen Kung, B.S., Emily Mounts, M.S., John Hesla, M.D., Brandon Bankowski, M.D., Elizabeth Barbieri, M.D., Baris Ata, M.D., Jacques Cohen, Ph.D., Santiago Munné, Ph.D.
Abstract:
Objective
To compare two commonly used protocols (fresh vs. vitrified) used to transfer euploid blastocysts after IVF with preimplantation genetic screening.
Design
Randomized controlled trial.
Setting
Private assisted reproduction center.
Patient(s)
A total of 179 patients undergoing IVF treatment using preimplantation genetic screening.
Intervention(s)
Patients were randomized at the time of hCG administration to either a freeze-all cycle or a fresh day 6 ET during the stimulated cycle.
Main Outcome Measure(s)
Implantation rates (sac/embryo transferred), ongoing pregnancy rates (PRs) (beyond 8 weeks), and live birth rate per ET in the primary transfer cycle.
Result(s)
Implantation rate per embryo transferred showed an improvement in the frozen group compared with the fresh group, but not significantly (75% vs. 67%). The ongoing PR (80% vs. 61%) and live birth rates (77% vs. 59%) were significantly higher in the frozen group compared with the fresh group.
Conclusion(s)
Either treatment protocol investigated in the present study can be a reasonable option for patients. Freezing all embryos allows for inclusion of all blastocysts in the cohort of embryos available for transfer, which also results in a higher proportion of patients reaching ET. These findings suggest a trend toward favoring the freeze-all option as a preferred transfer strategy when using known euploid embryos.
Clinical Trial Registration Number
2 Comments
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.