Pregnancy loss after frozen embryo transfer A comparison of three protocols

Frozen-embryo transfer in substituted cycles resulted in higher pregnancy rates but also increased pregnancy loss, leading to similar clinical pregnancy and delivery rates for the protocols studied.

Candido Tomás, M.D., Ph.D., Birgit Alsbjerg, M.D., Hannu Martikainen, M.D., Ph.D., Peter Humaidan, M.D., D.M.Sc.

Volume 98, Issue 5, Pages 1165-1169, November 2012


To compare the reproductive outcome of three protocols for frozen embryo transfer treatment.

Retrospective follow-up study.

Two public clinics and one private clinic.

Four thousand four hundred seventy frozen ET cycles between 2006 and 2010.

Thawing of embryos and embryo transfer.

Main Outcome Measure(s):
Pregnancy test rate, clinical pregnancy rate, and pregnancy loss rate.

The natural cycle followed by P (NC + P) was used in 26% of cycles, the natural cycle with hCG (NC + hCG) in 10%, and the substituted cycle with estrogen and P (E + P) in 64% of cycles. The rate of transfers after thawing was similar in all groups (87.2%, 73.9%, and 87.2%, respectively). There was a significantly higher positive pregnancy test rate in the E + P (34.3%) and NC + hCG (35.5%) cycles as compared with the NC + P cycles (26.7%). However, the clinical pregnancy rate was similar in all groups (27.7%, 29.1%, and 24.3%, respectively). Moreover, no differences were seen between groups regarding the live-birth rate (20.1%, 23.5%, and 20.7%, respectively). A logistic regression analysis showed that the type of protocol was the only predictor of pregnancy loss, while age, irregular cycles, endometrial thickness, number, and quality of embryos transferred did not correlate to pregnancy loss.

A higher positive pregnancy test rate was obtained in E+P FET cycles in comparison to other protocols; however, due to an increased preclinical and clinical pregnancy loss, comparable clinical pregnancy and delivery rates are reported for the three protocols.

  • Congratulations for your work, Candido. I agree with previous comment about the convenience of performing this study as a RCT. My question is about the 3 different protocols, as I don’t know why you supplemented with progesterone in a natural cycle, when, even in those in which you triggered with hCC no progesterone supplementation was used. I think that the main question is if a “completely natural” cycle, without hCG or P, will be the best one, specially at the time of implementing a “freeze all” policy. Thank you, friend.

  • laurenwroth

    This is an interesting study but does not answer the question they set out to answer secondary to its retrospective nature. In order to really answer the question of which protocol for FET is the best, a prospective RCT that has appropriate sample size would need to be undertaken. Additionally, many programs are vitrifying embryos now (rather than using a slow freeze technique) so vitrification would need to be done to make the study more generalizable. It is very interesting that this study showed higher pregnancy loss in 2 groups BUT the groups are not really “the same” so, again, it is difficult to apply this to clinical practice.

    • Thank you for your comments. In truth, the most interesting finding was to realize the high level of early and late pregnancy loss. Now we wonder if there is ways that could decrease this rate. I agree with you concerning RCT 😉 Best regards

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