Immediate versus delayed frozen embryo transfer in patients following a stimulated IVF cycle: a randomised controlled trial

Hum Reprod. 2021 Jun 18;36(7):1832-1840. doi: 10.1093/humrep/deab071.

Abstract

Study question: Is there any difference in the ongoing pregnancy rate after immediate versus delayed frozen embryo transfer (FET) following a stimulated IVF cycle?

Summary answer: Immediate FET following a stimulated IVF cycle produced significantly higher ongoing pregnancy and live birth rate than did delayed FET.

What is known already: Embryo cryopreservation is an increasingly important part of IVF, but there is still no good evidence to advise when to perform FET following a stimulated IVF cycle. All published studies are retrospective, and the findings are contradictory.

Study design, size, duration: This was a randomised controlled non-inferiority trial of 724 infertile women carried out in two fertility centres in China between 9 August 2017 and 5 December 2018.

Participants/materials, setting, methods: Infertile women having their first FET cycle after a stimulated IVF cycle were randomly assigned to either (1) the immediate group in which FET was performed in the first menstrual cycle following the stimulated IVF cycle (n = 362) or (2) the delayed group in which FET was performed in the second or later menstrual cycle following the stimulated IVF cycle (n = 362). All FET cycles were performed in hormone replacement cycles. The randomisation sequence was generated using an online randomisation program with block sizes of four. The primary outcome was the ongoing pregnancy rate, defined as a viable pregnancy beyond 12 weeks of gestation. The non-inferiority margin was -10%. Analysis was performed by both per-protocol and intention-to-treat approaches.

Main results and the role of chance: Women in the immediate group were slightly younger than those in the delayed group (30.0 (27.7-33.5) versus 31.0 (28.5-34.2), respectively, P = 0.006), but the proportion of women ≤35 years was comparable between the two groups (308/362, 85.1% in the immediate group versus 303/362, 83.7% in the delayed group). The ongoing pregnancy rate was 49.6% (171/345) in the immediate group and 41.5% (142/342) in the delayed group (odds ratios 0.72, 95% CI 0.53-0.98, P = 0.034). The live birth rate was 47.2% (163/345) in the immediate group and 37.7% (129/342) in the delayed group (odds ratios 0.68, 95% CI 0.50-0.92, P = 0.012). The miscarriage rate was 13.2% (26 of 197 women) in the immediate group and 24.2% (43 of 178 women) in the delayed group (odds ratios 2.10; 95% CI 1.23-3.58, P = 0.006). The multivariable logistic regression, which adjusted for potential confounding factors including maternal age, number of oocytes retrieved, embryo stage at transfer, number of transferred embryos/blastocysts, reasons for FET, ovarian stimulation protocol and trigger type, demonstrated that the ongoing pregnancy rate was still higher in the immediate group.

Limitations, reason for caution: Despite randomisation, the two groups still differed slightly in the age of the women at IVF. The study was powered to consider the ongoing pregnancy rate, but the live birth rate may be of greater clinical interest. Conclusions relating to the observed differences between the treatment groups in terms of live birth rate should, therefore, be made with caution.

Wider implications of the findings: Immediate FET following a stimulated IVF cycle had a significantly higher ongoing pregnancy and live birth rate than delayed FET. The findings of this study support immediate FET after a stimulated IVF cycle.

Study funding/competing interest(s): No external funding was used and no competing interests were declared.

Trial registration number: ClinicalTials.gov identifier: NCT03201783.

Trial registration date: 28 June 2017.

Date of first patient’s enrolment: 9 August 2017.

Keywords: IVF; embryo transfer; frozen embryo transfer; infertility; ongoing pregnancy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Birth Rate
  • China
  • Embryo Transfer
  • Female
  • Fertilization in Vitro
  • Humans
  • Infertility, Female* / therapy
  • Live Birth
  • Ovulation Induction
  • Pregnancy
  • Pregnancy Rate
  • Retrospective Studies

Associated data

  • ClinicalTrials.gov/NCT03201783