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Duration of estradiol supplementation in luteal phase support for frozen embryo transfer in hormone replacement treatment cycles: a randomized, controlled phase III trial

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

In this study, we intend to evaluate pregnancy outcomes in women who undergo artificial frozen embryo transfer (FET) and stop estradiol (E2) after vaginal ultrasound observation of a gestational sac and heartbeat.

Methods

In this randomized phase III clinical trial, we recruited 291 patients who underwent FET. We randomly assigned 64 pregnant women to a study or a control group after observation of a gestational sac and heartbeat at 6-week gestational age. E2 administration continued until week 12 of gestational age for the control group, but was discontinued for the study group. Progesterone-in-oil administration continued until week 12 of gestational age for both groups. Serum levels for E2 and progesterone were measured on the initial progesterone and embryo transfer (ET) days, and at weeks 6 and 12 of pregnancy in both groups.

Results

The miscarriage rate was 1/32 (3.13%) in the study group and 6/32 (18.75%) in the control group after the intervention and confirmation of a fetal heartbeat. This difference was statistically significant. All patients who remained under intervention, which included 29 in the study group and 24 in the control group, had live births. Although the mean serum E2 and progesterone levels steadily increased from the initial day of progesterone administration to week 12 of gestational age, they were not significantly different between the two groups. Maternal complications were significantly more common in the control group.

Conclusion

Earlier discontinuation of E2 for luteal phase support of FET cycles may be taken into consideration. Additional clinical studies should be conducted to determine an accurate estimation of the time when E2 should be discontinued during FET luteal phase support.

Trial registration

NCT04013438, registered 9 July 2019—Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT04013438?cond=NCT04013438&draw=2&rank=1.

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Acknowledgements

We express our appreciation to all of the participants in this clinical trial.

Funding

This study was funded by a grant from the Reproductive Biomedicine Research Center, Royan Institute, Tehran, Iran (94000295).

Author information

Authors and Affiliations

  1. Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Royan Allay, Eastern Hafez St, Banihashem Sq., Resalat Highway, 1665659711, Tehran, Iran

    Firouzeh Ghaffari & Zahra Chekini

  2. Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

    Samira Vesali

Authors
  1. Firouzeh Ghaffari
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  2. Zahra Chekini
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  3. Samira Vesali
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Contributions

FG study conception, design, administrative support, and literature review. ZC data collection and assembly, and drafted the manuscript. SV conducted statistical analysis of the data. All the authors were involved in revising the manuscript and approved the final version of the manuscript.

Corresponding author

Correspondence to Firouzeh Ghaffari.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This study was approved by the Ethical Committee of Royan Institute. All of the recruited patients signed an informed consent form for study participation.

Informed consent

All of the recruited patients gave their informed consent to participate in this study.

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Ghaffari, F., Chekini, Z. & Vesali, S. Duration of estradiol supplementation in luteal phase support for frozen embryo transfer in hormone replacement treatment cycles: a randomized, controlled phase III trial. Arch Gynecol Obstet 305, 767–775 (2022). https://doi.org/10.1007/s00404-021-06173-w

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  • DOI: https://doi.org/10.1007/s00404-021-06173-w

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