Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis

Pedro Melo, Yealin Chung, Oonagh Pickering, Malcolm Price, Simon Fishel, Mohammed Khairy, Charles Kingsland, Philip Lowe, Georgios Petsas, Madhurima Rajkhowa, Victoria Sephton, Amanda Tozer, Simon Wood, Elena Labarta, Mark Wilcox, Adam Devall, Ioannis Gallos, Arri Coomarasamy

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Objective: To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes.

Design: Systematic review and meta-analysis.

Setting: Not applicable.

Patient(s): Women undergoing FET.

Intervention(s): We conducted electronic searches of MEDLINE, PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science,, and grey literature (not widely available) from
inception to March 2021 to identify cohort studies in which the serum luteal progesterone level was measured around the time of FET.

Main Outcome Measure(s): Ongoing pregnancy or live birth rate, clinical pregnancy rate, and miscarriage rate.

Result(s): Among the studies analyzing serum progesterone level thresholds <10 ng/mL, a higher serum progesterone level was associated with increased rates of ongoing pregnancy or live birth (relative risk [RR] 1.47, 95% confidence interval [CI] 1.28 to 1.70), higher
chance of clinical pregnancy (RR 1.31, 95% CI 1.16 to 1.49), and lower risk of miscarriage (RR 0.62, 95% CI 0.50 to 0.77) in cycles using
exclusively vaginal progesterone and blastocyst embryos. There was uncertainty about whether progesterone thresholds R10 ng/mL
were associated with FET outcomes in sensitivity analyses including all studies, owing to high interstudy heterogeneity and wide CIs.

Conclusion(s): Our findings indicate that there may be a minimum clinically important luteal serum concentration of progesterone
required to ensure an optimal endocrine milieu during embryo implantation and early pregnancy after FET treatment. Future clinical trials are required to assess whether administering higher-dose luteal phase support improves outcomes in women with a low serum
progesterone level at the time of FET.

PROSPERO Number: CRD42019157071 (Fertil Steril 2021;-:-–-. 2021 by American Society for Reproductive Medicine.)
Original languageEnglish
Pages (from-to)1534-1556
JournalFertility and Sterility
Issue number6
Early online date10 Aug 2021
Publication statusE-pub ahead of print - 10 Aug 2021

Bibliographical note

Funding Information:
Supported by a doctoral research fellowship awarded by the Tommy's Charity and the University of Birmingham (to P.M.). M.J.P. is supported by the National Institute for Health Research Birmingham Biomedical Research Centre. P.M. has nothing to disclose. Y.C. has nothing to disclose. O.P. has nothing to disclose. M.J.P. has nothing to disclose. S.F. is a minor shareholder of CARE Fertility, but has no financial or other interest with progesterone testing or manufacturing companies. M.K. has nothing to disclose. C.K. has nothing to disclose. P.L. reports personal fees from Pharmasure, outside the submitted work. G.P. reports personal fees from Besins Healthcare, outside the submitted work. M.R. has nothing to disclose. V.S. has nothing to disclose. A.T. has nothing to disclose. S.W. has nothing to disclose. E.L. was the lead author in two of the manuscripts in this review (Labarta et al.[ 26]; and Labarta et al.[ 28]). She has additionally received a grant from Ferring in 2020, has provided consultancy services for MSD and Ferring Pharmaceuticals, and is part of the Ferring Pharmaceuticals LIFE program and Merck Global program for Fertility Innovation Leaders. During the past 12 months, E.L. has received honoraria from Angelini/IBSA, Gedeon Richter, and Ferring Pharmaceuticals for lecturing. M.W. reports personal fees from Ferring Pharmaceuticals, outside the submitted work. A.D. has nothing to disclose. I.G. has nothing to disclose. A.C. has conducted two trials evaluating the role of progesterone in miscarriage prevention (the PROMISE trial, published in 2015 [ 85]; and the PRISM trial, published in 2019 [ 75]). However, he has no financial or other interest with progesterone testing or manufacturing companies.

Publisher Copyright:
© 2021 American Society for Reproductive Medicine


  • Endometrial receptivity
  • frozen embryo transfer
  • live birth
  • luteal phase support
  • miscarriage
  • progesterone

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology


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