Live birth rates after different endometrial preparation methods in frozen cleavage-stage embryo transfer cycles: a randomized controlled trial

  • Tahereh Madani
  • Fariba Ramezanali
  • Azar Yahyaei
  • Fatemeh Hasani
  • Narges Bagheri Lankarani
  • Ladan Mohammadi YeganehEmail author
Gynecologic Endocrinology and Reproductive Medicine



This study aimed to compare the clinical outcomes in different endometrial preparation methods prior to frozen embryo transfer (FET) in women with normal menstrual cycles.


A total of 471 eligible patients were randomly allocated into four groups of endometrial preparation prior to FET: natural cycle with spontaneous ovulation (n = 120), natural cycle with human chorionic gonadotropin (hCG) for ovulation induction (n = 117), hormone replacement cycle (HRC) (n = 113) and HRC with pre-treatment with GnRH-a (n = 121). Natural cycle with hCG also received hCG in luteal phase. The primary outcome was live birth rate. The secondary outcomes included implantation, biochemical and clinical pregnancy, ongoing pregnancy, and late miscarriage rates. Data analysis included t test, ANOVA and χ2.


There were no statistically significant differences in the mean age (p = 0.31), duration (p = 0.43) and cause of infertility (p = 0.77) and the number (p = 0.33) and quality (p = 0.21) of embryos transferred between the groups. No significant differences regarding the implantation rates per embryo transfer (p = 0.97) and biochemical pregnancy rates (p = 0.90) were observed between the groups. The rates of clinical pregnancy were 34.2%, 32.5%, 31% and 36.4% in the natural cycle, natural with hCG, HRC and HRC with GnRH-a groups, respectively (p = 0.83). Ongoing pregnancy (p = 0.89) and miscarriage (p = 0.33) rates were comparable between groups. The rate of live birth was 30.8% in the natural group, 30% in the natural with hCG, 27.4% in the HRC and 31.4% in the HRC with GnRH-a groups (p = 0.91).


Four different types of endometrial preparation methods for FET cycles appear to be equally effective in terms of implantation, pregnancy, miscarriage and live birth rates in women with normal menstrual cycles.

Clinical Trial Registration Number: NCT02251925.


Endometrial preparation Frozen embryo transfer Hormone replacement cycle Natural cycle Pregnancy outcomes 



Authors would like to thank Miss Maryam Mohammadi for statistical support, the staff of Royan institute for their assistance in this study and the women who participated in this study.

Author contributions

TM: provided clinical expertise and supervision, protocol/project development, and manuscript editing/writing; FR: provided clinical expertise and supervision, protocol/project development, and manuscript editing; AY: data collection/management; FH: data collection/management; NBL: data analysis and manuscript editing; LMY: project development, study design, data analysis, and manuscript writing.


No financial support has been granted.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All the procedures performed in studies involving human participants were in accordance with the ethical standards committee of the Royan Institute and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Ethics Approval Code EC/91/1087.

Informed consent

Informed consent was obtained from all the individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research CenterRoyan Institute for Reproductive Biomedicine, ACECRTehranIran
  2. 2.Department of Embryology, Reproductive Biomedicine Research CenterRoyan Institute for Reproductive Biomedicine, ACECRTehranIran
  3. 3.Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research CenterRoyan Institute for Reproductive Biomedicine, ACECRTehranIran

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