Archives of Gynecology and Obstetrics

, Volume 298, Issue 3, pp 663–671 | Cite as

New trial of progestin-primed ovarian stimulation using dydrogesterone versus a typical GnRH antagonist regimen in assisted reproductive technology

  • Nanako IwamiEmail author
  • Miho Kawamata
  • Naoko Ozawa
  • Takahiro Yamamoto
  • Eri Watanabe
  • Osamu Moriwaka
  • Hirobumi Kamiya
Gynecologic Endocrinology and Reproductive Medicine



To compare the clinical and ongoing pregnancy rates between a protocol using oral dydrogesterone with human menopausal gonadotropin (HMG) for progestin-primed ovarian stimulation (PPOS) and the typical gonadotropin-releasing hormone (GnRH) antagonist regimen in women undergoing controlled ovarian hyperstimulation (COH).


This was a prospective, controlled study of 251 women who underwent COH for in vitro fertilization between October 2016 and July 2017. The patients were allocated alternately into two groups: a dydrogesterone protocol (study group) and a GnRH antagonist protocol (control group). In study group, dydrogesterone (20 mg/day) plus HMG (150 or 225 IU) were administered simultaneously beginning on days 2 or 3 of the menstrual cycle. In both groups, all high-quality embryos were cryopreserved for later transfer. The primary outcome was the ongoing pregnancy rate at 12 weeks per frozen–thawed embryo transfer (FET) and the secondary outcome was the clinical pregnancy rate.


None of the patients experienced a premature luteinizing hormone surge. During the follow-up period, 397 FET cycles were completed. The ongoing pregnancy rates at 12 weeks were 40.0% in study group versus 38.1% in control group (absolute difference 1.9%; 95% CI − 6.83 to 17.2%). The clinical pregnancy rate in study group (52.8%) was also not inferior to that in control group (49.5%; absolute difference 3.3%; 95% CI − 4.02 to 20.2%).


The clinical and ongoing pregnancy rates in study group were comparable to those in control group. Therefore, PPOS with dydrogesterone is a reasonable option to provide COH.


Dydrogesterone Progestin-primed ovarian stimulation Premature LH surge GnRH antagonist Controlled ovarian stimulation 



Anti-Müllerian hormone


Assisted reproductive technology


Body mass index


Confidence interval


Cumulus–oocyte complexes


Controlled ovarian hyperstimulation


Estradiol 2


Frozen embryo transfer


Gonadotropin-releasing hormone


Human chorionic gonadotropin


Human menopausal gonadotropin


Hormone replacement therapy


In vitro fertilization


Intra-cytoplasmic sperm injection


Luteinizing hormone


Ovarian hyperstimulation syndrome




Progestin-primed ovarian stimulation


Standard deviation


United States dollar



The authors wish to thank Ms. Mika Matsuoka for data collection, and Ms. Nami Hirayama and Ms. Yumiko Kobayashi for statistical analysis (clinical staff in the Kamiya Ladies Clinic). We also thank Dr. Shigeo Araki (Chief Director of the International Institute of Medical Technology IMT College) and Dr. Daiki Iwami (staff member of the Department of Renal and Genitourinary Surgery, Hokkaido University, Graduate School of Medicine) for proofreading the manuscript, and Dr. Kota Ono (staff member of the Department of Biostatistics, Hokkaido University, Graduate School of Medicine) as a statistical adviser. We thank Ellen Knapp, PhD, and James Cummins, PhD, from Edanz Group ( for editing drafts of this manuscript.

Author contribution

NI: Protocol development, data analysis, data collection, manuscript writing. MK: Data collection. NO: Data collection. TY: Data collection. EW: Data collection. OM: Data collection. HK: Data collection, protocol development.



Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the Kamiya Ladies Clinic and with the 1964 Helsinki declaration and its later amendments or similar ethical standards.

Informed consent

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


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Reproductive HealthKamiya Ladies ClinicSapporoJapan

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