New trial of progestin-primed ovarian stimulation using dydrogesterone versus a typical GnRH antagonist regimen in assisted reproductive technology
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.
KeywordsDydrogesterone Progestin-primed ovarian stimulation Premature LH surge GnRH antagonist Controlled ovarian stimulation
Assisted reproductive technology
Body mass index
Controlled ovarian hyperstimulation
Frozen embryo transfer
Human chorionic gonadotropin
Human menopausal gonadotropin
Hormone replacement therapy
In vitro fertilization
Intra-cytoplasmic sperm injection
Ovarian hyperstimulation syndrome
Progestin-primed ovarian stimulation
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 (http://www.edanzediting.com/ac) for editing drafts of this manuscript.
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.
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 was obtained from all individual participants included in the study.
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