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

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

Abstract

Purpose

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).

Methods

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.

Results

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%).

Conclusions

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.

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Abbreviations

AMH:

Anti-Müllerian hormone

ART:

Assisted reproductive technology

BMI:

Body mass index

CI:

Confidence interval

COCs:

Cumulus–oocyte complexes

COH:

Controlled ovarian hyperstimulation

E2:

Estradiol 2

FET:

Frozen embryo transfer

GnRH:

Gonadotropin-releasing hormone

hCG:

Human chorionic gonadotropin

HMG:

Human menopausal gonadotropin

HRT:

Hormone replacement therapy

IVF:

In vitro fertilization

ICSI:

Intra-cytoplasmic sperm injection

LH:

Luteinizing hormone

OHSS:

Ovarian hyperstimulation syndrome

P4:

Progesterone

PPOS:

Progestin-primed ovarian stimulation

SD:

Standard deviation

USD:

United States dollar

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Reproductive Health, Kamiya Ladies Clinic, Nittsu Bldg 2nd Floor 2-1, Nishi 2chome, Kita 3jo, Chuo-ku, Sapporo, Hokkaido, 060-0003, Japan

    Nanako Iwami, Miho Kawamata, Naoko Ozawa, Takahiro Yamamoto, Eri Watanabe, Osamu Moriwaka & Hirobumi Kamiya

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  1. Nanako Iwami
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Contributions

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.

Corresponding author

Correspondence to Nanako Iwami.

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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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Iwami, N., Kawamata, M., Ozawa, N. et al. New trial of progestin-primed ovarian stimulation using dydrogesterone versus a typical GnRH antagonist regimen in assisted reproductive technology. Arch Gynecol Obstet 298, 663–671 (2018). https://doi.org/10.1007/s00404-018-4856-8

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  • DOI: https://doi.org/10.1007/s00404-018-4856-8

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