Cocktail treatment by GnRH-antagonist, letrozole, and mifepristone for the prevention of ovarian hyperstimulation syndrome: a prospective randomized trial

Abstract

Objective

This study is aimed to determine the efficacy of a cocktail style treatment by combining GnRH-antagonist, letrozole, and mifepristone on the prevention of ovarian hyperstimulation syndrome (OHSS) in high-risk women.

Methods

This prospective, randomized controlled clinical trial was performed between January 2018 and December 2018. A total of 170 women who identified as high risk of OHSS during the ovarian hyperstimulation and underwent cryopreservation of whole embryos. On the day of oocyte retrieval, the combination group received 0.25 mg Cetrorelix for 3 d, 5 mg letrozole for 5 d, and 50 mg mifepristone for 3 d, the mifepristone group received 50 mg mifepristone for 3 d. A total of 156 cases were included in final analysis. All the frozen embryo transfer (FET) cycles were followed up until December 2021.

Results

The combination group showed significantly decreased incidence of moderate and severe OHSS than mifepristone group (20.5% vs. 42.3%), with remarkably reduced serum estradiol level on hCG + 3 and + 5 d, decreased ovarian diameter, and shortened luteal phase. Oocyte retrieval number, levels of estradiol on hCG + 0 and VEGF, and ovarian diameter on hCG + 5 were associated with the severity of the symptoms. There was no significant difference in cumulative live birth rates (LBRs) between the combination and mifepristone group (74.4% vs. 76.9%).

Conclusions

The combination treatment effectively reduces the incidence of moderate/severe OHSS in high-risk women.

Keywords:

• Ovarian hyperstimulation
• estradiol
• vascular endothelial growth factor
• luteolysis

Acknowledgments

We thank all the staffs in the Center for Reproductive Medicine, Renmin Hospital of Wuhan University for their help in clinical works.

Disclosure statement

The authors declare no conflict of interest.

Institutional review board statement

This is a prospective randomized controlled trial (Registration number: ChiCTR-INR-17014174) registered at the China Clinical Trials Registry (www.chictr.org.cn) on 2017-12-27 (indicated as Date of Registration on the Registration page), which was approved by Ethics Committee of Clinical Trials in Wuhan University Renmin Hospital (Reference number: 2018K-C001), the first participant was enrolled on 2018-01-01.

Informed consent statement

All participants signed informed consent before the enrollment.

Consent for publication

Not applicable.

Authors’ contribution

Conceptualization, Qingzhen Xie and Qianrong Qi; methodology, Yaqin Wang; software, Yi Xia; validation, Qianrong Qi, Yi Xia. and Jin Luo; formal analysis, Qianrong Qi; investigation, Yaqin Wang; resources, Qingzhen Xie; data curation, Yi Xia; writing – original draft preparation, Qianrong Qi; writing – review and editing, Qingzhen Xie; supervision, Yaqin Wang; project administration, Qingzhen Xie; funding acquisition, Qianrong Qi and Qingzhen Xie; All authors have read and agreed to the published version of the manuscript.

Clinical trial registration information

Date of registration: 12-27-2017

Date of initial participant enrollment: 01-01-2018

Clinical trial identification number: ChiCTR-INR-17014174

URL of the registration site: www.chictr.org.cn

Availability of data and materials

Not applicable.

Additional information

Funding

This study was supported by Guide Funding from Renmin Hospital of Wuhan University (RMYD2018M42, RMYD2018Z13), Innovation Funding from Medical School of Wuhan University (TFZZ2018023), and Research Funding from Hubei Health Department (WJ2019M181).