Immediate versus postponed single blastocyst transfer in modified natural cycle frozen embryo transfer (mNC-FET): a study protocol for a multicentre randomised controlled trial

Abstract

Introduction: Today, it is widespread practice to postpone frozen embryo transfer (FET) in a modified natural cycle (mNC) for at least one menstrual cycle after oocyte retrieval and failed fresh embryo transfer or freeze-all. The rationale behind this practice is the concern that suboptimal ovarian, endometrial or endocrinological conditions following ovarian stimulation may have a negative impact on endometrial receptivity and implantation. However, two recent systematic reviews and meta-analyses based on retrospective data did not support this practice. As unnecessary delay in time to transfer and pregnancy should be avoided, the aim of this study is to investigate if immediate single blastocyst transfer in mNC-FET is non-inferior to standard postponed single blastocyst transfer in mNC-FET in terms of live birth rate.

Methods and analysis: Multicentre randomised controlled non-blinded trial including 464 normo-ovulatory women aged 18-40 years undergoing single blastocyst mNC-FET after a failed fresh or freeze-all cycle. Participants are randomised 1:1 to either FET in the first menstrual cycle following the stimulated cycle (immediate FET) or FET in the second or subsequent cycle following the stimulated cycle (postponed FET). The study is designed as a non-inferiority trial and primary analyses will be performed as intention to treat and per protocol.

Ethics and dissemination: Ethical approval has been granted by the Scientific Ethical Committee of the Capital Region of Denmark (J-nr.: H-19086300). Data will be handled according to Danish law on personal data protection in accordance with the general data protection regulation. Participants will complete written consent forms regarding participation in the study and storage of blood samples in a biobank for future research. The study will be monitored by a Good Clinical Practice (GCP)-trained study nurse not otherwise involved in the study. The results of this study will be disseminated by publication in international peer-reviewed scientific journals.

Trial registration number: NCT04748874; Pre-results.

Keywords: clinical trials; reproductive medicine; subfertility.

Conflict of interest statement

Competing interests: ABP and KL has received a research grant from Merck supporting the present study. SJB has received a research grant from Rigshospitalet’s research fund supporting the present study. As a partner of Reprounion, ABP has received a grant from Ferring as well as a research grant from Gedeon Richter. ABP has received consulting fees from Novo Nordisk, honoraria from Merck and Ferring, honoraria as well as support for attending meetings from Gedeon Richter. KL has received honoraria from pharmakon and support for attending meetings from Gedeon Richter. PH has received unrestricted grants from Merck, Gedeon Richter, IBSA, Ferring and MSD as well as honoraria for lectures from Merck and Gedeon Richter. MF has received a research grant from Gedeon Richter. NLCF has received an unrestricted grant from Gedeon Richter, honoraria for lectures from Merck and support for attending meetings by Ferring, Merck and Gedeon Richter. Since 2018, NLCF is head of the steering committee for Danish fertility guidelines.

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