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. 2024 Jul 3;14(7):e082879.
doi: 10.1136/bmjopen-2023-082879.

Rectal versus vaginal progesterone administration for luteal phase support in the hormone replacement therapy frozen embryo transfer (HRT-FET) cycle: protocol for a non-inferiority randomised controlled trial

Birgit Alsbjerg  1   2 , Peter Humaidan  3   2
Affiliations

Rectal versus vaginal progesterone administration for luteal phase support in the hormone replacement therapy frozen embryo transfer (HRT-FET) cycle: protocol for a non-inferiority randomised controlled trial

Birgit Alsbjerg et al. BMJ Open. .

Abstract

Introduction: This study compares rectal administration with vaginal administration of progesterone as luteal phase support in hormone replacement therapy frozen embryo transfer (HRT-FET) cycles. The reason for comparing the two routes of administration is that rectal administration has been suggested to be more patient friendly.

Methods and analysis: This study is a randomised controlled trial comparing the ongoing pregnancy rate (OPR) at week 12 in HRT-FET cycles after rectal administered progesterone as the only administered progesterone compared with a vaginal luteal phase support regimen. All patients are enrolled from a Danish public fertility clinic and randomised to one of two groups, with 305 patients receiving embryo transfer assigned to each group. Endometrial preparation includes 6 mg oestradiol daily. The intervention group receives rectally administered progesterone (400 mg/12 hours) and the control group receives vaginally administered progesterone (400 mg/12 hours). If P4 is <35 nmol/L on blastocyst transfer day an additional rectal luteal phase rescue regimen is started (control group). Thawing and transferring of a single autologous vitrified blastocyst is scheduled on the sixth day of progesterone administration in both groups. The power calculation is based on a non-inferiority analysis with an expected OPR in both groups of 44% and the upper limit of a one-sided 95% CI will exclude a difference in favour of the control group of more than 10.0%. An interim analysis will be conducted once half of the study population has been enrolled.

Ethics and dissemination: The trial was approved on 21 November 2023 by the Danish National Ethical Committee and the Danish Medicines Agency and is authorised by the Clinical Trials Information System (EUCT number 2023-504616-15-02). All patients will provide informed consent before being enrolled in the study. The results will be published in an international journal.

Trial registration number: EUCT number: 2023-504616-15-02.

Keywords: maternal medicine; reproductive medicine.

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Conflict of interest statement

Competing interests: The study group has no personal economic interest in the project. Furthermore, Gedeon Richter Nordic was not involved in planning or designing the study and will not be involved in study flow, analysis or reporting. BA has received unrestricted grants from Gedeon Richter Nordic and Merck and honoraria for lectures from Gedeon Richter, Merck, IBSA and Marckyrl Pharma. PH has received honoraria for lectures from Gedeon Richter, Merck and IBSA.

Figures

Figure 1
Figure 1
Study treatments. *The primary endpoint. Ongoing pregnancy week 12. ET, embryo transfer; P4, serum progesterone measurement.
Figure 2
Figure 2
Study profile.
See this image and copyright information in PMC

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