Preparing and Timing of the Endometrium in Modified Natural Cycle Frozen-thawed Embryo Transfers

Summary

The increasing use of FET emphasizes the importance of preparing and timing the endometrium in FET cycles, however there is no consensus on luteal phase progesterone supplementation in mNC-FET and the optimal day of blastocyst warming and transfer. The aim of this multicenter RCT is to assess the effect of progesterone supplementation in hCG-triggered mNC-FET and the effect of embryo thawing and transfer at hCG+6 or hCG+7 days, respectively. In total 604 patients will be included with n=151 in each of the four study arms. The primary outcome is live birth rate per transfer (LBR) and the goal is to show a 10% increase in LBR after progesterone supplementation and to assess whether blastocyst warming+transfer 6 days after hCG trigger is superior to 7 days after hCG trigger in mNC-FET.

Timeline

Start

2019-01-06

Primary completion

2024-12-31

Completion

2024-12-31

Publications

• Saupstad M, Colombo C, Bergenheim SJ, Pistoljevic-Kristiansen N, Dam TV, Bogstad JW, Praetorius L, Freiesleben NC, Klajnbard A, Oxlund-Mariegaard B, Humaidan P, Lokkegaard ECL, Husth M, Knudsen UB, Gabrielsen A, Forman JL, Petersen MR, Lossl K, Pinborg A. Optimizing the protocol for modified natural cycle frozen embryo transfer (mNC-FET): a multicentre, single-blinded randomized controlled trial. Hum Reprod Open. 2026 Jan 13;2026(1):hoag003. doi: 10.1093/hropen/hoag003. eCollection 2026.
• Colombo C, Pistoljevic-Kristiansen N, Saupstad M, Bergenheim SJ, Spangmose AL, Klajnbard A, la Cour Freiesleben N, Lokkegaard EC, Englund AL, Husth M, Breth Knudsen U, Alsbjerg B, Praetorius L, Lossl K, Schmidt L, Pinborg A. Does luteal phase progesterone supplementation affect physical and psychosocial well-being among women undergoing modified natural cycle-FET? A sub-study of a randomized controlled trial. Hum Reprod. 2023 Oct 3;38(10):1970-1980. doi: 10.1093/humrep/dead171.
• Saupstad M, Freiesleben NC, Skouby SO, Andersen LF, Knudsen UB, Petersen KB, Husth M, Egeberg A, Petersen MR, Ziebe S, Andersen AN, Lossl K, Pinborg A. Preparation of the endometrium and timing of blastocyst transfer in modified natural cycle frozen-thawed embryo transfers (mNC-FET): a study protocol for a randomised controlled multicentre trial. BMJ Open. 2019 Dec 15;9(12):e031811. doi: 10.1136/bmjopen-2019-031811.

Drugs

Indications