GnRH-agonist supplementation in Hormonal Replacement Therapy Frozen Embryo Transfer (HRT-FET) cycles - A randomized controlled trial

Abstract Research Question Will two boluses of GnRHa during Hormonal Replacement Therapy Frozen Embryo Transfer (HRT-FET) cycles reduce the total pregnancy loss rate? Design Randomized controlled trial, including a total of 287 HRT-FET cycles performed between 2013 and 2019. After randomization participants allocated to the GnRHa Group (n=144) underwent a standard HRT protocol, supplemented with a total of two boluses of Triptorelin 0.1mg; one bolus 2 days before starting vaginal progesterone and one bolus on the 7th day of progesterone. The Control group (n=143) underwent a standard HRT-FET protocol, only. Results The intention to treat-analysis showed no significant difference in total pregnancy loss between the GnRHa group and the Control group, 21% vs. 33% (RR 0.63, 95% CI [0.35; 1.11]), nor was the biochemical pregnancy loss per positive hCG significantly lower in the GnRHa group (12%, 8/67) compared to (26%, 18/72) the Control group (RR 0.48, 95% CI [0.22; 1.02]). Participants with a live birth had a significantly higher mean progesterone level compared to participants without a live birth 25.0 ±12.2 vs. 23.8 ±8.9 nmol/l (p=0.001). Furthermore, a trend for a higher live birth rate correlated with the highest estradiol quartile level (E2 >0.957 nmol/l). Conclusions Although a difference of 14% in biochemical loss and 12% in total pregnancy loss in favour of GnRHa supplementation was seen this did not reach statistical difference. Luteal progesterone and estradiol levels correlate with live birth rates in the HRT-FET cycle, emphasizing the importance of luteal serum progesterone and estradiol monitoring. Trial registration number: Local ethical committee Central Denmark Region, registration number 1-10-72-249-13. ClinicalTrials.gov NCT01943812.