GnRH agonist supplementation in hormone replacement therapy-frozen embryo transfer cycles: a randomized controlled trial

Research question: Will two boluses of gonadotrophin-releasing hormone agonist (GnRHa) during hormone 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 0.1 mg; 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% versus 33%; relative risk [RR] 0.63, 95% confidence interval [CI] 0.35-1.11), nor was the biochemical pregnancy loss per positive human chorionic gonadotrophin (HCG) significantly lower in the GnRHa group (12%, 8/67) compared with the control group (25%, 18/72) (RR 0.48, 95% CI 0.22-1.02). Participants with a live birth had a significantly higher mean progesterone concentration compared with participants without a live birth (25.0 +/- 12.2 versus 23.8 +/- 8.9 nmol/l; P = 0.001). Furthermore, a trend for a higher live birth rate (LBR) correlated with the highest oestradiol quartile concentration (oestradiol >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 oestradiol concentrations correlate with LBR in the HRT-FET cycle, emphasizing the importance of luteal serum progesterone and oestradiol monitoring.