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

Abstract

Research questionWill two boluses of gonadotrophin-releasing hormone agonist (GnRHa) during hormone replacement therapy–frozen embryo transfer (HRT–FET) cycles reduce the total pregnancy loss rate? DesignRandomized 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. ResultsThe 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). ConclusionsAlthough 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.