The novel incorporation of aromatase inhibitor in hormonal replacement therapy cycles: a randomized controlled trial

Abstract

Research question: Does the incorporation of the aromatase inhibitor, letrozole, in hormone replacement therapy (HRT) improve the pregnancy outcome in vitrified-warmed blastocyst transfer cycles?

Design: A randomized controlled trial; HRT was used in all cycles. Exogenous oestradiol, 6 mg daily started on day 2 or day 3 of the cycle. Tri-laminar endometrium 9 mm or thicker was the targeted cut-off. Thereafter, participants were randomized into two groups. Group A (HRT plus letrozole): 2.5 mg oral letrozole was given twice daily for 5 days only with continuation of daily oestradiol. Then, daily intramuscular progesterone was started with continuation of oestradiol. Group B (HRT only): daily intramuscular progesterone was administered in addition to daily oestradiol. In both groups, good-quality day-5 blastocyst transfer was planned on the sixth progesterone day with continuation of oestradiol and progesterone. Ongoing pregnancy rate was the primary outcome.

Results: A total of 112 patients were randomized, 56 in each group. Three participants did not have good-quality blastocyst after warming (one in group A and two in group B) and were excluded from the study. Group A and B included 55 and 54 participants, respectively. Ongoing pregnancy rate was significantly higher in group A than group B (RR 1.39, 95% CI 1.04 to 1.86, P = 0.023). Additionally, clinical pregnancy rate was significantly higher in group A (RR 1.31, 95% CI 1.02 to 1.68, P = 0.030).

Conclusions: A new protocol of incorporating letrozole in HRT cycles seems to significantly increase probability of pregnancy, compared with HRT alone.

Keywords: HRT; Letrozole; Vitrified–warmed cycles.