Early initiation of gonadotropin-releasing hormone antagonist treatment results in a more stable endocrine milieu during the mid- and late-follicular phases: a randomized controlled trial comparing gonadotropin-releasing hormone antagonist initiation on cycle day 2 or 6

Objective To compare the effect of initiating GnRH antagonist (GnRH-a) on cycle day (CD) 2 vs. CD 6 on LH, E2 , and P levels in the mid and late follicular phases. Design Nested study within a multicenter randomized controlled trial. Setting Reproductive medicine center in an university hospital. Patient(s) One hundred sixty patients undergoing IVF/intracytoplasmic sperm injection (ICSI). Intervention(s) Recombinant FSH (150–225 IU) was administered daily from CD 2 onward. The study group (CD 2) started GnRH-a cotreatment on CD 2, whereas the control group (CD 6) started on CD 6. Main Outcome Measure(s) The follicular phase endocrine profile. Result(s) The LH levels on CD 6 were lower in the CD 2 group (0.6 ± 0.4 vs. 1.9 ± 1.4 IU/L). The CD 2 group demonstrated both lower E2 levels on CD 6 (520.1 ± 429.6 pmol/L vs. 1,071.7 ± 654.2 pmol/L) and on the day of hCG administration (3,341.4 ± 1,535.3 pmol/L vs. 4,573.2 ± 2,445.4 pmol/L). The P levels did not differ on CD 6 or on the day of hCG administration. Conclusion(s) Early initiation of GnRH-a cotreatment results in a more stable endocrine profile, with more physiological levels of E2 and LH during the follicular phase. The effect on clinical outcomes must be established in larger trials. Clinical Trial Registration Number NCT00866034.