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.