Letrozole administration during the luteal phase after ovarian stimulation impacts corpus luteum function: a randomized, placebo-controlled trial

Objective: To investigate the effect of letrozole-an oral aromatase inhibitor-on E-2, P, and LH levels when administered during the luteal phase after oocyte retrieval in IVF/intracytoplasmic sperm injection (ICSI) cycles. Design: Prospective, randomized, placebo controlled trial. Setting: University-affiliated private reproductive medicine center. Patient(s): Thirty oocyte donors undergoing standardized controlled ovarian hyperstimulation (COH) protocols. Intervention(s): Patients were randomized after successful egg retrieval to receive either 2.5 mg of letrozole (Femara; Novartis, Barcelona, Spain) or a placebo (folic acid tablets). All donors were under intrauterine device (IUD) contraception. Main Outcome Measure(s): Serum E-2, P, and LH the day of hCG administration and days +4, +7 and +10 after ovum pick-up. Result(s): Donors had a comparable serum E-2 level on the day of hCG administration (1,858 vs. 2,143 pg/mL. Interestingly, levels dramatically dropped 4 days after egg retrieval, reaching a statistically significant lower level in those receiving letrozole (279 vs. 1,586 pg/mL). Again, at the next time points serum E-2 levels were significantly lower (day +7: 240 vs. 855 pg/mL and day +10: 40 vs. 448 pg/mL). No significant differences were observed in P levels, but LH serum concentrations were lower in the control group on day +7 (0.18 vs. 0.02 mIU/mL and day + 10 (0.40 vs. 0.16 mIU/mL), when serum E-2 levels were higher. Conclusion(s): The administration of 2.5 mg of letrozole during the luteal phase has an impact on corpus luteum (CL) function. It reduces serum E-2 levels, which allows a faster recovery of LH concentration. This may be of interest not only for egg donors, but also in patients at high risk of ovarian hyperstimulation syndrome (OHSS) who freeze all their embryos or who cancel hCG administration to reduce the potential risk that high E-2 levels pose. (Fertil Steril (R) 2009;92:222-5. (C) 2009 by American Society for Reproductive Medicine.)