Letrozole in combination with gonadotropins decreases cancellation rates and improves ongoing pregnancy rates per transfer in poor responders

Abstract

To evaluate the impact of letrozole on follicular recruitment and outcomes in IVF patients with a history of known poor response. Case control study. 19 patients defined as poor responders based on previous IVF performance were treated with letrozole 5 mg/day on cycle days (CD) 2–6. Gonadotropin injections were started on CD3. Suppression, ovulation and egg retrieval were performed according to established protocols. Patients' previous cycles were used as controls. Cycles were divided into two groups: Letrozole with FSH/hMG protocol (19 cycles) and conventional FSH/hMG protocol (38 cycles). Data were evaluated using chi-square for categorical variables and student t test or Mann-Whitney for continuous variables. Statistical analysis was performed with STATA 9.1 and P value of < 0.05 was considered significant. Table summarizes the results. TableVariableConventional-IVF (Cycles = 38)Letrozole-IVF (Cycles = 19)P valueAge (yrs)36.7 ± 2.137.0 ± 1.90.58Cycle cancellation (%)57.9 (22/38)0 (0/19)<0.001FSH/hMG used (IUs)3722 ± 10574484 ± 14670.08E2 day of hCG (pg/mL)757 ± 486731 ± 4180.87Follicles ≥14 mm3.1 ± 2.15.8 ± 2.0<0.001Grade1–2 embryos1.69 ± 1.661.68 ± 2.350.53Embryos transferred2.44 ± 1.12.11 ± 1.10.29Clinical PR (%)7.9 (3/38)21.1 (4/19)0.15Ongoing PR (%)2.6 (1/38)15.8 (3/19)0.02Total SAB rate (%)66 (2/3)25 (1/4)0.27Implantation rate (%)7.69 (3/39)13.2 (5/38)0.42Data presented as mean ± SD. Open table in a new tab Data presented as mean ± SD. In poor responders the addition of letrozole to conventional IVF stimulation was associated with a statistically significant increase in number of follicles and a higher ongoing pregnancy rate. Additionally, the cancellation rate was significantly reduced using the same criteria for egg retrieval (at least 4 follicles ≥14 mm and an estradiol ≥500 pg/ml). Our data suggests a benefit of adding letrozole to FSH/hMG protocols for poor responders. We speculate that the accumulation of intra-ovarian androgens may locally increase FSH receptivity and potentiate IVF stimulation (Mitwally; Fertil Steril, 2002). These findings corroborate previous work that demonstrated similar benefits of letrozole in poor response protocols (Garcia-Velasco; Fertil Steril, 2005). A prospective randomized study is indicated to further define the potential beneficial effect of letrozole in ovarian stimulation protocols.