Safety of Fertility Preservation by Ovarian Stimulation With Letrozole and Gonadotropins in Patients With Breast Cancer: A Prospective Controlled Study

Abstract

Purpose: Because of the accompanying increase in estrogen levels, safety of performing in vitro fertilization (IVF) in women with breast cancer is unknown. Our goal was to determine the effect of controlled ovarian stimulation (COS) using a combination of letrozole with standard fertility medications on disease-free survival in women undergoing embryo or oocyte cryopreservation before adjuvant chemotherapy. Patients and Methods: A total of 215 women with breast cancer were prospectively evaluated for fertility preservation before adjuvant chemotherapy. Of those, 79 elected to undergo COS with letrozole and gonadotropins for embryo or oocyte cryopreservation. The remaining 136 patients underwent no fertility-preserving procedure and served as controls. Results: Study and control groups were similar at enrollment except for a trend for higher estrogen-receptor positivity in the COS group (P = .08). Time between surgery and chemotherapy was longer for IVF patients (45.08 v 33.46 days; P < .01). Peak estradiol levels ranged from 58.4 to 1,166 pg/mL (mean, 405.94 ± 256.64 pg/mL or 1,486.76 ± 942.13 pmol/L) in COS patients. The median follow-up after chemotherapy was 23.4 months (range, 7.5 to 63.6 months) in the COS group and 33.05 months (range, 4.5 to 63.6) in the control group. The hazard ratio for recurrence after IVF was 0.56 (95% CI, 0.17 to 1.9), and the survival was not compromised compared with controls (P = .36). Conclusion: Ovarian stimulation with gonadotropins and letrozole for the purpose of fertility preservation is unlikely to cause substantially increased recurrence risk. Further research, including longer-term follow-up is needed to confirm these findings.