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Letrozole Reduces Estrogen and Gonadotropin Exposure in Women with Breast Cancer Undergoing Ovarian Stimulation before Chemotherapy

Fertility Preservation Program (K.O., A.H., G.S., O.O., B.S., A.C.), Center for Reproductive Medicine and Infertility, and Department of Public Health (H.B.), Division of Biostatistics and Epidemiology, Weill Medical College of Cornell University, New York, New York 10021

Address all correspondence and requests for reprints to: Kutluk Oktay, M.D., F.A.C.O.G., Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University, 505 East 70th Street, Suite HT300, New York, New York 10021. E-mail: kuo9001{at}med.cornell.edu.

Context: Women with breast cancer are not typically offered embryo or oocyte cryopreservation to preserve their fertility before chemotherapy because of the potential risks associated with high estrogen levels arising from ovarian stimulation.

Objective: We aimed to determine whether the combination of an aromatase inhibitor with gonadotropin treatment in breast cancer patients produces comparable results to standard in vitro fertilization (IVF), without a significant increase in estradiol levels and delay in the initiation of chemotherapy.

Patients and Methods: Stages I-IIIA breast cancer patients (n = 47) received 5 mg/d letrozole and 150–300 IU FSH to cryopreserve embryos or oocytes. Age-matched retrospective controls (n = 56) were selected from women who underwent IVF for tubal disease.

Results: Whereas letrozole and FSH stimulation resulted in significantly lower peak estradiol levels (mean ± SD 483.4 ± 278.9 vs. 1464.6 ± 644.9 pg/ml; P < 0.001) and 44% reduction in gonadotropin requirement, compared with controls, the length of stimulation, number of embryos obtained, and fertilization rates were similar. The human chorionic gonadotropin administration criteria had to be adjusted to 20 mm after letrozole stimulation, compared with 17–18 mm in the controls. The mean delay from surgery to cryopreservation was 38.6 d, with 81% of all patients completing their IVF cycles within 8 wk of surgery.

Conclusion: Ovarian stimulation with letrozole and FSH appears to be a cost-effective alternative for fertility preservation in breast cancer patients with reduced estrogen exposure, compared with standard IVF. If patients are referred promptly, they may undergo embryo or oocyte cryopreservation without a delay in chemotherapy.

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