Originally published as JCO Early Release 10.1200/JCO.2005.05.037 on April 11 2005

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Fertility Preservation in Breast Cancer Patients: A Prospective Controlled Comparison of Ovarian Stimulation With Tamoxifen and Letrozole for Embryo Cryopreservation

From The Center for Reproductive Medicine and Infertility, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY

Address reprint requests to Kutluk Oktay, MD, The Center for Reproductive Medicine and Infertility, Department of Obstetrics and Gynecology, Joan and Sanford I. Weill Medical College of Cornell University, 505 E 70th St, HT-340, New York, NY 10021; e-mail: kuo9001{at}med.cornell.edu

PURPOSE: To develop safe ovarian stimulation methods to perform in vitro fertilization (IVF) in breast cancer patients who wish to preserve their fertility via embryo cryopreservation before chemotherapy.

PATIENTS AND METHODS: Sixty women (age range, 24 to 43 years) with breast cancer were prospectively studied. Twenty-nine patients underwent 33 ovarian stimulation cycles with either tamoxifen 60 mg/d alone (Tam-IVF) or in combination with low-dose follicle-stimulating hormone (TamFSH-IVF) or letrozole 5 mg in combination with FSH (Letrozole-IVF). After IVF, all resultant embryos were cryopreserved to preserve fertility. Recurrence rates were compared with controls (n = 31) who elected not to undergo IVF.

RESULTS: Compared with Tam-IVF, both TamFSH-IVF and Letrozole-IVF patients had greater numbers of follicles (2 ± 0.3 v 6 ± 1 and 7.8 ± 0.9, respectively; P < .0001), mature oocytes (1.5 ± 0.3 v 5.1 ± 1.1 and 8.5 ± 1.6, respectively; P < .001), and embryos (1.3 ± 0.2 v 3.8 ± 0.8 and 5.3 ± 0.8, respectively; P < .001). Peak estradiol (E₂) levels were lower with Letrozole-IVF and Tam-IVF compared with TamFSH-IVF. After 554 ± 31 days (range, 153 to 1,441 days) of follow-up, cancer recurrence rate was similar between IVF and control patients (three of 29 v three of 31 patients, respectively; hazard ratio, 1.5; 95% CI, 0.29 to 7.4), and this estimate was not affected by cancer stage.

CONCLUSION: The combination of low-dose FSH with tamoxifen (TamFSH-IVF) or letrozole (Letrozole-IVF) results in higher embryo yield compared with Tam-IVF. Recurrence rates do not seem to be increased, but the letrozole protocol may be preferred because it results in lower peak E₂ levels.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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