Reproductive outcomes after fertility preservation using tamoxifen or letrozole in women with breast cancer: a long-term follow-up

ObjectiveTo evaluate long-term pregnancy outcomes in young women with breast cancer after ovarian stimulation for fertility preservation, with the addition of tamoxifen or letrozole to standard stimulation vs. no addition.DesignFollow-up study of the STIM-RCT, which was a multicentre randomized open-label trial (NTR4108), and the STIM-cohort study.SubjectsWomen, aged 18–43 years, previously diagnosed with breast cancer who opted for fertility preservation through ovarian stimulation. All surviving women were eligible for follow-up (N = 216) and received an online questionnaire; 141 women from the STIM-RCT and 75 from the STIM-cohort.ExposureWomen receiving ovarian stimulation with the addition of tamoxifen, letrozole, or no addition.Main outcome measuresNatural conception, conception through assisted reproductive technology (ART), pregnancy rates, and live birth rates.ResultsOut of 95 STIM-RCT responders, 36 (38%) received the addition of tamoxifen, 32 (34%) received letrozole, and 27 (28%) no addition (mean follow-up 7 years). Forty-four women became pregnant at least once after cancer treatment, and overall 7 women (7%) used their cryopreserved oocytes or embryos. In total, 63 pregnancies followed, of which 48 (76%) were conceived naturally, i.e., unassisted. Compared with standard ovarian stimulation, adding tamoxifen or letrozole resulted in comparable pregnancy rates in women who had at least one pregnancy after cancer treatment (tamoxifen vs. standard relative risk [RR], 0.92; 95% confidence interval [CI], 0.54–1.58; letrozole vs. standard RR, 0.84; 95% CI, 0.48–1.50), and live birth rates thereafter (tamoxifen vs. standard RR, 0.81; 95% CI, 0.54–1.22; letrozole vs. standard RR, 0.82; 95% CI, 0.53–1.26). In the STIM-cohort, 20 women became pregnant at least once, leading to a total of 30 pregnancies, of which 90% were conceived naturally. One woman used her cryopreserved embryos.ConclusionAfter 7 years of follow-up, most women conceived naturally after cancer treatment, and 8 women used their cryopreserved oocytes or embryos. We found no evidence for a difference in pregnancy rates when adding tamoxifen or letrozole to standard ovarian stimulation compared with no addition.