Concomitant tamoxifen or letrozole for optimal oocyte yield during fertility preservation for breast cancer: the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) randomized clinical trial.

Purpose To determine whether concomitant tamoxifen 20 mg with gonadotropins (tamoxifen-gonadotropin) versus letrozole 5 mg with gonadotropins (letrozole-gonadotropin) affects mature oocyte yield.

Open-label, single-institution, randomized trial. Inclusion criteria included the following: females, ages 18–44 years old, with new diagnosis of non-metastatic breast cancer, who were undergoing fertility preservation with either oocyte or embryo cryopreservation. Those with estrogen-receptor-positive (ER+) breast cancer were randomized to tamoxifen-gonadotropin or letrozole-gonadotropin. Another group with estrogen-receptor-negative (ER−) breast cancer was recruited, as a prospectively collected comparison arm who took neither letrozole nor tamoxifen (gonadotropin only). The primary outcome was the number of mature oocytes obtained from the cycle. The randomized groups were powered to detect a difference of three or more mature oocytes.

Forty-five patients were randomized to tamoxifen-gonadotropin and fifty-one to letrozole-gonadotropin. Thirty-eight patients completed gonadotropin only. Age, antral follicle count, and body mass index were similar between the randomized groups. Our primary outcome of mature oocyte yield was similar between the tamoxifen-gonadotropin and letrozole-gonadotropin groups (12±8.6 vs. 11.6±7.5, p=0.81, 95%CI of difference =−2.9 to 3.7). In a pre-specified secondary comparison, mature oocyte yield was also similar with tamoxifen-gonadotropin or letrozole-gonadotropin versus gonadotropin only (12±8.6 vs. 11.6±7.5 vs. 12.4±7.2). There were no serious adverse events in any of the groups.

Tamoxifen-gonadotropin and letrozole-gonadotropin produced a similar number of mature oocytes. Women who received either tamoxifen-gonadotropin or letrozole-gonadotropin had a similar number of oocytes to the gonadotropin-only group. Trial registration NCT03011684 (retrospectively registered 1/5/2017, after 9% enrolled) Similar content being viewed by others Data availability The data from our manuscript have not been deposited in a data repository.

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This study was supported by internal departmental research funds. Code availability N/A Funding This study was supported by departmental research funding within the University of California, San Francisco Department of Obstetrics, Gynecology, and Reproductive Sciences. Author information Authors and Affiliations Contributions JL’s roles included study design, recruitment, data collection, data analysis, and manuscript writing. F J-H and KW’s roles included recruitment, data collection, and manuscript writing. SR and AW’s roles included data collection and manuscript writing. CM’s roles included data analysis and manuscript writing. EML’s roles included recruitment and manuscript writing. MD’s roles included study design and manuscript writing. AJC’s roles included study design and manuscript writing. MIC’s roles included study design and manuscript writing. MR’s roles included study design, recruitment, data analysis, and manuscript writing. Corresponding author Ethics declarations Ethics approval All study procedures were approved by the University of California, San Francisco Committee on Human Research. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Conflict of interest The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Letourneau, J., Juarez-Hernandez, F., Wald, K. et al. Concomitant tamoxifen or letrozole for optimal oocyte yield during fertility preservation for breast cancer: the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) randomized clinical trial. J Assist Reprod Genet 38, 2455–2463 (2021). https://doi.org/10.1007/s10815-021-02273-3 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10815-021-02273-3