Safety of ovarian stimulation

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Fertility preservation for people with cancer > Safety of ovarian stimulation

Clinical Question

In women with cancer does the use of ovarian stimulation for oocyte retrieval increase the risk of cancer recurrence?

Women diagnosed with cancer are often concerned about the safety of ovarian stimulation for oocyte retrieval and fertility preservation. The role of hormones in breast cancer has ensured the majority of studies on the impact of ovarian stimulation on cancer recurrence have examined outcomes in breast cancer patients. High quality evidence from randomised controlled trials of ovarian stimulation is unlikely in this setting due to ethical considerations.

Two prospective cohort studies have examined the question in breast cancer patients. The first study examined 215 women recently diagnosed with breast cancer. Controlled ovarian stimulation was performed with letrozole and gonadotropins in 79 women, with 136 women serving as controls. The study found that ovarian stimulation was unlikely to result in recurrence of breast cancer, although follow-up longer than two years is necessary to confirm these results.[1] A similar study of controlled ovarian stimulation with letrozole in breast cancer patients found that after five years there was no difference between the relapse-free survival of women who were treated for fertility preservation compared to those who were not.[2]

Four retrospective cohort studies of ovarian stimulation in breast cancer patients also came to the same conclusion; no change in recurrence rate for breast cancer patients who underwent ovarian stimulation for fertility preservation.[3][4][5][6] The strength of this conclusion is weakened by the limitations of the studies including low patient numbers, retrospective study design and the use of surrogate markers. The heterogeneous nature of breast cancers and breast cancer treatment also makes predicting individual risk of recurrence difficult.[7]

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Evidence Summary

Evidence summary Level References
Ovarian stimulation for fertility preservation purposes in women with low-risk breast cancer is unlikely to result in cancer recurrence. No data are available for tumour groups outside of breast cancer. II, III-3 [1], [2], [3], [4], [5], [6]


Evidence-based recommendationQuestion mark transparent.png Grade
Women with low-risk breast cancer disease can be reassured that ovarian stimulation for fertility preservation is unlikely to contribute to cancer recurrence after treatment.

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  1. 1.0 1.1 Azim AA, Costantini-Ferrando M, Oktay K. Safety of fertility preservation by ovarian stimulation with letrozole and gonadotropins in patients with breast cancer: a prospective controlled study. J Clin Oncol 2008 Jun 1;26(16):2630-5 Available from:
  2. 2.0 2.1 Kim J, Turan V, Oktay K. Long-Term Safety of Letrozole and Gonadotropin Stimulation for Fertility Preservation in Women With Breast Cancer. J Clin Endocrinol Metab 2016 Apr;101(4):1364-71 Available from:
  3. 3.0 3.1 Chien AJ, Chambers J, Mcauley F, Kaplan T, Letourneau J, Hwang J, et al. Fertility preservation with ovarian stimulation and time to treatment in women with stage II-III breast cancer receiving neoadjuvant therapy. Breast Cancer Res Treat 2017 Aug;165(1):151-159 Available from:
  4. 4.0 4.1 Muñoz E, Domingo J, De Castro G, Lorenzo I, García-Velasco JA, Bellver J, et al. Ovarian stimulation for oocyte vitrification does not modify disease-free survival and overall survival rates in patients with early breast cancer. Reprod Biomed Online 2019 Nov;39(5):860-867 Available from:
  5. 5.0 5.1 Rodriguez-Wallberg KA, Eloranta S, Krawiec K, Lissmats A, Bergh J, Liljegren A. Safety of fertility preservation in breast cancer patients in a register-based matched cohort study. Breast Cancer Res Treat 2018 Feb;167(3):761-769 Available from:
  6. 6.0 6.1 Rosenberg E, Fredriksson A, Einbeigi Z, Bergh C, Strandell A. No increased risk of relapse of breast cancer for women who give birth after assisted conception. Hum Reprod Open 2019;2019(4):hoz039 Available from:
  7. Rodgers RJ, Reid GD, Koch J, Deans R, Ledger WL, Friedlander M, et al. The safety and efficacy of controlled ovarian hyperstimulation for fertility preservation in women with early breast cancer: a systematic review. Hum Reprod 2017 May 1;32(5):1033-1045 Available from:

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A: Clinical question

B: Body of evidence

C: Literature search

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