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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]

Evidence Summary

Evidence summaryLevelReferences
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]


Recommendation

Evidence-based recommendationGrade
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.C


References

  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: http://www.ncbi.nlm.nih.gov/pubmed/18509175.
  2. 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: http://www.ncbi.nlm.nih.gov/pubmed/26751194.
  3. 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: http://www.ncbi.nlm.nih.gov/pubmed/28503722.
  4. 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: http://www.ncbi.nlm.nih.gov/pubmed/31564650.
  5. 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: http://www.ncbi.nlm.nih.gov/pubmed/29098528.
  6. 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: http://www.ncbi.nlm.nih.gov/pubmed/31872070.
  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: http://www.ncbi.nlm.nih.gov/pubmed/28333356.

Body of evidence

In female cancer patients does the use of ovarian stimulation for oocyte retrieval increase the risk of cancer recurrence? In breast cancer patients does the hormone receptor status of the tumor influence this outcome?

CitationLevel of EvidenceQuality of EvidenceSize of EffectNumber of PatientsRelevance of Evidence
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:http://www.ncbi.nlm.nih.gov/pubmed/18509175IILowN/A215N/A
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:http://www.ncbi.nlm.nih.gov/pubmed/28503722III-3LowN/A82N/A
Denschlag D, von Wolff M, Amant F, Kesic V, Reed N, Schneider A, et al. Clinical recommendation on fertility preservation in borderline ovarian neoplasm: ovarian stimulation and oocyte retrieval after conservative surgery. Gynecol Obstet Invest 2010;70(3):160-5 Available from:http://www.ncbi.nlm.nih.gov/pubmed/20558989IVN/AN/A62N/A
Ichinose M, Fujimoto A, Osuga Y, Minaguchi T, Kawana K, Yano T, et al. The influence of infertility treatment on the prognosis of endometrial cancer and atypical complex endometrial hyperplasia. Int J Gynecol Cancer 2013 Feb;23(2):288-93 Available from:http://www.ncbi.nlm.nih.gov/pubmed/23314282 III-3MediumN/A36N/A
Ichinose M, Fujimoto A, Osuga Y, Minaguchi T, Kawana K, Yano T, et al. The influence of infertility treatment on the prognosis of endometrial cancer and atypical complex endometrial hyperplasia. Int J Gynecol Cancer 2013 Feb;23(2):288-93 Available from:http://www.ncbi.nlm.nih.gov/pubmed/23314282 N/AN/AN/AN/AN/A
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:http://www.ncbi.nlm.nih.gov/pubmed/26751194 IILowN/A337N/A
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:http://www.ncbi.nlm.nih.gov/pubmed/31564650 III-3MediumN/A259N/A
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:http://www.ncbi.nlm.nih.gov/pubmed/28333356 III-3HighN/A397N/A
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:http://www.ncbi.nlm.nih.gov/pubmed/29098528 III-3HighN/A188N/A
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:http://www.ncbi.nlm.nih.gov/pubmed/31872070 III-3MediumN/A37N/A
Cancer Council would like to acknowledge the traditional custodians of the land on which we live and work. We would also like to pay respect to the elders past and present and extend that respect to all other Aboriginal people.
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Cancer Council Australia