COH outcomes in breast cancer patients for fertility preservation: a comparison with the expected response by age



Breast cancer is the most common cancer diagnosed during childbearing age, and fertility preservation is becoming increasingly more essential. However, recent studies indicate a possible poorer response to controlled ovarian hyperstimulation (COH) in cancer patients than in non-cancer controls and a negative impact of BRCA mutations on female fertility. This study aims to evaluate ovarian response and the number of mature oocytes (MII) vitrified in women with breast cancer, with or without BRCA mutation, comparing them to the expected response according to an age-related nomogram.


This is a retrospective observational study involving sixty-one breast cancer patients who underwent COH for oocyte cryopreservation. The age-specific nomogram was built using 3871 patients who underwent COH due to oocyte donation, fertility preservation for non-medical reasons, or FIVET for male factor exclusively.


The mean number of oocytes retrieved was 13.03, whereas the mean number of MII oocytes was 10.00. After the application of the z-score, no statistically significant differences were found compared with the expected response in the general population, neither by dividing patients according to the presence or absence of BRCA mutation nor according to the phase in which they initiated stimulation.


The results obtained do not support the notion of a negative impact of the BRCA mutation on the ovarian response of women with breast cancer. Women with breast cancer undergoing COH for fertility preservation can expect the ovarian response predicted for their age.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.

    PubMed  Article  Google Scholar 

  2. 2.

    Torre LA, Islami F, Siegel RL, Ward EM, Jemal A. Global cancer in women: burden and trends. Cancer Epidemiol Biomark Prev. 2017;26(4):444–57.

    Article  Google Scholar 

  3. 3.

    Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol. 2006;24(18):2917–31.

    PubMed  Article  Google Scholar 

  4. 4.

    Decanter C, Morschhauser F, Pigny P, Lefebvre C, Gallo C, Dewailly D. Anti-Mullerian hormone follow-up in young women treated by chemotherapy for lymphoma: preliminary results. Reprod BioMed Online. 2010;20(2):280–5.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Anderson RA, Themmen APN, Qahtani AA, Groome NP, Cameron DA. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum Reprod. 2006;21(10):2583–92.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Letourneau JM, Ebbel EE, Katz PP, Oktay KH, McCulloch CE, Ai WZ, et al. Acute ovarian failure underestimates age-specific reproductive impairment for young women undergoing chemotherapy for cancer. Cancer. 2012;118(7):1933–9.

    PubMed  Article  Google Scholar 

  7. 7.

    Kil WJ, Ahn SD, Shin SS, Lee SW, Choi EK, Kim JH, et al. Treatment-induced menstrual changes in very young (<35 years old) breast cancer patients. Breast Cancer Res Treat. 2006;96(3):245–50.

    PubMed  Article  Google Scholar 

  8. 8.

    Oktay K, Harvey BE, Partridge AH, Quinn GP, Reinecke J, Taylor HS, et al. Fertility preservation in patients with Cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018;36(19):1994–2001.

    PubMed  Article  Google Scholar 

  9. 9.

    Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge AH, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31(19):2500–10.

    PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    Martinez F. Update on fertility preservation from the Barcelona International Society for Fertility Preservation-ESHRE-ASRM 2015 expert meeting: indications, results and future perspectives. Hum Reprod. 2017;32(9):1802–11.

    PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Domingo J, Guillén V, Ayllón Y, Martínez M, Muñoz E, Pellicer A, et al. Ovarian response to controlled ovarian hyperstimulation in cancer patients is diminished even before oncological treatment. Fertil Steril. 2012;97(4):930–4.

    PubMed  Article  Google Scholar 

  12. 12.

    Klock SC, Zhang JX, Kazer RR. Fertility preservation for female cancer patients: early clinical experience. Fertil Steril. 2010;94(1):149–55.

    PubMed  Article  Google Scholar 

  13. 13.

    Moria A, Das M, Shehata F, Holzer H, Son WY, Tulandi T. Ovarian reserve and oocyte maturity in women with malignancy undergoing in vitro maturation treatment. Fertil Steril. 2011;95(5):1621–3.

    PubMed  Article  Google Scholar 

  14. 14.

    Levin I, Almog B. Effect of cancer on ovarian function in patients undergoing in vitro fertilization for fertility preservation: a reappraisal. Curr Oncol. 2013;20(1):e1–3.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Garcia-Velasco JA, Domingo J, Cobo A, Martínez M, Carmona L, Pellicer A. Five years' experience using oocyte vitrification to preserve fertility for medical and nonmedical indications. Fertil Steril. 2013;99(7):1994–9.

    PubMed  Article  Google Scholar 

  16. 16.

    Quinn MM, Cakmak H, Letourneau JM, Cedars MI, Rosen MP. Response to ovarian stimulation is not impacted by a breast cancer diagnosis. Hum Reprod. 2017;32(3):568–74.

    CAS  PubMed  Google Scholar 

  17. 17.

    Maxwell KN, Domchek SM, Nathanson KL, Robson ME. Population frequency of germline BRCA1/2 mutations. J Clin Oncol. 2016;34(34):4183–5.

    PubMed  Article  Google Scholar 

  18. 18.

    Balmana J, et al. BRCA in breast cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2011;22(Suppl 6):vi31–4.

    PubMed  Article  Google Scholar 

  19. 19.

    Nelson HD, Pappas M, Zakher B, Mitchell JP, Okinaka-Hu L, Fu R. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: a systematic review to update the U.S. preventive services task force recommendation. Ann Intern Med. 2014;160(4):255–66.

    PubMed  Article  Google Scholar 

  20. 20.

    Peccatori FA, Mangili G, Bergamini A, Filippi F, Martinelli F, Ferrari F, et al. Fertility preservation in women harboring deleterious BRCA mutations: ready for prime time? Hum Reprod. 2018;33(2):181–7.

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Lambertini M, Goldrat O, Toss A, Azim HA Jr, Peccatori FA, Ignatiadis M, et al. Fertility and pregnancy issues in BRCA-mutated breast cancer patients. Cancer Treat Rev. 2017;59:61–70.

    PubMed  Article  Google Scholar 

  22. 22.

    Devesa M, Martínez F, Coroleu B, Rodríguez I, González C, Barri PN. Ovarian response to controlled ovarian hyperstimulation in women with cancer is as expected according to an age-specific nomogram. J Assist Reprod Genet. 2014;31(5):583–8.

    PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Cakmak H, Katz A, Cedars MI, Rosen MP. Effective method for emergency fertility preservation: random-start controlled ovarian stimulation. Fertil Steril. 2013;100(6):1673–80.

    PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Azim AA, Costantini-Ferrando M, Lostritto K, Oktay K. Relative potencies of anastrozole and letrozole to suppress estradiol in breast cancer patients undergoing ovarian stimulation before in vitro fertilization. J Clin Endocrinol Metab. 2007;92(6):2197–200.

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Oktay K, Hourvitz A, Sahin G, Oktem O, Safro B, Cil A, et al. Letrozole reduces estrogen and gonadotropin exposure in women with breast cancer undergoing ovarian stimulation before chemotherapy. J Clin Endocrinol Metab. 2006;91(10):3885–90.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Oktay K, Buyuk E, Libertella N, Akar M, Rosenwaks Z. Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol. 2005;23(19):4347–53.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Sole M, Santalo J, Boada M, Clua E, Rodriguez I, Martinez F, et al. How does vitrification affect oocyte viability in oocyte donation cycles? A prospective study to compare outcomes achieved with fresh versus vitrified sibling oocytes. Hum Reprod. 2013;28(8):2087–92.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Rigby RA, Stasinopoulos DM. Generalized additive models for location, scale and shape. J R Stat Soc: Ser C: Appl Stat. 2005;54(3):507–54.

    Article  Google Scholar 

  29. 29.

    R Development Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2008.

    Google Scholar 

  30. 30.

    Quintero RB, Helmer A, Huang JQ, Westphal LM. Ovarian stimulation for fertility preservation in patients with cancer. Fertil Steril. 2010;93(3):865–8.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Turan V, Quinn MM, Dayioglu N, Rosen MP, Oktay K. The impact of malignancy on response to ovarian stimulation for fertility preservation: a meta-analysis. Fertil Steril. 2018;110(7):1347–55.

    PubMed  Article  Google Scholar 

  32. 32.

    Agarwal A, Said TM. Implications of systemic malignancies on human fertility. Reprod BioMed Online. 2004;9(6):673–9.

    PubMed  Article  Google Scholar 

  33. 33.

    Schenker JG, Meirow D, Schenker E. Stress and human reproduction. Eur J Obstet Gynecol Reprod Biol. 1992;45(1):1–8.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Oktay K, Turan V, Titus S, Stobezki R, Liu L. BRCA mutations, DNA repair deficiency, and ovarian aging. Biol Reprod. 2015;93(3):67.

    PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Gunnala V, Fields J, Irani M, D'Angelo D, Xu K, Schattman G, et al. BRCA carriers have similar reproductive potential at baseline to noncarriers: comparisons in cancer and cancer-free cohorts undergoing fertility preservation. Fertil Steril. 2019;111(2):363–71.

    CAS  PubMed  Article  Google Scholar 

Download references

Author information




Elisa Malacarne, Marta Devesa, and Francisca Martinez have designed and developed the study and participated in the literature review and manuscript drafting; Ignacio Rodriguez has contributed to the design and statistics and critically revised the manuscript; and Buenaventura Coroleu has contributed with the critical review of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Elisa Malacarne.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Institutional Review Board (CIOG 1020190522/01).

Additional information

This work was performed under the auspices of the Càtedra d’Investigació en Obstetrícia I Ginecologia of the Department of Obstetrics and Gynecology, Hospital Universitari Dexeus, Universitat Autònoma de Barcelona.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Malacarne, E., Devesa, M., Martinez, F. et al. COH outcomes in breast cancer patients for fertility preservation: a comparison with the expected response by age. J Assist Reprod Genet 37, 3069–3076 (2020).

Download citation


  • Fertility preservation
  • Breast Cancer
  • BRCA
  • Ovarian response
  • Controlled ovarian hyperstimulation
  • Nomogram