Skip to main content

Advertisement

SpringerLink
Log in

Antral follicle count recovery in women with menses after treatment with and without gonadotropin-releasing hormone agonist use during chemotherapy for breast cancer

  • Fertility Preservation
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

After chemotherapy for breast cancer, most women will recover some ovarian function, but the timing and extent of this recovery are poorly understood. We studied post-chemotherapy ovarian recovery in women with and without a history of ovarian suppression during chemotherapy.

Methods

Reproductive age breast cancer patients who were seen prior to chemotherapy for fertility preservation consult were consented for follow-up ovarian function assessment (every 3–6 months after chemotherapy) with antral follicle count (AFC) in this prospective cohort study. We restricted our analysis to those with menses present after chemotherapy. Box plots were used to demonstrate the change in follow-up AFC versus time elapsed after chemotherapy. A mixed effects regression model was used to assess differences in AFC.

Results

Eighty-eight patients with a history of newly diagnosed breast cancer were included. Forty-five patients (51%) had ovarian suppression with GnRH agonist (GnRHa) during chemotherapy. AFC recovery appeared to plateau at 1 year after completing chemotherapy at a median of 40% of pre-chemotherapy AFC. After adjustment for age, initial AFC, cyclophosphamide exposure, combined hormonal contraceptive (CHC) use, and tamoxifen use, AFC recovered faster and to a greater degree for those women who underwent GnRHa therapy for ovarian protection during chemotherapy (P = 0.032).

Conclusions

Women with menses after chemotherapy for breast cancer appear to recover their full potential AFC 1 year after their last chemotherapy dose. Treatment with GnRHa during chemotherapy is associated with a higher degree of AFC recovery. The findings of this study can aid in counseling patients prior to chemotherapy about expectations for ovarian recovery and planning post-treatment fertility preservation care to maximize reproductive potential when pre-treatment fertility preservation care is not possible or has limited oocyte yield.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemotherapeutic agents damage the ovary? Hum Reprod Update Oxford Univ Press. 2012;18:525–35.

    Article  CAS  Google Scholar 

  2. 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 Wiley Subscription Services, Inc., A Wiley Company; 2012;118:1933–9.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  4. D’Avila ÂM, Capp E, Corleta HVE. Antral follicles count and anti-Müllerian hormone levels after gonadotoxic chemotherapy in patients with breast cancer: cohort study. Rev Bras Ginecol Obstet. Thieme-Revinter Publicações Ltda; 2017.

  5. Anderson RA, Cameron DA. Pretreatment serum anti-Müllerian hormone predicts long-term ovarian function and bone mass after chemotherapy for early breast cancer. J Clin Endocrinol Metab. 2011;96:1336–43.

    Article  CAS  PubMed  Google Scholar 

  6. Rosendahl M, Andersen CY, la Cour FN, Juul A, Løssl K, Andersen AN. Dynamics and mechanisms of chemotherapy-induced ovarian follicular depletion in women of fertile age. Fertil Steril. 2010;94:156–66.

    Article  CAS  PubMed  Google Scholar 

  7. Fleming R, Seifer DB, Frattarelli JL, Ruman J. Assessing ovarian response: antral follicle count versus anti-Müllerian hormone. Reprod BioMed Online. 2015;31:486–96.

    Article  CAS  PubMed  Google Scholar 

  8. Letourneau JM, Cakmak H, Quinn M, Sinha N, I Cedars M, Rosen MP. Long-term hormonal contraceptive use is associated with a reversible suppression of antral follicle count and a break from hormonal contraception may improve oocyte yield. J Assist Reprod Genet. Springer US; 2017;103:1551–8.

  9. Sherman BM, West JH, Korenman SG. The menopausal transition: analysis of LH, FSH, estradiol, and progesterone concentrations during menstrual cycles of older women. J Clin Endocrinol Metab. 1976;42:629–36.

    Article  CAS  PubMed  Google Scholar 

  10. Lutchman Singh K, Muttukrishna S, Stein RC, McGarrigle HH, Patel A, Parikh B, et al. Predictors of ovarian reserve in young women with breast cancer. Br J Cancer Nat Publ Group. 2007;96:1808–16.

    CAS  Google Scholar 

  11. Oktem O, Oktay K. Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function. Cancer. Wiley Subscription Services, Inc., A Wiley Company; 2007;110:2222–9.

    Article  CAS  PubMed  Google Scholar 

  12. Anderson RA, Themmen APN, Al-Qahtani A, 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 Oxford Univ Press. 2006;21:2583–92.

    Article  CAS  Google Scholar 

  13. Dillon KE, Sammel MD, Prewitt M, Ginsberg JP, Walker D, Mersereau JE, et al. Pretreatment antimüllerian hormone levels determine rate of posttherapy ovarian reserve recovery: acute changes in ovarian reserve during and after chemotherapy. Fertil Steril. 2013;99:477–83.

    Article  CAS  PubMed  Google Scholar 

  14. Wenners A, Grambach J, Koss J, Maass N, Jonat W, Schmutzler A, et al. Reduced ovarian reserve in young early breast cancer patients: preliminary data from a prospective cohort trial. BMC Cancer. 3rd ed. BioMed Central; 2017;17:632.

  15. Lindsey H. ASCO Updates Fertility-Preservation Guidelines. Oncol Times. 2013;35:16–7.

    Google Scholar 

  16. Del Mastro L, Boni L, Michelotti A, Gamucci T, Olmeo N, Gori S, et al. Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial. JAMA Am Med Assoc. 2011;306:269–76.

    Google Scholar 

  17. Moore HCF, Unger JM, Phillips K-A, Boyle F, Hitre E, Porter D, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med Mass Med Soc. 2015;372:923–32.

    Article  CAS  Google Scholar 

  18. Gerber B, von Minckwitz G, Stehle H, Reimer T, Felberbaum R, Maass N, et al. Effect of luteinizing hormone-releasing hormone agonist on ovarian function after modern adjuvant breast cancer chemotherapy: the GBG 37 ZORO study. J Clin Oncol. 2011;29:2334–41.

    Article  CAS  PubMed  Google Scholar 

  19. Munster PN, Moore AP, Ismail-Khan R, Cox CE, Lacevic M, Gross-King M, et al. Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer. J Clin Oncol. 2012;30:533–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Elgindy EA, El-Haieg DO, Khorshid OM, Ismail EI, Abdelgawad M, Sallam HN, et al. Gonadatrophin suppression to prevent chemotherapy-induced ovarian damage: a randomized controlled trial. Obstet Gynecol. 2013;121:78–86.

    Article  CAS  PubMed  Google Scholar 

  21. Giuseppe L, Attilio G, Edoardo DN, Loredana G, Cristina L, Vincenzo L. Ovarian function after cancer treatment in young women affected by Hodgkin disease (HD). Hematol Taylor & Francis. 2007;12:141–7.

    Google Scholar 

  22. Chan JL, Johnson LNC, Efymow BL, Sammel MD, Gracia CR. Outcomes of ovarian stimulation after treatment with chemotherapy. J Assist Reprod Genet Springer US. 2015;32:1537–45.

    Article  Google Scholar 

Download references

Acknowledgements

We would like to make a special thanks to our nurses, Elizabeth Gomes, Cathy Chin-Yu, and Audra Katz, who provided patient education at fertility preservation counseling appointments. We also thank the UCSF Department of OB/GYN for their support of this study.

Funding

This study was supported by departmental research funding within the University of California, San Francisco Department of Obstetrics, Gynecology and Reproductive Sciences and by the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number TL1 TR001871.

Author information

Authors and Affiliations

  1. Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Reproductive Endocrinology and Infertility, University of California San Francisco School of Medicine, 550 16th Street, Seventh Floor, San Francisco, CA, 94158-2519, USA

    N. Sinha, J. M. Letourneau, K. Wald, P. Xiong, Tal Imbar, B. Li, E. Harris, E. Mok-Lin, M. I. Cedars & Mitchell P. Rosen

Authors
  1. N. Sinha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. M. Letourneau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Wald
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tal Imbar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E. Mok-Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. I. Cedars
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mitchell P. Rosen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

N.S.’s and J.M.L.’s roles included study design, data collection, data analysis, and manuscript writing. K.W., P.X., B.L., and E.H.’s roles included data collection and manuscript writing. E.M.-L. and M.I.C.’s roles included data analysis and manuscript writing. M.R.’s roles included study design, data analysis, and manuscript writing.

Corresponding author

Correspondence to N. Sinha.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the University of California, San Francisco (UCSF) Committee on Human Research and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sinha, N., Letourneau, J.M., Wald, K. et al. Antral follicle count recovery in women with menses after treatment with and without gonadotropin-releasing hormone agonist use during chemotherapy for breast cancer. J Assist Reprod Genet 35, 1861–1868 (2018). https://doi.org/10.1007/s10815-018-1203-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-018-1203-8

Keywords

Search

Navigation