Skip to main content
SpringerLink
Log in

Female patients with lymphoma demonstrate diminished ovarian reserve even before initiation of chemotherapy when compared with healthy controls and patients with other malignancies

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

Abstract

Purpose

The purpose of this study is to investigate if female patients with lymphoma demonstrate diminished ovarian reserve prior to initiation of the lymphoma treatment.

Methods

Sixty-four patients with newly diagnosed lymphoma undergoing controlled ovarian hyperstimulation for fertility preservation were compared with 365 healthy controls undergoing elective oocyte cryopreservation (controlled ovarian hyperstimulation (COH)) and 128 patients with other types of malignancy prompting fertility preservation. The data of all lymphoma patients, all elective, and all the patients with other types of malignancy who met the inclusion criteria and underwent COH for fertility preservation during the study period were retrospectively analyzed. Primary outcomes included serum anti-Müllerian hormone (AMH) levels (ng/mL) and antral follicle count (AFC).

Results

Patients in the lymphoma group demonstrated significantly lower AMH levels and AFC and had less oocytes harvested and cryopreserved when compared to healthy controls as well as patients with other malignancies.

Conclusion

Patients with lymphoma demonstrate diminished ovarian reserve when compared with healthy controls and patients with other malignancies. This should be taken into consideration when deciding on the dose for COH.

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

Similar content being viewed by others

References

  1. U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2012 incidence and mortality Web-based report. Atlanta: Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; 2015. Available at: www.cdc.gov/uscs.

    Google Scholar 

  2. Fleischer RT, Vollenhoven BJ, Weston GC. The effects of chemotherapy and radiotherapy on fertility in premenopausal women. Obstet Gynecol Surv. 2011;66(4):248–54.

    Article  PubMed  Google Scholar 

  3. Wo JY, Viswanathan AN. Impact of radiotherapy on fertility, pregnancy, and neonatal outcomes in female cancer patients. Int J Radiat Oncol Biol Phys. 2009;73(5):1304–12.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Jadoul P, Kim SS, ISFP Practice Committee. Fertility considerations in young women with hematological malignancies. J Assist Reprod Genet. 2012;29(6):479–87.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Viviani S, Ragni G, Santoro A, Perotti L, Caccamo E, Negretti E, et al. Testicular dysfunction in Hodgkin's disease before and after treatment. Eur J Cancer. 1991;27(11):1389–92.

    Article  CAS  PubMed  Google Scholar 

  6. Rueffer U, Breuer K, Josting A, Lathan B, Sieber M, Manzke O, et al. Male gonadal dysfunction in patients with Hodgkin's disease prior to treatment. Ann Oncol. 2001;12:1307–11.

    Article  CAS  PubMed  Google Scholar 

  7. Sklavos MM, Stratton P, Giri N, Alter BP, Savage SA, Pinto LP. Reduced serum levels of anti-Müllerian hormone in females with inherited bone marrow failure syndromes. J Clin Endocrinol Metabol. 2015;100:E197–203.

    Article  CAS  Google Scholar 

  8. Quintero RB et al. Ovarian stimulation for fertility preservation in patients with cancer. Fertil Steril. 2010;93:865–8.

    Article  CAS  PubMed  Google Scholar 

  9. Johnson LN et al. Response to ovarian stimulation in patients facing gonadotoxic therapy. Reprod Biomed Online. 2013;26:337–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Davis OK, Rosenwaks Z. Superovulation strategies for assisted reproductive technologies, 2001.19:207-12.

  11. Lawrenz B, Fehm T, von Wolff M, Soekler M, Huebner S, Henes J, et al. Reduced pretreatment ovarian reserve in premenopausal female patients with Hodgkin lymphoma or non-Hodgkin-lymphoma—evaluation by using antimüllerian hormone and retrieved oocytes. Fertil Steril. 2012;98(1):141–4.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Behringer K, Mueller H, Goergen H, Thielen I, Eibl AD, Stumpf V, et al. Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials. J Clin Oncol. 2013;31(2):231–9.

    Article  CAS  PubMed  Google Scholar 

  14. Behringer K, Breuer K, Reineke T, May M, Nogova L, Klimm B, et al. Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: a report from the German Hodgkin's lymphoma study group. J Clin Oncol. 2005;23:7555–64.

    Article  PubMed  Google Scholar 

  15. Johnson LN, Sammel MD, Dillon KE, Lechtenberg L, Schanne A, Gracia CR. Antimüllerian hormone and antral follicle count are lower in female cancer survivors and healthy women taking hormonal contraception. Fertil Steril. 2014;102:774–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bentzen JG, Forman JL, Pinborg A, Lidegaard Ø, Larsen EC, Friis-Hansen L, et al. Ovarian reserve parameters: a comparison between users and non-users of hormonal contraception. Reprod Biomed Online. 2012;25:612–9.

    Article  CAS  PubMed  Google Scholar 

  17. Lie Fong S, Visser JA, Welt CK, de Rijke YB, Eijkemans MJ, Broekmans FJ, et al. Serum anti-Müllerian hormone levels in healthy females: a nomogram ranging from infancy to adulthood. J Clin Endocrinol Metab. 2012;97(12):4650–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hagen CP, Aksglaede L, Sørensen K, Main KM, Boas M, Cleemann L, et al. Serum levels of anti-Müllerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 Turner syndrome patients. J Clin Endocrinol Metab. 2010;95(11):5003–10.

    Article  CAS  PubMed  Google Scholar 

  19. Checa MA, Brassesco M, Sastre M, et al. Random-start GnRH antagonist for emergency fertility preservation: a self-controlled trial. Int J Womens Health. 2015;7:219–25.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kuang Y, Hong Q, Chen Q, et al. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014;101(1):105–11.

    Article  CAS  PubMed  Google Scholar 

  21. Nayak SR, Wakim AN. Random-start gonadotropin-releasing hormone (GnRH) antagonist-treated cycles with GnRH agonist trigger for fertility preservation. Fertil Steril. 2011;96(1):e51–4.

    Article  PubMed  Google Scholar 

  22. Ozkaya E, San Roman G, Oktay K. Luteal phase GnRHa trigger in random start fertility preservation cycles. J Assist Reprod Genet. 2012;29(6):503–5.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Moore JA, Moore MB, Samaniego F, Pinnix CC, Moore Jr DF. Small lymphocytic lymphoma presenting with hypopituitarism. Am J Med. 2016;129(1):e9–e10.

    Article  PubMed  Google Scholar 

  24. Valeros KA, Khoo E. Anterior panhypopituitarism in diffuse large B-cell stage IV lymphoma. J Clin Neurosci. 2014;21(8):1464–6.

    Article  PubMed  Google Scholar 

  25. Schleinitz N, Bernit E, Mazodier K, Charbonnier A, Horchowski N, Andrac-Meyer L, et al. Two cases of intravascular lymphomatosis disclosing with hypopituitarism. Haematologica. 2002;87(6):ECR21.

    PubMed  Google Scholar 

  26. Mourand I, Menjot de Champfleur N, Bauchet L, Dumontel T, Corlobé A, Quittet P, et al. Reversible hypothalamic-pituitary axis involvement in a patient with intravascular lymphomatosis. J Neuroradiol. 2014;41(5):360–2.

    Article  PubMed  Google Scholar 

  27. Shapira M, Raanani H, Meirow D. IVF for fertility preservation in breast cancer patients—efficacy and safety issues. J Assist Reprod Genet. 2015 Jul 1.

  28. 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;26:2630–5.

    Article  CAS  PubMed  Google Scholar 

  29. Kim JH et al. Efficacy of random-start controlled ovarian stimulation in cancer patients. J Korean Med Sci. 2015;30:290–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Revelli A et al. Is letrozole needed for controlled ovarian stimulation in patients with estrogen receptor-positive breast cancer? Gynecol Endocrinol. 2013;29:993–6.

    Article  CAS  PubMed  Google Scholar 

  31. Johnson J, Canning J, Keneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004;428:145–50.

    Article  CAS  PubMed  Google Scholar 

  32. Johnson J, Bagley J, Skaznik-Wikiel M, Lee HJ, Adams GB, Niikura Y, et al. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell. 2005;122:303–15.

    Article  CAS  PubMed  Google Scholar 

  33. Hill JA, Haimovici D, Politich JA, Anderson DJ. Effects of soluble products of activated lymphocytes on macrophages (lymphokines and monokines) on human sperm motion parameters. Fertil Steril. 1987;47:460–5.

    Article  CAS  PubMed  Google Scholar 

  34. Hu R, Miao M, Zhang R, Li Y, Li J, Zhu K, et al. Ovary involvement of diffuse large B cell lymphoma. Am J Case Rep. 2012;13:96–8.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Chorlton I, Norris HJ, King FM. Malignant reticuloendothelial disease involving the ovary as a primary manifestation: a series of 19 lymphomas and 1 granulocytic sarcoma. Cancer. 1974;34(2):397–407.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, 1305 York Avenue, 6th floor, New York, NY, 10021, USA

    Jovana Lekovich, Alexandre L. S. Lobel, Nigel Pereira, Isaac Kligman & Zev Rosenwaks

  2. Department of Obstetrics and Gynecology, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA

    Joshua D. Stewart

Authors
  1. Jovana Lekovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandre L. S. Lobel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joshua D. Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nigel Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Isaac Kligman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zev Rosenwaks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jovana Lekovich.

Ethics declarations

The Weill Cornell Medical College institutional review board approved this study.

Conflict of interest

The authors declare that they have no competing interests.

Financial support

Institutional

Additional information

Capsule Female patients with lymphoma demonstrate diminished ovarian reserve when compared with healthy controls as well as patients with other type of malignancy even before initiation of chemotherapy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lekovich, J., Lobel, A.L.S., Stewart, J.D. et al. Female patients with lymphoma demonstrate diminished ovarian reserve even before initiation of chemotherapy when compared with healthy controls and patients with other malignancies. J Assist Reprod Genet 33, 657–662 (2016). https://doi.org/10.1007/s10815-016-0689-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-016-0689-1

Keywords

Search

Navigation