Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Qol and Patients' Care

Ovarian function after hematopoietic cell transplantation: a descriptive study following the use of GnRH agonists for myeloablative conditioning and observation only for reduced-intensity conditioning

Abstract

Gonadal failure is a health and quality-of-life concern in hematopoietic cell transplant (HCT) survivors. While ovarian dysfunction is nearly universal following myeloablative (MA) conditioning, the risk is unclear after reduced-intensity conditioning (RIC). Gonadotropin-releasing hormone agonists decrease ovarian failure rates following conventional chemotherapy, but little is known about its effectiveness with HCT. We investigated the impact of leuprolide on ovarian function after MA conditioning and monitored ovarian function after RIC in this descriptive pilot study. Post-menarchal females <50 years undergoing HCT with adequate baseline ovarian function (follicle-stimulating hormone (FSH) level <40 mIU/mL and normal menstruation) were eligible. Prior to MA conditioning, leuprolide was administered. Those undergoing RIC were observed. FSH was measured at various time points. Seventeen women aged 12–45 years were evaluated (7 in the intervention group and 10 in the observation group). Compared to the historical high rate of ovarian failure after MA conditioning, 3 of 7 evaluable Lupron recipients had ovarian failure at a median of 703 days post transplant. Ovarian failure occurred in 1 of 10 recipients of RIC at a median follow-up of 901 days. In conclusion, leuprolide may protect ovarian function after MA conditioning. Additionally, RIC with cyclophosphamide, fludarabine and low-dose TBI has a low risk of ovarian failure.

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

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Laml T, Schulz-Lobmeyr I, Obruca A, Huber JC, Hartmann BW . Premature ovarian failure: etiology and prospects. Gynecol Endocrinol 2000; 14: 292–302.

    Article  CAS  Google Scholar 

  2. Somali M, Mpatakoias V, Avramides A, Sakellari I, Kaloyannidis P, Smias C et al. Function of the hypothalamic-pituitary gonadal axis in long-term survivors of hematopoietic stem cell transplantation for hematological diseases. Gynecol Endocrinol 2005; 21: 18–26.

    Article  CAS  Google Scholar 

  3. Mertens AC, Ramsay NK, Kouris S, Neglia JP . Patterns of gonadal dysfunction following bone marrow transplantation. Bone Marrow Transplant 1998; 22: 345–350.

    Article  CAS  Google Scholar 

  4. Cheng YC, Saliba RM, Rondón G, Giralt SA, Lu KH, Bodurka DC et al. Low prevalence of premature ovarian failure in women given reduced-intensity conditioning regimens for hematopoietic stem-cell transplantation. Haematologica 2005; 90: 1725–1726.

    PubMed  Google Scholar 

  5. Shimizu M, Sawada A, Yamada K, Kondo W, Koyama-Sato M, Shimizu S et al. Encouraging results of preserving ovarian function after allo-HSCT with RIC. Bone Marrow Transplant 2012; 47: 141–142.

    Article  CAS  Google Scholar 

  6. Ghalie R, Porter C, Radwanska E, Fitzsimmons W, Richman C, Kaizer H . Prevention of hypermenorrhea with leuprolide in premenopausal women undergoing bone marrow transplantation. Am J Hematol 1993; 42: 350–353.

    Article  CAS  Google Scholar 

  7. Chiusolo P, Salutari P, Sica S, Scirpa P, Laurenti L, Piccirillo N et al. Luteinizing hormone-releasing hormone analogue: leuprorelin acetate for the prevention of menstrual bleeding in premenopausal women undergoing stem cell transplantation. Bone Marrow Transplant 1998; 21: 821–823.

    Article  CAS  Google Scholar 

  8. Blumenfeld Z . How to preserve fertility in young women exposed to chemotherapy? The role of GnRH agonist cotreatment in addition to cryopreservation of embrya, oocytes, or ovaries. Oncologist 2007; 12: 1044–1054.

    Article  Google Scholar 

  9. Badawy A, Elnashar A, El-Ashry M, Shahat M . Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study. Fertil Steril 2009; 91: 694–697.

    Article  CAS  Google Scholar 

  10. Blumenfeld Z, Avivi I, Linn S, Epelbaum R, Ben-Shahar M, Haim N . Prevention of irreversible chemotherapy-induced ovarian damage in young women with lymphoma by a gonadotrophin-releasing hormone agonist in parallel to chemotherapy. Hum Reprod 1996; 11: 1620–1626.

    Article  CAS  Google Scholar 

  11. 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 2011; 306: 269–276.

    CAS  PubMed  Google Scholar 

  12. Pereyra Pacheco B, Méndez Ribas JM, Milone G, Fernandez I, Kvicala R, Mila T et al. Use of GnRH analogs for functional protection of the ovary and preservation of fertility during cancer treatment in adolescents: a preliminary report. Gynecol Oncol 2001; 81: 391–397.

    Article  CAS  Google Scholar 

  13. Borgmann-Staudt A, Rendtorff R, Reinmuth S, Hohmann C, Keil T, Schuster FR et al. Fertility after allogeneic haematopoietic stem cell transplantation in childhood and adolescence. Bone Marrow Transplant 2012; 47: 271–276.

    Article  CAS  Google Scholar 

  14. Loren AW, Chow E, Jacobsohn DA, Gileece M, Halter J, Joshi S et al. Pregnancy after hematopoietic cell transplantation: a report from the late effects working committee of the Center for International Blood and Marrow Transplant Research (CIBMTR). Biol Blood Marrow Transplant 2011; 17: 157–166.

    Article  Google Scholar 

  15. Vatanen A, Wilhelmsson M, Borgström B, Gustafsson B, Taskinen M, Saarinen-Pihkala UM et al. Ovarian function after allogeneic hematopoietic stem cell transplantation in childhood and adolescence. Eur J Endocrinol 2014; 170: 211–218.

    Article  CAS  Google Scholar 

  16. Tauchmanovà L, Selleri C, Rosa GD, Pagano L, Orio F, Lombardi G et al. High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases. Cancer 2002; 95: 1076–1084.

    Article  Google Scholar 

  17. Clowse ME, Behera MA, Anders CK, Copland S, Coffman CJ, Leppert PC et al. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J Womens Health (Larchmt) 2009; 18: 311–319.

    Article  Google Scholar 

  18. Blumenfeld Z, Evron A . Preserving fertility when choosing chemotherapy regimens—the role of gonadotropin-releasing hormone agonists. Expert Opin Pharmacother 2015; 16: 1009–1020.

    Article  CAS  Google Scholar 

  19. Cheng YC, Takagi M, Milbourne A, Champlin RE, Ueno NT . Phase II study of gonadotropin-releasing hormone analog for ovarian function preservation in hematopoietic stem cell transplantation patients. Oncologist 2012; 17: 233–238.

    Article  CAS  Google Scholar 

  20. Blumenfeld Z, Patel B, Leiba R, Zuckerman T . Gonadotropin-releasing hormone agonist may minimize premature ovarian failure in young women undergoing autologous stem cell transplantation. Fertil Steril 2012; 98: 1266–1270.

    Article  CAS  Google Scholar 

  21. Nakagawa K, Kanda Y, Yamashita H, Hosoi Y, Oshima K, Ohtomo K et al. Preservation of ovarian function by ovarian shielding when undergoing total body irradiation for hematopoietic stem cell transplantation: a report of two successful cases. Bone Marrow Transplant 2006; 37: 583–587.

    Article  CAS  Google Scholar 

  22. Nakagawa K, Kanda Y, Yamashita H, Nakagawa S, Sasano N, Ohtomo K et al. Ovarian shielding allows ovarian recovery and normal birth in female hematopoietic SCT recipients undergoing TBI. Bone Marrow Transplant 2008; 42: 697–699.

    Article  CAS  Google Scholar 

  23. Kanda Y, Wada H, Yamasaki R, Kawamura K, Ishihara Y, Sakamoto K et al. Protection of ovarian function by two distinct methods of ovarian shielding for young female patients who receive total body irradiation. Ann Hematol 2014; 93: 287–292.

    Article  Google Scholar 

  24. Ishibashi N, Maebayashi T, Aizawa T, Sakaguchi M, Abe O, Saito T et al. Successful Pregnancy and Delivery After Radiation With Ovarian Shielding for Acute Lymphocytic Leukemia Before Menarche. J Pediatr Hematol Oncol 2015; 37: e292–e294.

    Article  CAS  Google Scholar 

  25. Grigg AP, Shuttleworth P, Reynolds J, Schwarer AP, Szer J, Bradstock K et al. Pamidronate reduces bone loss after allogeneic stem cell transplantation. J Clin Endocrinol Metab 2006; 91: 3835–3843.

    Article  CAS  Google Scholar 

  26. Kananen K, Volin L, Laitinen K, Alfthan H, Ruutu T, Välimäki MJ . Prevention of bone loss after allogeneic stem cell transplantation by calcium, vitamin D, and sex hormone replacement with or without pamidronate. J Clin Endocrinol Metab 2005; 90: 3877–3885.

    Article  CAS  Google Scholar 

  27. Tauchmanovà L, Colao A, Lombardi G, Rotoli B, Selleri C . Bone loss and its management in long-term survivors from allogeneic stem cell transplantation. J Clin Endocrinol Metab 2007; 92: 4536–4545.

    Article  Google Scholar 

  28. Assouline E, Crocchiolo R, Prebet T, Broussais F, Coso D, Gamerre M et al. Impact of reduced-intensity conditioning allogeneic stem cell transplantation on women's fertility. Clin Lymphoma Myeloma Leuk 2013; 13: 704–710.

    Article  Google Scholar 

  29. Meattini I, Saieva C, Meacci F, Scotti V, De Luca Cardillo C, Desideri I et al. Impact of age on cytotoxic-induced ovarian failure in breast cancer treated with adjuvant chemotherapy and triptorelin. Future Oncol 2016; 12: 625–635.

    Article  CAS  Google Scholar 

  30. Wallace WH, Anderson RA, Irvine DS . Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol 2005; 6: 209–218.

    Article  Google Scholar 

  31. Blumenfeld Z . Gynaecologic concerns for young women exposed to gonadotoxic chemotherapy. Curr Opin Obstet Gynecol 2003; 15: 359–370.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the University of Minnesota Grant-in-Aid program and the Minnesota Medical Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A R Smith.

Ethics declarations

Competing interests

The authors declare 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

Phelan, R., Mann, E., Napurski, C. et al. Ovarian function after hematopoietic cell transplantation: a descriptive study following the use of GnRH agonists for myeloablative conditioning and observation only for reduced-intensity conditioning. Bone Marrow Transplant 51, 1369–1375 (2016). https://doi.org/10.1038/bmt.2016.150

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2016.150

This article is cited by

Search

Quick links