Skip to main content
SpringerLink
Log in

Medical Treatments for Ovarian Protection

  • Chapter
  • First Online:
Female and Male Fertility Preservation

  • 1297 Accesses

Abstract

Cancer treatments, as chemotherapy or radiotherapy, often induce ovarian follicular depletion and subsequent infertility. Several fertility preservation techniques have been developed to preserve some gametes from the gonadotoxic effects of chemotherapy. Oocyte or embryo cryopreservation with or without ovarian stimulation and cryopreservation of ovarian cortex represent the available strategies. Nevertheless, these methods may be difficult to perform, and the future utilization of cryopreserved germ cells remains uncertain. Thus, improving the techniques currently performed and developing new methods to preserve fertility represent major challenges in the area of oncofertility. Among them, the possibility to limit, in vivo, the negative impact of chemotherapy on ovaries is of particular interest.

To develop such treatment, it is crucial to better understand the effects of chemotherapy on ovarian function. Animal and ovarian culture models have been used to decipher the impact of different cytotoxic agents on ovaries. Several theories regarding chemotherapy gonadotoxicity have been raised. Such might have a direct detrimental effect on the DNA of primordial follicles that constitute the ovarian reserve, inducing apoptosis and a massive growth of dormant follicles which are then destroyed or inducing vascular ovarian damage. Thanks to the improvements in the understanding of the mechanisms involved, a large number of studies have been carried out to develop molecules whose concomitant administration with chemotherapy might limit follicular depletion, therefore representing a promising option for preserving fertility in women suffering from cancer.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Donnez J, Dolmans M-M. Fertility Preservation in Women. N Engl J Med. 2017;377(17):1657–65.

    Article  PubMed  Google Scholar 

  2. Donnez J, Martinez-Madrid B, Jadoul P, Van Langendonckt A, Demylle D, Dolmans M-M. Ovarian tissue cryopreservation and transplantation: a review. Hum Reprod Update. 2006;12(5):519–35.

    Article  PubMed  Google Scholar 

  3. Roness H, Kashi O, Meirow D. Prevention of chemotherapy-induced ovarian damage. Fertil Steril. 2016;105(1):20–9.

    Google Scholar 

  4. Woodruff TK. A win-win for women’s reproductive health: a nonsteroidal contraceptive and fertoprotective neoadjuvant. Proc Natl Acad Sci USA. 2017;114(9):2101–2.

    Google Scholar 

  5. Roness H, Kalich-Philosoph L, Meirow D. Prevention of chemotherapy-induced ovarian damage: possible roles for hormonal and non-hormonal attenuating agents. Hum Reprod Update. 2014;20(5):759–74.

    Google Scholar 

  6. Reddy P, Zheng W, Liu K. Mechanisms maintaining the dormancy and survival of mammalian primordial follicles. Trends Endocrinol Metab TEM. 2010;21(2):96–103.

    Article  CAS  PubMed  Google Scholar 

  7. Adhikari D, Liu K. Molecular mechanisms underlying the activation of mammalian primordial follicles. Endocr Rev. 2009;30(5):438–64.

    Article  CAS  PubMed  Google Scholar 

  8. Hsueh AJW, Kawamura K, Cheng Y, Fauser BCJM. Intraovarian control of early folliculogenesis. Endocr Rev. 2015;36(1):1–24.

    Article  CAS  PubMed  Google Scholar 

  9. De Vos M, Devroey P, Fauser BCJM. Primary ovarian insufficiency. Lancet Lond Engl. 2010;376(9744):911–21.

    Article  Google Scholar 

  10. Winship AL, Stringer JM, Liew SH, Hutt KJ. The importance of DNA repair for maintaining oocyte quality in response to anti-cancer treatments, environmental toxins and maternal ageing. Hum Reprod Update. 2018;24(2):119–34.

    Google Scholar 

  11. Kerr JB, Hutt KJ, Michalak EM, Cook M, Vandenberg CJ, Liew SH, et al. DNA damage-induced primordial follicle oocyte apoptosis and loss of fertility require TAp63-mediated induction of Puma and Noxa. Mol Cell. 2012;48(3):343–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tanaka T, Utsunomiya T, Utsunomiya H, Umesaki N. Irinotecan HCl, an anticancer topoisomerase I inhibitor, frequently induces ovarian failure in premenopausal and perimenopausal women. Oncol Rep. 2008;19(5):1123–33.

    CAS  PubMed  Google Scholar 

  13. Bedoschi G, Navarro PA, Oktay K. Chemotherapy-induced damage to ovary: mechanisms and clinical impact. Future Oncol Lond Engl. 2016;12(20):2333–44.

    Article  CAS  Google Scholar 

  14. Arnon J, Meirow D, Lewis-Roness H, Ornoy A. Genetic and teratogenic effects of cancer treatments on gametes and embryos. Hum Reprod Update. 2001;7(4):394–403.

    Article  CAS  PubMed  Google Scholar 

  15. Meirow D, Schiff E. Appraisal of chemotherapy effects on reproductive outcome according to animal studies and clinical data. J Natl Cancer Inst Monogr. 2005;34:21–5.

    Article  CAS  Google Scholar 

  16. Oktem O, Oktay K. A novel ovarian xenografting model to characterize the impact of chemotherapy agents on human primordial follicle reserve. Cancer Res. 2007;67(21):10159–62.

    Article  CAS  PubMed  Google Scholar 

  17. Luan Y, Edmonds ME, Woodruff TK, Kim S-Y. Inhibitors of apoptosis protect the ovarian reserve from cyclophosphamide. J Endocrinol. 2019;240(2):243–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Petrillo SK, Desmeules P, Truong T-Q, Devine PJ. Detection of DNA damage in oocytes of small ovarian follicles following phosphoramide mustard exposures of cultured rodent ovaries in vitro. Toxicol Appl Pharmacol. 2011;253(2):94–102.

    Article  CAS  PubMed  Google Scholar 

  19. Ganesan S, Keating AF. The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion. Toxicol Appl Pharmacol. 2016;292:65–74.

    Article  CAS  PubMed  Google Scholar 

  20. Nguyen QN, Zerafa N, Liew SH, Findlay JK, Hickey M, Hutt KJ. Cisplatin- and cyclophosphamide-induced primordial follicle depletion is caused by direct damage to oocytes. Mol Hum Reprod. 2019;25(8):433–44.

    Article  CAS  PubMed  Google Scholar 

  21. Gonfloni S, Di Tella L, Caldarola S, Cannata SM, Klinger FG, Di Bartolomeo C, et al. Inhibition of the c-Abl-TAp63 pathway protects mouse oocytes from chemotherapy-induced death. Nat Med. 2009;15(10):1179–85.

    Article  CAS  PubMed  Google Scholar 

  22. Rossi V, Lispi M, Longobardi S, Mattei M, Rella FD, Salustri A, et al. LH prevents cisplatin-induced apoptosis in oocytes and preserves female fertility in mouse. Cell Death Differ. 2017;24(1):72–82.

    Article  CAS  PubMed  Google Scholar 

  23. Bildik G, Acılan C, Sahin GN, Karahuseyinoglu S, Oktem O. C-Abl is not actıvated in DNA damage-induced and Tap63-mediated oocyte apoptosıs in human ovary. Cell Death Dis [Internet]. 2018;9(10). Disponible sur: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148240/

  24. Soleimani R, Heytens E, Darzynkiewicz Z, Oktay K. Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise. Aging. 2011;3(8):782–93.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Roti Roti EC, Ringelstetter AK, Kropp J, Abbott DH, Salih SM. Bortezomib prevents acute doxorubicin ovarian insult and follicle demise, improving the fertility window and pup birth weight in mice. PLoS One. 2014;9(9):e108174.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Kalich-Philosoph L, Roness H, Carmely A, Fishel-Bartal M, Ligumsky H, Paglin S, et al. Cyclophosphamide triggers follicle activation and « burnout »; AS101 prevents follicle loss and preserves fertility. Sci Transl Med. 2013;5(185):185ra62.

    Article  PubMed  CAS  Google Scholar 

  27. Li J, Kawamura K, Cheng Y, Liu S, Klein C, Liu S, et al. Activation of dormant ovarian follicles to generate mature eggs. Proc Natl Acad Sci U S A. 2010;107(22):10280–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Spears N, Lopes F, Stefansdottir A, Rossi V, De Felici M, Anderson RA, et al. Ovarian damage from chemotherapy and current approaches to its protection. Hum Reprod Update. 2019;25(6):673–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lande Y, Fisch B, Tsur A, Farhi J, Prag-Rosenberg R, Ben-Haroush A, et al. Short-term exposure of human ovarian follicles to cyclophosphamide metabolites seems to promote follicular activation in vitro. Reprod Biomed Online. 2017;34(1):104–14.

    Article  CAS  PubMed  Google Scholar 

  30. Kitajima M, Dolmans M-M, Donnez O, Masuzaki H, Soares M, Donnez J. Enhanced follicular recruitment and atresia in cortex derived from ovaries with endometriomas. Fertil Steril. 2014;101(4):1031–7.

    Article  PubMed  Google Scholar 

  31. Gavish Z, Peer G, Roness H, Cohen Y, Meirow D. Follicle activation and « burn-out » contribute to post-transplantation follicle loss in ovarian tissue grafts: the effect of graft thickness. Hum Reprod Oxf Engl. 2015;30(4):1003.

    Article  Google Scholar 

  32. Gavish Z, Spector I, Peer G, Schlatt S, Wistuba J, Roness H, et al. Follicle activation is a significant and immediate cause of follicle loss after ovarian tissue transplantation. J Assist Reprod Genet. 2018;35(1):61–9.

    Article  PubMed  Google Scholar 

  33. Ben-Aharon I, Meizner I, Granot T, Uri S, Hasky N, Rizel S, et al. Chemotherapy-induced ovarian failure as a prototype for acute vascular toxicity. Oncologist. 2012;17(11):1386–93.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Meirow D, Dor J, Kaufman B, Shrim A, Rabinovici J, Schiff E, et al. Cortical fibrosis and blood-vessels damage in human ovaries exposed to chemotherapy. Potential mechanisms of ovarian injury. Hum Reprod Oxf Engl. 2007;22(6):1626–33.

    Article  CAS  Google Scholar 

  35. Bar-Joseph H, Ben-Aharon I, Tzabari M, Tsarfaty G, Stemmer SM, Shalgi R. In vivo bioimaging as a novel strategy to detect doxorubicin-induced damage to gonadal blood vessels. PLoS One. 2011;6(9):e23492.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Jang H, Hong K, Choi Y. Melatonin and Fertoprotective adjuvants: prevention against premature ovarian failure during chemotherapy. Int J Mol Sci. 2017;18(6):1221.

    Article  PubMed Central  CAS  Google Scholar 

  37. Morita Y, Perez GI, Paris F, Miranda SR, Ehleiter D, Haimovitz-Friedman A, et al. Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nat Med. 2000;6(10):1109–14.

    Article  CAS  PubMed  Google Scholar 

  38. Guzel Y, Bildik G, Dilege E, Oktem O. Sphingosine-1-phosphate reduces atresia of primordial follicles occurring during slow-freezing and thawing of human ovarian cortical strips. Mol Reprod Dev. 2018;85(11):858–64.

    Article  CAS  PubMed  Google Scholar 

  39. Tan S-J, Lee L-J, Tzeng C-R, Wang C-W, Hsu M-I, Chen C-H. Targeted anti-apoptosis activity for ovarian protection against chemotherapy-induced ovarian gonadotoxicity. Reprod Biomed Online. 2014;29(5):612–20.

    Article  CAS  PubMed  Google Scholar 

  40. Hancke K, Strauch O, Kissel C, Göbel H, Schäfer W, Denschlag D. Sphingosine 1-phosphate protects ovaries from chemotherapy-induced damage in vivo. Fertil Steril. 2007;87(1):172–7.

    Article  CAS  PubMed  Google Scholar 

  41. Li F, Turan V, Lierman S, Cuvelier C, De Sutter P, Oktay K. Sphingosine-1-phosphate prevents chemotherapy-induced human primordial follicle death. Hum Reprod Oxf Engl. 2014;29(1):107–13.

    Article  CAS  Google Scholar 

  42. Meng Y, Xu Z, Wu F, Chen W, Xie S, Liu J, et al. Sphingosine-1-phosphate suppresses cyclophosphamide induced follicle apoptosis in human fetal ovarian xenografts in nude mice. Fertil Steril. 2014;102(3):871–877.e3.

    Article  CAS  PubMed  Google Scholar 

  43. Pascuali N, Scotti L, Di Pietro M, Oubiña G, Bas D, May M, et al. Ceramide-1-phosphate has protective properties against cyclophosphamide-induced ovarian damage in a mice model of premature ovarian failure. Hum Reprod Oxf Engl. 2018;33(5):844–59.

    Article  CAS  Google Scholar 

  44. Kaya H, Desdicioglu R, Sezik M, Ulukaya E, Ozkaya O, Yilmaztepe A, et al. Does sphingosine-1-phosphate have a protective effect on cyclophosphamide- and irradiation-induced ovarian damage in the rat model? Fertil Steril. 2008;89(3):732–5.

    Article  CAS  PubMed  Google Scholar 

  45. Mumusoglu S, Turan V, Uckan H, Suzer A, Sokmensuer LK, Bozdag G. The impact of a long-acting Oral Sphingosine-1-phosphate analogue on ovarian aging in a rat model. Reprod Sci Thousand Oaks Calif. 2018;25(9):1330–5.

    Article  CAS  Google Scholar 

  46. Maiani E, Di Bartolomeo C, Klinger FG, Cannata SM, Bernardini S, Chateauvieux S, et al. Reply to: cisplatin-induced primordial follicle oocyte killing and loss of fertility are not prevented by imatinib. Nat Med. 2012;18(8):1172–4.

    Article  CAS  PubMed  Google Scholar 

  47. Morgan S, Lopes F, Gourley C, Anderson RA, Spears N. Cisplatin and doxorubicin induce distinct mechanisms of ovarian follicle loss; imatinib provides selective protection only against cisplatin. PLoS One. 2013;8(7):e70117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kim S-Y, Cordeiro MH, Serna VA, Ebbert K, Butler LM, Sinha S, et al. Rescue of platinum-damaged oocytes from programmed cell death through inactivation of the p53 family signaling network. Cell Death Differ. 2013;20(8):987–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kerr JB, Hutt KJ, Cook M, Speed TP, Strasser A, Findlay JK, et al. Cisplatin-induced primordial follicle oocyte killing and loss of fertility are not prevented by imatinib. Nat Med. 2012;18(8):1170–2. author reply 1172-1174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kujjo LL, Laine T, Pereira RJG, Kagawa W, Kurumizaka H, Yokoyama S, et al. Enhancing survival of mouse oocytes following chemotherapy or aging by targeting Bax and Rad51. PLoS One. 2010;5(2):e9204.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Hayun M, Naor Y, Weil M, Albeck M, Peled A, Don J, et al. The immunomodulator AS101 induces growth arrest and apoptosis in multiple myeloma: association with the Akt/survivin pathway. Biochem Pharmacol. 2006;72(11):1423–31.

    Article  CAS  PubMed  Google Scholar 

  52. Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek JT, Grootegoed JA, et al. Control of primordial follicle recruitment by anti-Müllerian hormone in the mouse ovary. Endocrinology. 1999;140(12):5789–96.

    Article  CAS  PubMed  Google Scholar 

  53. Durlinger ALL, Gruijters MJG, Kramer P, Karels B, Ingraham HA, Nachtigal MW, et al. Anti-Müllerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology. 2002;143(3):1076–84.

    Article  CAS  PubMed  Google Scholar 

  54. Hayes E, Kushnir V, Ma X, Biswas A, Prizant H, Gleicher N, et al. Intra-cellular mechanism of anti-Müllerian hormone (AMH) in regulation of follicular development. Mol Cell Endocrinol. 2016;433:56–65.

    Article  CAS  PubMed  Google Scholar 

  55. Kano M, Sosulski AE, Zhang L, Saatcioglu HD, Wang D, Nagykery N, et al. AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy. Proc Natl Acad Sci U S A. 2017;114(9):E1688–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sonigo C, Beau I, Grynberg M, Binart N. AMH prevents primordial ovarian follicle loss and fertility alteration in cyclophosphamide-treated mice. FASEB J Off Publ Fed Am Soc Exp Biol. 2018;33(1):1278–87.

    Google Scholar 

  57. Roness H, Spector I, Leichtmann-Bardoogo Y, Savino AM, Dereh-Haim S, Meirow D. Pharmacological administration of recombinant human AMH rescues ovarian reserve and preserves fertility in a mouse model of chemotherapy, without interfering with anti-tumoural effects. J Assist Reprod Genet. 2019;36(9):1793–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sun Y-C, Wang Y-Y, Sun X-F, Cheng S-F, Li L, Zhao Y, et al. The role of autophagy during murine primordial follicle assembly. Aging. 2018;10(2):197–211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Delcour C, Amazit L, Patino LC, Magnin F, Fagart J, Delemer B, et al. ATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure. Genet Med Off J Am Coll Med Genet. 2019;21(4):930–8.

    CAS  Google Scholar 

  60. Mills E, Wu P, Seely D, Guyatt G. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res. 2005;39(4):360–6.

    Article  CAS  PubMed  Google Scholar 

  61. Reiter RJ, Tan D-X, Tamura H, Cruz MHC, Fuentes-Broto L. Clinical relevance of melatonin in ovarian and placental physiology: a review. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. 2014;30(2):83–9.

    Article  CAS  Google Scholar 

  62. Lee CJ, Do BR, Lee YH, Park JH, Kim SJ, Kim JK, et al. Ovarian expression of melatonin Mel(1a) receptor mRNA during mouse development. Mol Reprod Dev. 2001;59(2):126–32.

    Article  CAS  PubMed  Google Scholar 

  63. Woo MM, Tai CJ, Kang SK, Nathwani PS, Pang SF, Leung PC. Direct action of melatonin in human granulosa-luteal cells. J Clin Endocrinol Metab. 2001;86(10):4789–97.

    Article  CAS  PubMed  Google Scholar 

  64. Jang H, Lee O-H, Lee Y, Yoon H, Chang EM, Park M, et al. Melatonin prevents cisplatin-induced primordial follicle loss via suppression of PTEN/AKT/FOXO3a pathway activation in the mouse ovary. J Pineal Res. 2016;60(3):336–47.

    Article  CAS  PubMed  Google Scholar 

  65. Jang H, Na Y, Hong K, Lee S, Moon S, Cho M, et al. Synergistic effect of melatonin and ghrelin in preventing cisplatin-induced ovarian damage via regulation of FOXO3a phosphorylation and binding to the p27Kip1promoter in primordial follicles. J Pineal Res. 2017;63(3):e12432.

    Article  CAS  Google Scholar 

  66. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell. 2006;124(3):471–84.

    Article  CAS  PubMed  Google Scholar 

  67. Adhikari D, Zheng W, Shen Y, Gorre N, Hämäläinen T, Cooney AJ, et al. Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Hum Mol Genet. 2010;19(3):397–410.

    Article  CAS  PubMed  Google Scholar 

  68. Sun X, Su Y, He Y, Zhang J, Liu W, Zhang H, et al. New strategy for in vitro activation of primordial follicles with mTOR and PI3K stimulators. Cell Cycle Georget Tex. 2015;14(5):721–31.

    Article  CAS  Google Scholar 

  69. Goldman KN, Chenette D, Arju R, Duncan FE, Keefe DL, Grifo JA, et al. mTORC1/2 inhibition preserves ovarian function and fertility during genotoxic chemotherapy. Proc Natl Acad Sci U S A. 2017;114(12):3186–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Zhou L, Xie Y, Li S, Liang Y, Qiu Q, Lin H, et al. Rapamycin prevents cyclophosphamide-induced over-activation of primordial follicle pool through PI3K/Akt/mTOR signaling pathway in vivo. J Ovarian Res. 2017;10(1):56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Tanaka Y, Kimura F, Zheng L, Kaku S, Takebayashi A, Kasahara K, et al. Protective effect of a mechanistic target of rapamycin inhibitor on an in vivo model ofcisplatin-induced ovarian gonadotoxicity. Exp Anim. 2018;67(4):493–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Skaznik-Wikiel ME, McGuire MM, Sukhwani M, Donohue J, Chu T, Krivak TC, et al. Granulocyte colony-stimulating factor with or without stem cell factor extends time to premature ovarian insufficiency in female mice treated with alkylating chemotherapy. Fertil Steril. 2013;99(7):2045–2054.e3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Akdemir A, Zeybek B, Akman L, Ergenoglu AM, Yeniel AO, Erbas O, et al. Granulocyte-colony stimulating factor decreases the extent of ovarian damage caused by cisplatin in an experimental rat model. J Gynecol Oncol. 2014;25(4):328–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ataya K, Rao LV, Lawrence E, Kimmel R. Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamide-induced ovarian follicular depletion in rhesus monkeys. Biol Reprod. 1995;52(2):365–72.

    Article  CAS  PubMed  Google Scholar 

  75. Meirow D, Assad G, Dor J, Rabinovici J. The GnRH antagonist cetrorelix reduces cyclophosphamide-induced ovarian follicular destruction in mice. Hum Reprod Oxf Engl. 2004;19(6):1294–9.

    Article  CAS  Google Scholar 

  76. Kishk EAF, Mohammed Ali MH. Effect of a gonadotropin-releasing hormone analogue on cyclophosphamide-induced ovarian toxicity in adult mice. Arch Gynecol Obstet. 2013;287(5):1023–9.

    Article  CAS  PubMed  Google Scholar 

  77. Li X, Kang X, Deng Q, Cai J, Wang Z. Combination of a GnRH agonist with an antagonist prevents flare-up effects and protects primordial ovarian follicles in the rat ovary from cisplatin-induced toxicity: a controlled experimental animal study. Reprod Biol Endocrinol RBE. 2013;11:16.

    Article  CAS  Google Scholar 

  78. Detti L, Uhlmann RA, Zhang J, Diamond MP, Saed GM, Fletcher NM, et al. Goserelin fosters bone elongation but does not prevent ovarian damage in cyclophosphamide-treated prepubertal mice. Fertil Steril. 2014;101(4):1157–1164.e1.

    Article  CAS  PubMed  Google Scholar 

  79. Hasky N, Uri-Belapolsky S, Goldberg K, Miller I, Grossman H, Stemmer SM, et al. Gonadotrophin-releasing hormone agonists for fertility preservation: unraveling the enigma? Hum Reprod Oxf Engl. 2015;30(5):1089–101.

    Article  CAS  Google Scholar 

  80. Horicks F, Van Den Steen G, Gervy C, Clarke HJ, Demeestere I. Both in vivo FSH depletion and follicular exposure to gonadotrophin-releasing hormone analogues in vitro are not effective to prevent follicular depletion during chemotherapy in mice. Mol Hum Reprod. 2018;24(4):221–32.

    Article  CAS  PubMed  Google Scholar 

  81. 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(9):1044–54.

    Article  PubMed  Google Scholar 

  82. Blumenfeld Z. Fertility preservation using GnRH agonists: rationale, possible mechanisms, and explanation of controversy. Clin Med Insights Reprod Health. 2019;13:1179558119870163.

    Google Scholar 

  83. Poggio F, Lambertini M, Bighin C, Conte B, Blondeaux E, D’Alonzo A, et al. Potential mechanisms of ovarian protection with gonadotropin-releasing hormone agonist in breast Cancer patients: a review. Clin Med Insights Reprod Health. 2019;13:1179558119864584.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Lambertini M, Horicks F, Del Mastro L, Partridge AH, Demeestere I. Ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy in cancer patients: from biological evidence to clinical application. Cancer Treat Rev. 2019;72:65–77.

    Article  CAS  PubMed  Google Scholar 

  85. Vitek WS, Shayne M, Hoeger K, Han Y, Messing S, Fung C. Gonadotropin-releasing hormone agonists for the preservation of ovarian function among women with breast cancer who did not use tamoxifen after chemotherapy: a systematic review and meta-analysis. Fertil Steril. 2014;102(3):808–815.e1.

    Article  CAS  PubMed  Google Scholar 

  86. Shen Y-W, Zhang X-M, Lv M, Chen L, Qin T-J, Wang F, et al. Utility of gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage in premenopausal women with breast cancer: a systematic review and meta-analysis. OncoTargets Ther. 2015;8:3349–59.

    Article  Google Scholar 

  87. Munhoz RR, Pereira AAL, Sasse AD, Hoff PM, Traina TA, Hudis CA, et al. Gonadotropin-releasing hormone agonists for ovarian function preservation in premenopausal women undergoing chemotherapy for early-stage breast Cancer: a systematic review and Meta-analysis. JAMA Oncol. 2016;2(1):65–73.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Senra JC, Roque M, Talim MCT, Reis FM, Tavares RLC. Gonadotropin-releasing hormone agonists for ovarian protection during cancer chemotherapy: systematic review and meta-analysis. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol. 2018;51(1):77–86.

    Article  CAS  Google Scholar 

  89. Ting AY, Petroff BK. Tamoxifen decreases ovarian follicular loss from experimental toxicant DMBA and chemotherapy agents cyclophosphamide and doxorubicin in the rat. J Assist Reprod Genet. 2010;27(11):591–7.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Piasecka-Srader J, Blanco FF, Delman DH, Dixon DA, Geiser JL, Ciereszko RE, et al. Tamoxifen prevents apoptosis and follicle loss from cyclophosphamide in cultured rat ovaries. Biol Reprod. 2015;92(5):132.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Xia T, Fu Y, Gao H, Zhao Z, Zhao L, Han B. Recovery of ovary function impaired by chemotherapy using Chinese herbal medicine in a rat model. Syst Biol Reprod Med. 2014;60(5):293–303.

    Article  PubMed  Google Scholar 

  92. Hassanpour A, Yousefian S, Askaripour M, Sharififar F, Ezzatabadipour M. Ovarian protection in cyclophosphamide-treated mice by fennel. Toxicol Rep. 2017;4:160–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Taskin MI, Yay A, Adali E, Balcioglu E, Inceboz U. Protective effects of sildenafil citrate administration on cisplatin-induced ovarian damage in rats. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. 2015;31(4):272–7.

    Article  CAS  Google Scholar 

  94. Saleh HS, Omar E, Froemming GRA, Said RM. Tocotrienol preserves ovarian function in cyclophosphamide therapy. Hum Exp Toxicol. 2015;34(10):946–52.

    Article  CAS  PubMed  Google Scholar 

  95. Saleh DO, Mansour DF. Ovario-protective effects of genistein against cyclophosphamide toxicity in rats: role of anti-müllerian hormone and oestradiol. Eur J Pharmacol. 2016;789:163–71.

    Article  CAS  PubMed  Google Scholar 

  96. Sayan CD, Tulmac OB, Karaca G, Ozkan ZS, Yalcin S, Devrim T, et al. Could erythropoietin reduce the ovarian damage of cisplatin in female rats? Gynecol Endocrinol. 2018;34(4):309–13.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Reproductive Medicine and Fertility Preservation, Hôpital Antoine-Béclère, Clamart, France

    Charlotte Sonigo & Michael Grynberg

  2. Inserm U1185 Univ. Paris-Sud, Université Paris Saclay, Le Kremlin Bicêtre, France

    Charlotte Sonigo, Isabelle Beau & Nadine Binart

  3. Univ. Paris-Sud, Université Paris Saclay, Le Kremlin Bicêtre, France

    Michael Grynberg

  4. Inserm U1133 Université Paris Diderot, Paris, France

    Michael Grynberg

Authors
  1. Charlotte Sonigo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Isabelle Beau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nadine Binart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Grynberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charlotte Sonigo .

Editor information

Editors and Affiliations

  1. Reproductive Medicine and Fertility Preservation, Hôpital Antoine-Béclère, Clamart, France

    Michael Grynberg

  2. Division of Reproductive Endocrinology and Infertility-Department Obstetrics, Gynecology and Reproductive Sciences, University of Miami, Miami, FL, USA

    Pasquale Patrizio

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sonigo, C., Beau, I., Binart, N., Grynberg, M. (2022). Medical Treatments for Ovarian Protection. In: Grynberg, M., Patrizio, P. (eds) Female and Male Fertility Preservation. Springer, Cham. https://doi.org/10.1007/978-3-030-47767-7_27

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-47767-7_27

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-47766-0

  • Online ISBN: 978-3-030-47767-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation