Browse > Article
http://dx.doi.org/10.5653/cerm.2020.04049

The role of gonadotropin-releasing hormone agonists in female fertility preservation  

Lee, Jae Hoon (Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine)
Choi, Young Sik (Institute of Women's Life Medical Science, Yonsei University College of Medicine)
Publication Information
Clinical and Experimental Reproductive Medicine / v.48, no.1, 2021 , pp. 11-26 More about this Journal
Abstract
Advances in anticancer treatments have resulted in increasing survival rates among cancer patients. Accordingly, the quality of life after treatment, particularly the preservation of fertility, has gradually emerged as an essential consideration. Cryopreservation of embryos or unfertilized oocytes has been considered as the standard method of fertility preservation among young women facing gonadotoxic chemotherapy. Other methods, including ovarian suppression and ovarian tissue cryopreservation, have been considered experimental. Recent large-scale randomized controlled trials have demonstrated that temporary ovarian suppression using gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy is beneficial for preventing chemotherapy-induced premature ovarian insufficiency in breast cancer patients. It should also be emphasized that GnRHa use during chemotherapy does not replace established fertility preservation methods. All young women facing gonadotoxic chemotherapy should be counseled about and offered various options for fertility preservation, including both GnRHa use and cryopreservation of embryos, oocytes, and/or ovarian tissue.
Keywords
Chemotherapy; Fertility preservation; Gonadotropin-releasing hormone agonist; Premature menopause;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Chen H, Xiao L, Li J, Cui L, Huang W. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev 2019;3:CD008018.
2 Oktay K, Turan V. Failure of ovarian suppression with gonadotropin-releasing hormone analogs to preserve fertility: an assessment based on the quality of evidence. JAMA Oncol 2016;2:74-5.   DOI
3 Ortmann O, Weiss JM, Diedrich K. Gonadotrophin-releasing hormone (GnRH) and GnRH agonists: mechanisms of action. Reprod Biomed Online 2002;5 Suppl 1:1-7.   DOI
4 Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, et al. Invasive breast cancer version 1.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2016; 14:324-54.   DOI
5 Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, et al. Tailoring therapies: improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 2015;26:1533-46.   DOI
6 Paluch-Shimon S, Pagani O, Partridge AH, Bar-Meir E, Fallowfield L, Fenlon D, et al. Second international consensus guidelines for breast cancer in young women (BCY2). Breast 2016;26:87-99.   DOI
7 Dunlop CE, Anderson RA. Uses of anti-Mullerian hormone (AMH) measurement before and after cancer treatment in women. Maturitas 2015;80:245-50.   DOI
8 Lambertini M, Moore HC, Leonard RC, Loibl S, Munster P, Bruzzone M, et al. Gonadotropin-releasing hormone agonists during chemotherapy for preservation of ovarian function and fertility in premenopausal patients with early breast cancer: a systematic review and meta-analysis of individual patient-level data. J Clin Oncol 2018;36:1981-90.   DOI
9 Demeestere I, Brice P, Peccatori FA, Kentos A, Dupuis J, Zachee P, et al. No evidence for the benefit of gonadotropin-releasing hormone agonist in preserving ovarian function and fertility in lymphoma survivors treated with chemotherapy: final long-term report of a prospective randomized trial. J Clin Oncol 2016;34: 2568-74.   DOI
10 Zhang Y, Ji Y, Li J, Lei L, Wu S, Zuo W, et al. Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal breast cancer patients: effects on ovarian function, disease-free survival, and overall survival. Breast Cancer Res Treat 2018;168:679-86.   DOI
11 Zhong Y, Lin Y, Cheng X, Huang X, Zhou Y, Mao F, et al. GnRHa for ovarian protection and the association between amh and ovarian function during adjuvant chemotherapy for breast cancer. J Cancer 2019;10:4278-85.   DOI
12 Meirow D, Biederman H, Anderson RA, Wallace WH. Toxicity of chemotherapy and radiation on female reproduction. Clin Obstet Gynecol 2010;53:727-39.   DOI
13 Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959;22: 719-48.
14 Blumenfeld Z. ZORO study: discrepancy between the conclusion and the results. J Clin Oncol 2011;29:3340.   DOI
15 Glode LM, Robinson J, Gould SF. Protection from cyclophosphamide-induced testicular damage with an analogue of gonadotropin-releasing hormone. Lancet 1981;1:1132-4.   DOI
16 Soleimani R, Heytens E, Darzynkiewicz Z, Oktay K. Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise. Aging (Albany NY) 2011;3:782-93.   DOI
17 Jung KW, Won YJ, Kong HJ, Lee ES. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2016. Cancer Res Treat 2019;51:417-30.   DOI
18 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;31:2500-10.   DOI
19 Blumenfeld Z, Evron A. Preserving fertility when choosing chemotherapy regimens: the role of gonadotropin-releasing hormone agonists. Expert Opin Pharmacother 2015;16:1009-20.   DOI
20 Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 2004;428:145-50.   DOI
21 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 2014;29:989-96.   DOI
22 Perez GI, Knudson CM, Leykin L, Korsmeyer SJ, Tilly JL. Apoptosis-associated signaling pathways are required for chemotherapy-mediated female germ cell destruction. Nat Med 1997;3: 1228-32.   DOI
23 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;15:1179-85.   DOI
24 Steiner AZ, Pritchard D, Stanczyk FZ, Kesner JS, Meadows JW, Herring AH, et al. Association between biomarkers of ovarian reserve and infertility among older women of reproductive age. JAMA 2017;318:1367-76.   DOI
25 Miyoshi Y, Yasuda K, Miyamura T, Miyashita E, Hashii Y, Ozono K. Anti-Mullerian hormone is a useful marker of gonadotoxicity in girls treated for cancer: a prospective study. Horm Res Paediatr 2015;84:479.
26 Anderson RA, Wallace WH. Antimullerian hormone, the assessment of the ovarian reserve, and the reproductive outcome of the young patient with cancer. Fertil Steril 2013;99:1469-75.   DOI
27 Freour T, Barriere P, Masson D. Anti-mullerian hormone levels and evolution in women of reproductive age with breast cancer treated with chemotherapy. Eur J Cancer 2017;74:1-8.   DOI
28 Hamy AS, Porcher R, Eskenazi S, Cuvier C, Giacchetti S, Coussy F, et al. Anti-Mullerian hormone in breast cancer patients treated with chemotherapy: a retrospective evaluation of subsequent pregnancies. Reprod Biomed Online 2016;32:299-307.   DOI
29 Janse F, Donnez J, Anckaert E, de Jong FH, Fauser BC, Dolmans MM. Limited value of ovarian function markers following orthotopic transplantation of ovarian tissue after gonadotoxic treatment. J Clin Endocrinol Metab 2011;96:1136-44.   DOI
30 Desmeules P, Devine PJ. Characterizing the ovotoxicity of cyclophosphamide metabolites on cultured mouse ovaries. Toxicol Sci 2006;90:500-9.   DOI
31 Smith ML, Kumar MA. The "two faces" of tumor suppressor p53-revisited. Mol Cell Pharmacol 2010;2:117-9.
32 Gonfloni S. DNA damage stress response in germ cells: role of c-Abl and clinical implications. Oncogene 2010;29:6193-202.   DOI
33 Patsoula E, Loutradis D, Drakakis P, Michalas L, Bletsa R, Michalas S. Messenger RNA expression for the follicle-stimulating hormone receptor and luteinizing hormone receptor in human oocytes and preimplantation-stage embryos. Fertil Steril 2003;79:1187-93.   DOI
34 Babu PS, Danilovich N, Sairam MR. Hormone-induced receptor gene splicing: enhanced expression of the growth factor type I follicle-stimulating hormone receptor motif in the developing mouse ovary as a new paradigm in growth regulation. Endocrinology 2001;142:381-9.   DOI
35 Chapman RM, Sutcliffe SB. Protection of ovarian function by oral contraceptives in women receiving chemotherapy for Hodgkin's disease. Blood 1981;58:849-51.   DOI
36 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.   DOI
37 Grundker C, Emons G. Role of gonadotropin-releasing hormone (GnRH) in ovarian cancer. Reprod Biol Endocrinol 2003;1:65.   DOI
38 Zelinski MB, Murphy MK, Lawson MS, Jurisicova A, Pau KY, Toscano NP, et al. In vivo delivery of FTY720 prevents radiation-induced ovarian failure and infertility in adult female nonhuman primates. Fertil Steril 2011;95:1440-5.   DOI
39 Bedoschi G, Turan V, Oktay K. Utility of GnRH-agonists for fertility preservation in women with operable breast cancer: is it protective? Curr Breast Cancer Rep 2013;5:302-8.   DOI
40 Turner NH, Partridge A, Sanna G, Di Leo A, Biganzoli L. Utility of gonadotropin-releasing hormone agonists for fertility preservation in young breast cancer patients: the benefit remains uncertain. Ann Oncol 2013;24:2224-35.   DOI
41 Woods KE, Randolph JK, Gewirtz DA. Antagonism between tamoxifen and doxorubicin in the MCF-7 human breast tumor cell line. Biochem Pharmacol 1994;47:1449-52.   DOI
42 Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, et al. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet 2009;374:2055-63.   DOI
43 International Breast Cancer Study Group. Late effects of adjuvant oophorectomy and chemotherapy upon premenopausal breast cancer patients. Ann Oncol 1990;1:30-5.   DOI
44 Arriagada R, Le MG, Spielmann M, Mauriac L, Bonneterre J, Namer M, et al. Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy. Ann Oncol 2005;16:389-96.   DOI
45 Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 2014;371:107-18.   DOI
46 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: 2917-31.   DOI
47 Yasmin E, Balachandren N, Davies MC, Jones GL, Lane S, Mathur R, et al. Fertility preservation for medical reasons in girls and women: British fertility society policy and practice guideline. Hum Fertil (Camb) 2018;21:3-26.   DOI
48 Bar-Joseph H, Ben-Aharon I, Rizel S, Stemmer SM, Tzabari M, Shalgi R. Doxorubicin-induced apoptosis in germinal vesicle (GV) oocytes. Reprod Toxicol 2010;30:566-72.   DOI
49 Marcello MF, Nuciforo G, Romeo R, Di Dino G, Russo I, Russo A, et al. Structural and ultrastructural study of the ovary in childhood leukemia after successful treatment. Cancer 1990;66:2099-104.   DOI
50 Flaws JA, Abbud R, Mann RJ, Nilson JH, Hirshfield AN. Chronically elevated luteinizing hormone depletes primordial follicles in the mouse ovary. Biol Reprod 1997;57:1233-7.   DOI
51 Sofiyeva N, Siepmann T, Barlinn K, Seli E, Ata B. Gonadotropin-releasing hormone analogs for gonadal protection during gonadotoxic chemotherapy: a systematic review and meta-analysis. Reprod Sci 2019;26:939-53.   DOI
52 Scaruffi P, Stigliani S, Cardinali B, Massarotti C, Lambertini M, Sozzi F, et al. Gonadotropin releasing hormone agonists have an anti-apoptotic effect on cumulus cells. Int J Mol Sci 2019;20:6045.   DOI
53 Waxman JH, Ahmed R, Smith D, Wrigley PF, Gregory W, Shalet S, et al. Failure to preserve fertility in patients with Hodgkin's disease. Cancer Chemother Pharmacol 1987;19:159-62.   DOI
54 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;36:1994-2001.   DOI
55 Peigne M, Decanter C. Serum AMH level as a marker of acute and long-term effects of chemotherapy on the ovarian follicular content: a systematic review. Reprod Biol Endocrinol 2014;12:26.   DOI
56 Ortin TT, Shostak CA, Donaldson SS. Gonadal status and reproductive function following treatment for Hodgkin's disease in childhood: the Stanford experience. Int J Radiat Oncol Biol Phys 1990;19:873-80.   DOI
57 Paluch-Shimon S, Cardoso F, Partridge AH, Abulkhair O, Azim HA Jr, Bianchi-Micheli G, et al. ESO-ESMO 4th International Consensus Guidelines for Breast Cancer in Young Women (BCY4). Ann Oncol 2020;31:674-96.   DOI
58 Wallace WH, Kelsey TW. Human ovarian reserve from conception to the menopause. PLoS One 2010;5:e8772.   DOI
59 Gilani MM, Hasanzadeh M, Ghaemmaghami F, Ramazanzadeh F. Ovarian preservation with gonadotropin-releasing hormone analog during chemotherapy. Asia Pac J Clin Oncol 2007;3:79-83.   DOI
60 ISFP Practice Committee; Kim SS, Donnez J, Barri P, Pellicer A, Patrizio P, et al. Recommendations for fertility preservation in patients with lymphoma, leukemia, and breast cancer. J Assist Reprod Genet 2012;29:465-8.   DOI
61 Behringer K, Wildt L, Mueller H, Mattle V, Ganitis P, van den Hoonaard B, et al. No protection of the ovarian follicle pool with the use of GnRH-analogues or oral contraceptives in young women treated with escalated BEACOPP for advanced-stage Hodgkin lymphoma: final results of a phase II trial from the German Hodgkin Study Group. Ann Oncol 2010;21:2052-60.   DOI
62 Imai A, Sugiyama M, Furui T, Tamaya T, Ohno T. Direct protection by a gonadotropin-releasing hormone analog from doxorubicin-induced granulosa cell damage. Gynecol Obstet Invest 2007; 63:102-6.   DOI
63 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;5:185ra62.   DOI
64 Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemotherapeutic agents damage the ovary? Hum Reprod Update 2012;18:525-35.   DOI
65 Petrek JA, Naughton MJ, Case LD, Paskett ED, Naftalis EZ, Singletary SE, et al. Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study. J Clin Oncol 2006;24:1045-51.   DOI
66 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;118:1933-9.   DOI
67 Blumenfeld Z, Evron A. Endocrine prevention of chemotherapy-induced ovarian failure. Curr Opin Obstet Gynecol 2016;28: 223-9.   DOI
68 Blumenfeld Z, von Wolff M. GnRH-analogues and oral contraceptives for fertility preservation in women during chemotherapy. Hum Reprod Update 2008;14:543-52.   DOI
69 Ben-Aharon I, Bar-Joseph H, Tzarfaty G, Kuchinsky L, Rizel S, Stemmer SM, et al. Doxorubicin-induced ovarian toxicity. Reprod Biol Endocrinol 2010;8:20.   DOI
70 Utsunomiya T, Tanaka T, Utsunomiya H, Umesaki N. A novel molecular mechanism for anticancer drug-induced ovarian failure: irinotecan HCl, an anticancer topoisomerase I inhibitor, induces specific FasL expression in granulosa cells of large ovarian follicles to enhance follicular apoptosis. Int J Oncol 2008;32:991-1000.
71 Petrillo SK, Desmeules P, Truong TQ, 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;253:94-102.   DOI
72 Leonard RC, Adamson DJ, Bertelli G, Mansi J, Yellowlees A, Dunlop J, et al. GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial. Ann Oncol 2017;28:1811-6.   DOI
73 Hickman LC, Llarena NC, Valentine LN, Liu X, Falcone T. Preservation of gonadal function in women undergoing chemotherapy: a systematic review and meta-analysis of the potential role for gonadotropin-releasing hormone agonists. J Assist Reprod Genet 2018;35:571-81.   DOI
74 Lambertini M, Boni L, Michelotti A, Gamucci T, Scotto T, Gori S, et al. Ovarian suppression with triptorelin during adjuvant breast cancer chemotherapy and long-term ovarian function, pregnancies, and disease-free survival: a randomized clinical trial. JAMA 2015;314:2632-40.   DOI
75 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 2007;22:1626-33.   DOI
76 Matzuk MM, Burns KH, Viveiros MM, Eppig JJ. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 2002;296:2178-80.   DOI
77 Oktem O, Oktay K. Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function. Cancer 2007;110:2222-9.   DOI
78 Abir R, Ben-Haroush A, Felz C, Okon E, Raanani H, Orvieto R, et al. Selection of patients before and after anticancer treatment for ovarian cryopreservation. Hum Reprod 2008;23:869-77.   DOI
79 Downs SM, Utecht AM. Metabolism of radiolabeled glucose by mouse oocytes and oocyte-cumulus cell complexes. Biol Reprod 1999;60:1446-52.   DOI
80 Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003;22:7265-79.   DOI
81 Lobo RA. Potential options for preservation of fertility in women. N Engl J Med 2005;353:64-73.   DOI
82 Adriaens I, Cortvrindt R, Smitz J. Differential FSH exposure in preantral follicle culture has marked effects on folliculogenesis and oocyte developmental competence. Hum Reprod 2004;19:398-408.   DOI
83 Edson MA, Nagaraja AK, Matzuk MM. The mammalian ovary from genesis to revelation. Endocr Rev 2009;30:624-712.   DOI
84 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;12:1044-54.   DOI
85 Webb R, Garnsworthy PC, Gong JG, Armstrong DG. Control of follicular growth: local interactions and nutritional influences. J Anim Sci 2004;82 E-Suppl:E63-74.
86 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.
87 Harrison GS, Wierman ME, Nett TM, Glode LM. Gonadotropin-releasing hormone and its receptor in normal and malignant cells. Endocr Relat Cancer 2004;11:725-48.   DOI
88 Patel H, Bhartiya D, Parte S, Gunjal P, Yedurkar S, Bhatt M. Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3. J Ovarian Res 2013;6:52.   DOI
89 Oktay K, Briggs D, Gosden RG. Ontogeny of follicle-stimulating hormone receptor gene expression in isolated human ovarian follicles. J Clin Endocrinol Metab 1997;82:3748-51.   DOI
90 Kitajima Y, Endo T, Nagasawa K, Manase K, Honnma H, Baba T, et al. Hyperstimulation and a gonadotropin-releasing hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-5. Endocrinology 2006; 147:694-9.   DOI
91 Zheng W, Magid MS, Kramer EE, Chen YT. Follicle-stimulating hormone receptor is expressed in human ovarian surface epithelium and fallopian tube. Am J Pathol 1996;148:47-53.
92 Knight PG, Glister C. TGF-beta superfamily members and ovarian follicle development. Reproduction 2006;132:191-206.   DOI
93 Saitta A, Altavilla D, Cucinotta D, Morabito N, Frisina N, Corrado F, et al. Randomized, double-blind, placebo-controlled study on effects of raloxifene and hormone replacement therapy on plasma no concentrations, endothelin-1 levels, and endothelium-dependent vasodilation in postmenopausal women. Arterioscler Thromb Vasc Biol 2001;21:1512-9.   DOI
94 Leung PC, Cheng CK, Zhu XM. Multi-factorial role of GnRH-I and GnRH-II in the human ovary. Mol Cell Endocrinol 2003;202:145-53.   DOI
95 Gargett CE. Review article: stem cells in human reproduction. Reprod Sci 2007;14:405-24.   DOI
96 Chiarelli AM, Marrett LD, Darlington G. Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964-1988 in Ontario, Canada. Am J Epidemiol 1999; 150:245-54.   DOI
97 Zhao XJ, Huang YH, Yu YC, Xin XY. GnRH antagonist cetrorelix inhibits mitochondria-dependent apoptosis triggered by chemotherapy in granulosa cells of rats. Gynecol Oncol 2010;118:69-75.   DOI
98 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.   DOI
99 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;6:1109-14.   DOI
100 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 2014;29:107-13.   DOI
101 Blumenfeld Z. Fertility preservation using GnRH agonists: rationale, possible mechanisms, and explanation of controversy. Clin Med Insights Reprod Health 2019;13:1179558119870163.
102 Coccia PF, Pappo AS, Beaupin L, Borges VF, Borinstein SC, Chugh R, et al. Adolescent and young adult oncology, version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2018;16:66-97.   DOI
103 Klemp JR, Kim SS; ISFP Practice Committee. Fertility preservation in young women with breast cancer. J Assist Reprod Genet 2012; 29:469-72.   DOI
104 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). Hematology 2007;12:141-7.   DOI
105 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;91:694-7.   DOI
106 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.
107 Munhoz RR, Pereira AA, 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;2:65-73.   DOI
108 Rivkin SE, Green S, O'Sullivan J, Cruz AB, Abeloff MD, Jewell WR, et al. Adjuvant CMFVP versus adjuvant CMFVP plus ovariectomy for premenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a SouthwestOncology Group study. J Clin Oncol 1996;14:46-51.   DOI
109 Lunsford AJ, Whelan K, McCormick K, McLaren JF. Antimullerian hormone as a measure of reproductive function in female childhood cancer survivors. Fertil Steril 2014;101:227-31.   DOI
110 Senra JC, Roque M, Talim MC, Reis FM, Tavares RL. Gonadotropin-releasing hormone agonists for ovarian protection during cancer chemotherapy: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2018;51:77-86.   DOI
111 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.   DOI
112 Moore HC, Unger JM, Phillips KA, Boyle F, Hitre E, Porter D, et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med 2015;372:923-32.   DOI
113 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.   DOI
114 Bai F, Lu Y, Wu K, Chen Q, Ding L, Ge M, et al. Protecting effects of gonadotropin-releasing hormone agonist on chemotherapy-induced ovarian damage in premenopausal breast cancer patients: a systematic review and meta-analysis. Breast Care (Basel) 2017;12:48-52.   DOI
115 Elgindy E, Sibai H, Abdelghani A, Mostafa M. Protecting ovaries during chemotherapy through gonad suppression: a systematic review and meta-analysis. Obstet Gynecol 2015;126:187-95.   DOI
116 Lambertini M, Ceppi M, Poggio F, Peccatori FA, Azim HA Jr, Ugolini D, et al. Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies. Ann Oncol 2015;26:2408-19.   DOI
117 Silva C, Caramelo O, Almeida-Santos T, Ribeiro Rama AC. Factors associated with ovarian function recovery after chemotherapy for breast cancer: a systematic review and meta-analysis. Hum Reprod 2016;31:2737-49.   DOI
118 Von Wolff M, Germeyer A, Liebenthron J, Korell M, Nawroth F. Practical recommendations for fertility preservation in women by the FertiPROTEKT network. Part II: fertility preservation techniques. Arch Gynecol Obstet 2018;297:257-67.   DOI
119 Sverrisdottir A, Nystedt M, Johansson H, Fornander T. Adjuvant goserelin and ovarian preservation in chemotherapy treated patients with early breast cancer: results from a randomized trial. Breast Cancer Res Treat 2009;117:561-7.   DOI
120 Karimi-Zarchi M, Forat-Yazdi M, Vafaeenasab MR, Nakhaie-Moghadam M, Miratashi-Yazdi A, Teimoori S, et al. Evaluation of the effect of GnRH agonist on menstrual reverse in breast cancer cases treated with cyclophosphamide. Eur J Gynaecol Oncol 2014;35: 59-61.
121 Goldenberg GJ, Froese EK. Antagonism of the cytocidal activity and uptake of melphalan by tamoxifen in human breast cancer cells in vitro. Biochem Pharmacol 1985;34:763-70.   DOI
122 Lambertini M, Del Mastro L, Pescio MC, Andersen CY, Azim HA Jr, Peccatori FA, et al. Cancer and fertility preservation: international recommendations from an expert meeting. BMC Med 2016;14:1.   DOI
123 Jurisicova A, Lee HJ, D'Estaing SG, Tilly J, Perez GI. Molecular requirements for doxorubicin-mediated death in murine oocytes. Cell Death Differ 2006;13:1466-74.   DOI
124 Song G, Gao H, Yuan Z. Effect of leuprolide acetate on ovarian function after cyclophosphamide-doxorubicin-based chemotherapy in premenopausal patients with breast cancer: results from a phase II randomized trial. Med Oncol 2013;30:667.   DOI