Skip to main content
Erschienen in: Journal of Assisted Reproduction and Genetics 4/2018

22.02.2018 | Fertility Preservation

Preservation of gonadal function in women undergoing chemotherapy: a systematic review and meta-analysis of the potential role for gonadotropin-releasing hormone agonists

verfasst von: Lisa C. Hickman, Natalia C. Llarena, Lindsey N. Valentine, Xiaobo Liu, Tommaso Falcone

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 4/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To evaluate the available randomized controlled trials (RCTs) in the literature investigating the use of gonadotropin-releasing hormone agonist (GnRHa) co-treatment for ovarian preservation in women receiving chemotherapy.

Methods

A systematic review of the literature was performed from 1960 through 2017 to identify relevant RCTs. Included patients had lymphoma, ovarian cancer, or breast cancer. The primary outcome was the proportion of women who retained ovarian function after chemotherapy. Extracted data points included study design, patient characteristics, and proportion of women who developed premature ovarian failure (POF). A risk of bias assessment was performed according to the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The pooled odds ratio was calculated, and outcomes of individual studies were compared using the random-effects model with the inverse-variance method and the DerSimonian-Laird estimator.

Results

Twenty-nine RCTs were identified, and 10 met criteria for inclusion in the meta-analysis. An analysis of patients who did not develop POF after chemotherapy revealed eight studies supporting the use of GnRHa (OR 1.83; 95% CI 1.34–2.49). The duration of benefit of GnRHa is unclear. An analysis of three studies with outcome data at 2 years revealed a non-significant OR of 0.53 (95% CI 0.22–1.30) for the preservation of ovarian function with GnRHa treatment.

Conclusion

GnRHa may have a protective effect against the development of POF after gonadotoxic chemotherapy; however, the duration of benefit is unclear and requires further study.
Literatur
5.
Zurück zum Zitat Hickman LC, Valentine LN, Falcone T. Preservation of gonadal function in women undergoin chemotherapy: a review of the potential role for gonadotropin-releasing hormone agonists. Am J Obstet Gynecol. 2016;215(4):415–22.CrossRefPubMed Hickman LC, Valentine LN, Falcone T. Preservation of gonadal function in women undergoin chemotherapy: a review of the potential role for gonadotropin-releasing hormone agonists. Am J Obstet Gynecol. 2016;215(4):415–22.CrossRefPubMed
7.
Zurück zum Zitat Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemothera-peutic agents damage the ovary? Hum Reprod Update. 2012;18:525–35.CrossRefPubMed Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemothera-peutic agents damage the ovary? Hum Reprod Update. 2012;18:525–35.CrossRefPubMed
8.
Zurück zum Zitat Hasky N, Uri-Belapolsky S, Goldberg K, et al. Gonadotropin-releasing hormone agonists for fertility preservation: unraveling the enigma? Hum Reprod. 2015;30:1089–101.CrossRefPubMed Hasky N, Uri-Belapolsky S, Goldberg K, et al. Gonadotropin-releasing hormone agonists for fertility preservation: unraveling the enigma? Hum Reprod. 2015;30:1089–101.CrossRefPubMed
10.
Zurück zum Zitat Moore HC, Unger JM, Phillips KA, Boyle F, Hitre E, Porter D, Francis PA, Goldstein LJ, Gomez HL, Vallejos CS, Partridge AH, Dakhil SR, Garcia AA, Gralow J, Lombard JM, Forbes JF, Martino S, Barlow WE, Fabian CJ, Minasian L, Meyskens FL, Gelber RD, Hortobagyi GN, Albain KS, POEMS/S0230 Investigators Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med 2015;372:923–932; doi: https://doi.org/10.1056/NEJMoa1413204. Moore HC, Unger JM, Phillips KA, Boyle F, Hitre E, Porter D, Francis PA, Goldstein LJ, Gomez HL, Vallejos CS, Partridge AH, Dakhil SR, Garcia AA, Gralow J, Lombard JM, Forbes JF, Martino S, Barlow WE, Fabian CJ, Minasian L, Meyskens FL, Gelber RD, Hortobagyi GN, Albain KS, POEMS/S0230 Investigators Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med 2015;372:923–932; doi: https://​doi.​org/​10.​1056/​NEJMoa1413204.
16.
Zurück zum Zitat Waxman JH, Ahmed R, Smith D, Wrigley PF, Gregory W, Shalet S, Crowther D, Rees LH, Besser GM, Malpas JS Failure to preserve fertility in patients with Hodgkin’s disease. Cancer Chemother Pharmacol 1987;19:159–162. Waxman JH, Ahmed R, Smith D, Wrigley PF, Gregory W, Shalet S, Crowther D, Rees LH, Besser GM, Malpas JS Failure to preserve fertility in patients with Hodgkin’s disease. Cancer Chemother Pharmacol 1987;19:159–162.
18.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
22.
Zurück zum Zitat 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;306:269–76. https://doi.org/10.1001/jama.2011.991.PubMed 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;306:269–76. https://​doi.​org/​10.​1001/​jama.​2011.​991.PubMed
26.
Zurück zum Zitat 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. 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.
27.
Zurück zum Zitat Randolph JF, Crawford S, Dennerstein L, Cain K, Harlow SD, Little R, et al. The value of follicle-stimulating hormone concentration and clinical findings as markers of the late menopausal transition. J Clin Endocrinol Metab. 2006;91:3034–40.CrossRefPubMed Randolph JF, Crawford S, Dennerstein L, Cain K, Harlow SD, Little R, et al. The value of follicle-stimulating hormone concentration and clinical findings as markers of the late menopausal transition. J Clin Endocrinol Metab. 2006;91:3034–40.CrossRefPubMed
28.
Zurück zum Zitat Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.0.2. The Cochrane Collaboration 2009:2015. Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.0.2. The Cochrane Collaboration 2009:2015.
29.
Zurück zum Zitat Light RJ, Pillemer DB. Summing up. The science of reviewing research. Cambridge: Harvard University Press; 1984. Light RJ, Pillemer DB. Summing up. The science of reviewing research. Cambridge: Harvard University Press; 1984.
31.
Zurück zum Zitat Oktay K, Sonmezer M. Questioning GnRH analogs for gonadal protection in cancer patients. Fertil Steril. 2009;92:e32. author reply e34CrossRefPubMed Oktay K, Sonmezer M. Questioning GnRH analogs for gonadal protection in cancer patients. Fertil Steril. 2009;92:e32. author reply e34CrossRefPubMed
32.
Zurück zum Zitat Peccatori F, Demeestere I. GnRH analogue for chemotherapy-induced ovarian damage: too early to say? Fertil Steril. 2009;92:e33. author reply e34CrossRefPubMed Peccatori F, Demeestere I. GnRH analogue for chemotherapy-induced ovarian damage: too early to say? Fertil Steril. 2009;92:e33. author reply e34CrossRefPubMed
33.
Zurück zum Zitat Leonard RCF, Adamson DJA, Bertelli G, Mansi J, Yellowlees A, Dunlop J, Thomas GA, Coleman RE, Anderson RA. GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial. Ann Oncol. 2017;28:1811–1816. Leonard RCF, Adamson DJA, Bertelli G, Mansi J, Yellowlees A, Dunlop J, Thomas GA, Coleman RE, Anderson RA. GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial. Ann Oncol. 2017;28:1811–1816.
34.
Zurück zum Zitat 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;102:808–815.e1.CrossRefPubMed 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;102:808–815.e1.CrossRefPubMed
35.
Zurück zum Zitat Ben-Aharon I, Gafter-Gvili A, Leibovici L, Stemmer SM. Pharmacological interventions for fertility preservation during chemotherapy: a systematic review and meta-analysis. Breast Cancer Res Treat. 2010;122:803–11.CrossRefPubMed Ben-Aharon I, Gafter-Gvili A, Leibovici L, Stemmer SM. Pharmacological interventions for fertility preservation during chemotherapy: a systematic review and meta-analysis. Breast Cancer Res Treat. 2010;122:803–11.CrossRefPubMed
36.
Zurück zum Zitat Chen H, Li J, Cui T, Hu L. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev. 2011a:(11):CD008018. Chen H, Li J, Cui T, Hu L. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev. 2011a:(11):CD008018.
37.
Zurück zum Zitat 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 Women's Health (Larchmt). 2009;18:311–9.CrossRef 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 Women's Health (Larchmt). 2009;18:311–9.CrossRef
38.
Zurück zum Zitat Del Mastro L, Ceppi M, Poggio F, Bighin C, Peccatori F, Demeestere I, et al. Gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in cancer women: systematic review and meta-analysis of randomized trials. Cancer Treat Rev. 2014;40:675–83.CrossRefPubMed Del Mastro L, Ceppi M, Poggio F, Bighin C, Peccatori F, Demeestere I, et al. Gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in cancer women: systematic review and meta-analysis of randomized trials. Cancer Treat Rev. 2014;40:675–83.CrossRefPubMed
39.
Zurück zum Zitat Kim SS, Lee JR, Jee BC, Suh CS, Kim SH, Ting A, et al. Use of hormonal protection for chemotherapy-induced gonadotoxicity. Clin Obstet Gynecol. 2010;53:740–52.CrossRefPubMed Kim SS, Lee JR, Jee BC, Suh CS, Kim SH, Ting A, et al. Use of hormonal protection for chemotherapy-induced gonadotoxicity. Clin Obstet Gynecol. 2010;53:740–52.CrossRefPubMed
40.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
41.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
42.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
43.
Zurück zum Zitat Sun X, Dongol S, Jiang J, Kong B. Protection of ovarian function by GnRH agonists during chemotherapy: a meta-analysis. Int J Oncol. 2014;44:1335–40.CrossRefPubMed Sun X, Dongol S, Jiang J, Kong B. Protection of ovarian function by GnRH agonists during chemotherapy: a meta-analysis. Int J Oncol. 2014;44:1335–40.CrossRefPubMed
44.
Zurück zum Zitat Yang B, Shi W, Yang J, Liu H, Zhao H, Li X, et al. Concurrent treatment with gonadotropin-releasing hormone agonists for chemotherapy-induced ovarian damage in premenopausal women with breast cancer: a meta-analysis of randomized controlled trials. Breast. 2013;22:150–7.CrossRefPubMed Yang B, Shi W, Yang J, Liu H, Zhao H, Li X, et al. Concurrent treatment with gonadotropin-releasing hormone agonists for chemotherapy-induced ovarian damage in premenopausal women with breast cancer: a meta-analysis of randomized controlled trials. Breast. 2013;22:150–7.CrossRefPubMed
45.
Zurück zum Zitat Zhang Y, Xiao Z, Wang Y, Luo S, Li X, Li S. Gonadotropin-releasing hormone for preservation of ovarian function during chemotherapy in lymphoma patients of reproductive age: a summary based on 434 patients. PLoS One. 2013;8:e80444.CrossRefPubMedPubMedCentral Zhang Y, Xiao Z, Wang Y, Luo S, Li X, Li S. Gonadotropin-releasing hormone for preservation of ovarian function during chemotherapy in lymphoma patients of reproductive age: a summary based on 434 patients. PLoS One. 2013;8:e80444.CrossRefPubMedPubMedCentral
46.
Zurück zum Zitat Wang C, Chen M, Fu F, Huang M. Gonadotropin-releasing hormone analog cotreatment for the preservation of ovarian function during gonadotoxic chemotherapy for breast cancer: a meta-analysis. PLoS One. 2013;8:e66360.CrossRefPubMedPubMedCentral Wang C, Chen M, Fu F, Huang M. Gonadotropin-releasing hormone analog cotreatment for the preservation of ovarian function during gonadotoxic chemotherapy for breast cancer: a meta-analysis. PLoS One. 2013;8:e66360.CrossRefPubMedPubMedCentral
47.
Zurück zum Zitat Lambertini M, Falcone T, Unger JM, Phillips KA, Del Mastro L, Moore HC. Debated role of ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy for preservation of ovarian function and fertility in women with cancer. J Clin Oncol. 2017;35:804–5.CrossRefPubMed Lambertini M, Falcone T, Unger JM, Phillips KA, Del Mastro L, Moore HC. Debated role of ovarian protection with gonadotropin-releasing hormone agonists during chemotherapy for preservation of ovarian function and fertility in women with cancer. J Clin Oncol. 2017;35:804–5.CrossRefPubMed
48.
Zurück zum Zitat Blumenfeld Z, Katz G, Evron A. ‘An ounce of prevention is worth a pound of cure’: the case for and against GnRH-agonist for fertility preservation. Ann Oncol. 2014;25:1719–28.CrossRefPubMed Blumenfeld Z, Katz G, Evron A. ‘An ounce of prevention is worth a pound of cure’: the case for and against GnRH-agonist for fertility preservation. Ann Oncol. 2014;25:1719–28.CrossRefPubMed
49.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
50.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
51.
Zurück zum Zitat Steiner A, Pritrchard D, Stancyzk F. Association between biomarkers of ovarian reserve and infertility among older women of reproductive age. JAMA. 2017;318(14):1367–76.CrossRefPubMedPubMedCentral Steiner A, Pritrchard D, Stancyzk F. Association between biomarkers of ovarian reserve and infertility among older women of reproductive age. JAMA. 2017;318(14):1367–76.CrossRefPubMedPubMedCentral
Metadaten
Titel
Preservation of gonadal function in women undergoing chemotherapy: a systematic review and meta-analysis of the potential role for gonadotropin-releasing hormone agonists
verfasst von
Lisa C. Hickman
Natalia C. Llarena
Lindsey N. Valentine
Xiaobo Liu
Tommaso Falcone
Publikationsdatum
22.02.2018
Verlag
Springer US
Erschienen in
Journal of Assisted Reproduction and Genetics / Ausgabe 4/2018
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-018-1128-2

Weitere Artikel der Ausgabe 4/2018

Journal of Assisted Reproduction and Genetics 4/2018 Zur Ausgabe

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.