Get Adobe Flash player
Ovarian Cancer menses resumption and of spontaneous pregnancy were not significantly different between the two arms. Although GnRH-agonist suppression of the reproductive axis causes typical symptoms of menopause, the meta- analysis did not find a significant difference in adverse events between the two groups. Conclusion Cancer treatments may temporarily or definitively damage the ovarian function. Premature menopause and irreversible sterility are the most dramatic outcome of ovarian dysfunction and these are associated with an impaired quality of life and influence patient’s treatment compliance. Discussions about fertility and fertility preservation are of great importance to patients with cancer. Hence the interest in identifying effective, tolerable, safe and non-invasive methods to prevent the consequences of premature menopause and, in particular, to preserve fertility in young women exposed to chemotherapy. The role of temporary ovarian suppression with the administration of the GnRH analogue during chemotherapy has been evaluated in several studies from which are derived conflicting results. Evaluating the results of these studies together is difficult because these are influenced by many factors: the different age of the study populations, the different type of chemotherapy used, the inclusion or exclusion of oestrogen receptor-positive patients and the treatment with tamoxifen, the different endpoints (amenorrhoea vs menstruation vs laboratory values) and the different timing of ovarian function assessment. In addition, the limited length of follow up in these studies preclude the possibility to determine the long-term impact of GnRH analogues on preservation of ovarian function and fertility. Another important aspect is the possible detrimental effect of the maintenance of ovarian function in 1. SEER Stat Fact Sheets: breast. Surveillance, Epidemiology and Results Web site. Accessed June 2011 (available at: http:// 2. Partridge AH, Gelber S, Peppercorn J et al., Web-based survey of fertility issue in young women with breast cancer, J Clin Oncol, 2004;22:4174–83. 3. Familiari G, Caggiati A, Nottola SA et al., Ultrastructure of human ovarian primordial follicles after combination chemotherapy for Hodgkin’s disease, Hum Reprod, 1993;6:2080–7. 4. Meirow D, Dor J, Kaufman B et al. Cortical fibrosis and blood- vessels damage in human ovaries exposed to chemotherapy. Potential mechanism of ovarian injury, Hum Reprod, 2007;22:1626–33. 5. Oktem O, Oktay K, A novel ovarian xenografting model to characterize the impact of chemotherapy agents on human primordial follicle reserve, Cancer Research, 2007;67:10159–62. 6. Fornier MN, Modi S, Panageas KS et al., Incidence of chemotherapy-induced, long-term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane, Cancer, 2005;104:1575–9. 7. Swain SM, Jeong JH, Geyer CE et al., Longer therapy, iatrogenic amenorrhea and survival in early breast cancer, N Engl J Med, 2010;362:2053–65. 8. Rosen MP, Johnstone E, Addauan-Andersen C et al., A lower antral follicle count is associated with infertility, Fertil Steril, 2011;95:1950–4. 9. Petrek JA, Naughton MJ, Case LD, et al., Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study, J Clin Oncol, 2006;24:1045–51. 10. Partridge A.H., Ruddy KJ, Gelber S et al., Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer, Fertil Steril, 2010;94:638–44. 11. Partridge AH, Gelber S, Gelber RD, et al., Age of menopause among women who remain premenopausal following treatment for early breast cancer: long-term results from International Breast Cancer Study Group Trials V and VI, Eur Cancer, 2007;43:1646–33. 16 patients with hormone-sensitive breast cancer. The available data show an improvement in survival in patients with hormone-sensitive breast cancer that achieve amenorrhoea with adjuvant chemotherapy. However, available data seem to rule out the possible negative interference of GnRH analogues on the effectiveness of adjuvant chemotherapy. 30 Finally, a limitation to the use of GnRH analogue to preserve the ovarian function is the assumption that resumption of menses corresponds to retained fertility; these women may continue to menstruate after chemotherapy, despite having abnormal fertility. Since this has not been proved, other options should be considered, such as oocyte or embryo cryopreservation. These options are actually the only established fertility- preservation methods: newer hormonal stimulation regimens (letrozole and tamoxifen) may be effective as traditional methods and their use may be preferred in women with hormone-sensitive cancer; letrozole, for instance, can enhance ovarian stimulation while keeping oestrogen levels near physiological levels. Despite the attractiveness of the use of GnRH analogue in preventing ovarian failure for many advantages (simplicity in administration, no significant side effects, non-invasive method and the relatively low cost of the therapy), the question regarding its effectiveness, especially as method of fertility preservation, is still not resolved. Given the current state of knowledge regarding these agents, the recent update of American Society of Clinical Oncology (ASCO) clinical practice guidelines on fertility preservation for patients with cancer judged GnRH analogues, to date, as a not proved effective method of fertility preservation and stressed the need for a decisive study in which a larger number of more homogeneous patients will be randomised to a treatment with or without GnRH analogues, will be followed for a longer period of time and more sensitive ovarian reserve markers such as anti-Mullerian hormone or antral follicle counts will be used. 31 n 12. Davies C, Pan H, Godwin J, et al., Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomized trial, Lancet, 2013;381:805–16. 13. Gray RG, Rea D, Handley K et al., aTTom: long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6953 women with early breast cancer, JCO, 2013;31 (Suppl.) abstr 5. 14. Azim HA, Peccatori FA, Liptrott SJ, et al., Breast cancer and pregnancy: how safe is trastuzumab?, Nat Rev Clin Oncol, 2009;6:367–70. 15. Anderson RA, Themmen AP, Al-Qathani A et al., The effects of chemotherapy and long-term gonadotropin suppression on the ovarian reserve in premenopausal women with breast cancer, Hum Reprod, 2006;21:2583–92. 16. Blumenfeld Z, How to preserve fertility in young women exposed to chemotherapy? The role of GnRH agonist cotreatment in addition to cryopreservation of embryo, oocytes or ovaries, The Oncologist, 2007;12:1044–54. 17. Leonard RC, Adamson D, Anderson R, et al., The OPTION trial of adjuvant ovarian protection by goserelin in adjuvant chemotherapy for early breast cancer, J Clin Oncol, 2010;28 (Suppl. 15): 89s, abstr 590. 18. Gerber B, von Minckwitz G, Stehle H, 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. 19. Loibl S, von Minckwitz G, Gerber B, Reply to L. Del Mastro and Z. Blumenfeld, J Clin Oncol, 2011;29:3341–2. 20. Blumenfeld Z, ZORO Study: Discrepancy Between the Conclusion and the Results, J Clin Oncol, 2011;29:3340. 21. Del Mastro L, Temporary ovarian suppression with goserelin and ovarian function protection in patients with breast cancer undergoing chemotherapy, J Clin Oncol, 2011;29:3339–40. 22. Munster NP, Moore AP, Ismail-Khan R, 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. 23. Blumenfeld Z, Gonadotropin-releasing hormone agonist for preservation of ovarian function during (Neo) adjuvant chemotherapy for breast cancer, J Clin Oncol, 2012;30:3310. 24. Elgindy EA, El-Haieg DO, Khorshid OM et al., Gonadotropin suppression to prevent chemotherapy-induced ovarian damage: a randomized controlled trial, Obstet Gynecol, 2013;121:78–86. 25. Badawy A, Elnashar A, El-Ashry M, et al., Gonadotropin- releasing hormone agonists for prevention of chemotherapy- induced ovarian damage: prospective randomized study, Fertil Steril, 2009;91:694–7. 26. Del Mastro L, Boni L, Michelotti A, et al., Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurence of chemotherapy-induced early menopause in premenopausal women with breast cancer, JAMA, 2011;306:269–76. 27. Chen H, Li j, Cui T, et al., Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women, Cochrane Database Syst Rev, 2011;(11):CD008018. 28. Del Mastro L, Levaggi A, Poggio F, et al., Role of temporary ovarian suppression obtained with GnRH analog in reducing premature ovarian failure (POF) induced by chemotherapy in premenopausal cancer patients: a meta-analysis of randomized studies, Ann Oncol, 2012;23 (Suppl. 9) ix501, abstr.1551PD 29. Yang B, Shi W, Yang J 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, The Breast, 2013;22:150–57. 30. Cuzick J, Ambroisine L, Davidson N et al., Use of luteinizing- hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer; a meta-analysis of individual patient data from randomized adjuvant trials, Lancet, 2007;369:1711–23. 31. Loren AW, Mangu PB, Nohr Beck L, et al., Fertility Preservation for Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update, J Clin Oncol, 2013;31(19):2500–10. Eur op ean On c olog y & H a e matolog y