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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:// seer.cancer.gov/statfacts/html/breast.html). 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. 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