COSA:AYA cancer fertility preservation/Options for fertility preservation/Ovarian suppression with GnRH analogues during chemotherapy

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Fertility preservation for AYAs diagnosed with cancer: Guidance for health professionals. > COSA:AYA cancer fertility preservation/Options for fertility preservation/Ovarian suppression with GnRH analogues during chemotherapy

Ovarian suppression with GnRH analogues during chemotherapy

Recommendation Grade
Ideally GNRH analogues for ovarian protection should be used within the context of a clinical trial setting.

Where this is not possible, administration is supported provided the patient and family are fully informed of the lack of large randomised trials addressing the potential benefit.

B

The use of gonadotrophin-releasing hormone analogues (GnRH), administered throughout the time of chemotherapy treatment, may reduce the gonadotoxic effects of chemotherapy on ovarian function.

It is still not clear exactly how GnRH analogues have a protective effect, but potential mechanisms include suppression of follicular recruitment or reduction of ovarian blood flow.[1][2]

Options include depot preparations (which are preferred because of ease of administration and prolonged activity) and formulations administered daily, either by injection or intranasal administration.

When used for durations longer than six months, additional low-dose oestrogen support should be considered to reduce the consequences of protracted hypooestrogenism, unless the patient has an oestrogen-sensitive tumour.

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Likelihood of success

There is evidence that GnRH agonists reduce the risk of acute and more prolonged ovarian failure, although there is still controversy about the magnitude of benefit. It appears that the risk of ovarian failure may be reduced by approximately 40%. However there is no evidence that GnRH analogues provide benefit in the context of very high dose chemotherapy as part of pretreatment for bone-marrow transplant.

A single well-conducted study in patients with lymphoma did not show any benefit with GnRh agonist. However recent evidence, including a systematic review of randomised trials, has suggested that GnRH agonists do provide some ovarian protection. The heterogeneity of studies and results, and the fact that most trials only assessed ovarian function in the short term (8 months to 2.5 years) means that there is not yet conclusive evidence of benefit.[3][4][5][6][7]

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Risks and side effects

The side effects of GnRH analogues relate predominantly to the induced hypooestrogenic state and so include hot flushes and reduction in vaginal secretions. When used for prolonged periods (i.e. > 6 months) without add-back oestrogen treatment, there is a risk of bone depletion.

There is no evidence that use of GnRH analogues during chemotherapy reduces the efficacy of the cancer treatment.

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Cost

Currently in Australia, use of GnRH analogues for ovarian protection during chemotherapy is not an indication supported by the PBS, so administration is either self-funded (approximately $340 to $400 per injection for goserelin monthly injections, and usually 3 to 4 injections required for duration of chemotherapy) or provided by the treating institution.

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References

  1. Blumenfeld Z, Avivi I, Eckman A, Epelbaum R, Rowe JM, Dann EJ. Gonadotropin-releasing hormone agonist decreases chemotherapy-induced gonadotoxicity and premature ovarian failure in young female patients with Hodgkin lymphoma. Fertil Steril 2008 Jan;89(1):166-73 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17601603.
  2. Erickson GF, Shimasaki S. The role of the oocyte in folliculogenesis. Trends Endocrinol Metab 2000 Jul;11(5):193-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10856922.
  3. Bedaiwy MA, Abou-Setta AM, Desai N, Hurd W, Starks D, El-Nashar SA, et al. Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis. Fertil Steril 2011 Mar 1;95(3):906-14.e1-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21145541.
  4. 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 Aug;122(3):803-11 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20571868.
  5. Beck-Fruchter R, Weiss A, Shalev E. GnRH agonist therapy as ovarian protectants in female patients undergoing chemotherapy: a review of the clinical data. Hum Reprod Update 2008;14(6):553-61 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18820006.
  6. 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 Womens Health (Larchmt) 2009 Mar;18(3):311-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19281314.
  7. 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 Mar;91(3):694-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18675959.

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