Question: 38 yo nulliparous anxious to preserve fertility is about to start chemotherapy for breast cancer. Should gonadotrophin agonist be commenced prior to treatment?
Answer: A number of recent small trials have reported conflicting results on the effectiveness of gonadotrophin agonists in the preservation of fertility in breast cancer patients:
- Ismail-Khan et al (1) have reported a randomised controlled trial of the effect of triptorelin in 49 pre-menopausal women during chemotherapy for breast cancer. They found no significant differences in return to menstruation or FSH levels.
- Badawy et al (2), following an RCT including 80 patients, concluded that GnRHa administration before and during combination chemotherapy for breast cancer may preserve posttreatment ovarian function in women <40 years.
- Recchia et al (3) report a retrospective evaluation of 100 consecutive premenopausal women with high-risk, early breast carcinoma who received a gonadotropin-releasing hormone (Gn-RH) analogue as ovarian protection during adjuvant chemotherapy. After a median follow-up of 75 months, normal menses were resumed by all patients younger than age 40 years and by 56% of patients older than age 40 years. Three pregnancies were observed that resulted in two normal deliveries and one voluntary abortion.
(Evidence level 1b)
The American Society of Clinical Oncology recommendations on fertility preservation in cancer patients (4) comments additionally that:
“Ovarian suppression through gonadotropin releasing hormone (GnRH) agonist or antagonist treatment during chemotherapy is highly controversial as a method to maintain fertility. A small study evaluating 54 patients compared with retrospective controls suggested a benefit in preserving menstrual function from ovarian suppression with GnRH analogs in women undergoing chemotherapy for Hodgkin’s and non-Hodgkin’s lymphoma, (102) but a small prospective study of 18 women receiving chemotherapy for Hodgkin’s lymphoma did not show a benefit of this approach.(52) Retrospective studies have been criticized for longer follow-up time and higher incidence/dose of usage of alkylating agents in controls.(100) Two small case series of 64 and 24 cancer patients without controls report resumption of menses and/or pregnancies after ovarian suppression.(103,104)
52. Waxman JH, Ahmed R, Smith D, et al: Failure to preserve fertility in patients with Hodgkin’s disease. Cancer Chemother Pharmacol 19:159-162, 1987
100. Sonmezer M, Oktay K: Fertility preservation in female patients. Hum Reprod Update 10:251-266, 2004
102. Blumenfeld Z, Avivi I, Linn S, et al: Prevention of irreversible chemotherapy-induced ovarian damage in young women with lymphoma by a gonadotrophin-releasing hormone agonist in parallel to chemotherapy. Hum Reprod 11:1620-1626, 1996
103. Fox KR, Scialla J, Moore H: Preventing chemotherapy-associated amenorrhea (CRA) with leuprolide during adjuvant chemotherapy for early stage breast cancer. Proc Am Soc Clin Oncol 22:13, 2003 (abstr 50)
104. Recchia F, Sica G, De Filippis S, et al: Goserelin as ovarian protection in the adjuvant treatment of premenopausal breast cancer: A phase II pilot study. Anticancer Drugs 13:417-424, 2002”
A joint working party report by the RCOG, Royal College of Physicians, and Royal College of Radiologists(5) discusses recommended procedures before commencing chemotherapy/ radiotherapy likely to affect fertility, including embryo, egg or ovarian tissue storage.
(Evidence level IV)
References:
- Ismail-Khan R, Minton S, Cox C, Sims I, Lacevic M, Gross-King M, Xu P, Carter B, Munster PN, Lee H. Preservation of ovarian function in young women treated with neoadjuvant chemotherapy for breast cancer: A randomized trial using the GnRH agonist (triptorelin) during chemotherapy [abstract no. 524] Journal of Clinical Oncology: ASCO annual meeting proceedings. 2008 26(15S part I): 12 Abstract
- Badawy A. Elnashar A. El-Ashry M. Shahat M. Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study. Fertility & Sterility. 91(3):694-7, 2009 Mar.
- Recchia F. Saggio G. Amiconi G. Di Blasio A. Cesta A. Candeloro G. Rea S. Gonadotropin-releasing hormone analogues added to adjuvant chemotherapy protect ovarian function and improve clinical outcomes in young women with early breast carcinoma. Cancer. 106(3):514-23, 2006 Feb 1.
- Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, Beck LN, Brennan LV, Oktay K. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol 2006 Jun 20;24(18):1-15. Full text
- The effects of cancer treatment on reproductive function. Guidance on management. Royal College of Physicians, Royal College of Radiologists, Royal College of Obstetricians and Gynaecologists. London: Royal College of Physicians, 2007
Search date: June 2009
Classification of evidence levels
Ia Evidence obtained from meta-analysis of randomised controlled trials.
Ib Evidence obtained from at least one randomised controlled trial.
IIa Evidence obtained from at least one well-designed controlled study without randomisation.
IIb Evidence obtained from at least one other type of well-designed quasi-experimental study.
III Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case studies.
IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities.
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