Human Reproduction Update Advance Access published online on September 29, 2008
Human Reproduction Update, doi:10.1093/humupd/dmn022
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GnRH-analogues and oral contraceptives for fertility preservation in women during chemotherapy
1 Reproductive Endocrinology and Infertility Section, Department of Obstetrics and Gynaecology, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa 31096, Israel 2 Department of Endocrinology and Reproductive Medicine, University of Heidelberg, Vossstrasse 9, Heidelberg 69115, Germany
To whom correspondence should be addressed at: 3 Correspondence address. Tel: +972-4-8542577; Fax: +972-4-8542612/972-4-8515710; E-mail: bzeev{at}techunix.technion.ac.il and z_blumenfeld{at}rambam.health.gov.il
BACKGROUND: For preserving fertility in women during chemotherapy, the character of invasive techniques, such as ovarian cryopreservation and other techniques, await further experience. Meanwhile, non-invasive techniques have attempted to minimize the gonadotoxic effect of chemotherapy, by using gonadotrophin-releasing hormone-analogues (GnRH-a) or oral contraceptives (OC).
METHODS: We performed a computerized MEDLINE search to identify articles published on fertility preservation using GnRH-a or OCs.
RESULTS: Nine human-controlled studies reported the use of GnRH-a and four reported the use of OCs in parallel to chemotherapy. All nine studies analysing the effect of GnRH-a found lower rates of premature ovarian failure (POF) in patients receiving GnRH-a compared with the controls. Summarizing the studies resulted in 11.1% incidence of POF in patients who received GnRH-a compared with 55.5% incidence in the controls. Evidence using the fertility preserving effect of OC is limited. Two studies showed lower POF rates in OC-treated patients. The summarized data revealed a POF rate of 13.2% in patients who received OCs compared with that of 29.8% in the controls.
CONCLUSIONS: The published clinical studies provide evidence, but do not prove statistically, that GnRH-a co-treatment reduces gonadotoxicity. Owing to the retrospective and non-randomized nature of most of the studies, definite conclusions concerning the reduction of POF by GnRH-a can still not be unequivocally drawn. As GnRH-a and OC have no serious side effects and as GnRH-a can even reduce chemotherapy-induced complications, such as severe menometrorrhagia, GnRH-a are considered by many clinicians as a clinically useful co-treatment in chemotherapy. The published clinical studies on OC also suggest a possible effect on the reduction of POF under certain conditions.
Key words: gonadotoxicity / premature ovarian failure (POF) / chemotherapy / GnRH-agonist / oral contraceptives
Received on December 17, 2007; revised May 8, 2008; accepted on May 19, 2008
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