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Human Reproduction Update Advance Access first published online on September 23, 2008
This version published online on October 16, 2008
Human Reproduction Update, doi:10.1093/humupd/dmn033
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
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Use of letrozole in assisted reproduction: a systematic review and meta-analysis

Antonio Requena1,12, Julio Herrero2, José Landeras1, Esperanza Navarro3, José L. Neyro4, Cristina Salvador5, Rosa Tur6, Justo Callejo5, Miguel A. Checa7, Magí Farré8, Juan J. Espinós9, Francesc Fábregues10, María Graña-Barcia11 Reproductive Endocrinology Interest Group of the Spanish Society of Fertility

1 IVI—Madrid, Santiago de Compostela 88, E-28035 Madrid, Spain 2 Servei de Ginecologia, Hospital Materno-infantil Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain 3 Clínica Euskalduna, Bilbao, Bizkaia, Spain 4 Service of Obstetrics and Gynecology, Universidad del País Vasco, Barakaldo, Bizkaia, Spain 5 Servei d'Obstetricia i Ginecologia, Hospital de Sant Joan de Déu, Universitat de Barcelona, Esplugues del Llobregat, Barcelona, Spain 6 Servicio de Medicina de la Reproducción, Departamento de Obstetricia, Ginecología y Reproducción, Institut Universitari Dexeus, Universitat Autònoma de Barcelona, Barcelona, Spain 7 Department of Obstetrics and Gynecology, Hospital Universitari del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain 8 Unit of Pharmacology, IMIM-Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain 9 Department of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain 10 Servei de Ginecologia, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain 11 ZYGOS, Centro Gallego de Reproducción, Santiago de Compostela, Spain

To whom correspondence should be addressed at: 12 Correspondence address. Tel: +34-91-3769920; Fax: +34-91-3867133. E-mail: arequena{at}ivi.es

BACKGROUND: Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis.

METHODS: A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled.

RESULTS: Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66–2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73–2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70–2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78–1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67–2.91).

CONCLUSIONS: Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction.

Key words: androgens / FSH / IVF

This paper should have been published as Open Access.

Received on December 5, 2007; revised June 2, 2008; accepted on July 4, 2008


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