Use of letrozole in assisted reproduction: a systematic review and meta-analysis

Requena A, Herrero J, Landeras J, Navarro E, Neyro J L, Salvador C, Tur R, Callejo J, Checa M A, Farre M, Espinos J J, Fabregues F, Grana-Barcia M, Reproductive Endocrinology Interest Group of Spanish Society of Fertility,
Hum Reprod Update. Nov-Dec. 2008 doi: 10.1093/humupd/dmn033
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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.