http://humupd.oxfordjournals.org/content/14/6/571.long
Hum Reprod Update. 2008 Nov-Dec;14(6):571-82. doi: 10.1093/humupd/dmn033. Epub 2008 Sep 23.
Use of letrozole in assisted reproduction: a systematic review and meta-analysis.
Requena A, Herrero J, Landeras J, Navarro E, Neyro JL, Salvador C, Tur R, Callejo J, Checa MA, Farré M, Espinós JJ, Fábregues F,Graña-Barcia M; Reproductive Endocrinology Interest Group of Spanish Society of Fertility.
Source
IVI-Madrid, Santiago de Compostela 88, E-28035 Madrid, Spain. arequena@ivi.es
Abstract
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.
Data | Goswami et al. (2004) | Garcia-Velasco et al. (2005) | Schoolcraft et al. (2008) | |||
---|---|---|---|---|---|---|
Letrozole + FSH | FSH | Letrozole + FSH | FSH | Letrozole + FSH | FSH | |
Cycles, no. | 13 | 25 | 71 | 76 | 179 | 355 |
Days of stimulation | Not stated | Not stated | 9.3 (0.3) | 8.9 (0.2) | 9.9 (1.3) | 10.1 (1.6) |
FSH dose, IU | 150 (0)* | 2865 (/228)* | 3627 (116) | 3804 (127) | 4222 (742) | 3937 (975) |
Oocytes retrieved | 1.6 (0.8) | 2.1 (/0.7) | 6.1 (0.4) | 4.3 (0.3) | 12 (6) | 13 (5.3) |
Estradiol on hCG day, pg/ml | 227 (45)* | 380 (46)* | 770 (67) | 813 (60) | 1403 (965)** | 3147 (1189)** |
Pregnancy rate, % | 23 | 24 | 22.4 | 15.2 | Not stated | Not stated |
Implantation rate, % | Not stated | Not stated | 25** | 9.4** | 15 | 21 |
Ongoing pregnancy rate, % | Not stated | Not stated | Not stated | Not stated | 37** | 52** |
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