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.
Table III.
Comparison of patients (ovulatory infertility) treated with gonadotrophins and those treated with gonadotrophins plus letrozole in IVF treatment.
| 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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