Use of letrozole in assisted reproduction: a systematic review and meta-analysis.
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.
Requena
Antonio
A
IVI-Madrid, Santiago de Compostela 88, E-28035 Madrid, Spain. arequena@ivi.es
Herrero
Julio
J
Landeras
José
J
Navarro
Esperanza
E
Neyro
José L
JL
Salvador
Cristina
C
Tur
Rosa
R
Callejo
Justo
J
Checa
Miguel A
MA
Farré
Magí
M
Espinós
Juan J
JJ
Fábregues
Francesc
F
Graña-Barcia
María
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D002996:Clomiphene / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000009:adverse effects / Q000627:therapeutic use; D006062:Gonadotropins / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007247:Infertility, Female / Q000517:prevention & control; D000077289:Letrozole; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D010062:Ovulation Induction; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D006062:Gonadotropins; D009570:Nitriles; D014230:Triazoles; D002996:Clomiphene; D000077289:Letrozole; D005640:Follicle Stimulating Hormone