Clomiphene outperforms letrozole in ovarian stimulation

An aromatase inhibitor was safe for use in ovarian stimulation but produced fewer live births than a standard clomiphene citrate (CC) regimen, according to results of a multicenter trial. The findings, presented by investigators from the National Institute of Child Health and Human Development (NICHD) at the American Society of Reproductive Medicine meeting in Hawaii, indicate that CC plus intrauterine insemination (IUI) should remain first-line therapy for couples with infertility.

The objective of NICHD’s AMIGOS (Assessment of Multiple Intrauterine Gestations from Ovarian Gestations from Ovarian Stimulation) trial was to determine whether use of letrozole-an aromatase inhibitor-would result in fewer multiple gestations than standard CC/IUI without lowering the live birth rate. The prospective, randomized, multicenter clinical trial enrolled 900 couples with unexplained infertility.  

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Ovarian stimulation with gonadotropins (300 menotropin, 301 CC, 299 letrozole) followed by IUI for up to 4 cycles was the treatment protocol in women ages 18 to 40 who had at least one patent fallopian tube and regular menses. The rate of conception was 46.8% in the menoptropin arm, versus 35.7% and 28.4% in the CC and letrozole arms, respectively. The rate of pregnancy was significantly lower with letrozole stimulation than with menotropin (P<0.0001) or CC (P<0.015).

Rates of multiple birth were eightfold higher with menotropin (10.3%) than with CC (1.3) and fourfold higher than with letrozole (2.7%). In pregnancies with fetal heart rates identified, letrozole was associated with fewer multiple pregnancies (9/67, 13.4%) than was menotropin (34/107, 31.5%, P<0.006) but the outcome was similar with CC (8/85, 9.4%, NS). The multiple pregnancies with letrozole and CC were all twins, whereas the menotrpin group had 24 twin and 10 triplet gestations. Neither rates of congenital anomalies nor rates of fetal and neonatal complications differed among the three drugs.

Letrozole, the NICHD researchers concluded, was safe for ovarian stimulation but associated with a lower rate of live birth than CC or menotropin and a rate of multiple pregnancy that fell between the two other drugs. 

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