Letrozole linked to lower rate of multiple gestation and live birth vs gonadotropin: The AMIGOS study

1. The rate of multiple clinical pregnancy was significantly higher in patients treated with gonadotropin compared to treatment groups with clomiphene or letrozole.

2. The rate of multiple gestation was not significantly reduced in women in the letrozole group compared to women in either the clomiphene or gonadotropin group.

Evidence Rating: 1 (Excellent)  

Study Rundown: For patients with unexplained infertility, empirical ovarian stimulation combined with intrauterine insemination is one therapeutic option. The standard treatment regimen in ovarian stimulation for these patients – clomiphene citrate and/or gonadotropin – pose the risk of ovarian hyperstimulation, resulting in multiple gestations. In this randomized trial, researchers evaluated the frequency of multiple gestations and live births resulting from use of letrozole, an aromatase inhibitor, compared to those of clomiphene or gonadotropin. Their results demonstrated that letrozole resulted in the lowest rate of live births compared to the clomiphene and gonadotropin groups. Additionally, gonadotropin use resulted in a higher rate of multiple gestations compared to the use of either letrozole or clomiphene alone. Limitations of this study include possible bias from lack of blinding for the gonadotropin group.

Click to read the study, published today in NEJM

Relevant Reading: Ovarian stimulation and intrauterine insemination at the quarter centennial: implications for the multiple births epidemic

In-Depth [randomized controlled trial]: In this multicenter randomized trial – The Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) – researchers analyzed data from 900 couples with unexplained infertility. Patients were women between 18-40 years of age with ≥9 menstrual cycles per year, normal uterine cavities with at least one patent fallopian tube and had a male partner with a semen specimen of at least 5 million sperm/mL. The participants were randomized to either receive clomiphene, gonadotropin, or letrozole. The primary study outcome was the rate of multiple gestations. Secondary outcomes included rates of live birth, multiple gestation with live birth, pregnancy loss, length of gestation and maternal-fetal and neonatal complications. Treatment with gonadotropin yielded a statistically significant higher rate of live births (32.2%) compared to clomiphene (23.3%) and letrozole (18.7%), p<0.003. Gonadotropin demonstrated a higher rate of cumulative serious adverse effects compared to the letrozole and clomiphene groups (p=0.009).

In terms of multiple gestations, patients receiving gonadotropin had significantly more multiple gestations compared with clomiphene or letrozole. However, in comparing gonadotropin and clomiphene as a combined group, versus patients receiving letrozole, there was no significant difference in multiple gestations (p=0.15). Lastly, there were no significant differences in secondary outcomes.

Image: PD

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