For a study, researchers sought to create a simulation of a hypothetical trial comparing the efficacy of letrozole against clomiphene citrate for ovulation induction in all women, then stratified by PCOS and unexplained infertility. Investigators used data from a large healthcare claims database in the United States from 2011 to 2015. They looked at data from 18,120 women who started letrozole and 49,647 women who started clomiphene between 2011 and 2014 and who were between the ages of 18 and 45, had no history of diabetes, thyroid disease, liver disease, or breast cancer, and had not had any fertility treatments for 3 months before trial initiation. For 6 consecutive cycles, the patients were given either clomiphene citrate or letrozole. The outcomes were pregnancy, live birth, multiple gestations, preterm birth, short for gestational age (SGA), NICU admission, and significant congenital abnormalities. They used pooled logistic regression to estimate the likelihood of each outcome under each method and standardization to account for confounding and selection bias due to loss of follow-up. Overall, and among patients with unexplained infertility, the predicted odds of pregnancy, live birth, and neonatal outcomes were similar under each technique. In the intention-to-treat studies, the probability of pregnancy was 43% for letrozole and 37% for clomiphene in women with PCOS (risk difference [RD] = 6.0%; 95% CI: 4.4, 7.7). The likelihood of a live birth was 32% vs 29% (RD = 3.1%; 95% CI: 1.5, 4.8). Multiple gestations were 19% vs 9%, preterm delivery was 20% vs 15%, SGA was 5% vs 3%, NICU admission was 22% vs 16%, and congenital deformity was 8% vs 2% among those with live birth, according to protocol analyses.