OBJECTIVES: Differences in drug effects on the QOL of patients undergoing assisted reproductive techniques have been little. The objective of this study was to perform a QOL analysis using the Short Form-36 combined with mathematical modeling to determine whether differences in QOL exist between patients undergoing COS with follitropin alfa (Gonal-FÒ, Serono) and follitropin beta (FollistimÒ/PuregonÒ liquid, Organon). METHODS: The SF-36 questionnaire was administered to patients who received COS with follitropin alfa (n = 22) or follitropin beta (n = 21) in a randomized controlled clinical study. SF-36 scores before and after COS were obtained for each patient. Results for the eight 'dimensions' of the SF-36 were projected using multifactorial analysis to produce a composite QOL score. Statistical tests were performed to determine the percentage of relevant information captured by the multifactorial analysis and hence the quality of the composite score. The bootstrap technique was used to generate additional random samples. The Kolmogorov-Smirnov test was used to compare the distributions of the composite scores for the follitropin alfa and beta groups. RESULTS: The test performed to validate the composite QOL score gave a value of 0.55 (55% of relevant information captured), compared with an expected score of 0.125 for a random projection of eight dimensions into one. The distribution of composite scores for the two groups was significantly different after 30 simulations (p = 0.004), suggesting a difference in the effects of the two treatments on QOL. A graphical plot of the results of 5000 simulations showed that the follitropin beta group had a greater reduction in QOL as a result of COS compared with the follitropin alfa group. CONCLUSIONS: Mathematical modeling confirms a statistically significant difference in QOL effects of the two r-hFSH preparations in favor of follitropin alfa.