OBJECTIVES: The focus on cost-containment imposed by shrinking national health care budgets is increasingly putting pressure on investigators to demonstrate that newer interventions are cost-effective. In assisted reproductive technology (ART), a shift in usage is occurring from urinary derived to biotechnology - derived (recombinant) gonadotropins for ovarian stimulation. Provision of treatment with ART involves several cycles, each associated with multiple steps with varying outcomes at each step. To take into account all the situations that are possible during the repeated cycles of treatment when trying to evaluate different ovarian stimulation regimens is a complex task that requires large numbers of subjects to adequately address the cost-effectiveness A more efficient approach is to employ modeling techniques that can easily be applied to the different national health care systems. The objective of this study was to compare the cost-effectiveness of recombinant(r) FSH with urinary(u) FSH in the UK, USA, Germany and Spain. METHODS: The analyses used the Markov model and Monte-Carlo simulations taking into account the different health care environments in the four countries. For each nation, costs were provided by their national formulary and clinic tariff, and probabilities for outcomes were obtained from randomized controlled trials, the medical literature and national registries. The data were they validated by a panel of national experts and the estimation of variability in the transition probabilities was also ratified by the panel. This approach provided a range of transitional probabilities from which a precise standard deviation could be obtained for each outcome. The final Markov matrix included 300-600 health states that represented the complete ART process over multiple cycles involving the transfer of fresh or cryopreserved embryos. RESULTS: Country Mean cost per pregnancy uFSH rFSH Difference UK £ 6060 5906 154 USA $ 47,096 40,688 6408 Germany DM 45,510 43,311 2199 Spain PTAS 3,405,347 3,284,241 121,106 CONCLUSION: The studies confirmed that rFSH is more cost-effective than uFSH for ovarian stimulation. The lower average cost per pregnancy was observed consistently in each country.