Background and Aims: A mathematical procedure and a decision support tool, Opt-IVF, were developed to overcome the shortcomings of the current IVF practice of dosage profile determination by trial and error, which can provide a personalized model and optimized drug treatment. This paper describes the decision support tool for improving outcomes of IVF treatment for both antagonist and agonist protocols used in real practice. We present the results of two clinical trials. Method: Our earlier work developed models for agonist and antagonist protocols based on an analogy between superovulation and batch crystallization. This model was customized for each patient using two days of follicular data, and the optimal control method was applied to optimize the dosage profile. Validation of the model was conducted with retrospective data from 150 patients from India and 50 from the United States. Opt-IVF reduced total hormone dosage by 20 to 60%, reduced US testing by 50 to 75%, and provided a higher number of oocytes and high-quality embryos. Results: The primary outcome measures studied for two clinical trials with Opt-IVF include total hormonal dosage, % follicles retrieved, MII oocytes, Embryos, and Grade A Embryos. Results showed that Opt-IVF reduces drug dosage and testing and increases the number of embryos, Grade A embryos, and high-quality blastocysts significantly. Subgroup analysis showed improvements in outcomes were more significant for both Poor-responder and PCOS patients than for normal responders. Pregnancy rates were significantly higher with Opt-IVF patients than with standard protocol control patients. Conclusions: A mathematics-based approach to dosage profile determination results in optimal mature follicles, better embryos, and higher pregnancy with reduced dosage and the need for testing.