In vitro fertilization (IVF) is the most common technique in assisted reproductive technology and in most cases the last resort for infertility treatment. It has four basic stages: superovulation, egg retrieval, fertilization, and embryo transfer. Superovulation is a drug-induced method to enable multiple ovulation per menstrual cycle. The success of IVF majorly depends upon successful superovulation, defined by the number and uniformly high quality of eggs retrieved in a cycle. Currently, this step is executed using almost daily monitoring of the follicular development using ultrasound and blood test. The daily dosage of hormones is customized for each patient based on these tests. Although there are the general guidelines for dosage, the dose is not optimized for each patient, and complications, such as overstimulation, can occur. The cost of testing and drugs makes this stage very expensive. To overcome the shortcomings of these general guidelines system, a mathematical procedure and software is developed, which can provide a customized model of this stage regarding the size distribution of eggs (follicles/oocytes) obtained per cycle as a function of the chemical interactions of the drugs used and the conditions imposed on the patient during the cycle, which provide a basis for predicting the possible outcome. Customized optimal drug-dosage procedures are developed for each patient using optimal control methods with the targeted follicle size distribution (FSD) as the expected outcome. This chapter describes the theory, model, and the optimal control procedure for improving outcomes of IVF treatment for one of the four protocols used in real practice. The validation of the procedure is performed using clinical data from the patients’ previously undergone IVF cycles. Customized patient-specific model parameters are obtained by using initial two-day data for each patient. Subsequently, this model is used to predict the FSD for the remaining days of the cycle. This procedure was conducted for 49 patients. The results of the customized models are found to be closely matching with the observed FSD.