(118d) Personalized Medicine for in Vitro Fertilization (IVF) Procedure with Ganirelix Protocol

In-vitro fertilization (IVF) is the most common technique in assisted reproductive technology. 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 and key component towards a successful IVF cycle. Although there are the general guidelines for dosage, the dose is not optimized for each patient.

A mathematical procedure is developed based on analogy between crystallization and superovulation stage in IVF treatment. A moment model which describes the dynamics of follicle size distribution is derived. This model 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. This model and optimal control procedure were previously developed for one of the agonist dosage protocols used in clinical practice. Ganirelix is used in conjunction with FSH to prevent premature ovulation and results in a shorter treatment protocol which produces high quality eggs and is known to reduce occurrence of Ovarian Hyperstimulation Syndrome. This paper uses the same principles to model an antagonist dosage protocol using Ganirelix (GnRH) and the optimal control procedure for improving outcomes of IVF treatment. However, in case of Ganirelix, two more reaction terms are added which corresponds to change in growth rate due to introduction of Ganirelix in mid cycle.

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 13 patients. The results of the customized models are found to be closely matching with the observed FSD. Rise in estrogen levels indicate the successful progress of cycle and estrogen level determine quality of eggs. We found that the estrogen level is a linear function of third moment of follicle size distribution at any time. A good fit was observed between the customized patient model and the experimental estrogen data, thus indicating a successful model. Optimal control is then used to find personalized optimal dosage for each patient for each day of cycle.