Modelling ovarian follicle dynamics within assisted reproductive technology treatments

Infertility affects from 12% to 15% of reproductive couples in Western Europe. Most of infertility cases are related to female endocrinological problems and costs around 1 billion Euro per year. Assisted Reproduction Techniques have made huge improvements on chances of infertile couples. However, the success rate is drastically low. Systems biology is an complex approach to tackle an entire organism, instead of singling out it’s fractions and trying to understand them. The intention of this thesis is to apply systems biology to the problem of infertility. Sufficient amount of research has been done towards design a whole-body model. However, none of them closely deal with endocrinological problems thus, they do not fully covers the problem of infertility. A great deal of work was done specifically oriented on recreating the dynamics of reproductive hormones. Such models have a high complexity and more than 100 parameters to be identified. Despite the ability to simulate concentration of hormones, the problem of identifing values for such a large amount of unknown parameters remains unresolved or highly complex. Whereas models as (Röblitz et al., 2013) oriented on simulating the dynamics of multiple hormones such as Progesterone, Follicle-Stimulating Hormone, Luteinizing Hormone within normal cycle, this thesis oriented on establishing several models designed specifically for Estradiol concentration and follicle dynamics within stimulation treatment. Main aim is to reduce or eliminate number of measurements taken from a patient in order to increase patient comfort and reduce cost of a treatment. This thesis was done within European Project PAEON, as a part of collaboration between Model Checking Group Laboratory (Sapienza University of Rome) and experts in reproductive medicine (University Hospital of Zürich).