Modeling Follicle Stimulating Hormone (FSH) Levels in Serum for Controlled Ovarian Hyperstimulation II: The Underlying Mechanisms

David      H. McCulloh; Jose      M. Colon; Peter      G. McGovern

Abstract

Background: Serum levels of follicle stimulating hormone (FSH) in patients change slowly during repeated daily injections of gonadotropin, requiring several days to achieve stable values. Using a numerical (computer) model we mimicked the serum levels of FSH using two kinetic constants that describe biological phenomena: diffusion of FSH from the injection site into the blood (τin) and disappearance of FSH from the blood by excretion/degradation (τout). We investigated the effects of these two parameters on the FSH profiles seen in the model. Methods: The parameters, τin and τout, were systematically changed to determine their effects on the delay from injection to the peak following a single injection (Tmax). Other values were investigated systematically during repeated daily injections. Results: The models parameters τin and tout affected Tmax and several features of FSH level during daily injections of gonadotropin. These included the maximum level of FSH in the serum (relative to the level attained following the first injection), the rate of rise of peaks following injections after the first, and the shortening of the delay from injection to peak. Conclusion: Knowledge of τin and τout permits us to predict serum FSH levels and time course during daily injections of gonadotropin.

Keywords: Controlled ovarian hyperstimulation, FSH pharmacodynamics, gonadotropin administration, Serum levels, biological phenomena, pharmacokinetic processes, temporal profiles of gonadotropin levels, predict serum, gonadotropin product, compartment numerical model, pharmacokinetics, mathematical model, exponential function, blood volume, biological responses