Modeling Follicle Stimulating Hormone Levels in Serum for Controlled Ovarian Hyperstimulation I: Comparing Gonadotropin Products

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

Abstract

Background: Despite the dangers of gonadotropin administration, our understanding of serum levels of gonadotropins in our patients is poor. We created a mathematical model of gonadotropin administration in order to learn about the temporal profiles of Follicle Stimulating Hormone (FSH) levels in patients related to the doses of different gonadotropin products administered. Methods: Model parameters for each product were determined from published pharmacokinetic information available from the manufacturers. Results: For each product, serum levels of FSH rose then fell following a single injection of FSH. When a gonadotropin dose was injected repeatedly (daily), each injection resulted in a peak level of FSH that was higher than the level attained from the previous injection. Daily FSH peaks rose asymptotically, requiring 3-10 days to approach the maximum. The maximum averaged 3.5 times the peak of the first injection. Decline of FSH following the final injection required 3-10 days to approach the baseline. Time courses and peak values of FSH using different gonadotropin preparations varied widely. Conclusion: Knowledge of the slow changes of FSH that occur during modeled FSH administration will provide a framework for understanding the gonadotropin profiles that occur in patients during controlled ovarian hyperstimulation.

Keywords: Controlled ovarian hyperstimulation, FSH pharmacokinetics, gonadotropin administration, infertility treatments, ovarian response, clinical parameters, serum estradiol levels, numerical model, serum, asymptotically, FSH declines, surrounding tissue(s), administering gonadotropins, single injection site, mathematical model