الفهرس 
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Abstract
Abstract
Background: Invitro-fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are the most widely used assisted reproduction techniques (ARTs) for management of female infertility. Since the pharmacometrics is concerned with the quantifying and interpreting the different patterns of variability in drug response, we hypothesize that the implementation of pharmacometric-based modeling and simulation of the developed models would help to optimize the safety and efficacy outcomes of COS.
Aims: To develop pharmacometric-based models addressing the different sources of variability attained through COS.
Methods: The current work included two distinct studies. In the first study, women with unexplained infertility who underwent IVF/ICSI, treated with agonist, short, or antagonist protocols, were retrospectively analyzed. In the second study, a prospective analysis of women IVF/ICSI candidates with unexplained infertility treated using the antagonist protocol with the standard gonadotrophin dosing (225 IU daily). The concluded models from both studies were translated to an interactive web app named GonadGuide.
Results: In the first study, a total of 636 women were analyzed. Among different dose-response models, the modified Poisson model demonstrated was found to best describe the data. In the second study, a PK-PD-PD model for prediction of inhibin B and oocyte retrieval was developed and validated adequately. For both studies, the developed models were evaluated and validated using the standard pharmacometric model assessment tests. Based on the proposed novel models from both studies, interactive web applications were constructed and validated.
Conclusion: The developed models were shown to be valid and reliable. The model-based web applications would help the choice of the downregulation protocol and the gonadotrophin dose. The constructed GonadGuide web application would further guide the incremental gonadotrophin dose increase.