TY - JOUR A1 - Fischer, Sophie A1 - Ehrig, Rainald A1 - Schäfer, Stefan A1 - Tronci, Enrico A1 - Mancini, Toni A1 - Egli, Marcel A1 - Ille, Fabian A1 - Krüger, Tillmann H. C. A1 - Leeners, Brigitte A1 - Röblitz, Susanna T1 - Mathematical Modelling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation JF - Frontiers in Endocrinology N2 - New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle which is especially useful when time for assisted reproductive technology is limited, e.g. for emergency fertility preservation in cancer patients. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts ("waves") of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modelling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle. Y1 - 2021 U6 - https://doi.org/10.3389/fendo.2021.613048 VL - 12 ER - TY - JOUR A1 - Fischer-Holzhausen, Sophie A1 - Röblitz, Susanna T1 - Hormonal regulation of ovarian follicle growth in humans: Model-based exploration of cycle variability and parameter sensitivities JF - Journal of Theoretical Biology N2 - We present a modelling and simulation framework for the dynamics of ovarian follicles and key hormones along the hypothalamic-pituitary-gonadal axis throughout consecutive human menstrual cycles. All simulation results (hormone concentrations and ovarian follicle sizes) are in biological units and can easily be compared to clinical data. The model takes into account variability in follicles' response to stimulating hormones, which introduces variability between cycles. The growth of ovarian follicles in waves is an emergent property in our model simulations and further supports the hypothesis that follicular waves are also present in humans. We use Approximate Bayesian Computation and cluster analysis to construct a population of virtual subjects and to study parameter distributions and sensitivities. The model can be used to compare and optimize treatment protocols for ovarian hyperstimulation, thus potentially forming the integral part of a clinical decision support system in reproductive endocrinology. Y1 - 2022 U6 - https://doi.org/https://doi.org/10.1016/j.jtbi.2022.111150 ER - TY - JOUR A1 - Fischer-Holzhausen, Sophie A1 - Röblitz, Susanna T1 - Mathematical modelling of follicular growth and ovarian stimulation JF - Current Opinion in Endocrine and Metabolic Research Y1 - 2022 U6 - https://doi.org/https://doi.org/10.1016/j.coemr.2022.100385 ER -