Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway.
Computational Systems Biology Group, Zuse Institute Berlin (ZIB), Berlin, Germany.
Front Endocrinol (Lausanne). 2021 Mar 11;12:613048. doi: 10.3389/fendo.2021.613048. eCollection 2021.
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. 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 modeling 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 ovarian stimulation protocols . 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.
新的卵巢刺激方案，如黄体期启动、随机启动或双刺激，允许在月经周期的不同阶段灵活地进行卵巢刺激。有人提出，这些方法的成功基于在整个月经周期中多个卵泡群（“波”）的持续生长，这导致在多个时间点可以获得卵巢卵泡进行卵巢控制性刺激。尽管已经发表了几项初步研究，但它们的科学证据还不够充分，无法将这些结果整合到常规临床实践中。这项工作旨在通过数学建模和数值模拟进一步提供关于可变启动方案的效率的科学证据，并支持卵泡波理论。为此，我们修改并耦合了两个以前发表的模型，一个描述激素的时间过程，一个描述正常月经周期中的卵泡竞争生长。所耦合的模型用于测试卵巢刺激方案。模拟结果显示在正常月经周期中以波状方式发生卵泡，并且定性地预测在月经周期的不同时间点开始的卵巢刺激的结果。
