New Model Suggests Ovary's Egg Selection Is a Random, Yet Precise, Process

Researchers at Rice University have developed a mathematical model indicating that the selection of a single follicle for maturation during the menstrual cycle is a random process. The model, published in the Journal of the Royal Society Interface, correlates with real-world data on follicle development and twin births.

"Our model suggests selection is 'completely random and still very precise,'" said Zhuoyan Lyu, first author of the paper.

Background: The Monthly Selection

During a typical menstrual cycle, a woman's ovaries prepare 10-20 antral follicles for potential maturation. Yet, in the vast majority of cycles, only one follicle is selected to fully mature and release an egg. This biological precision is evident in the low rate of natural fraternal twins, which results from two eggs being released and is observed in only 2-3% of natural pregnancies.

Previous theories to explain this single selection have focused on differences between follicles, such as size or sensitivity to hormones.

How the Model Works

The Rice University model centers on the interaction of two key hormones:

• Follicle-Stimulating Hormone (FSH)
• Estradiol

During the follicular phase, FSH levels rise. The model proposes that once FSH crosses a specific threshold, one follicle is randomly selected for full development. Following this selection, the growing follicle produces estradiol, which causes FSH levels to fall back below the critical threshold.

This drop in FSH prevents any other follicles from being selected, and the unselected follicles subsequently die off. The researchers found that the selection event most likely occurs during a brief window when FSH rises only slightly above the threshold before quickly falling again—a mechanism that usually limits selection to a single follicle.

The random nature of this initial selection means that, on rare occasions, a second follicle could be chosen before FSH drops below the threshold, potentially explaining some instances of fraternal twins.

Implications for Fertility

Professor Anatoly Kolomeisky, a co-author of the study, stated the team was driven by a fundamental question: "We were interested in understanding how and why a single follicle is selected."

Kolomeisky said the model could be used to interrogate fertility questions.

The framework suggests several possibilities:

• Age and Twin Probability: Looser control of the FSH-estradiol feedback cycle with age could increase the probability of FSH staying above the selection threshold long enough to choose a second follicle, potentially raising the chance of fraternal twins for women over 35.
• Conditions like PCOS: Women with polycystic ovarian syndrome (PCOS), who often have chronically low FSH levels, may struggle with infertility if their FSH levels never reach the required threshold to trigger follicle selection.

Funding

This work was supported by the Welch Foundation (C-1559), the National Institutes of Health (R01GM148537), and the Center for Theoretical Biological Physics sponsored by the National Science Foundation (PHY-2019745).