Most of the growing follicles wither and die; but each month one (and sometimes two or three) will fully mature and release an egg for potential fertilization. This process repeats every month until menopause, when fewer than a thousand follicles remain.
(Scientists are finally studying women’s bodies. This is what we’re learning.)
Years before menopause, however, the feedback mechanisms between the brain and the ovaries (and the follicles they contain) become chaotic as follicle numbers dwindle, Pepin explains. “But it’s a complete black box” as far as how this impacts the trajectory of ovarian aging or whether it differs in different people, he says.
If these feedback mechanisms are important, though, one way to preserve healthy ovarian function may be to hold onto the follicles you have.
Pepin demonstrated that anti-Müllerian hormone, which is made in the follicles and controls the number that are activated (and therefore eventually lost in a menstrual cycle), can do just that.
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When mice exposed to chemotherapy (which seems to jumpstart the development of dormant follicles, increasing the pool of eggs that die in each cycle) were injected with the hormone, fewer follicles were activated and more eggs were kept in reserve than controls that received saline.
Similarly, when a short two-week course of rapamycin—a drug that also prevents dormant follicles from developing—was given to female mice, the compound was shown to extend fertility, particularly in older mice (equivalent to humans in their late 40s), and increase the number of follicles in reserve.
Another benefit of rapamycin use: egg quality improved. In other words, eggs from treated mice had fewer chromosomal abnormalities and healthier mitochondria.
Yousin Suh, a geneticist at Columbia University, believes rapamycin holds a lot of promise. Used to treat some cancers, rapamycin has a strong safety record—smoothing the way for testing it in other contexts.
Suh and collaborators are currently conducting a Phase II clinical trial that will measure the ovarian reserve of subjects—between the ages of 38 and 45, when about 20,000 follicles remain—after three months of treatment with the drug.
