How long can menopause be delayed? Model developed by mathematician points to answers

At birth, ovaries in girls can contain about a million tiny structures called primordial follicles, each of which contains an egg cell. As girls grow and experience adulthood, most of these follicles will die while only one follicle will survive each month to ovulate a mature egg. When the loss of primordial follicles is nearly complete, and only hundreds remain, women experience menopause, a time when menstrual cycles have ceased for 12 months.

New research, which relies on a mathematical model developed by a University of Utah mathematician, indicates that it is possible to delay the onset of menopause, perhaps indefinitely, by implanting a woman’s own previously harvested ovarian tissue back into her body. This technique has been successfully used to restore fertility in cancer patients, according to Sean Lawley, associate professor of mathematics and co-author of a study published in the American Journal of Obstetrics and Gynecology (AJOG).

This interdisciplinary work is a collaboration between Lawley, Joshua Johnson, an ovarian biologist at the University of Colorado School of Medicine; Jay Emerson, professor of statistics and data science at Yale University; and Kutluk Oktay, a prominent physician, professor of obstetrics, gynecology, and reproductive sciences and ovarian biologist at Yale School of Medicine.

In the late 1990s, Oktay developed ways to harvest ovarian tissue from young cancer patients, freeze it (“cryopreserve” it), and then transplant it after she has undergone cancer treatments that would have left her menopausal and infertile. This technique is referred to as “ovarian tissue cryopreservation and transplantation.”

The technique has enabled hundreds of cancer survivors to conceive and have children. It is substantially different from the common procedure of freezing eggs, which is effective in helping older women conceive through in vitro fertilization, but has no impact on menopause.

How mathematical models answer otherwise unanswerable questions

“A lot of the interest behind delaying menopause is fertility, but a lot of it also comes from the idea that functioning ovaries are better for a woman’s health,” Lawley said. “Menopause is associated with many health issues relating to cardiovascular disease, bone density, obesity, etc. Keeping ovaries functioning longer might delay or even prevent these health issues from starting.”

Lawley continued, “Math is being used to address the question of how long you can delay menopause and how that depends on different factors. We have developed a model of how ovaries age. The data comes from a number of places, chiefly from primordial follicle counts inside ovaries.”

Oktay, the world’s leading expert in fertility preservation, wondered if the ovarian tissue cryopreservation and transplantation procedure could be applied to healthy women to forestall menopause and its negative effects.

“In the past few years, we’ve been developing mathematical models of how the ovaries age and what triggers menopause,” Lawley said. “It was extremely exciting when he [Oktay] contacted our group to see if our model could be used to help explore whether this procedure could be used to delay menopause.”

It turned out that Lawley’s model helped a lot. The new AJOG study concluded that the procedures Oktay pioneered for cancer patients would be likely to delay menopause in healthy women under certain conditions.

“We were faced with a number of important questions. The first is, will it work? Will it delay menopause and by how much?” Lawley said. “Next, how do you optimize the procedure? Are there age ranges that tissue should be removed? How does the number of follicles in a woman’s ovarian tissue influence how long the tissue will function?”