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There's a Future in Which Old Women Are Fertile, Too

A surprising study suggests that a cancer drug could spur aging ovaries to create new eggs.

Usually the medical conversation around cancer drugs and fertility revolves around tactics to protect a woman's finite number of egg cells from the destructive effects of chemotherapy. But according to research published online earlier this week, one common cancer drug may actually help female fertility by possibly stimulating the production of new eggs in patients' ovaries. A feat long deemed impossible, it could lead to the total and joyous destruction of the ol' biological clock—if researchers can confirm and advance their findings.

The study, first presented at a conference this summer by a team of scientists from Edinburgh, Scotland, initially sought to explore why Hodgkin's lymphoma patients treated with a drug called ABVD did not suffer the same immediate fertility issues as other cancer patients. They biopsied the ovaries of 13 women with Hodgkin's lymphoma (some of whom received ABVD, some of whom got other drugs, and some of whom took no drugs) and one without, then examined the quality of the samples' filaments, hairlike things that mature into eggs. 

To their immense surprise, they discovered that the ABVD patients all had many times more filaments than the other sample patients, and also other populations of their healthy peers.

"It looked like pre-pubescent tissue with a high density of follicles and clustering that you don't normally see in an adult," one of the study's authors, Evelyn Telfer of the University of Edinburgh, told The Telegraph. "To find new eggs being made, in such huge numbers, that was very surprising to see."

Longstanding accepted theories of female fertility maintain that women are born with about 800,000 follicles in their ovaries, only a handful of which grow every month, and only one of which typically develops into an egg. Generally it's believed that this finite population of potential eggs depletes and gets damaged over time, leading to the stark drop-off in fertility in women aged 40 to 50. 

This has understandably led many to doubt Telfer and her team's interpretation that they're seeing the creation of new filaments. "The findings are preliminary and even [Dr. Telfer] agrees with that," says Kutluk Oktay, a leading expert on fertility preservation at the New York Medical College, who recently spoke with her about her findings. "There could be many alternative explanations."

But Telfer has an explanation for how new eggs could form: The treatment may have shocked ovarian stem cells into overdrive. Identified in mice in 2004, the existence of ovarian stem cells, which some believe constantly make new egg filaments over a woman's lifetime (just not strong or long enough to outpace decay and infertility), has long been disputed by reproductive experts. However numerous studies over recent years (including some by Telfer and company) claim to have identified stem cells in human ovaries—explaining that they long went undetected because they are incredibly rare. Their existence has been affirmed this year alone by multiple papers from scientific bodies as far afield as Greece and China.

Oktay notes that many organs have stem cells into adulthood, so it's logical that these cells could exist, despite doubts about the techniques used to identify them. But not all adult-organ stem cells are active. "These may not have physiological functions" in adult ovaries, he adds.

Still, researchers are already exploring methods based on the manipulation of these stem cells to offer late-life fertility. One of the scientists behind the 2004 discovery of mouse ovarian stem cells created the firm OvaScience, which currently attempts to revitalize women's aging filaments (using material from their purported ovarian stem cells) in a handful of countries (but not America). That firm is also working on generating new, young eggs from stem cells for use by older women seeking to get pregnant with their own eggs and without freezing.

Telfer's research is the first purported observation of a new follicle forming within a human ovary, though, rather than just the identification of stem cells within them and their manipulation in a lab. At present they're only immature filaments. Telfer and her colleagues still need to see if they can be coaxed to maturity and fertilized without issue—and they need to conduct further research on the individual components of ABVD to isolate a causal mechanism for this phenomenon.

"If there was such an effect," Oktay says of the potential of an ABVD-based therapy, "would we have missed it in [many previous] patients?" Oktay believes Telfer's hypothesis is possible and logical—it could be that the drugs lead to an immediate filament-regeneration process that might not be sufficient or long-lasting enough to have been observable in previous patients. He thinks it's too early to call, though, and currently believes a more fruitful line of research for extending the age of fertility lies in restoring the viability of aging egg cells.

But if Telfer can beef up her research, that'd massively boost the potential for the induced generation of new, functional eggs in older or infertile women—perhaps even by non-invasive chemical treatment methods. If Telfer or other researchers can achieve that, it could destroy the biological clock concept and open the door for women to achieve reliable, viable pregnancies at much later stages of life.

Banking on the research making it to that point soon, or at all, is not wise. Nor is developing or engaging with any therapy based on these early findings. (To wit, no one ought to be scarfing down anti-cancer chemicals to get pregnant at this point.) But the prospect it portends, of breaking a major barrier in human reproduction, is impossibly tantalizing.