Image courtesy of Science Translational Medicine/AAAS

For some women with cancer, the chemotherapy that could be their salvation will also steal their fertility. A study on mice has now revealed how those drugs damage ovaries1, offering a way to ward off the effect.

The results are an important contribution to the field, says Evelyn Telfer, a reproductive biologist at the University of Edinburgh, UK, who was not involved in the study. “If you’re going to try to develop fertility-preserving drugs, you want to know where the primary damage is,” she says. “This holds a lot of promise.”

Every human ovary contains thousands of follicles that shelter developing eggs. Roughly once a month, some of those follicles become activated and the eggs within them mature. The ovary normally releases one of those eggs for possible fertilization.

Currently, women who are treated with cyclophosphamide — a drug used to combat ovarian and breast cancers, among others — or other ovary-damaging chemotherapies must take steps to preserve their ability to have children. This usually means either having some eggs frozen or having them fertilized and then storing the embryos for later implantation. For some patients, including young girls who cannot yet produce mature eggs, doctors can harvest and freeze ovarian tissue for later transplantation.

Fertile ground

To investigate the effect of chemotherapy on fertility, Dror Meirow of Tel Aviv University in Israel and his team treated female mice with cyclophosphamide. They found that the drug increased the number of actively growing follicles in the ovaries and triggered a cellular pathway associated with follicle activation. This left the activated follicles vulnerable to subsequent doses of the drug, which kills actively dividing cells.

The activation pathway stimulated by cyclophosphamide is controlled by a protein called PI3K. Meirow’s team knew that this protein is targeted by an experimental drug called AS101, which is in clinical trials for reducing the negative effects of chemotherapy on the blood and skin.

When the researchers tested AS101 in mice treated with cyclophosphamide, they found that fewer follicles were activated or damaged and that fertility was preserved.

Although the results are tantalizing, it is a big leap to extrapolate from female mice — which release between 8 and 20 eggs every four days — to humans, cautions Telfer. But the work provides an important lead that can be followed up in larger animals and human cells grown in culture, she says.

Meirow, meanwhile, is eager to see the project through to ease the burden on his patients. “It’s not easy to say to a patient, ‘You have cancer, and now you’re also sterile’,” he says. “We are working on many methods to keep that from happening.”