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Cold Comfort: Young Women with Cancer Can Freeze an Ovary to Keep Kids in the Picture

Radiation and chemotherapies that save young women from cancer can leave them infertile. But a novel procedure can keep motherhood on ice without delaying treatment



ISTOCKPHOTO/JSEMENIUK

As chemotherapy and radiation treatments improve, children with cancer are living longer. The average five-year survival rate for a range of childhood cancers increased from 58 percent to 81 percent between 1975 and 2005, according to statistics from the National Cancer Institute. But although many of these children now survive cancer-free into their reproductive years, their fertility might not. In young women and girls, direct radiation and chemotherapy drugs can stop egg production by the ovaries—meaning that along with the tumor, hopes for pregnancy are often eradicated.

There are ways to preserve fertility: Eggs can be removed and fertilized in vitro, and the embryos can be frozen until pregnancy is safe. Or, the eggs themselves can be frozen and fertilized later.

But these options are off the table for young women with hormone-dependent cancers or ones requiring immediate treatment because of the ovary-stimulating drugs that also feed the tumor and the time (at least two weeks depending on the menstrual cycle) required to stimulate ovulation and collect the eggs. They are also ruled out for prepubescent girls whose ovaries have yet to start producing eggs.

More recently, a relatively new procedure can preserve fertility by removing and freezing the "biological clock" itself: The ovary.

Before starting cancer treatment, one walnut-size ovary is removed in a 30-minute, minimally invasive laparoscopic procedure. The tissue is then cut into pieces the size of rice grains and flash frozen in liquid nitrogen at temperatures nearing –200 degrees Celsius by a process called vitrification.

After the treatment regime is completed, should the survivor choose to become pregnant, the tissue is thawed and re-implanted onto the surface of the remaining ovary or the ligament next to the fallopian tube. Four months later—the time it takes for thawed primordial follicles (the functional units of the ovary) to mature and start ovulating—the survivor can conceive without hormones and in vitro fertilization, making the procedure a "natural" and effective way to preserve fertility in young women and girls with cancer, says Sherman Silber, director of Saint Luke's Hospital's Infertility Center of Saint Louis.

"Five to 10 years down the line these women are going to want to have babies, even though when they're 19 they're only thinking about their cancer," Silber says. Whereas childbearing might not be on the minds of these girls and young women, eager to start their therapy, this quick procedure can keep kids in the picture without interfering with the fight to survive. "We just take out the ovarian tissue and two days later they can start their treatment," Silber says.

Although the procedure is still relatively new, Silber insists that it is no longer experimental. Nine babies have been born to women who had prematurely stopped menstruating (not all cancer survivors) and later received frozen ovarian tissue implants in his clinic.

Because of the natural variation in the number of egg-producing follicles over time, little is known about the dosage levels of radiation and chemotherapy that cause sterility. New research published in the January 27 issue of PLoS One might offer reliable estimates, which could be useful in guiding recommendations for ovarian tissue freezing.

Using histological data obtained from tissue samples of more than 300 ovaries, Hamish Wallace from the University of Edinburgh's Division of Reproductive and Developmental Sciences and Tom Kelsey from the University of Saint Andrews School of Computer Science, both in Scotland, generated a mathematical model of the ovarian reserve (the number of productive follicles) from conception to menopause. As directors of the Wallace–Kelsey Research Foundation, a London-based charity studying the subsequent effects of radio- and chemotherapies on the fertility of childhood cancer survivors, the team plans to use the model to improve estimates of the sterilizing doses of cancer therapies. These estimates, they report, might be helpful in identifying good candidates for the ovarian tissue freezing procedure.



But Silber thinks all young patients beginning certain cancer treatment regimes should freeze ovarian tissue regardless of the model. "These young women do lose their fertility. They do become menopausal," Silber says. "Maybe they do hit menstruation, but they do go into menopause early. Up to 90 percent of young women with cancer will lose their fertility from the treatment that cures them."

The procedure costs roughly $4,000, according to Silber, an expense that he says should be (and usually is) covered by health insurance providers. "Insurance is paying $200,000 for cancer treatment; $4,000 isn't too much to preserve fertility," he says.

In the early days of the procedure (about five years ago) the frozen ovarian tissue was re-implanted under the skin of the forearm (for ease of egg retrieval) where it became revascularized and, under stimulation, resumed its natural role producing eggs, despite the very unnatural environment. The eggs would then be collected from the arm and fertilized in vitro. But Silber says that re-implanting the tissue at the ovary site where it belongs using microsurgical techniques allows the woman to conceive naturally.

Wallace and Kelsey's model also predicts that by the age of 30, the ovarian reserve for a normal woman is roughly 12 percent of its original capacity, dropping to three percent by age 40. Unlike some women with cancer, healthy women who put off childbearing because of career demands or a lack of a partner can freeze their eggs. But a 30 to 50 percent in vitro fertilization rate makes this a risky bet. Silber says that rather than putting all their eggs in one basket, so to speak, even healthy women should freeze an ovary to ensure fertility later in life.

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