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Published On Jun 13, 2017

Clinical Research

Near Death, New Life

More children survive cancer, but infertility is often the cost. New techniques offer hope.

In her youth, Moaza Al Matrooshi battled beta thalassaemia, a serious genetic blood disease. At age 9 she began chemotherapy, a treatment that would likely make it impossible for her to have children. Had she been an adult, she might have chosen to freeze her eggs before treatment began. Al Matrooshi, however, was too young. Her ovaries contained only small, immature eggs that wouldn’t fully develop until she had gone through puberty.

She and her parents agreed to have some of her ovarian tissue removed, frozen and stored. The girl recovered from the disease and later, in her early 20s, had that tissue thawed and transplanted back into her ovary. Within three months she began experiencing normal reproductive cycles and producing mature and fertile eggs. In December 2016, at age 24, Al Matrooshi became the first woman to give birth using ovarian tissue that was collected before her puberty.

Survivors of childhood cancers may stand to benefit the most from such breakthroughs in fertility research. “Today, 85% of children survive their cancers,” says Teresa Woodruff, vice chair for research in OB/GYN at Northwestern University. Yet infertility is one of the long-term effects that can haunt them (“After the Cure,” Fall 2014). In 2006, Woodruff coined the term “oncofertility” to describe the new field of research that looked at how to preserve the reproductive capacity of people with cancer. She has been working since then to extend what she has learned to younger patients.

Freezing a child’s reproductive tissue is a promising frontier. But it can also carry risks. “Preserving that tissue can preserve cancer cells, and a transplant runs the risk of reseeding the cancer,” says Helen Picton, head of reproduction and early development at the University of Leeds in England. Picton, who froze Al Matrooshi’s ovarian tissue, notes that some cancers pose a greater danger of being reintroduced, especially the blood-borne cancers leukemia—common in childhood—and lymphoma. “But approximately 70 babies have now been born to women who have had ovarian tissue transplants following cancer,” says Picton, noting that the women had types of cancers that weren’t likely to return. “The vast majority of these women are healthy.”

In cases in which there’s a larger threat of rekindling cancer, one experimental strategy is to let the early-stage eggs contained within the ovarian tissue grow and mature in the laboratory. A healthy, full-size egg can then be plucked out and fertilized, and the embryo can be transferred to the woman. “This is very challenging science, and to date it has only worked to completion in mouse models,” says Picton. Her own experiments are with sheep, whose eggs, ovaries and reproductive cycles are similar to those of humans.

Male patients face problems as well, because boys don’t produce sperm until puberty. As many as 2,000 young boys at high risk of becoming sterile from cancer treatment have had their testicular tissue frozen, according to published reports, “but the number is likely higher,” says Kyle Orwig, director of the Fertility Preservation Program at the University of Pittsburgh Medical Center. In theory, cells from that frozen tissue could later be transplanted back into the testes to restore sperm production and fertility. The tissue could also be grafted into the scrotum or under the skin, where reproductive hormones would cause it to mature. Sperm could then be harvested and used to fertilize an egg in vitro.

But reseeding cancer might also be a concern in boys. One alternative might be to graft a boy’s frozen and thawed testicular tissue onto an animal to mature and produce sperm. This strategy has worked with prepubertal monkey tissue implanted in a mouse, which generated sperm that could fertilize monkey eggs and produce monkey embryos. “Or it may be possible one day to reprogram a patient’s skin cells or blood cells into stem cells that can be differentiated to produce sperm,” says Orwig. This approach has worked in mice, leading to the birth of live offspring, but has yet to be tried in people.

Less toxic cancer treatments may eventually make oncofertility obsolete. “But for today, it’s important to keep thinking about oncofertility as a strategy—or at least something to discuss—for our young cancer patients,” says Woodruff.

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