Canadian doctors exploring ‘radical’ new procedure that promises to save fertility of child cancer patients
Canadian doctors are looking at offering a fascinating new procedure for saving the fertility of pre-pubescent cancer patients, where pieces of ovary or testicle are frozen before toxic treatments, then transplanted back years or decades later.
A national study recently found strong support for the service among parents and health-care workers, and at least one hospital is actively exploring the experimental techniques.
Scientific and ethical questions still hang over the concept, and a little-known Canadian law could actually prevent lab research on it here.
But the ovary procedure has already produced almost 40 babies elsewhere, and raised the prospect of remarkable spin-off benefits that could transform the lives of healthy older people, too.
Why wouldn’t you want a nice, young ovary in the freezer?
Some experts say transplanting younger, preserved ovaries into middle-aged women might stave off or even eliminate menopause altogether.
“This whole thing sounds very, very radical … [But] it isn’t some wild idea or theory I’m throwing at you. It’s all backed up by data,” says Sherman Silber, an American obstetrician-gynecologist and pioneer of the technique. “Why wouldn’t you want a nice, young ovary in the freezer?”
The procedures’ most conventional applications lie with child cancer patients, who are increasingly likely to be cured by modern medicine, but are often left unable to have children.
For patients at or beyond puberty, egg or sperm samples can be taken and frozen for future use — a relatively novel process itself called “onco-fertility.” Until now, though, there was no way to reverse the sterilizing effects of chemotherapy and radiation on the youngest of patients — babies, toddlers and grade-schoolers.
- In response, several facilities internationally have begun taking out pieces of immature ovary or testicle before treatment, then freezing them. When the patient wants to have children, the tissue or specially prepared cells would be transplanted back and, ideally, produce viable sperm or eggs. Alternatively, the eggs could be extracted to use in fertility treatments.
A national study of parents, cancer survivors and health-care workers in Canada recently found strong support for offering even the more experimental testicular procedure, a conference of the Canadian Bioethics Society heard last month.
Toronto’s Hospital for Sick Children is now doing the ethical and legal groundwork for eventually offering at least the male procedure, said Dr. Abha Gupta, the Sick Kids oncologist who spearheaded the study.
Yet the concept faces a major impediment in Canada. Continued research is needed, especially to determine exactly how to use that frozen, prepubertal testicular tissue to create sperm. Federal legislation, however, bans scientific experimentation on reproductive material from anyone under 18, said Dr. Gupta.
“It’s truly obsolete and quite a barrier,” she said. “We’re not protecting children, we’re actually preventing science from moving forward.”
Chemotherapy leaves almost half the boys with cancer unable to produce sperm and brings on menopause as early as the late 20s for many girls, while radiation and stem-cell transplants can render some girls infertile, said Dr. Gupta.
Even amid the life-and-death drama of the cancer ward, it seems those risks are taken seriously by patients and parents. The Sick Kids oncologist encourages doctors to overcome a traditional reluctance to discuss fertility preservation, and says families are invariably thankful when the topic is raised.
For pre-pubertal children who cannot produce mature eggs or sperm for preservation, the new ovarian-transplant procedure is at the most advanced stage.
Thin slices of one of two ovaries are removed in a procedure that Dr. Silber said is less invasive than extracting eggs, and lasts as little as 15 minutes. The excised tissue is later grafted back onto the remaining ovary.
Vardit Ravitsky, a University of Montreal bio-ethicist, worked with a team in Israel which took ovary tissue from girls as young as three.
“Most of these parents desperately want to have grandchildren,” said Dr. Silber. “The parents are very highly motivated.”
Most of these parents desperately want to have grandchildren
It will be years before tissue is transplanted back into those young girls, proving whether the procedure works for them. At Dr. Silber’s Infertility Center of St. Louis, though, he has grafted preserved tissue into 22 older patients whose ovaries were mature when they had cancer treatment.
Just under 60% had babies — 15 in total. About 37 births have occurred worldwide.
The testicular procedure is less developed. It involves freezing spermatogonial stem cells, sort of baby sperm, then transplanting them back into the testicles. Studies in mice have successfully made male animals fertile again, but human evidence is so far lacking.
The field is also clouded by ethical issues, including the financial burden on parents of storing frozen tissue for years, and whether that would put undue pressure on survivors to have children.
Evidence also suggests that cancer cells could be reintroduced during transplants, though techniques are being explored to negate the risk. Dr. Silber said all 22 of his transplanted patients remained cancer-free.
They’re cured of cancer and now they have a 17-year-old ovary in the freezer just waiting for when they need it
Despite the unresolved issues, Prof. Ravitsky said she believes parents of young, pre-pubertal children should at least be offered the choice of having tissue extracted, “rather than have regrets later.”
“It’s a complicated topic, at a complicated time for the family, with very little data,” she said. “[But] it’s a parent’s responsibility and ethical obligation to do anything they can to allow their child in the future to make those decisions.”
In the meantime, Dr. Silber has already removed tissue from healthy women who desire simply to have young ovaries as they age. The process offers the potential to delay menopause — and extend child-bearing potential — for decades, and evidence from animal studies suggests that could actually help women live longer, said Dr. Silber.
The number and quality of eggs declines dramatically over the years, meaning teenagers who have frozen ovaries re-implanted during their early 30s gain a substantial fertility benefit, an exciting prospect for many young patients, he said.
“They talk about how grateful they are,” said the physician. “They’re cured of cancer and now they have a 17-year-old ovary in the freezer just waiting for when they need it.”
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