In a first for primates, sperm extracted from a once-frozen sample of testicle tissue was used to create a baby monkey, according to a new study. If this feat is replicated in humans, it could give some young children undergoing cancer treatment a way to preserve their fertility.
The treatments that help childhood cancer patients survive may also reduce their fertility later in life. One potential safeguard against future fertility problems is to freeze testicle tissue, and use it to generate sperm when survivors are ready to have kids — but this hasn’t been tested in humans. To find out whether that strategy can produce a healthy baby, researchers decided to test it in monkeys. The result was announced today in the journal Science: a healthy baby Rhesus macaque named Grady.
Chemotherapy drugs and radiation can wipe out the stem cells that produce sperm. Adults facing cancer treatment can bank their sperm. But children’s testicles that haven’t gone through puberty aren’t making sperm. Kyle Orwig, a professor of obstetrics, gynecology, & reproductive sciences at the University of Pittsburgh School of Medicine, wants to help these kids keep their options open in case they someday want to produce their own genetic offspring. “Cancer survivors tell us that their fertility status has a really important impact on their quality of life,” he says. “The psychological impact of not being able to have a child can be devastating.”
Some fertility centers have started experimentally freezing tissue biopsied from testicles before kids start cancer treatment in the hopes that, one day, there might be a way to use that tissue to produce viable sperm. Now, a team of researchers led by Orwig and postdoctoral researcher Adetunji Fayomi have shown in monkeys that frozen testicular tissue can, eventually, make a baby. “I think it’s pretty amazing,” says Michael Eisenberg, an associate professor of urology at Stanford Medical Center who was not involved in the research. “This could potentially help a lot of young boys.”
The idea is that a kid about to undergo cancer treatment could freeze and bank testicular tissue, preserving some of those stem cells that make sperm. Then, later in life, if they decide they want to have biological offspring, they could have that tissue thawed and transplanted into their own body. Hormones would help the testicular transplant mature, and start producing sperm. Since the transplant doesn’t get hooked back up to the reproductive plumbing, the sperm stays inside the tissue. So the transplant would have to be removed and the sperm extracted to be used in in vitro fertilization.
Previous studies in monkeys got part of the way there: researchers showed that the transplanted testicle tissue could produce sperm — but stopped short of proving that the sperm could actually produce offspring.Orwig’s team took the research the rest of the way. They removed one testicle each from five different monkeys, and froze them. Five months later, after the monkeys went through chemotherapy, the researchers removed each monkey’s remaining testicle, and transplanted tissue from the fresh and frozen testicles into the monkeys’ backs and scrotums.They wanted to know if freezing — which is a key part of this process — hurt their chances of producing sperm or, eventually, a baby.
Then, the team monitored the monkeys. The grafts grew, and testosterone levels climbed to typical levels in the monkeys’ blood — showing that the grafts were acting as healthy testicles would. Eight months to a year later, the researchers took out the transplants, examined them under a microscope, and pulverized them with forceps and enzymes to recover live sperm. The team succeeded for most of the transplants — even the ones that had been frozen.
The researchers collected sperm from one of the frozen transplants, and shipped it to the Oregon National Primate Research Center. It took a few tries to get the timing of fertilization and the monkeys’ breeding season to align. Of the 138 eggs they fertilized, only 11 embryos matured enough to eventually be transferred into monkeys’ uteruses.
Ultimately, one monkey carried a successful pregnancy to term and gave birth to a baby monkey named Grady. “You can’t believe how proud I was,” says Orwig, who met Grady when she was just a few weeks old. “It took us a lot of years. It was a big undertaking. And we produced a baby in a way that nobody has ever produced a baby before.”
Right now, the study is a one-off, and there are still some major questions to answer before it can be tested in people. For one thing, it’s possible that the testicular tissue could carry some cancer cells — which means it might not work for survivors of certain blood or testicular cancers. The research team also doesn’t know the ideal way to freeze testicular tissue. That will be key to figure out, says Stanford’s Eisenberg. “To show that this can work in people also needs to be established — not just producing sperm, but safely producing sperm,” Eisenberg says. “But this is certainly a huge step.”