Future fertility

Sam Hornikel celebrated his sixth birthday at Johns Hopkins Hospital in Baltimore. Diagnosed with cancer at age 2, he is now free of the disease but was rendered infertile.
Sam Hornikel celebrated his sixth birthday at Johns Hopkins Hospital in Baltimore. Diagnosed with cancer at age 2, he is now free of the disease but was rendered infertile.

Boys treated for cancer before puberty often grow up unable to father a child. Researchers at Children's Hospital of Philadelphia see hope in frozen tissue and stem cells.

Posted: November 24, 2013

Being just a kid himself, 7-year-old Sam Hornikel isn't concerned about his ability to have children of his own yet. He's thinking more about the soccer game he missed, or his math homework.

But researchers around the world are working to give boys like Sam - who fought off cancer when he was only 3 years old - the opportunity to have their own family one day. Often, chemotherapy or radiation treatments can harm fertility.

Typically, older patients can bank sperm, but for those who haven't gone through puberty yet, researchers are deep-freezing tiny pieces of their testicular tissue. The hope is that research will advance far enough in the future to turn that tissue into working sperm.

Sam's parents agreed to have him participate in the still-experimental cryopreservation study at Children's Hospital of Philadelphia, where he received his cancer care. A biopsy removed a piece of his testicular tissue smaller than the eraser on a pencil: one-half goes to a research lab, the other into a subzero freeze for Sam's future use.

"If it helps Sam or doesn't, I just hope the research helps someone," said his mother, Erin Hornikel, 40, of Egg Harbor Township, N.J.

Hornikel has been a New Jersey state trooper for 16 years, working assignments from Atlantic City casinos to the aftermath of Hurricane Sandy. When she needs a dose of strength, she thinks about her son for inspiration.

At 2 years old, he was diagnosed with rhabdomyosarcoma, a cancer that forms in muscle attached to bones. His doctors at Children's found a tumor the size of a grapefruit in his prostate and bladder.

With remarkable advances in pediatric cancer care, up to 80 percent of children survive their disease. Thinking about life after cancer is a new focus for families, said Children's pediatric oncologist Jill Ginsberg.

"One of the most difficult conversations is talking about the risk of infertility," she said. As director of the hospital's Cancer Survivorship Program, she meets with families shortly after diagnosis to explain options that depend on the patient's age and sex, and on the planned treatment's risk to fertility.

Given the opportunity, most teenage male patients will bank their sperm, a process with high success rates for future pregnancy. But prepubertal boys like Sam typically had to face infertility without even a glimmer of hope.

The stem cells in the testicles that produce new, mature sperm need to stay intact for fertility to remain unharmed. But stem cells can be prime targets for chemotherapy drugs, since they divide rapidly, as cancer cells do. Roughly a third of boys will end up sterile or infertile, said geneticist Ralph Brinster of the University of Pennsylvania's School of Veterinary Medicine.

Brinster, who won the National Medal of Science in 2011, has successfully restored fertility in animals by implanting cells from testicular tissue. Although cases of reimplanted ovarian tissue have produced successful pregnancies in humans, no one has managed to bridge the gap from transplanted testicular cells to human sperm.

But his lab is working on it. Half of the pediatric patient tissue samples from the Children's cryopreservation study go to his lab so he can modify the technique for humans.

It's a win-win scenario: Ginsberg gives her young male patients a potential option for child-bearing in the future, while Brinster gets more tissue to work with. So far, they have accumulated 46 samples.

In 2000, Brinster restored sperm-making capability by transplanting testicular tissue and its stem cells from a fertile mouse into an infertile one. The procedure started up sperm production, and the mice were able to have a normal family.

"The biopsy takes a tiny piece of tissue with only 3 to 5 stem cells," said Ginsberg. "He has been trying to multiply and culture them so there's thousands of stem cells."

But therein lies the puzzle. The stem cells will divide a few times as expected, but they never advance far enough in the process to become a sperm cell.

"There's something missing; they grow to 8 to 16 cells, and then they appear to get tired," Brinster said.

Even for mice, he needed 10 years to unlock the right mix of chemicals to have stem cells grow and develop outside the body. In 2011, another lab had success developing the right conditions for rabbits, considered a higher form of animal. Now Brinster uses the information from rabbit culture studies, making tweaks here and there, for human use.

"We've made some progress, but it's science - it's slow," he said - but he believes there is "no question" that researchers will figure it out, with numerous lab groups worldwide now working on the problem. But will it be soon enough to help Sam and his peers?

No one can know for sure yet, which is why Ginsberg stresses to parents that the benefits of tissue cryopreservation for their high-risk prepubertal sons may be minimal, if any. But Hornikel, at such a devastating time, saw a conversation about fertility preservation from Ginsberg as a hopeful message about her son.

"For her to even think that Sam has a future - that he could be around in 20 years - was so good to hear," Hornikel said.

In fact, a focus group study with pediatric cancer survivors and their families by Northwestern University urologist Robert Brannigan found that parents in such a situation could assume the worst if their doctors didn't bring it up.

"When the issue was not brought up with the patient and their parents, some of the parents took that as a sign that the clinician did not think they had much hope of survival," said Brannigan.

Because it's experimental, tissue cryopreservation isn't yet covered by insurance. But Children's has been getting donor funds and grants so that they can offer the service at no cost to families.

Although the study focuses only on boys, freezing ovarian tissue is also presented as an option for high-risk girls. Egg and embryo cryopreservation is more difficult than sperm banking, however, since they require weeks of egg stimulation. Often doctors don't want to take the risk of delaying cancer treatment. So far, none of Children's patients - either girls or boys - have used their specimens.

Interest in the option for prepubertal kids has been slowly bubbling up at children's hospitals across the nation. Ginsberg receives a number of e-mails from parents wanting their sons to participate in the study, and she has opened satellite operations of the experiment at the Memorial Sloan-Kettering Cancer Center in New York City and Seattle Children's Hospital.

"This is an area of medicine that has garnered a lot of attention in the last five or six years," said Brannigan, whose hospital is not currently offering cryopreservation. "We're moving closer and closer to offering this as a service."

As for Sam - nicknamed "Braveheart" - he fought off cancer in a year of chemotherapy and surgeries. His treatments have left him unable to have children in the future, but his mother has hope for the research being done by doctors like Ginsberg and Brinster.

"Even if it takes them 20 more years, or 30 . . . my husband and I just had a baby in our late 30s," she said. "It could be available when he is ready."

He's becoming old enough to notice and ask about his surgical scars. Hornikel tells him the truth, that he used to be sick.

"He's come a long way and is cancer-free, that's the best thing. He's the strongest, bravest person I know."