A Hope for Parenthood: Research Study Aims to Preserve Fertility for Young Cancer Patients

The oncology team at Cook Children’s had calculated a high probability that the chemotherapy Zechariah Silva needed to fight Hodgkin’s lymphoma would damage the cells in his reproductive organs.

So before starting chemo, Zechariah underwent a quick surgical procedure as part of a nationwide research study aimed at saving the fertility of children with cancer. He’s just 6 years old, but his doctors and parents wanted to try to safeguard Zechariah’s chance at biological fatherhood some day.

That surgery on June 6 made Zechariah the first research participant at Cook Children’s to have testicular tissue removed in an experimental effort to help young boys who have cancer. Gerald V. and Whittany Silva say they’re grateful for the option to freeze and store their son’s tissue for possible use down the road as fertility technology advances. In other words: The tissue is there, untainted by chemo, if Zechariah needs it years from now to make sperm.

“We talked a little about it with him, just so he understood it was to help him in the long run,” Gerald said. “We explained to him that we did it for him. When he’s older and an adult, he’ll understand.”

Zechariah completed four cycles of chemotherapy this summer. Family and nurses joined in the celebration Aug. 23 as he rang the bell at Cook Children’s to celebrate the end of his treatment. This story profiles Zechariah in September, which is Childhood Cancer Awareness Month, to showcase the expanding scope of oncofertility resources at Cook Children’s.

For young girls with cancer, the science is further along than for boys. A 4-year-old girl with a kidney tumor had an ovary removed and frozen – a technique known as cryopreservation -- last October. She was the first female patient at Cook Children’s to undergo this procedure that is clinically approved for girls. Zechariah was the first male participant eight months later, and both surgeries were performed by Blake Palmer, M.D., medical director for Cook Children’s Urology.

The intersection of oncology and fertility comes into clearer focus with background on a few basic points:

• Infertility can be an unintended and unfortunate result of chemotherapy and/or radiation, as these treatments kill healthy cells in the process of attempting to kill cancer cells. Sometimes the reproductive organs don’t recover, resulting in permanent loss.
• Teenage boys are able to preserve sperm through a semen sample, and the eggs of teenage girls can be removed before beginning cancer treatment. But those options aren’t available prior to puberty. That’s because the precursor cells in boys the same age as Zechariah cannot make sperm yet.
• Improved treatment practices have boosted the five-year survival rate for children with cancer to 84%, according to the American Cancer Society. That statistic raises the stakes when it comes to their future reproductive health.

“We know from our adult survivors of pediatric cancers that infertility significantly impacts their quality of life,” said Toni Leavitt, fertility program coordinator at Cook Children’s. She provides information to patients and their parents. “For many families, fertility is a primary concern at diagnosis, and it is important for us to offer options to preserve fertility prior to initiating treatment.”

Fertility wasn’t on the Silvas’ radar when they brought Zechariah to Cook Children’s in May on a referral from their pediatrician back home in Amarillo. Zechariah had been struggling for months with muscle weakness and nerve pain as a result of an autoimmune disorder called Guillain-Barré syndrome. He was also battling a chronic neurological disorder closely related to the Guillain-Barré. Tests run at Cook Children’s found the cause of a swollen lymph node in his neck: Hodgkin's lymphoma, a type of cancer that develops in the white blood cells. Chemo had to start right away.

Whittany remembers feeling overwhelmed by the amount of new information coming at her and Gerald. Zechariah’s oncologist, Ashraf Mohamed, M.D., was the first to bring up the topic of cryopreservation. Dr. Mohamed considered Zechariah a great candidate for the research study, Whittany said.

Leavitt then told the Silvas that Zechariah was eligible because the high dose and type of chemotherapy in his treatment protocol put him at an elevated risk for infertility. If his parents consented, Leavitt told them, a small piece from one of Zechariah’s testicles could be removed, frozen and stored in hopes of producing sperm when he reaches adulthood.

“She explained it a couple of different times,” Whittany recalled. “The thing that was making me a little bit more worried was how are we going to explain it to him? Would the incision hurt? I thought Zechariah might have questions that I wouldn’t have the answer to.”

The Silvas’ decision to say “yes” was influenced by the fact that the operation would take place while Zechariah was already sedated for placement of his chemo port. He wouldn’t have to be anesthetized twice. Leavitt made it clear that cryopreservation for prepubescent boys is an experimental and elective procedure. 

“She was great, very reassuring of the studies and the process,” Gerald said. “I don’t think we needed a whole lot of convincing, we just needed to discuss it as parents.” 

The next day, Dr. Palmer made a tiny incision in Zechariah’s scrotum and harvested about 5 millimeters of testicular tissue, which was frozen and delivered by courier to the University of Pittsburgh Medical Center, the lead site of the research study. The procedure involved low risk of bleeding, infection or injury, Dr. Palmer said. 

Zechariah is one of more than 400 research participants in the collaborative study, which involves a dozen institutions across the country. Most of Zechariah’s specimen has been set aside for his own use, Dr. Palmer said. But a fraction of the specimen goes toward finding ways to efficiently and safely mature and utilize the frozen-thawed tissue via in vitro, grafting or other methods. Animals in the lab have given birth in experiments using harvested testicular tissue.

“This is going to happen, I just don’t know exactly when,” he said. “This could be two years from now. It could be five years from now. But for a kid who’s 6, like Zechariah, we have a lot of confidence that this is something that is going to be readily available for him when he’s ready.”

Dr. Palmer called Zechariah’s procedure a cutting-edge step that brings new hope for young boys with cancer. He looks forward to the day when the guaranteed ability to restore fertility will take away a worrisome side effect of cancer treatment.

Dr. Palmer is passionate, too, about advocating to defray the cost of fertility preservation (currently, it’s not covered by insurance). He gives credit to his Cook Children’s colleagues, Leavitt, clinical research coordinator Kristy Reyes, and Dr. Karen Albritton, M.D., medical director for the Adolescent and Young Adult Program, of the Hematology and Oncology Center whom are all involved with the research study.

Not all children and teens with cancer run the risk of permanent fertility loss. But for those who face that prospect, the specialty of oncofertility steps in right after diagnosis. Leavitt makes it her goal to educate and support, not attempt to persuade families into any particular choice.

She starts by helping each family understand the projected impact of chemotherapy, radiation or cancer surgery on the patient’s long-term fertility outlook. Each consultation takes into account whether the patient has already gone through puberty, a fact that determines which measures are available. The consent process is extensive; the parents of some research participants sign on, she said, and some decline.

“Your child could become a parent someday no matter what, if they want to be. We talk about adoption, and fostering and being a stepparent -- that there are many ways to become a parent,” Leavitt said. Cryopreservation is only one option, “and we want to keep this door open for our patients if that is their wish.”

Chemotherapy made Zechariah tired and caused hair loss, mouth sores and fever, his mom said. Because there’s also a strong possibility of damage to testicular cells, his parents say they’re glad that a fragment of tissue was saved so that Zechariah as an adult can decide if he wants to pursue biological paternity.

“Zechariah is super loving and caring, and I didn’t want us to take that opportunity away from him,” Whittany said. The gist of the conversation so far? She told her young son: “Later in life when you’re way older, you’ll probably want to have your own babies. You’re super smart and you know a lot of things, but it’s not the time now for you to know everything about it.’” 

Zechariah’s parents are counting on oncofertility technology to keep improving over the next 15 years, by the time their son turns 21. But for now, he’s a first-grader busy with puzzles, chess and playing with his little sister, Andersynn. His latest PET scan was clear of tumors.

“He has come such a long way. He’s got so much fight,” Gerald said. “He feels great, and I think he’s in a good place.”