A New Dawn for Fertility Preservation in Childhood Cancer Survivors

On the morning of Jaiwen Hsu’s stem cell transplant in November 2023, the atmosphere in the hospital felt electric. This was a groundbreaking moment; doctors had never before attempted a procedure like this on someone with Hsu’s background.

“There was this building buzz,” he recalls, describing the combination of anticipation and hope that filled the air. Unlike the daunting surgeries Hsu had faced in the past—15 to 20 procedures since his bone cancer diagnosis at age 11—this day was marked by excitement rather than fear.

A Journey of Preservation

In 2011, during an intense chemotherapy regimen aimed at treating a tumor in his femur, doctors harvested a small piece of Hsu’s testicular tissue. They froze his cells using a method known as testicular tissue cryopreservation, designed to safeguard his future fertility.

Normal sperm freezing is unfeasible for boys who haven’t reached puberty, making the preservation of testicular tissue a viable alternative. The hope was that once Hsu matured, doctors could reimplant those cells, potentially allowing him the chance to father a child.

At 24, Hsu’s time had come. Under anesthesia, doctors carefully injected his prepubescent cells back into one of his testicles. “It was completely pain-free,” he affirms, adding that he was back home by lunchtime.

Hsu became the first childhood cancer survivor in the world to undergo this innovative procedure, as reported by reproductive scientist Kyle Orwig and his team in March in a preprint on medRxiv. While it may take years to determine the procedure’s success, developments like Hsu’s are pivotal in enhancing the quality of life for young cancer survivors and similar initiatives are in the pipeline for those with diseases like leukemia.

Beyond Survival: The New Health Paradigm

The narrative surrounding childhood cancer care has shifted significantly over the decades. Once regarded as a death sentence, the prognosis for many children diagnosed with cancer has dramatically improved. From the period spanning 1975 to 1979, nearly 5 in 100,000 children died from the disease. By 2019, this number has diminished to about 2 per 100,000.

Today, children diagnosed with cancer boast an 85 percent chance of surviving five years or more, according to the American Cancer Society. As survival rates soar, a critical focus has emerged: helping these young survivors lead productive, fulfilling lives. “We don’t want you just to survive,” oncologist Tyler Ketterl of Seattle Children’s Hospital insists. “We want you to thrive.”

Transplants like Hsu’s are likely to become more common. Around the world, over 3,000 boys under 18 have safely frozen their testicular tissue, few of whom have yet reclaimed it. Orwig noted, “It’s exactly the time for it to start happening.”

Women who had their ovarian tissue frozen will likely follow suit. As Veronica Gomez-Lobo, from the National Institute of Child Health and Human Development, pointed out, “In the next 10 years, we’re going to see a tsunami of these patients starting to come back for their tissue.”

Hope for Female Patients

Charlie Stenson, only three years old at the time, had one of her ovaries removed due to cancer. In 2023, her surgeon extracted the organ through a small incision in her abdomen, and scientists subsequently prepared and froze the tissue. This method, called ovarian tissue cryopreservation, was once considered experimental until 2019.

For families like the Stensons, the decision to freeze reproductive tissue isn’t easy. “We knew this would give her the best chance of having a family in the future,” her mother, Emily Stenson, reflected.

Around 200 babies have been born worldwide to women who relied on frozen ovarian tissue, but most have utilized it as adults or teenagers, not as young children. The potential success of ovarian tissue obtained from toddlers remains untested, and researchers acknowledge that uncertainty looms ahead.

Conversely, no babies have yet been born from fathers who’ve undergone cryopreserved testicular tissue. Yet, Hsu remains optimistic. “Despite everything I’ve been through,” he says, “I still might be able to have kids in a few years.”

The Vigilant Wait

Every six months, Hsu will provide a semen sample for Orwig’s team and undergo an ultrasound to check for sperm production. The transplanted testicular cells contain stem cells capable of producing sperm. While many variables remain, and even if he returns to fertility, producing enough sperm for it to become viable is uncertain.

“There’s no rush,” Hsu maintains, even as he acknowledges being the first child cancer survivor to undergo such a procedure. He understands the significance and hopes for a family in the future.

Indeed, a large percentage of male childhood cancer survivors expressed the desire to have children, according to a 2023 survey of over 1,300 survivors. Innovations like Hsu’s may pave the way for achieving these dreams. Notably, researchers are exploring the transplantation of entire testicular tissue chunks.

A recent groundbreaking surgery in Belgium involved the first transplant of frozen testicular tissue fragments from a man who had undergone childhood cancer treatment, setting another precedent in this emerging field.

Caution in the Face of Innovation

Amidst the hopeful advancements, researchers are carefully evaluating the potential risks of reintroducing cancer cells during transplant procedures. The Universitè Catholique de Louvain is investigating strategies to detect and eradicate malignant cells prior to transplantation or contain any risks within specialized gels during the process.

Leukemia survivors face a unique challenge, as these cancer cells can spread throughout the body. Various experimental methods aim to safely isolate or eliminate cancer cells in these victims’ reproductive tissues.

Moreover, as the field of oncofertility continues to expand, awareness and education are essential. Unfortunately, many patients remain uninformed about the fertility preservation options available to them.

Despite the plethora of healthcare advancements, only about half of patients reported discussing fertility preservation with their healthcare providers beforehand. Barriers also include the high costs associated with fertility preservation techniques—costs that are often not covered by insurance.

The Road Ahead

While these revolutionary developments offer hope to childhood cancer survivors, accessibility remains an issue. Only about 20 states require insurance companies to provide any coverage for fertility preservation, and experimental procedures often leave patients waiting.

Nevertheless, both Hsu and the Stenson family recognize the significance of these advancements in medical technology. “If it works, that’s fantastic,” Hsu says. “And if it doesn’t, I know we’re helping the field progress.”

Investments in research, education, and improved healthcare policies are necessary to ensure that every child facing cancer has an equal opportunity to preserve their future fertility and health. With ongoing advancements in the field of oncofertility, the future holds great promise for all childhood cancer survivors.