“What we expected from the initial transplant was to prove that the method was safe and feasible,” said Orvig. Ultrasound showed that the surgery did not damage the testicular tissue of the HSU, and its hormone levels were within the normal range. For now, his semen is still lacking in sperm.
More transplants may happen soon. Orwig’s team has been performing testicular tissue from children since 2011, and some of these patients are now entering reproductive age. As part of the clinical trial, his team has been licensed by the U.S. Food and Drug Administration for stem cell transplantation and testicular tissue.
Transplanting immature testicular tissue is another method researchers are exploring. In this technique, a piece of retained tissue is hidden under the skin of the scrotum. Hopefully the tissue will mature and eventually produce sperm. In the monkey, Orwig and his team transplanted the testicular tissue, then removed the tissue transplanted after 8 to 12 months, and sperm was extracted from it. They fertilized with sperm and transferred the obtained embryos from female macaques to the surrogate, which led to live births.
To retrieve sperm, a piece of tissue is cut open from the skin, which is an invasive procedure than stem cell transplantation, which requires opening the testicles.
When Orwig’s team first started collecting testicular tissue, he thought they would get more stem cells by first isolating it from the tissue and then freezing it. They did this with the first few patients, including HSU. But later, they found that they could get the same number of stem cells or more stem cells from the entire tissue, and then thaw them and extract the cells. This means that HSU can only undergo stem cell transplantation, because only his cells are frozen. Other patients who freeze the entire tissue may choose to try stem cell or tissue transplantation.
In January, researchers from Vrije Universiteit Brussel and Brussels IVF in Belgium announced that patients who received chemotherapy had undergone the first chemotherapy testicular tissue transplant. The patient will be monitored for one year and his semen receives the presence of sperm. A year later, the doctor will remove some transplanted tissue to check for sperm.
“For those who receive life-saving cancer treatments, they are often permanently impaired in fertility,” said Robert Brannigan, president-elect, American Society of Reproductive Medicine and Northwestern University professor of urology. “It’s hard to say which approach will be a more effective approach, but I think both approaches really deserve further research.”
Similar surgery, known as ovarian tissue transplant, can be used in female cancer patients and has produced more than 200 live births worldwide. It is more advanced than testicular freezing and transplantation because frozen sperm is usually available in adult men who require chemotherapy, while equivalent exercises for women (frozen eggs) can take two to three weeks, and patients may not have time to receive it before starting chemotherapy. When eggs cannot be frozen, a piece of tissue in the ovary can be collected and stored for later use.
“It’s great to see that we are catching up with some so we can give young men the same opportunity we can offer young women,” said Jonathan Rout, a pediatric urologist at Duke Health. “Let the kids live always have the goal first, but allowing them to live is indeed the second goal, and I think this is where this research will really have an impact on the future.”
HSU realizes that the technology is still in its infancy and may not work for him. Even if he doesn’t have a biological child, he hopes that these technologies will eventually open up options for other childhood cancer patients. “It’s a practice that’s just beginning,” he said. “The more support and the more research we have, the more data we have, and for someone like me, the better.”
