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A relatively common consequence of chemotherapy and radiation treatments for various cancers is permanent infertility through exposure to gonadotoxic agents. This is true in both adults and children, but it is particularly important for children because the survival rates for most childhood cancers now exceeds 85 percent because of the steady improvements in treatment options over many decades. The treatments for childhood cancers are still toxic, however, and can have lasting consequences.
“Prepubertal boys present a particular challenge with respect to preserving their future fertility when they will require gonadotoxic chemotherapy for some form of cancer or hematologic disorder, or another condition whose treatment would be expected to render them infertile,” says Glenn Cannon, MD, chief of the Division of Pediatric Urology at UPMC Children’s.
The reason is simple: prepubertal boys have yet to reach a point where their bodies can manufacture viable sperm cells that can be harvested and preserved. To circumvent this challenge, researchers at UPMC, including Kyle Orwig, PhD, (above, right) professor of obstetrics, gynecology, and reproductive sciences at UPMC Magee-Womens Hospital, who is also director of research in reproductive endocrinology and infertility, director of the Fertility Preservation Program in Pittsburgh, and principal investigator in the Orwig Laboratory, have developed several novel experimental protocols and clinical trials to help this patient population to possibly retain their future reproductive abilities.
For those individuals who meet the specific criteria for these protocols, the urologic surgical team at UPMC Children’s can conduct an open testicular biopsy or a complete simple orchiectomy to derive the necessary tissues from which Dr. Orwig’s team can isolate the spermatogonial stem cells and preserve them for future reimplantation when the technology is developed in the future.
“Since the program began in 2011, we have had more than 150 children (boys) from across the United States come to UPMC Children’s for spermatogonial stem cell harvest with the future goal of reimplanting those cells once the technology for doing so is proven safe and effective in humans,” says Dr. Cannon.
Important Information for Families and Providers
Children who already have undergone chemotherapy but have not undergone a fully gonadotoxic dose of chemotherapy can still have their spermatogonial stem cells retrieved and preserved.
“This is important for families to know because many families do not necessarily learn about these fertility preservation options until after their child has received at least one dose of chemotherapy that may be gonadotoxic. Sometimes this is the case because the child does not reside locally in our immediate area or simply because their treatment needed to begin immediately,” says Dr. Cannon.
Reimplantation Under Ultrasound Guidance
The fertility preservation program at UPMC has reached a level of maturation that is now close to the point where it can begin to reimplant spermatogonial stem cells back into pediatric patients who have successfully undergone chemotherapy for their original disease process.
Clinical trials with Dr. Orwig’s group are currently ramping up in adult subjects to determine the safety and efficacy of the reimplantation protocol before the program can apply for and receive IRB approval to begin the treatment in pediatric patients. However, with Dr. Orwig’s past studies and clinical trials in various model systems, it is fully expected that these initial human trials will be successful, thereby opening the door to the first reimplantations in pediatric patients in the near future.
The reimplantation procedure involves an ultrasound-guided needle injection into the remaining testis, into which the previously preserved spermatogonial stem cells are injected. The ultrasound-guided procedure also uses a microbubble contrast agent to aid in ensuring adequate and complete distribution of the spermatogonial stem cells throughout the entire testis.
The Future Is Approaching Fast
The ultimate measure of the success of this novel approach to fertility preservation will be paternity: that these boys will grow up and father children of their own.
“It will take many years to determine success by that measure, but in the more immediate future, it is our firm belief that within the next five years we will be able to reimplant cells into adolescents who underwent the harvest procedure when they were younger and restore their fertility potential.