Preserving Prepubescent Boys’ Fertility

The good news is that more children survive cancer now than ever before, as doctors are able to cure nearly 80 percent of patients. But that doesn’t mean that those pediatric patients who survive cancer stop fighting once their treatment ends, because many face a variety of physical and emotional challenges as a result of their treatment.

The Children’s Hospital of Philadelphia’s Cancer Survivorship Program “helps patients and families navigate life after cancer, including both the physical and emotional issues they may have.” The program, which is led by Jill P. Ginsberg, MD, offers a variety of services and has a number of studies currently underway, including research into the neurobehavioral outcomes of acute lymphoblastic leukemia survivors, and key adverse events following childhood cancer.

Another research initiative, one targeting prepubescent boys who have been diagnosed with cancer, was the subject of recent media attention, with articles appearing in Nature Medicine and The Wall Street Journal. Led by Dr. Ginsberg and Thomas F. Kolon, MD, the experimental program seeks to collect and preserve testicular tissue from young boys who are set to receive cancer treatment, in the hope that their tissue could one day be used to produce viable sperm.

An estimated 35 percent of prepubescent boys are at risk of sterility following cancer treatment, Dr. Ginsberg said, and because prepubescent boys cannot produce sperm, CHOP’s testicular tissue cryopreservation (TTCP) program can offer families hope. Based on pioneering work by the University of Pennsylvania’s Ralph L. Brinster, PhD, the procedure involves the removal of a small amount of testicular tissue containing spermatogonial stem cells, “about half the size of a pencil eraser,” according to the Nature Medicine article.

The hope is that these stem cells can either be transplanted back into the boys to grow spermatogonial tissue following cancer treatment, or be used to grow sperm in vitro. However, because the procedure remains experimental, only boys at the highest risk for infertility are approached to take part in the program. Though researchers have yet to produce sperm using human spermatogonial tissue, work by Dr. Brinster’s lab has shown that the approach works in a mouse model.

Dr. Ginsberg has compared the development of TTCP to that of in vitro fertilization (IVF). IVF took 15 years to go from the lab to the birthing suite, Dr. Ginsberg pointed out, whose work on TTCP began in 2007.

“If everyone keeps saying ‘it’s too experimental,’ we’ll never get anywhere,” Dr. Ginsberg said in the Nature Medicine. “Everyone was saying IVF was too experimental years ago, and now it’s not. All of these things have to start somewhere.”

“Really Positive” Reaction

 However, there have been concerns associated with TTCP. In addition to the usual skepticism that accompanies any new research, there have been ethical concerns about the tissue removal surgery. In particular, there are worries that the surgery is too invasive, given TTCP’s experimental nature.

To allay these concerns, the tissue removal surgery is coupled with another regularly scheduled procedure. “We don’t want to expose the children to another general anesthesia since there is a risk with any general anesthesia, so we wanted to make sure it was coupled with another trip to the operating room,” Dr. Ginsberg said.

Indeed, according to a questionnaire handed out after the treatment, coupling the testicular tissue removal procedure with another has led some families to agree to take part in the program when they might not have been interested, Dr. Ginsberg pointed out.

Moreover, “even though this is experimental, and we basically tell the families that we’re not even sure the tissue will be usable for their children, 80 percent of the patients approached are agreeing to do the procedure,” Dr. Ginsberg said.

And thanks to a recent award from the St. Baldrick’s Foundation, the TTCP program is set to expand to two other institutions. For the first few years of CHOP’s TTCP work, Children’s Hospital was the only center that could accept patients and “we were getting calls from all over,” Dr. Ginsberg said, so she knew the work would be appealing to other centers. The $125,000 St. Baldrick’s grant will allow the Testicular Cryopreservation Consortium to expand beyond CHOP to include Seattle Children’s Hospital and Memorial Sloan-Kettering Cancer Center.

“We are hopeful that advances in the laboratory will make it possible for these boys to achieve fertility when they are ready to start a family. This work could not have been accomplished without the support of St. Baldrick’s Foundation,” said Dr. Ginsberg after the award was announced.

In addition to its groundbreaking work with prepubescent boys, Children’s Hospital also has a robust sperm-banking program for postpubescent boys. Every postpubescent boy set to be treated for cancer at CHOP is approached about banking, “independent of their risk,” Dr. Ginsberg said, noting that roughly 85% of boys agree to bank.

The Children’s Hospital of Philadelphia is one of few, if not the only, institution in country that approaches all postpubescent boys set to undergo cancer treatment, Dr. Ginsberg pointed out, and the program is “one of the programs here at CHOP that I’m most proud of.” And overall, families’ reaction to the TTCP program has been “really positive,” Dr. Ginsberg said.

To learn more about CHOP’s cancer treatment, survivorship program, and research, see the Cancer Center.

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