David Miller, M.D., Emad Ibrahim, M.D., and Brian Ledesma, M.D., from the team that performed the Miller School’s first prepubertal male fertility preservation procedure.
made history recently by performing the institute’s first prepubertal male fertility preservation.
The investigational procedure, done in collaboration with University of Pittsburgh Medical Center (UPMC), harvests testicular tissue containing stem cells in prepubertal boys who are about to undergo treatments for cancer or other conditions that might result in infertility.
The tissue is then frozen and stored for reimplantation potentially decades later, allowing those patients to have biological children.
DSUI’s first case to preserve sperm-making stem cells was in a 7-year-old diagnosed with cancer and undergoing bone marrow transplant.
“DSUI is the only center in South Florida that is collaborating with UPMC to offer prepubertal male fertility preservation,” said , director of the at The Miami Project to Cure Paralysis and assistant professor of urology at at the University of Miami Miller School of Medicine. “It is a complex procedure that requires extensive coordination with different departments and physicians at the Miller School, as well as with University of Pittsburgh, which developed the procedure’s protocol and does the tissue processing and research.”
“The goal is to offer male fertility preservation to all the Miller School’s male patients who have yet to go through puberty and face treatment that could render them temporarily or permanently infertile later in life,” said Dr. Daniel Nassau, M.D., a pediatric urologist and an assistant professor of urology at the Miller School of Medicine who is collaborating with Dr. Ibrahim and his team.
The option is much needed.
“The five-year survival for childhood cancer patients is more than 85%. Without an option like this, many of the children who survive will have lost their ability to have biological children in adulthood,” Dr. Ibrahim said.
Fertility Preservation: The Rationale and Approach
Spermatogonial stem cells differentiate, multiply and divide until they become mature sperm cells. That process is spermatogenesis.
“Spermatogonial stem cells are present in the tissue before puberty,” Dr. Ibrahim said.
Prepubertal boys do not yet make their own sperm and are not candidates for traditional male fertility preservation procedures. Researchers at UPMC, led by , aimed to create an option specifically for the youngest male patients.
Dr. Orwig and colleagues were among the first in the U.S. to develop a protocol for cryopreserving testicular tissue. The procedure surgically collected, processed and froze tissue with spermatogonial stem cells from prepubertal boys.
The protocol remains investigational and it’s too early to tell if humans who have their testicular tissues and stem cells preserved will go onto have healthy biological children. But Dr. Orwig and his team have shown that transplantation of cryopreserved testicular stem cells or testicular tissue including the birth of a rhesus monkey from prepubertal testicular tissue.
Dr. Orwig and coauthors recovered testicular tissue from monkeys and reimplanted it several months later. The grafted tissue resembled testes tissue and had sperm cells. In vitro fertilization (IVF) produced an animal embryo.
“The embryo was then transferred, and, on April 16, 2018, a baby rhesus monkey was born by C-section,” Dr. Ibrahim said. “That was the first-ever monkey born from autologously grafted frozen and thawed prepubertal testicular tissue.”
Miami and Pittsburgh Collaboration
Early on, UPMC was one of a few sites in the world that could offer this experimental prepubertal fertility preservation option. Patients and families had to travel to Pittsburgh to participate.
“The need to travel often created a barrier to access, especially given that many of these children are so sick that they’re unable to travel,” Dr. Orwig said.
By collaborating with UPMC, Dr. Ibrahim was trained in the protocol and able to collect the patient’s testicular tissue at the Miller School, where the patient was receiving treatment for his cancer. UPMC sent a special cooler the day of the surgery to pick up the collected tissue, which was shipped to Pittsburgh overnight for processing.
“We guided the patient’s parents through arranging for long-term storage because 25% of the tissue that we collected goes to University of Pittsburgh for research and 75% goes to long-term storage based on the hope that the patient will be able to use that tissue to have biological children,” Dr. Ibrahim said.
DSUI is one of more than 20 U.S. centers working with UPMC to offer patients research protocol for testicular tissue. This coordinated network allows patients to have surgery to obtain testicular tissue where they are being treated for their primary disease.
Some centers offer a fee-for-service arrangement. Patients at the Miller School do not pay the costs associated processing and freezing the tissue because it is part of a research study.
“The benefits of these collaborations go beyond improving patient access. We now have the opportunity to learn from the experiences of patients at multiple sites around the country, which accelerates the pace of our research,” Dr. Orwig said. “The reality is that we see so many patients with so many different types of diseases and different treatment plans. Through collaborations like that at DSUI, we learn about how all of those different circumstances might impact testicular tissue’s reproductive potential.”
The first case went extremely well, according to Dr. Ibrahim, the principal investigator for the protocol at DSUI.
“We have established our own protocol for performing this procedure smoothly, efficiently and safely while collaborating with different departments and multidisciplinary physicians,” Dr. Ibrahim said. “It’s a history-making step for South Florida patients, and one that we’re proud to be part of.”
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