In a groundbreaking fertility trial, a man whose testicular tissue was frozen before he underwent chemotherapy as a child has been able to produce sperm after the tissue was re-transplanted 16 years later. This is the first time a transplant of cryopreserved prepubertal testicular tissue has been demonstrated to restore sperm production in an adult patient.
The 27-year-old man had the sample frozen when he was 10, before undergoing potent chemotherapy as part of treatment for sickle cell disease. "This is a huge finding," said Prof Ellen Goossens of the Vrije Universiteit Brussel, who led the trial. "Many more people will have hope that they can have biological children."
Treatments such as chemotherapy and radiotherapy can be life-saving for childhood cancer and sickle cell patients but can also leave them infertile. After puberty, male patients can preserve sperm for later use in IVF, but this is not an option for prepubescent boys. In 2002, the Belgian clinic became the first to start banking testicular tissue of prepubertal patients. The immature testes contain spermatogonial stem cells, the precursors of sperm, and sertoli cells, essential "nurse" cells that support developing sperm.
First Patient's Journey
The clinic's first wave of patients are now reaching their mid-20s, and some have reached the point of wanting to start a family. The first patient had received high-dose chemotherapy in 2008 to wipe out his own blood cells before undergoing a bone marrow transplant. Before treatment, the clinic surgically removed one testicle, segmented it into small pieces, and froze the tissue.
Last year, four tissue fragments were grafted back into the remaining testicle and four under the skin of the scrotum. After a year inside the body, the grafts were removed and analysed. Two of the grafts from inside the testicle had produced mature sperm, which was collected and frozen. Because the tissue fragments are not directly connected to the sperm duct, the researchers do not expect sperm cells to naturally enter the semen. "The sperm that was isolated looked normal," said Goossens. "We still have to see whether it's able to fertilise an egg."
UK Trial Progress
Prof Rod Mitchell, a paediatric endocrinologist, is running a similar trial at the Centre for Reproductive Health at the University of Edinburgh, which began banking testicular tissue in 2014. Together with colleagues in Oxford and London, they have samples cryopreserved for more than 1,000 UK patients. "There is now proof of principle in humans that this approach is going to work, which is amazing," he said. Mitchell expects his clinic to carry out the first transplants imminently.
More than 3,000 patients worldwide already have testicular tissue banked. In the UK, it is estimated that about 200 patients each year would be likely to benefit. Mitchell added: "We're at a point where, internationally, we've been working on this for 15 years. It's all been about collecting tissue from the boys. Now it's coming to fruition."
The first patient is considering whether to undergo a second round of grafts to collect more sperm or to proceed with IVF in the near future.
