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Childhood cancer rates have increased over recent decades and remarkable improvements in cure rate has resulted in an increase in young adults experiencing subsequent health effects of their cancer treatment. This project will, for the first time, prove that fertility potential can be restored in patients who would otherwise be unable to have their own biological children.
Transplantation of Cryopreserved Testicular Tissue to restore fertility after childhood cancer
Professor Rod Mitchell
University of Edinburgh
Edinburgh, EH16 4TJ
1 June 2023
36 months
£290,454.69
Childhood cancer rates have increased over recent decades and remarkable improvements in cure rate has resulted in an increase in young adults experiencing subsequent health effects of their cancer treatment. Ensuring long-term health of this new and expanding patient cohort is one of the most pressing areas of clinical need in paediatric oncology. Infertility occurs in the majority of males receiving high-dose chemotherapy with drugs known as alkylating agents, which are commonly used in childhood cancer. Unlike the situation in men, cryopreservation of sperm is not an option to preserve fertility in these boys as their testicles are not capable of making sperm in childhood. As a result, there is currently no established clinical option to prevent infertility in prepubertal boys receiving chemotherapy. Preservation of fertility in children receiving cancer treatment is dependent on survival of the spermatogonial stem cells (SSC) in the testicle. These stem cells will generate sperm in males after puberty. We are currently able to cryopreserve testicular tissue, containing SSCs, from boys before they receive cancer treatment. Establishing this fertility preservation programme was supported by funding from Children with Cancer UK. This tissue is available for future use to restore fertility in these patients in adulthood. Transplantation of the tissue back to the patient represents a good potential option to restore fertility in these patients and this has proved to be successful in primate studies. However, transplantation has not been performed in humans yet.
Professor Rod Mitchell and his team aim to restore fertility in male patients who have had childhood cancer treatment that has made them infertile. The aim of this project is to undertake the first clinical trial to transplant testicular tissue to restore fertility in patients who had their tissue cryopreserved in childhood. The project will involve developing a safe and effective protocol to conduct the transplants, in addition to obtaining the necessary ethics and regulatory approvals. The project will undertake the transplants in carefully selected cases. Once the transplanted tissue has begun to produce sperm, these will be extracted and stored or used to make embryos if the patient wants to have a child at the time. This would represent an important breakthrough to enable young people treated for cancer during childhood to have children of their own.
This project will, for the first time, prove that fertility potential can be restored in patients who would otherwise be unable to have their own biological children. Successful completion of the project will potentially open the door to future fertility for greater than 800 patients in the UK (greater than 2500 worldwide) who have had testicular tissue stored for fertility preservation, as well as providing an option for all future patients due to receive childhood cancer treatment that can impair their fertility. This would represent a major step for improving the quality of life for survivors of childhood cancer.
Professor Rod Mitchell is a Clinician Scientist and Paediatric Endocrinologist at the University of Edinburgh and one of the co-founders of the Edinburgh Fertility Preservation programme.
The clinical research team consists of the leading UK fertility preservation experts for children with cancer who are world-leaders in the field. The team includes doctors who provide fertility counselling for children with cancer and their families. They also support the collection of testicular tissue for storage prior to their treatment. Surgeons with expertise in testicular surgery and tissue transplantation are also part of the research team. Doctors and scientists with expertise in freezing human tissues for future clinical use are also involved in the project. Scientists with expertise in IVF will perform experiments to test the function of sperm obtained from the transplanted tissues. The team has all of the expertise necessary to conduct the first clinical trial of testicular transplantation to restore fertility in males who have received sterilising cancer treatment in childhood.
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