Protecting spermatogonial stem cells from chemotherapy-induced damage for fertility preservation in childhood cancer
Lead Research Organisation:
University of Edinburgh
Department Name: MRC Centre for Reproductive Health
Abstract
Childhood cancer rates have increased dramatically (38% since 1960) over recent decades and currently 1 in 500 adults (~35000 in UK) is a survivor of childhood cancer. The increasing incidence, coupled with remarkable improvements in cure rates (>80% 5-year survival), have 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. Alkylating agents are used commonly in childhood cancer and increasingly for stem cell transplant in non-malignant disorders. Unlike the situation in men, semen cryopreservation 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. Experimental approaches for fertility preservation in children undergoing cancer treatment could include taking a biopsy of the testicle before the patient receives their treatment and storing it for future use to restore fertility, although no methods to restore fertility using this approach have been developed so far. In addition, this requires invasive surgery, could carry a risk of re-introducing malignant cells and may require artificial reproductive techniques to restore fertility. Therefore, developing strategies to protect the testicles during chemotherapy treatment would represent a major advance for the clinical care of children with cancer.
The aim of this renewal is to use the understanding generated during the intial period of the Fellowship regarding SSC development, mechanisms of chemotherapy-induced damage and drugs identified as having 'chemo-protective' effects on testicular cells. These 'chemo-protective' drugs will be taken forward into co-culture and in-vivo studies to demonstrate their efficacy and safety in order that future clinical trials aimed at preserving fertility in children with cancer can be performed.
We anticipate that this renewal will be another important step towards development of treatments that will preserve fertility in boys receiving chemotherapy treatment.
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. Experimental approaches for fertility preservation in children undergoing cancer treatment could include taking a biopsy of the testicle before the patient receives their treatment and storing it for future use to restore fertility, although no methods to restore fertility using this approach have been developed so far. In addition, this requires invasive surgery, could carry a risk of re-introducing malignant cells and may require artificial reproductive techniques to restore fertility. Therefore, developing strategies to protect the testicles during chemotherapy treatment would represent a major advance for the clinical care of children with cancer.
The aim of this renewal is to use the understanding generated during the intial period of the Fellowship regarding SSC development, mechanisms of chemotherapy-induced damage and drugs identified as having 'chemo-protective' effects on testicular cells. These 'chemo-protective' drugs will be taken forward into co-culture and in-vivo studies to demonstrate their efficacy and safety in order that future clinical trials aimed at preserving fertility in children with cancer can be performed.
We anticipate that this renewal will be another important step towards development of treatments that will preserve fertility in boys receiving chemotherapy treatment.
Organisations
- University of Edinburgh (Lead Research Organisation)
- Catholic University of Louvain (Collaboration)
- University of Leeds (Collaboration)
- University of Copenhagen (Collaboration)
- Karolinska Institute (Collaboration)
- Academic Medical Center (Collaboration)
- University of Dundee (Collaboration)
- University of Melbourne (Collaboration)
- Vrije Universiteit Brussel (Collaboration)
- University College Hospital (Collaboration)
- University of Pittsburgh (Collaboration)
- University of Oxford (Collaboration, Project Partner)
- University Hospital of Münster (Collaboration)
- University of Rouen (Collaboration)
- NHS Lothian (Project Partner)
- Queen Mary University of London (Project Partner)
- University of Bradford (Project Partner)
- Oxford University Hospitals NHS Trust (Project Partner)
| Description | ESHRE Good Practice Recommendations for Fertility Preservation in Boys |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| URL | https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Guidelines-in-development/Fertility-preservatio... |
| Description | Royal College of Paedicatrics and Child Health (RCPCH) - Academic Training Representative, South East Scotland |
| Geographic Reach | National |
| Policy Influence Type | Participation in a guidance/advisory committee |
| URL | https://www.rcpch.ac.uk/membership/committees/academic-training-committee |
| Description | Impact of treatment regimens on fertility in boys |
| Amount | £11,840 (GBP) |
| Funding ID | 5166 |
| Organisation | Royal Society of Edinburgh (RSE) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2025 |
| End | 02/2027 |
| Description | Preserving fertility in children with cancer by protecting the testis from chemotherapy-induced damage |
| Amount | £101,239 (GBP) |
| Funding ID | 13946344_13946353 |
| Organisation | Melville Trust for Care and Cure of Cancer |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 07/2024 |
| End | 08/2027 |
| Description | Childrens Cancer and Leukaemia Group |
| Organisation | University of Leeds |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have joined a collaboration to create a UK patient registry for young people who receive gonadal tissue cryopreservation for fertility preservation. We are co-ordinating the Scottish dataset for the register. |
| Collaborator Contribution | The partner is hosting and maintaining the registry. |
| Impact | Development of the contracts, agreements and patient materials for the register. |
| Start Year | 2022 |
| Description | ESHRE Grant Partnership |
| Organisation | University College Hospital |
| Department | University College London Hospitals Charity (UCLH) |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | P-I - lead the research project |
| Collaborator Contribution | Co-I - patient recruitment and experimental work |
| Impact | ESHRE Grant awarded 2021 |
| Start Year | 2021 |
| Description | ESHRE Grant Partnership |
| Organisation | University of Dundee |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | P-I - lead the research project |
| Collaborator Contribution | Co-I - patient recruitment and experimental work |
| Impact | ESHRE Grant awarded 2021 |
| Start Year | 2021 |
| Description | ESHRE Grant Partnership |
| Organisation | University of Oxford |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | P-I - lead the research project |
| Collaborator Contribution | Co-I - patient recruitment and experimental work |
| Impact | ESHRE Grant awarded 2021 |
| Start Year | 2021 |
| Description | ORCHID-NET |
| Organisation | Academic Medical Center |
| Country | Netherlands |
| Sector | Academic/University |
| PI Contribution | I have created and co-ordinated this consortium of clinicians and researchers involved in the provision of fertility preservation for prepubertal boys. I chair the meetings and chair the ESHRE consensus being developed by the consortium. |
| Collaborator Contribution | Each partner contributes to the activities of the consortium. These activities include a worldwide survey of practice (due for publication 2023), ESHRE good practice recommendations and auto-transplantation expert consensus (submitted for publication). |
| Impact | ESHRE good practice recommendations draft for stakeholder testing. |
| Start Year | 2022 |
| Description | ORCHID-NET |
| Organisation | Catholic University of Louvain |
| Country | Belgium |
| Sector | Academic/University |
| PI Contribution | I have created and co-ordinated this consortium of clinicians and researchers involved in the provision of fertility preservation for prepubertal boys. I chair the meetings and chair the ESHRE consensus being developed by the consortium. |
| Collaborator Contribution | Each partner contributes to the activities of the consortium. These activities include a worldwide survey of practice (due for publication 2023), ESHRE good practice recommendations and auto-transplantation expert consensus (submitted for publication). |
| Impact | ESHRE good practice recommendations draft for stakeholder testing. |
| Start Year | 2022 |
| Description | ORCHID-NET |
| Organisation | Karolinska Institute |
| Country | Sweden |
| Sector | Academic/University |
| PI Contribution | I have created and co-ordinated this consortium of clinicians and researchers involved in the provision of fertility preservation for prepubertal boys. I chair the meetings and chair the ESHRE consensus being developed by the consortium. |
| Collaborator Contribution | Each partner contributes to the activities of the consortium. These activities include a worldwide survey of practice (due for publication 2023), ESHRE good practice recommendations and auto-transplantation expert consensus (submitted for publication). |
| Impact | ESHRE good practice recommendations draft for stakeholder testing. |
| Start Year | 2022 |
| Description | ORCHID-NET |
| Organisation | University Hospital of Münster |
| Country | Germany |
| Sector | Hospitals |
| PI Contribution | I have created and co-ordinated this consortium of clinicians and researchers involved in the provision of fertility preservation for prepubertal boys. I chair the meetings and chair the ESHRE consensus being developed by the consortium. |
| Collaborator Contribution | Each partner contributes to the activities of the consortium. These activities include a worldwide survey of practice (due for publication 2023), ESHRE good practice recommendations and auto-transplantation expert consensus (submitted for publication). |
| Impact | ESHRE good practice recommendations draft for stakeholder testing. |
| Start Year | 2022 |
| Description | ORCHID-NET |
| Organisation | University of Copenhagen |
| Country | Denmark |
| Sector | Academic/University |
| PI Contribution | I have created and co-ordinated this consortium of clinicians and researchers involved in the provision of fertility preservation for prepubertal boys. I chair the meetings and chair the ESHRE consensus being developed by the consortium. |
| Collaborator Contribution | Each partner contributes to the activities of the consortium. These activities include a worldwide survey of practice (due for publication 2023), ESHRE good practice recommendations and auto-transplantation expert consensus (submitted for publication). |
| Impact | ESHRE good practice recommendations draft for stakeholder testing. |
| Start Year | 2022 |
| Description | ORCHID-NET |
| Organisation | University of Melbourne |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | I have created and co-ordinated this consortium of clinicians and researchers involved in the provision of fertility preservation for prepubertal boys. I chair the meetings and chair the ESHRE consensus being developed by the consortium. |
| Collaborator Contribution | Each partner contributes to the activities of the consortium. These activities include a worldwide survey of practice (due for publication 2023), ESHRE good practice recommendations and auto-transplantation expert consensus (submitted for publication). |
| Impact | ESHRE good practice recommendations draft for stakeholder testing. |
| Start Year | 2022 |
| Description | ORCHID-NET |
| Organisation | University of Oxford |
| Department | Oxford Hub |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I have created and co-ordinated this consortium of clinicians and researchers involved in the provision of fertility preservation for prepubertal boys. I chair the meetings and chair the ESHRE consensus being developed by the consortium. |
| Collaborator Contribution | Each partner contributes to the activities of the consortium. These activities include a worldwide survey of practice (due for publication 2023), ESHRE good practice recommendations and auto-transplantation expert consensus (submitted for publication). |
| Impact | ESHRE good practice recommendations draft for stakeholder testing. |
| Start Year | 2022 |
| Description | ORCHID-NET |
| Organisation | University of Pittsburgh |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | I have created and co-ordinated this consortium of clinicians and researchers involved in the provision of fertility preservation for prepubertal boys. I chair the meetings and chair the ESHRE consensus being developed by the consortium. |
| Collaborator Contribution | Each partner contributes to the activities of the consortium. These activities include a worldwide survey of practice (due for publication 2023), ESHRE good practice recommendations and auto-transplantation expert consensus (submitted for publication). |
| Impact | ESHRE good practice recommendations draft for stakeholder testing. |
| Start Year | 2022 |
| Description | ORCHID-NET |
| Organisation | University of Rouen |
| Country | France |
| Sector | Academic/University |
| PI Contribution | I have created and co-ordinated this consortium of clinicians and researchers involved in the provision of fertility preservation for prepubertal boys. I chair the meetings and chair the ESHRE consensus being developed by the consortium. |
| Collaborator Contribution | Each partner contributes to the activities of the consortium. These activities include a worldwide survey of practice (due for publication 2023), ESHRE good practice recommendations and auto-transplantation expert consensus (submitted for publication). |
| Impact | ESHRE good practice recommendations draft for stakeholder testing. |
| Start Year | 2022 |
| Description | ORCHID-NET |
| Organisation | Vrije Universiteit Brussel |
| Country | Belgium |
| Sector | Academic/University |
| PI Contribution | I have created and co-ordinated this consortium of clinicians and researchers involved in the provision of fertility preservation for prepubertal boys. I chair the meetings and chair the ESHRE consensus being developed by the consortium. |
| Collaborator Contribution | Each partner contributes to the activities of the consortium. These activities include a worldwide survey of practice (due for publication 2023), ESHRE good practice recommendations and auto-transplantation expert consensus (submitted for publication). |
| Impact | ESHRE good practice recommendations draft for stakeholder testing. |
| Start Year | 2022 |
| Title | Autotransplantation of testicular tissue for fertility preservation |
| Description | Ethical approval to perform first in human study to re-transplant testicular tissue into patients who have infertility following cancer treatment. Funding secured to perform first transplants and actively seeking recruitment of first patient. |
| Type | Therapeutic Intervention - Surgery |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2023 |
| Development Status | Under active development/distribution |
| Impact | Protocol has been shared with collaborators wishing to adopt the technique. |
| Description | Bits and Bobs - The Anatomy of Sex |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Join the experts for an intriguing event where we delve into the fascinating world of reproductive anatomy. From the basics to the complexities, this event will uncover the mysteries of human anatomy in an engaging and interactive way. Don't miss out on this unique opportunity to explore the wonders of the human body! The event will be held in the Anatomical Museum, Old Medical School, Doorway 3. What better way to spend Valentine's night! Book at Eventbrite https://srfpresents.eventbrite.com. |
| Year(s) Of Engagement Activity | 2025 |
| URL | https://biomedical-sciences.ed.ac.uk/anatomyedinburgh/bits-and-bobs-the-anatomy-of-sex |