Srdjan Saso1, Gemma Petts2, Jayanta Chatterjee3, Meen-Yau Thum4, Anna L David5, David Corless6, Michael Boyd7, David Noakes8, Iain Lindsay9, Giuseppe Del Priore10, Sadaf Ghaem-Maghami3, J Richard Smith11. 1. Clinical Research, Division of Surgery and Cancer, Institute of Reproductive & Developmental Biology, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK. Electronic address: srdjan.saso@imperial.ac.uk. 2. Department of Pathology, Imperial College Healthcare NHS Trust, St Mary's Hospital, Praed Street, London W2 1NY, UK. 3. Clinical Research, Division of Surgery and Cancer, Institute of Reproductive & Developmental Biology, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK. 4. The Lister Hospital, Chelsea, London SW1W 8RH, UK. 5. Obstetrics and Maternal Fetal Medicine, Institute for Women's Health, Faculty of Population Health Sciences, University College London, 86-96 Chenies Mews, London WC1E 6HX, UK. 6. Mid Cheshire NHS Trust, Leighton Hospital, Crewe CW1 4QJ, UK. 7. Biological Services Unit, Royal Veterinary College, Royal College Street, London NW1 0TU, UK. 8. Veterinary Reproduction and Obstetrics, Royal Veterinary College, Royal College Street, London NW1 0TU, UK. 9. Department of Pathology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK. 10. Southeastern Regional Medical Center, Atlanta, Georgia, USA. 11. West London Gynaecological Cancer Centre, Queen Charlotte's Hospital, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, London W12 0NN, UK.
Abstract
OBJECTIVE: Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility. Allogeneic UTx has been attempted in a number of animal models, but achieving an adequate blood supply for the transplanted uterus still presents the biggest challenge. Microvascular re-anastomosis was unsuccessful in a number of animal models. The aim was to assess whether a large vessel aortic-caval vascular patch technique can bring about long-term graft survival after allogeneic UTx in a rabbit model. STUDY DESIGN: A longitudinal study involving uterine cross transplantations (n=9 donors, n=9 recipients) was performed in New Zealand white rabbits using an aortic-caval macrovascular patch harvested as part of the uterine allograft. All rabbits were allogeneic and of proven fertility, with at least one previous litter each. The end result of the donor graft harvest was a total hysterectomy transecting across the vagina and the most lateral aspects of the uterine horns together with an aortic-caval macrovascular patch (aorta, inferior vena cava, common and internal iliacs, and uterine arterial and venous tree). Tacrolimus (500 μg twice daily) was administered for immunosuppression post-transplant. The recipients were closely monitored until death or euthanasia. RESULTS: In this case series, long-term rabbit survival was 11% (n=1). Surgical survival was 56% (n=5). Three rabbits (UTx #3, #4 and #8) died intra-operatively as a result of blood aspiration, ventricular hematoma, and massive hemorrhage. Three does (#1, #2, #7 and #9) died within the first 24 h as a result of the veno-vena and anastomosis breakdown. Does #6 and #9 died secondary to pre-operative pneumonia and a pulmonary embolus, respectively. Only one rabbit survived longer than a month. CONCLUSION: Our method used a macrovascular patch technique to ensure adequate blood supply to the donor uterine graft. We have demonstrated the feasibility of uterine allotransplantation using this technique in the rabbit, but were unable to demonstrate a higher long-term survival percentage because of issues related to using a rabbit model.
OBJECTIVE: Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility. Allogeneic UTx has been attempted in a number of animal models, but achieving an adequate blood supply for the transplanted uterus still presents the biggest challenge. Microvascular re-anastomosis was unsuccessful in a number of animal models. The aim was to assess whether a large vessel aortic-caval vascular patch technique can bring about long-term graft survival after allogeneic UTx in a rabbit model. STUDY DESIGN: A longitudinal study involving uterine cross transplantations (n=9 donors, n=9 recipients) was performed in New Zealand white rabbits using an aortic-caval macrovascular patch harvested as part of the uterine allograft. All rabbits were allogeneic and of proven fertility, with at least one previous litter each. The end result of the donor graft harvest was a total hysterectomy transecting across the vagina and the most lateral aspects of the uterine horns together with an aortic-caval macrovascular patch (aorta, inferior vena cava, common and internal iliacs, and uterine arterial and venous tree). Tacrolimus (500 μg twice daily) was administered for immunosuppression post-transplant. The recipients were closely monitored until death or euthanasia. RESULTS: In this case series, long-term rabbit survival was 11% (n=1). Surgical survival was 56% (n=5). Three rabbits (UTx #3, #4 and #8) died intra-operatively as a result of blood aspiration, ventricular hematoma, and massive hemorrhage. Three does (#1, #2, #7 and #9) died within the first 24 h as a result of the veno-vena and anastomosis breakdown. Does #6 and #9 died secondary to pre-operative pneumonia and a pulmonary embolus, respectively. Only one rabbit survived longer than a month. CONCLUSION: Our method used a macrovascular patch technique to ensure adequate blood supply to the donor uterine graft. We have demonstrated the feasibility of uterine allotransplantation using this technique in the rabbit, but were unable to demonstrate a higher long-term survival percentage because of issues related to using a rabbit model.
Authors: Che-Ying Kuo; Hannah Baker; Melissa H Fries; James J Yoo; Peter C W Kim; John P Fisher Journal: Tissue Eng Part B Rev Date: 2017-02-03 Impact factor: 6.389
Authors: Srdjan Saso; Neil T Clancy; Benjamin P Jones; Timothy Bracewell-Milnes; Maya Al-Memar; Eleanor M Cannon; Simran Ahluwalia; Joseph Yazbek; Meen-Yau Thum; Tom Bourne; Daniel S Elson; James Richard Smith; Sadaf Ghaem-Maghami Journal: Future Sci OA Date: 2018-02-06
Authors: Srdjan Saso; Maria Tziraki; Neil T Clancy; Lipei Song; Timothy Bracewell-Milnes; Benjamin P Jones; Maya Al-Memar; Joseph Yazbek; Meen-Yau Thum; Ahmad Sayasneh; Tom Bourne; James Richard Smith; Daniel S Elson; Sadaf Ghaem-Maghami Journal: Future Sci OA Date: 2018-08-01