title: Uterine allotransplantation in a rabbit model using aorto-caval anastomosis: a long-term viability study.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Saso
authors.affiliation: Department of Pathology, Imperial College Healthcare NHS Trust, St Mary's Hospital, Praed Street, London W2 1NY, UK.
authors.forename: Gemma
authors.initials: G
authors.lastname: Petts
authors.affiliation: 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.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chatterjee
authors.affiliation: The Lister Hospital, Chelsea, London SW1W 8RH, UK.
authors.forename: Meen-Yau
authors.initials: MY
authors.lastname: Thum
authors.affiliation: 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.
authors.forename: Anna L
authors.initials: AL
authors.lastname: David
authors.affiliation: Mid Cheshire NHS Trust, Leighton Hospital, Crewe CW1 4QJ, UK.
authors.forename: David
authors.initials: D
authors.lastname: Corless
authors.affiliation: Biological Services Unit, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Boyd
authors.affiliation: Veterinary Reproduction and Obstetrics, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
authors.forename: David
authors.initials: D
authors.lastname: Noakes
authors.affiliation: Department of Pathology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK.
authors.forename: Iain
authors.initials: I
authors.lastname: Lindsay
authors.affiliation: Southeastern Regional Medical Center, Atlanta, Georgia, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Priore
authors.affiliation: 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.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Ghaem-Maghami
authors.affiliation: West London Gynaecological Cancer Centre, Queen Charlotte's Hospital, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: J Richard
authors.initials: JR
authors.lastname: Smith
mesh_terms: D064591:Allografts / Q000098:blood supply*; D000714:Anastomosis, Surgical; D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery*; D016063:Blood Loss, Surgical; D005260:Female; D006085:Graft Survival; D007083:Iliac Artery / Q000601:surgery; D007084:Iliac Vein / Q000601:surgery; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008137:Longitudinal Studies; D023421:Models, Animal; D011817:Rabbits; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage; D014184:Transplantation, Homologous / Q000379:methods* / Q000401:mortality; D014599:Uterus / Q000098:blood supply* / Q000637:transplantation*; D014682:Vena Cava, Inferior / Q000601:surgery*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: Allogeneic; Fertility; Graft survival; Rabbit; Transplantation; Uterus