title: Preclinical report on allogeneic uterus transplantation in non-human primates.
abstract: OBJECTIVE
  Is it possible to perform allogeneic uterus transplantation (UTx) with a donation from a live donor in a non-human primate species and what immunosuppression is needed to prevent rejection?
  
  
  CONCLUSIONS
  Allogeneic UTx in the baboon is a donor- and recipient-safe surgical procedure; immunosuppression with induction therapy and a triple protocol should be used.
  
  
  BACKGROUND
  UTx may become a treatment for absolute uterine factor infertility. Autologous UTx models have been developed in non-human primates with reports on long-term survival of the uterine grafts. STUDY DESIGN, SIZEAND DURATION: This experimental study included 18 female baboons as uterus donors and 18 female baboons as uterus recipients. The follow-up time was 5-8 weeks.
  
  
  METHODS
  Uterus retrieval was performed with extended hysterectomy including bilateral uterine and internal iliac arteries and ovarian veins. After UTx, with vascular anastomoses unilateral to the internal iliac artery and the external iliac vein, the uterus recipients received one of the following: no immunosuppression (n = 4); monotherapy (oral slow release tacrolimus) (n = 4) or induction therapy (antithymocyte globulin) followed by triple therapy (tacrolimus, mycophenolate, corticosteroids; n = 10). Surgical parameters, survival, immunosuppression and rejection patterns were evaluated.
  
  
  RESULTS
  The durations of uterus retrieval and recipient surgery were around 3 and 3.5 h, respectively. The total ischemic time was around 3 h. All the recipients and the donors survived the surgery. All the recipients presented rejection to some extent within the first weeks following UTx. In one recipient, the uterus was of normal appearance at the end of the study period. In spite of occasional high (>60 ng/ml) blood levels of tacrolimus, there was no evidence of nephrotoxicity.
  
  
  CONCLUSIONS
  This initial non-human primate allogeneic UTx study indicates that further research is needed to optimize immunosuppression protocols in order to avoid uterine rejection.
  
  
  CONCLUSIONS
  The findings suggest that allogeneic UTx in primate species is feasible but continued work on this issue is needed.
  
  
  BACKGROUND
  The study was funded by the Swedish Research Council, ALF University of Gothenburg, Hjalmar Svensson Foundation and by Jane and Dan Olsson Research Foundation. The authors do not have any competing interest.
authors.affiliation: Department of Obstetrics and Gynecology, Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, 413 45 Göteborg, Sweden. liza.johannesson@vgregion.se
authors.forename: L
authors.initials: L
authors.lastname: Johannesson
authors.forename: A
authors.initials: A
authors.lastname: Enskog
authors.forename: J
authors.initials: J
authors.lastname: Mölne
authors.forename: C
authors.initials: C
authors.lastname: Diaz-Garcia
authors.forename: A
authors.initials: A
authors.lastname: Hanafy
authors.forename: P
authors.initials: P
authors.lastname: Dahm-Kähler
authors.forename: A
authors.initials: A
authors.lastname: Tekin
authors.forename: P
authors.initials: P
authors.lastname: Tryphonopoulos
authors.forename: P
authors.initials: P
authors.lastname: Morales
authors.forename: K
authors.initials: K
authors.lastname: Rivas
authors.forename: P
authors.initials: P
authors.lastname: Ruiz
authors.forename: A
authors.initials: A
authors.lastname: Tzakis
authors.forename: M
authors.initials: M
authors.lastname: Olausson
authors.forename: M
authors.initials: M
authors.lastname: Brännström
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D007165:Immunosuppression Therapy / Q000379:methods*; D060828:Induction Chemotherapy; D007247:Infertility, Female / Q000209:etiology / Q000601:surgery*; D019520:Living Donors; D060046:Maintenance Chemotherapy; D009173:Mycophenolic Acid / Q000627:therapeutic use; D010215:Papio; D016559:Tacrolimus / Q000627:therapeutic use; D014184:Transplantation, Homologous; D014591:Uterine Diseases / Q000503:physiopathology*; D014599:Uterus / Q000276:immunology / Q000637:transplantation*
chemical_list: D000305:Adrenal Cortex Hormones; D000961:Antilymphocyte Serum; D009173:Mycophenolic Acid; D016559:Tacrolimus