Keio Uterus Transplantation Research: From Basic Research toward Future Clinical Application.

Uterus transplantation (UTx) is now a potential option to allow women with uterine factor infertility to give birth. However, UTx is still at an experimental stage, and basic animal studies, including in non-human primates, are needed for the accumulation of data prior to clinical application. Considering that UTx may provide new hope to Japanese women, we launched UTx research in 2009 and have since accumulated a large archive of results in the UTx research field. Furthermore, we have carried out various activities aimed at the implementation of clinical applications of UTx in Japan while clarifying the ethical and social issues involved. Currently, the clinical application of UTx in Japan is just around the corner, and it is expected that UTx research will develop further in the future. Herein, we summarize our basic experiences using non-human primates and our activities with the goal of future clinical applications.

[1]  R. Farrell,et al.  Uterus transplantation: state of the art in 2021 , 2021, Journal of Assisted Reproduction and Genetics.

[2]  D. Aoki,et al.  Understanding of the position of patients with Mayer–Rokitansky–Küster–Hauser syndrome revealed by uterus transplantation research in Japan , 2021, The journal of obstetrics and gynaecology research.

[3]  Iana Malasevskaia,et al.  A New Approach for Treatment of Woman With Absolute Uterine Factor Infertility: A Traditional Review of Safety and Efficacy Outcomes in the First 65 Recipients of Uterus Transplantation , 2021, Cureus.

[4]  D. Aoki,et al.  Operative and Clinical Outcomes of Minimally Invasive Living-Donor Surgery on Uterus Transplantation: A Literature Review , 2020, Journal of clinical medicine.

[5]  D. Aoki,et al.  Concerns Associated with Uterus Transplantation in Japan. , 2020, The Keio journal of medicine.

[6]  T. Shiina,et al.  First Successful Delivery after Uterus Transplantation in MHC-Defined Cynomolgus Macaques , 2020, Journal of clinical medicine.

[7]  T. Shiina,et al.  Clinical features of irreversible rejection after allogeneic uterus transplantation in cynomolgus macaques , 2020, Scientific Reports.

[8]  T. Hibi,et al.  Current status of liver transplantation in Asia. , 2020, International journal of surgery.

[9]  A. Israni,et al.  OPTN/SRTR 2018 Annual Data Report: Deceased Organ Donation , 2020, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[10]  Y. Osuga,et al.  A survey of public attitudes toward uterus transplantation, surrogacy, and adoption in Japan , 2019, PloS one.

[11]  T. Shiina,et al.  Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques , 2019, Journal of clinical medicine.

[12]  T. Shiina,et al.  The Cynomolgus Macaque MHC Polymorphism in Experimental Medicine , 2019, Cells.

[13]  D. Aoki,et al.  Uterus transplantation: advantages and disadvantages of a deceased donor , 2019, Archives of Gynecology and Obstetrics.

[14]  M. Madeleine,et al.  Gynecologic cancers and solid organ transplantation , 2019, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[15]  E. Baracat,et al.  Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility , 2018, The Lancet.

[16]  D. Aoki,et al.  Basic research on uterus transplantation in nonhuman primates in Japan , 2018, The journal of obstetrics and gynaecology research.

[17]  D. Aoki,et al.  Allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/reperfusion injury in cynomolgus macaque: a basic study for uterus transplantation. , 2017, Human reproduction.

[18]  T. Shiina,et al.  Surgical technique for allogeneic uterus transplantation in macaques , 2016, Scientific Reports.

[19]  T. Nagai,et al.  Evaluation of allowable time and histopathological changes in warm ischemia of the uterus in cynomolgus monkey as a model for uterus transplantation , 2016, Acta obstetricia et gynecologica Scandinavica.

[20]  S. Nakagawa,et al.  Clinical outcomes of abnormal cervical cytology and human papillomavirus-related lesions in patients with organ transplantation: 11-year experience at a single institution , 2016, International Journal of Clinical Oncology.

[21]  D. Aoki,et al.  Survey of Attitudes toward Uterus Transplantation among Japanese Women of Reproductive Age: A Cross-Sectional Study , 2016, PloS one.

[22]  D. Aoki,et al.  Organ Perfusion for Uterus Transplantation in Non-Human Primates With Assumed Procurement of a Uterus From a Brain-Dead Donor. , 2016, Transplantation proceedings.

[23]  D. Aoki,et al.  A surgical technique using the ovarian vein in non‐human primate models of potential living‐donor surgery of uterus transplantation , 2015, Acta obstetricia et gynecologica Scandinavica.

[24]  Milan Milenkovic,et al.  Livebirth after uterus transplantation , 2015, The Lancet.

[25]  A. Israni,et al.  OPTN/SRTR 2013 Annual Data Report: Deceased Organ Donation , 2015, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[26]  M. Brännström,et al.  Pregnancy after allogeneic uterus transplantation in the rat: perinatal outcome and growth trajectory. , 2014, Fertility and sterility.

[27]  T. Shiina,et al.  Uterus allotransplantation in cynomolgus macaque: A preliminary experience with non‐human primate models , 2014, The journal of obstetrics and gynaecology research.

[28]  D. Aoki,et al.  Uterus transplantation in nonhuman primates. , 2013, Fertility and sterility.

[29]  D. Aoki,et al.  Current status of uterus transplantation in primates and issues for clinical application. , 2013, Fertility and sterility.

[30]  A. Tzakis.  Nonhuman primates as models for transplantation of the uterus. , 2013, Fertility and sterility.

[31]  D. Aoki,et al.  Risks for Donors in Uterus Transplantation , 2013, Reproductive Sciences.

[32]  D. Aoki,et al.  Indocyanine green fluorescence imaging in the pregnant cynomolgus macaque: childbearing is supported by a unilateral uterine artery and vein alone? , 2013, Archives of Gynecology and Obstetrics.

[33]  D. Aoki,et al.  Uterine autotransplantation in cynomolgus macaques: the first case of pregnancy and delivery. , 2012, Human reproduction.

[34]  Li-yu Lin,et al.  Indocyanine Green Fluorescence Imaging for Evaluation of Uterine Blood Flow in Cynomolgus Macaque , 2012, PloS one.

[35]  D. Aoki,et al.  Uterus autotransplantation in cynomolgus macaques: intraoperative evaluation of uterine blood flow using indocyanine green. , 2011, Human reproduction.

[36]  K. Banno,et al.  Current status of surrogacy in Japan and uterine transplantation research. , 2011, European journal of obstetrics, gynecology, and reproductive biology.

[37]  D. Aoki,et al.  A new surgical technique of uterine auto-transplantation in cynomolgus monkey: preliminary report about two cases , 2011, Archives of Gynecology and Obstetrics.

[38]  T. Shaffer,et al.  Pregnancy and outcome of uterine allotransplantation and assisted reproduction in sheep. , 2011, Journal of minimally invasive gynecology.

[39]  M. Brännström,et al.  Experimental uterus transplantation. , 2010, Human reproduction update.

[40]  H. Raffa,et al.  Transplantation of the human uterus , 2002, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[41]  H. Amemiya.  Current status of organ transplantation in Japan. , 1999, Transplantation proceedings.