Uterine Transplantation: Towards Clinical Application (2013)

I read with great interest the recent report by Ozkan et al. [1], who performed the second uterine transplantation (UTx) in humans in August 2011 in Turkey. The donor was a patient aged 22 years who was braindead due to a traffic accident and the recipient was a patient aged 21 years with Rokitansky syndrome. Menstruation resumed on postoperative day 20 and continued cyclically without marked rejection. At present, at more than 1 year after surgery, pregnancy based on embryo implantation is being attempted.Assisted reproductive technology has improved markedly in recent years and many infertile patients have had children using this technology. However, women with infertility due to an absent or nonfunctional uterus currently have no option of having a genetically linked child, other than gestational surrogacy, which is restricted by legal, ethical and religious issues in many countries.With this background, the first UTx procedure between humans was conducted in Saudi Arabia in 2000 [2]. Menstruation was observed twice after transplantation, but transplanted uterus was removed at 99 days posttransplantation due to prolapse and necrosis.This attempt led to a greater focus on basic UTx experiments in animal models, combined with recent development of technology for organ transplantation, microvascular anastomosis, and immunosuppressant therapy. These studies have been conducted in mice, rats, rabbits, swine, sheep, cynomolgus monkey and baboon, and numerous data in animals have thus been accumulated. These findings have made UTx an option for uterine infertility, which led to performance of the second UTx in humans by the group in Turkey [1].The detailed report from Turkey is important for the establishment of a platform for further attempts at human UTx, but it is of note that the procedure was performed by a group without basic research experience in the UTx field. The ethical guidelines of the International Federation of Gynecology and Obstetrics indicate that adequate studies in large animals, including primates, should be conducted before the clinical application of UTx in humans [3]. A group in Sweden has conducted experiments in baboons as non-human primate models and we have used the cynomolgus macaque for this purpose for several years, with the first successful delivery after uterine autotransplantation in non-human primates. The group in Sweden accumulated data in animal models to establish the requirements for UTx before clinical application and then conducted two UTx with living donors in September 2012, as the first procedures between mother and daughter [4].UTx has been brought within reach of clinical application in humans due to the report from Turkey. However, there are many medical, ethical, social and legal problems that require thorough discussion prior to widespread clinical application of this procedure. UTx in humans has begun, but pregnancy by allogeneic UTx has only been shown in rats and sheep, which suggests that further basic data, including in non-human primates, need to be accumulated for the establishment of UTx in humans. The outcomes of the procedures performed in Turkey and Sweden provide very important information and these studies are key steps towards the clinical application of UTx.