Uterus transplantation: from research, through human trials and into the future

Abstract

Women suffering from absolute uterine factor infertility (AUFI) had no hope of childbearing until clinical feasibility of uterus transplantation (UTx) was documented in 2014 with the birth of a healthy baby. This landmark accomplishment followed extensive foundational work with a wide range of animal species including higher primates. In the present review, we provide a summary of the animal research and describe the results of cases and clinical trials on UTx. Surgical advances for graft removal from live donors and transplantation to recipients are improving, with a recent trend away from laparotomy to robotic approaches, although challenges persist regarding optimum immunosuppressive therapies and tests for graft rejection. Because UTx does not involve transplantation of the Fallopian tubes, IVF is required as part of the UTx process. We provide a unique focus on the intersection between these two processes, with consideration of when oocyte retrieval should be performed, whether, and for whom, preimplantation genetic testing for aneuploidy should be used, whether oocytes or embryos should be frozen and when the first embryo transfer should be performed post-UTx. We also address the utility of an international society UTx (ISUTx) registry for assessing overall UTx success rates, complications, and live births. The long-term health outcomes of all parties involved—the uterus donor (if live donor), the recipient, her partner and any children born from the transplanted graft—are also reviewed. Unlike traditional solid organ transplantation procedures, UTx is not lifesaving, but is life-giving, although as with traditional types of transplantation, costs, and ethical considerations are inevitable. We discuss the likelihood that costs will decrease as efficiency and efficacy improve, and that ethical complexities for and against acceptability of the procedure sharpen the distinctions between genetic, gestational, and social parenthood. As more programs wish to offer the procedure, we suggest a scheme for setting up a UTx program as well as future directions of this rapidly evolving field. In our 2010 review, we described the future of clinical UTx based on development of the procedure in animal models. This Grand Theme Review offers a closing loop to this previous review of more than a decade ago. The clinical feasibility of UTx has now been proved. Advancements include widening the criteria for acceptance of donors and recipients, improving surgery, shortening time to pregnancy, and improving post-UTx management. Together, these improvements catalyze the transition of UTx from experimental into mainstream clinical practice. The procedure will then represent a realistic and accessible alternative to gestational surrogacy for the treatment of AUFI and should become part of the armamentarium of reproductive specialists worldwide.

Genetics of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: advancements and implications

“…The possibility of recurrence in offspring was demonstrated in a recent report, describing the first case of mother-to-daughter inheritance following surrogacy ( 22 ). As UTx approaches clinical implementation ( 24 ) and the evidence for genetic causes increases, questions about offspring recurrence risk and reproductive choices will likely become more prevalent and so will requests for preimplantation genetic testing as part of the in vitro fertilization preceding the UTx procedure.…”

“…A 4 Mb deletion of 2q37.1q37.3 of unknown significance was identified in both patients, but not in the mother’s parents ( 22 ). This case exemplifies the potential risk of MRKH syndrome recurrence following assisted reproduction and with the expected increasing availability of UTx as this field moves towards clinical care ( 24 ), identifying causal variants and providing genetic counseling regarding recurrence risk and reproductive choices will become more relevant.…”

“…MRKH syndrome causes absolute uterine factor infertility (AUFI) but patients may achieve genetic motherhood through gestational surrogacy ( 21 , 22 ). In 2014, the first baby was born following pregnancy after uterus transplantation (UTx) in Sweden, offering the first fertility treatment of AUFI achieving both gestational and genetic motherhood ( 23 , 24 ).…”

Living donor uterus transplant in the UK: A case report

“…Following more than 90 cases, and the achievement of 49 livebirths, 2 there is no question regarding the feasibility of the procedure as it now transitions from research concept to clinical practice. 3 Given that the goal is to achieve the livebirth of healthy offspring, it is important to note that there does not appear to be an increased risk of fetal growth restriction in cases so far, 4 and age-appropriate neonatal and developmental outcomes have been observed for the first 2 years of life. 5 However, it remains a procedure associated with significant risk.…”

Multilayered Shape-Morphing Scaffolds with a Hierarchical Structure for Uterine Tissue Regeneration

“…Allogeneic uterus transplantation is a practical option to deal with uterine injuries and hence can help to realize the dreams of many couples to become biological parents of their children . Dozens of publications have already reported successful live births by women who had received transplanted uteri. , However, facing problems of donor shortage and possible immunological rejection, uterus transplantation cannot be widely practiced. Therefore, new and promising clinical treatments should be developed to treat uterine damage, which will assist in reconstructing the structure and restoring the functions of the human uterus.…”