A decade of human uterus transplantation

Abstract

On September 4, 2014, the birth of the first child from a transplanted uterus marked a monumental milestone in the fields of gynecology, reproductive medicine, and obstetrics.1 This historic achievement, realized in Sweden, established uterus transplantation (UTx) as a groundbreaking treatment for absolute uterine factor infertility—a condition affecting approximately 1 in 500 women. Since that pioneering UTx birth, over 70 children have been born globally following more than 130 UTx procedures.2 The world's first eight live births after UTx took place at Sahlgrenska University Hospital, Sweden. On September 5, 2024, the International Society of Uterus Transplantation convened in Gothenburg for its 4th State-of-the-Art Meeting. The event began with a heartwarming moment: the first UTx child born, who had celebrated his 10th birthday the day before, addressed the audience. Speaking in fluent English, he described himself as “an ordinary boy who loves sports, especially golf and ice hockey.” He shared how proud his parents were of him and encouraged the attendees to continue their work to make UTx widely accessible. His words deeply moved the delegates, many of whom shed tears of joy, reflecting on the remarkable progress made in just a decade and the profound human impact of this groundbreaking medical advancement within our medical field. The UTx journey from concept to reality is widely regarded as a prime example of a translational project in innovative surgery, meticulously prepared and monitored according to the highest standards outlined in the Moore Criteria3 and the IDEAL framework4 for introducing major surgical innovations. As part of this rigorous approach, systematic animal research was conducted across several species,5 before the first clinical UTx-trial started in 2012–2013.6 The field of UTx has evolved rapidly over the past decade, with continuous methodological advancements aimed at improving both the safety and efficacy of the procedure. The surgery itself, particularly live donor (LD) hysterectomy, is highly complex. For a LD-UTx, the total surgical time—including hysterectomy, back-table preparation, and transplantation—is around 15 h.6 To reduce tissue trauma, robotic surgery has been introduced for LD hysterectomy, leading to shorter hospital stays and reduced recovery time.7 However, this approach has not yet resulted in a reduction in overall surgical duration. In terms of immunosuppression (IS), the initial high-IS induction regimen with antithymocyte globulin and high tacrolimus levels has now been adjusted to a moderate-IS induction protocol using basiliximab and moderate tacrolimus levels. Our experience is that this modified IS protocol does not increase the risk of rejection episodes and has reduced the previously observed nephrotoxic effects of IS in UTx patients.8 For diagnosing rejection, the gold standard remains the histological evaluation of ectocervical biopsies, a method initially developed in a non-human primate UTx model.9 This theme issue of AOGS contains 11 original research papers, one bibliographic analysis, and one systematic review, all with the common scientific goal of advancing the UTx field. The issue opens with a bibliometric analysis by Akbari and coworkers covering UTx research from 1960 to 2024, highlighting the growth of this expanding discipline.10 The origins of UTx research date back to the 1960s, initially focusing on utero-tubal transplantation as a more feasible surgical approach compared to isolated tubal transplantation, to treat tubal factor infertility. Following more than a decade of preclinical studies, the groundbreaking birth of Louise Joy Brown in 1978—made possible through the pioneering work of the reproductive biologist Robert Edwards, the laparoscopist Patrick Steptoe, and the nurse/embryologist Jean Purdy—demonstrated that in vitro fertilization (IVF) was a viable solution for tubal infertility. The challenges faced by Edward's team, including skepticis