The Swedish uterus transplantation project: the story behind the Swedish uterus transplantation project

Abstract

Reproductive medicine has made remarkable advances ever since Edwards and Steptoe reported the arrival of Louise Brown, the first in vitro fertilization (IVF) baby, in 1978. After introduction of intra-cytoplasmic sperm injection (ICSI) in the early 1990s, the majority of subtypes of male and female infertility were treatable. There has remained one group of women with no available infertility treatment until now. These women with absolute uterine factor infertility (AUFI) have uterine absence either from birth, as part of the Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, or after hysterectomy for cervical malignancy or major obstetric bleeding. A large group of AUFI women have a uterus, but it is non-functional because of severe Asherman's syndrome, major uterine malformation or radiation damage. It is estimated that around 13 000 women of fertile age in the UK suffer from AUFI 1, and this number corresponds to around 4500 AUFI women in the Nordic countries. The options for becoming a mother for a woman with AUFI are adoption, to become a mother by law, or the utilization of a gestational surrogate carrier, to accomplish genetic motherhood and after adoption also legal motherhood. Gestational surrogacy is not currently legal in any Nordic country, or in the majority of nations and societies worldwide. We recently reported 2 the first live birth after uterus transplantation (UTx) and thereby introduced the first true treatment of AUFI. This birth has been followed by two more uneventful births (M. Brännström et al. unpublished data) and another pregnancy is near term. Thus, we have not only provided a proof-of-concept that UTx is a treatment for AUFI by a single case but also that this AUFI treatment, of combined IVF and UTx, is relatively effective at its very initial stage of introduction. Below I will give some insights into how the Swedish UTx project was initiated and its long research journey, spanning more than a decade, prior to launching the first clinical UTx trial in early 2013 3. I obtained the idea to initiate this thought-provoking UTx project when I did a fellowship in gynecologic-oncology surgery in Adelaide, Australia, in 1998. Before that I had a background of research in ovarian physiology for 20 years and my intention was consequently to subspecialize in reproductive medicine in the same city where I had performed postdoctoral research on ovarian immune mechanisms, some years earlier. However, after arriving in Australia I found out that although the position in reproductive medicine was already filled by a local colleague, they had the gynecologic-oncology spot open for me. Obviously, I had to adapt to this amendment and fully devote my efforts to learn the complex retroperitoneal surgery that this involves. From the start, I liked the extensive surgery and my comprehensive experience in microsurgery in rodents probably helped me to quickly incorporate the gynecologic-oncology specific tricks-of-the-trade into my surgical arsenal. After some months in training, I and my resident doctor took care of all standard surgical procedures. On a Friday morning in October 1998, we had the usual preoperative informative talk with a patient, this time with Angela, a charismatic woman in her mid-twenties. She was informed about the consequences and possible complications associated with the open radical hysterectomy that we would perform on her the following week because of stage 1b cervical cancer. We told her that she would become permanently infertile, although her ovaries would be preserved. Apparently, she had a solution-oriented mind and quickly responded to us: I know the solution to the problem – you can transplant the womb from my mother. We were astonished by her suggestion since this was a concept that had not been in our minds before. Since it was Friday afternoon, we went for the usual Friday beer at the University pub together with our colleagues. The conversation around the table this time was not abou