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 unpublished data) and another pregnancy is near term.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 about science, sports, and weekend plans, but rather about the unexpected concept of UTx that had been presented to us. My science background in reproductive medicine with infertility and the newly acquired skills in retroperitoneal peritoneal surgery, made me realize that there was a true need for UTx and that the procedure would be technically feasible. Thus, our discussion that afternoon ended with a consensus that Angela's idea of UTx, to cure her infertility, was realistic. I had performed mainstream research in ovarian physiology for many years and was now eager to get involved in a project that would confront the principal thinking in a field. But I was aware that it would be a project that would involve serious discussions on the ethics. How did Angela come up with this totally new concept? Perhaps it was because the patient of the world's first hand transplantation 4, which had been performed some weeks before, was from New Zealand and this medical breakthrough brought massive media attention in this part of the world. The innovative surgery of hand transplantation and also the first-ever larynx transplantation 5, also performed in 1998, represented a turning point in transplantation surgery, which had now gone from life-saving transplantations to include quality-of-life-enhancing transplantations. After a year in Australia I went back to Sweden to continue my training in gynecologic-oncology surgery, but I was also fully determined to initiate this risky UTx-research project to find a cure for the many thousands of women who were permanently infertile because of absence of a functional uterus. I personally had a long experience in microsurgical interventions in rodents and I decided to start to examine the feasibility of UTx in a murine model. I was lucky to recruit biomedical technician Randa El-Akouri as a PhD student. I knew she had the microsurgical skills that would be needed and also the great determination that is so important in research, so that a project can pass through those repeated failures that are so common in all developmental work. The great difficulty for Randa would be to master the complicated microsurgery that would be needed to perform this extensive UTx surgery in a very small animal. Randa developed a UTx model in the mouse, with the uterine graft in a heterotopic position, and the native uterus was left intact as an internal control uterus. The microsurgical challenge was to perform a radical hysterectomy in the donor mouse, with all vessels preserved up to and including the lower aorta/vena cava, and also to accomplish vascular anastomoses end-to-side to the aorta and vena cava of the recipient using 11–0 sutures to connect these vessels with diameters of around 1 mm. Already in 2002 we reported the first-ever pregnancy after UTx 6 in any species and the following year, live offspring that developed normally until adulthood 7. These initial results were accomplished in a syngeneic mouse model. Thus, the experiments tested all aspects of UTx, except the effects of immunosuppression to suppress rejection. However, it is clear that in the event that Randa had been unsuccessful in her development of this first UTx model, I would have stopped this high-risk project, which was draining my research budget. Around the same time that the news of our successful results in the murine UTx model were announced, the world's first human UTx attempt was published as a case report 8. This operation, that had taken place in Jeddah, Saudi Arabia, in year 2000, was a total surprise to us, since we thought that we were fairly unique in our interest in UTx. Interestingly, the concept of UTx in Saudi Arabia was also presented by a patient, who in this case became the first-ever UTx recipient. She had undergone peripartum emergency hysterectomy some years before. No research had been done to prepare for this first UTx case. As would be predicted, the case was unsuccessful and a necrotic uterus had to be removed three months after the UTx. The team was criticized internally in Saudi Arabia and was not allowed to continue further by the national health authorities. We continued with our research efforts to find a suitable large animal model to develop the surgical UTx method further, with uterine and pelvic blood vessels with sizes similar to the human. There had been reports in the media, based on an abstract (“Uterine transplant: a successful porcine model”) from the American Society of Reproductive Medicine (ASRM) meeting in Orlanda in 2001, that a collaborative US–UK group had successfully transplanted the uterus in the pig. Consequently, we started to develop the pig UTx model. After two years of experiments, trying to perform autologous UTx in this species, with its large bicornuate uterus and tiny uterine vessels, we had to confess that we could not master this model. At the same time I was asked to be the reviewer for the scientific article that had evolved from the ASRM abstract on UTx in the porcine model. I found out that the surgery was far from a UTx procedure, since it was only a transection of the uterine vessels with immediate end-to-end re-anastomosis. We had learned the hard way that any scientific results published as an abstract or in the media should be treated with scepticism until properly evaluated and published as a peer-reviewed research article in a scientific journal of high standard. However, these many hours in the operating room, with the difficult pig method, were very important for our team-building efforts involving the gynecologists, transplantation surgeons, anesthesiologists, and operating room-nurses. We would then proceed with this team-building during many years of surgery in animals and at last in the human UTx trial. The famous transplant surgeon Jean Michel Dubernard, who was leading the teams behind the first hand transplantation and the first face transplantation, once stated that the biggest challenge of these endeavours was not the complicated operations, but to build a strong team. This is also true for UTx. When we had given up the pig model I met professor John McCracken at a Society of the Study of Reproduction (SSR) meeting in the USA. He had done pioneering research on ovarian physiology, with the help of a model where he had transplanted the uterus and ovaries to the neck of the sheep 9, to permit frequent blood sampling of the venous drainage of the ovaries. He was eager to help us to develop a sheep UTx model, with orthotopic UTx 10, which later proved to be very useful for us 11. One of the most important collaborators during the many hours of surgery in large animals, including primates, and also in the clinical UTx trial, has been gynecologic-oncology surgeon Pernilla Dahm-Kähler. Through the years of collaborative, complicated surgery in the UTx research, but also in clinical gynecologic-oncology surgery, we have developed our surgical skills to be highly synergistic. There is a feeling that nothing is impossible to master surgically when our four hands work together. In 2010, we were the first to report pregnancies in an allogeneic transplanted uterus in a landmark article in AOGS 12. This finding was of paramount importance since now we had evidence that a pregnancy can also progress normally in a transplanted uterus under the extraordinarily negative influence of immunosuppression. However, I was convinced that we could not jump from these results in rodents and large domestic animals to a clinical trial in the human. Thus, a non-human primate UTx model would be needed to transfer the technology relatively safely to a human experimental setting. Since there is no facility for primate research in Sweden or anywhere else in the Nordic countries, we decided to perform our experiments at the Institute of Primate Research (IPR) in Karen, Kenya. This is a WHO-collaborating center in reproductive research, and many European and American groups have performed research at the site during the past 25 years. Identical ethical guidelines and regulations concerning animal experimentation, exist at IPR as in European and US primate centers. We spent several years at the IPR facility developing UTx further in the baboon species. The most important results were the development of surgical techniques in a very human-like setting 13 and finding the optimal immunosuppression protocol to avoid uterine allograft rejection 14. Equally important was the further team-building required in these non-optimal conditions, with sudden power failures during surgery, lack of water for the morning shower, and animal care takers that were not used to extensive surgery or to administration of immunosuppressive medications. In late 2011, the world's second human UTx attempt was performed in Turkey and announced in the media as the first successful UTx procedure. This case, performed by a skilled plastic surgeon, was also a surprise to us, since the group had no publication record in the UTx field. The initial outcome was later published 15 and it should be pointed out that the case has not yet after multiple IVF attempts been successful. In this second UTx case, unlike in the Saudi Arabian case, a uterus from a young brain-dead, heart-beating donor was used. An essential factor was that although the uterus donor was of young age (23 years), the organ had never carried a pregnancy and thereby had not shown that it was truly functional. In 2012, we applied to the Human Ethics Committee of the University of Gothenburg to perform a prospective observational clinical trial on human UTx with the live donor concept. We thought it was important to perform a series of cases to acquire enough data for a scientific evaluation of the method. We naturally expected a variation in outcome of the cases and hoped that our data would provide information to optimize the procedure further in new trials. Importantly, the prospective observational design included not only accumulation of medical data but also of several parameters relating to psychology and quality of life. This first clinical UTx trial is ongoing and published results are available concerning the outcomes of surgery 3 and events during the first post-transplantation year 16. The first live birth ever after any UTx procedure, occurred in early September 2014, when the fifth woman in our cohort delivered 2. This was also the first strictly successful UTx, since the definition of success should not be completed and uneventful UTx surgery, but a positive outcome of the purpose of the transplantation procedure. In this sense, UTx has a far longer observation time from transplantation to proof of success, in comparison with all other types of transplantations. The first live birth after UTx, represents an important proof-of-concept of UTx as the first AUFI treatment. In this case 2 the recipient had MRKH syndrome, with uterine agenesis and also unilateral renal agenesis. The uterus was from a 61-year-old altruistic donor, who had been postmenopausal for seven years. The uterus had harbored two normal pregnancies. The donor received cyclic estrogen-progestagen treatment before uterus donation, to ascertain that the uterus was still functional in terms of menstrual bleeding. The 35-year-old recipient became pregnant at the first embryo transfer attempt, which occurred 12 months after UTx. She had a mild rejection episode (detected on cervical biopsy) in gestational week 18, which was handled by intravenous corticosteroid treatment for three days. The pregnancy then proceeded normally until gestational week 31+5, when the patient was admitted for preeclampsia. She was given bethamethasone i.v. as a neonatal respiratory distress syndrome prophylaxis. Because of repeated episodes of abnormal cardiotocography we decided to perform a cesarean section the morning after admission. A healthy baby of normal weight (1775 g) for the gestational time and with Apgar scores of 9/1, 9/5, and 10/10 was delivered. The boy, named Vincent (“to conquer”), is now in April 2015 seven months old with a weight of around 8 kg. In November 2014, two more deliveries from our UTx cohort occurred. These were elective cesarean sections that were performed around gestational week 35. Importantly, preeclampsia did not develop in these two cases. The babies were of normal birthweight and are in good health. These, the UTx deliveries number 2 and 3, also represent the world's first deliveries from a uterus of a woman bearing the same uterus that she was delivered from. The mothers donating their uteri were around 50 years of age when the UTx procedures occurred. This mind-boggling concept of giving birth from the same uterus that you have had your own growth and development in, from an embryo to a newborn, may be looked upon as a philosophical concept that is new to humanity. We will continue to publish all data from our UTx trial. Importantly, we also cover the psychological and quality-of-life aspects by detailed questionnaires and in-depth interviews. We are currently planning a new smaller prospective trial with live donation UTx, and we will focus on reducing the surgical time for the donor, which in the first trial was between 10 and 12 h. We predict that we can shorten the time considerably by performing 3D angiographic mapping of the uterine arteries and veins before surgery, to allow detailed advance planning of the procedure. Another approach will be to do the major part of the donor surgery as a robotic-assisted laparoscopic procedure, which would facilitate the dissection and clearance of the vessels deep in the pelvis. The future in transplantation surgery will most certainly be in the creation of bioengineered organs for transplantation. The principle of this is to create a scaffold for formation of an organ, either by a synthetic construct or using a de-cellularized organ from a dead person. The scaffold would then be re-cellularized by the future recipient's own stem cells to create an organ in a bioreactor that later can be transplanted. This would circumvent the organ shortage, a complex donor operation, and immunosuppression. We have started initial animal research on this concept 17 but it is likely that it will take at least 10 years until the first successful UTx procedure is done with a bioengineered organ.