I was talking about womb transplantation and effectively we’ve got a twenty year programme of research which is almost about to come to fruition. So we, in the autumn, certainly the back end of this year, hope to do three live donor uterine transplants and to start a process whereby we’re going to do ten DBD, which is Brain Dead Donor, transplants where the donors, obviously, are heart beating cadaveric donations from an intensive care type setting. The live donor cases are going to be where the donors, in fact the first three women who we have got teed up, it’s two mothers and daughters and one sister and sister. So the sister has completed her family, donating her uterus to her sister who hasn’t got a uterus. Principally, although the subject of the talk was uterine transplantation in endometrial cancer, in fact there are very few people who have approached us who have had endometrial cancer and the majority of women who have approached us looking to have a transplanted uterus are women who have got Mayer-Rokitansky-Küster-Hauser syndrome, so they were born without a uterus. They’ve usually got a vagina and they’ve got ovaries but there’s no womb. So that’s 90% of the people who have approached us looking for a womb transplant.
10% of the people who have approached us had an oncological diagnosis and they’ve had a hysterectomy, mostly because of cervix cancer. So there have been 42 uterine transplants in the world so far and, of those, there’s only one woman who had a cancer diagnosis, the rest are mostly Mayer-Rokitansky.
What issues have you encountered during this process?
21 years ago was when we started this and it started with a procedure called abdominal radical trachelectomy, which is a fertility sparing procedure for cervix cancer. During that operation if it’s done open you’ve got the patient’s abdomen open and the uterus is actually out, attached to the aorta via the ovarian vessels and you cut the cervix cancer off and then stitch it back in. It was kind of on the back of that that the idea that perhaps we could transplant uteruses came about. One of my great friends, a guy called Hossam Abdalla, who is the director of Lister Fertility Clinic in Chelsea which is the country’s biggest IVF clinic, he and I have worked together since the early ‘80s and he and I sat together and he said, ‘It’s the one group of women that as a fertility specialist we can’t treat is women who don’t have a uterus. There’s surrogacy, there’s adoption but that’s it.’ That was the kind of genesis of the idea and we’ve gone down multiple dead-end routes. So we started off using small vessel anastomosis and that doesn’t work. The first human uterine transplant was in 2000 and it failed and it was done using small vessels. The woman, the recipient, got microvascular thrombosis of her uterus three months out and her uterus had to be removed. We had exactly the same results in a series… we’d worked in the porcine model and we’d actually had the same results in our pig model.
It’s a long time ago, seventeen, eighteen years ago, we went to Nadey Hakim, who was Professor of Transplant Surgery at St Mary’s at the time, and he said, ‘You should use a large vessel patch technique.’ We did a series of work where we showed that if you remove the uterus with the uterine vessels and the internal iliac arteries and veins as you unblock a graft, and in fact we did actually originally also bring out the aorta and inferior vena cava, you can put a Venflon into the aorta, or canula, open it and ten minutes later you’ve got clear fluid flowing out the inferior vena cava, no leakage and a white uterus because all the blood has gone. And that became the model which, in fact, the Swedish group who got way ahead of us and delivered their first baby in 2014, but they used a large vessel patch technique to do their transplants. As of 2014, we’d got to the point where we had, it’s quite interesting, we had seventy peer reviewed publications and the Swedes went for ethics when they’d got seventy publications and that’s when we felt comfortable that we’d done quite a lot of animal work and we’d had the third pregnancy in the world in an animal model where the uterus had been transplanted and we felt it was time for us to go live into a human setting.
We then got National Ethics Committee approval in 2015 but because we were looking not to do live donors at that time but to only do brain dead donors we’ve then, and rightly, got into the huge regulatory process that goes with NHS Blood and Transplantation because we mustn’t do anything to besmirch the reputation of NHS BT in any way to do with vital organ donation, so heart, lungs, liver, kidneys, pancreas and now small bowel, there’s various things being transplanted. So we’ve been through that regulatory process which has effectively taken us about two years and we’ve been to multiple meetings.
Then ironically, having got full approval to run a research project to do ten DBD transplants, brain dead donor transplants, November last year, so November ’17, Liza Johannesson, who used to work with Mats Brannstrom in Sweden where the first series was done, Liza moved to Dallas and they utilised a new retrieval technique in their live donors. So the Brannstrom technique is to have an internal iliac artery and vein as the main patch but that means that the retrieval operations were lasting between 10-13 hours and they had one ureteric injury because the uterine veins run above and below the ureter sometimes. So it was a very long retrieval process and there’s nothing ethically wrong with it but in that length of retrieval somebody is going to get a deep venous thrombosis pulmonary embolism just because the operations are way over six hours. So we said we wouldn’t do it. Liza Johannesson gave a presentation, new technique, you can do the retrieval in three hours and there is a vast irony because the new graft is the uterine artery, internal iliac artery, but the venous drainage is not through the uterine veins at all, it comes up the ovarian veins. The irony is that that’s the original trachelectomy technique. So in the trachelectomy the uterus is supplied, the arterial blood goes down the ovarian vessel and it comes back up the ovarian vessel. So suddenly we’re actually doing the retrieval that actually it’s where the whole thing started. The whole team, none of us can believe it because it’s like how stupid are we? We originally described trachelectomy and we never saw that was actually going to be the retrieval method. So on the back of that we know we can retrieve in three hours so we’re now about to do live donors.
Where in the UK will this be rolled out to?
I suspect that when it comes to DBD we know through the specialist nurses in organ donation and all the data that exists that there will only be across London/Southeast, which is effectively a twenty million conurbation, there will be ten appropriate uteruses per annum. If you want my guess, there will be another centre in the north somewhere, kind of that Liverpool, Manchester, Leeds, Newcastle swathe where there’s another twenty million conurbation, and that there will be a centre in each doing DBDs at the rate of probably one a month because that’s the entirety of the organs that are available for DBD.
When it comes to the live donation aspect, and that’s at the moment all the babies born worldwide have all come from live donation uteruses, there are no DBD uteruses that have produced a baby yet but that’s partly because there’s only nine that have been done DBD and they’ve been done much more recently. With the live donation that’s something I suspect that may end up being done maybe in a couple of places in London, somewhere, maybe a couple of places in the north, I’m guessing a few more. But there are issues around funding. So we’ve applied and registered with NHS England to have funding for a national DBD uterine transplant centre perhaps to open in about four years’ time when we’ve completed that research project and produced babies. The live donor procedure is not a research procedure anymore because it is established and plenty of babies have been born. But how the funding for that would work is not clear yet and that’s not what we’ve put into NHS England at this point but I suspect that we may well do that later.
What are the concluding points?
Live donation uterine transplantation is an established procedure. It is highly successful – the fertility rates are really high, I mean astoundingly high. In the Swedish group the fertility rate, so they planned to do ten transplants, they did nine, one got sepsis at three months, uterus out, one got thrombosis, seven left. Of those seven, six have had one or more babies and the seventh woman has had multiple pregnancies which sadly have miscarried but she is a woman who has got a neovagina and that may have upset the microbiome. And that was the first series and since then there are more babies. So that, to my mind, is an established technique. The DBD, our research project, should show in a viable way whether this is a viable procedure which has got a long-term future and we’ll know that within two years. There’s no reason why it shouldn’t work at all, all the preliminary work, everything around this, suggests that it will.
So I suppose the concluding message is this is very close to happening in the UK and there’s very good prospects that it’s going to work. But really important to say the number of women who are likely to want to access it is actually relatively small.
