The idea for a radical type of organ transplantation was born in Australia when a young surgeon was working in Adelaide.
Three decades ago, a young Swedish doctor training in gynaecological cancer surgery at Royal Adelaide Hospital had to break the news to a 25-year-old cervical cancer patient that she needed a radical hysterectomy to save her life.
Professor Mats Brännström explained to her that surgeons could preserve her ovaries but that she could never carry her own pregnancy.
“And then she actually suggested to me, ‘can’t you do a uterus transplantation?’ And I was astonished because I had never thought about the concept of uterus transplantation,” he remembers.
That conversation changed the course of Professor Brännström’s career, and like so many simple but wonderfully complex ideas, like spray-on skin and cochlear implants, uterus transplantation has its roots firmly in Australian soil.
Professor Brännström made that idea his life’s work, returning to Sweden and spending almost 20 years researching and trialling uterus transplants in animals. In 2014 he performed the first human uterus transplant that resulted in a live birth.
And on 10 January this year his vision came full circle, when Coffs Harbour woman Kirsty Bryant, 30, received the uterus of her mother Michelle Hayton, 54, in a 16-hour dual surgery at the Royal Hospital for Women in Sydney.
Lead surgeon, Sydney paediatric and adolescent gynaecologist and fertility specialist Dr Rebecca Deans has been working with Professor Brännström for more than 10 years and he and his team were there to oversee the marathon surgery.
The hospital is home to one of two teams in Australia that have secured $1 million in research project funding to perform six uterus transplants this year. They have approval for another six, which will be dependent on more funding.
Uterine transplantation offers the chance of conception for women for whom conception and pregnancy are impossible. That includes women who have had a hysterectomy due to gynaecological cancer, postpartum bleeding or severe endometriosis, for example, or the one in 500 women with uterine factor infertility (UFI) in which there is either no uterus or the organ isn’t functioning.
Dr Deans has seen women with congenital absence of the vagina or uterus, known as Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome, at the Royal Hospital for Women for nearly 20 years. Dr Deans and her team perform vaginal dilation and surgical procedures to create a vagina for women who are born without one at Australia’s only inpatient vaginal dilation service. Participants in the uterus transplant trial have come from the MRKH clinic and through the Uterus Tx Australia and Royal Hospital for Women Foundation websites.
“The patients really drive this,” Dr Deans tells The Medical Republic. “The patients really do want it.
“It’s really about that improvement of quality of life. And I think that in Australia where surrogacy is pretty hard to achieve, it gives another option for women.”
The projects at Royal Hospital for Women and at Sydney’s Royal Prince Alfred Hospital are operating under research funding, and there are no plans for uterus transplants to become widely available or publicly funded. But even for those people who hope to take part, many of them don’t fit the criteria, Dr Deans says.
“They’re either too old for inclusion or they don’t have a matched donor,” she says.
“In my project, the donors are either deceased or living and a lot more people want a deceased donor because they don’t have an eligible living donor – like most transplants. Some are lucky enough to have one.”
HOW IT EVOLVED
Professor Brännström’s commitment to his patients is clear. As he tells The Medical Republic, he receives Christmas cards in the mail each year from the families of babies who wouldn’t exist without a donated uterus. The baby born from his first successful uterus transplant bears his name.
He says that from the very first conversation he had with his young Australian cancer patient he felt confident it was possible to master the technique.
After returning to Sweden, he worked on developing the technique in animals in 1989, first in mice, then bats, pigs, sheep and baboons for a non-human primate model. It was slow and painstaking research that took decades.
Dr Deans first heard about Professor Brännström’s research in 2009 was inspired to go to Sweden to train with him in the animal trials. A few years later she assisted with human transplants.
“It was a great experience training in the sheep model and then scrubbing in to do the human transplant surgeries in Sweden,” she says.
Professor Brännström recalls the first hysterectomy in a woman took longer than the team expected.
“We thought it could take four to six hours,” says the professor and chairman in the department of obstetrics and gynaecology at Sahlgrenska Academy, University of Gothenburg. “It actually took 11 hours, so it was a lot more difficult than we thought.”
That transplant was a success and resulted in two pregnancies and healthy babies.
Since then, 12 babies have been born in Sweden thanks to uteruses donated by mothers, sisters, aunts, cousins and good friends of the recipients.
“They are all healthy and normal weight,” Professor Brännström tells TMR by phone as he catches public transport to work in Gothenburg.
“The oldest is now eight years old and we haven’t seen any differences and he seems to be healthy. And we follow the donors for five years afterwards and they’re fine both physically and mentally.
“I can see that I actually helped to create a family which they thought was impossible. I’m happy that I can help patients who were not able to have that before.”
THE QUESTION OF ETHICS
The concept of uterus transplants is certainly not short of ethical questions, and one of the most common is around the issue of whether a uterus transplant is medically necessary.
While uterus transplantation is the only reproductive transplant available, it’s certainly not the only non-life-saving transplant – face, hand and even penis transplants are now possible, says Dr Mianna Lotz, associate professor of philosophy at Macquarie University.
“Even kidney transplants in a sense are about quality of life because it’s about getting people off dialysis rather than necessarily saving lives,” says Dr Lotz, who gave ethical advice to the uterus transplant team and the patient safety and data monitoring board.
Dr Lotz was reticent about the idea of uterus transplantation at first.
“I felt that it was best to be involved rather than to be standing on the sidelines,” she says.
“I felt like if it is going to happen, then it needs to be as ethical as possible, and we need to make sure that there are no unscrupulous providers here. We need to make sure that proper processes are in place to ensure that the women who are undertaking the procedure are fully informed, not coerced, not feeling compelled or pressured.”
PHYSICAL AND MENTAL IMPACTS
It’s a major procedure for both the recipient and the living donor, for whom the procedure is a much bigger deal than a standard hysterectomy, Dr Deans says.
“It’s long surgery of eight to 12 hours,” she explains.
“There’s a higher risk of vessel and ureteric injury as well as shortening of the vagina as the upper cuff is removed also, so there are possible sexual function impacts.”
There are also potential psychological impacts for the donor if the uterus doesn’t function well or fails after transplant and there’s the potential psychological rejection of the organ, which has been known to occur with a hand transplant.
But worldwide, no women who have had the procedure have psychologically rejected the uterus, Dr Lotz says.
“It’s not visible to the patient so that they are less likely to psychologically reject it,” she says. “To the best of my knowledge, we’ve got no cases of psychological rejection in recipients in the case of uterus transplants. This is partly because it is transient and temporary, and partly because it’s not visible.”
As with any organ transplant, recipients need to take immunosuppression therapy, but for women with transplanted uteruses that immunosuppression is kept at levels that are safe for the baby.
“With a uterus transplant the recipient only keeps the transplanted organ in to have a baby, or at most two. So you don’t have the extended exposure to immunosuppression and you also don’t need as high a dose of immunosuppression as compared to permanent transplants and face or hand transplants,” Dr Lotz says.
Dr Lotz says that if conception is successful, immunosuppression is carefully monitored.
“That has to be monitored extremely closely to ensure that the recipient is not getting infections through loss of immune response, but the level of immunosuppression can be reduced to a level that’s deemed compatible with the wellbeing of the fetus developing in utero,” she says.
And it’s only temporary. Once the recipient has a baby (or two), the uterus is removed, and that temporary nature of the transplant brings the advantage of limiting the need for immunosuppression to five years, at the most.
For the recipient, there’s a long road to recovery and then once menstruation has started they will try to conceive via IVF and embryo transfer.
As for the organ itself, that’s the end of its service, but Dr Deans says research is being planned by other teams to see whether uteruses can be donated to a second person.
LIVING OR DECEASED?
Internationally, around 75% of all transplants have been from living donors, and the Royal Hospital for Women project has approval to use both living and deceased donors, Dr Deans says.
Dr Lotz says there are pros and cons for both.
“I regard it to still be a genuine matter of research equipoise and for that reason, we should be going ahead with developing the research for both the deceased donor and the living donor model,” she says.
For instance, using living donors has the advantage of enabling the surgical team to be well-rested and reducing the ischemic time, thus improving the success rate of the transplant.
On the other hand, using living donors involves major surgery for someone who doesn’t medically need any intervention, exposing them to potential harms and risks. There are also the potential psychological and emotional impacts on the donor if something goes wrong or if there are poor outcomes for the recipient, pregnancy or baby.
Using organs from deceased donors allow surgeons to remove longer lengths of vasculature, a process which carries a risk of injury when carried out in a living donor.
“For the living donor there is a concern that we’re putting a perfectly healthy person through a significant and lengthy surgery. Whether a donor is known to the recipient or not, it’s a lot to go through,” Dr Lotz says.
“We’re only taking peri-menopausal women as living donors, to ensure they have finished with their own reproductive plans. But still, it’s a big surgery and it’s one that they are not medically indicated for.”
HOW SUCCESSFUL IS IT?
As uterus transplants are done in more and more countries and the data accumulates, evidence grows to support its efficacy.
Professor Brännström says their data shows that if the transplant and embryo transfers are successful, the take-home baby rate is about 85%.
“That’s a very high success rate for fertility treatment,” he says.
A review of the first five years of uterus transplants in the US found there was no donor or recipient mortality, and one-year graft survival was 74%. Among the 33 recipients, 19 delivered 21 live-born children.
“Uterus transplant is safe for mother and child; success is reproducible and not limited to single centres; success is achieved with both DDs and LDs; and success rate is comparable with the most effective infertility treatments,” the JAMA Surgery review concluded.
“For these reasons, uterus transplant should be considered a clinical reality in the US and presented as an option for individuals with AUFI interested in parenthood.”
WHICH BOX TO TICK
Whether uterus transplants will one day be publicly funded raises the broader ethical concern that relates to all fertility services: that it’s more accessible to wealthier people, Dr Lotz says.
“There’s the concern that if we don’t make it publicly funded, then that means that only those who can privately afford it get access to it,” she says.
“And if we do, we may be signalling something that is perhaps concerning around making a priority of something that has the risk profile that it does, that isn’t life-saving and uses the resources that it does.
“At this point, my view on it is that at the research level, it’s appropriate to apply for National Health and Medical Research Council funding and government funding through that. But I’m remaining on the fence about whether it should be Medicare funded in the future. And I think opinion definitely diverges on that question.”
When it comes to deceased donation, there’s also the question of whether the uterus could one day be included in the organ donor list.
That’s still some way down the track, and it will depend on the results of the trials in Australia which are still in the research phase, according to a spokesperson for the Organ and Tissue Authority.
“Once the results of these trials are finalised our medical experts can begin the process of reviewing the findings and determine the next steps,” the spokesperson says.
Dr Lotz says that while the uterus would be part of multi-organ retrieval, it would be retrieved only after the life-supporting organs had been removed.
“Uterus removal for transplantation would never jeopardise the ability for life-saving organs to be taken and utilised first, and that’s pretty standard for quality-of-life transplants,” she says.
WATCH THIS SPACE
For now, all eyes are on Ms Bryant, who Dr Deans says has a good chance of conceiving by the end of the year.
While there were no major complications during the two surgeries, Ms Bryant had significant blood loss 24 hours after the surgery and needed blood transfusions, while her mother had a serious infection and lack of sensation in her bladder.
Ms Bryant told media that she started menstruating 32 days after the transplant in January. All going well, about three to six months after the operation she will try to conceive through IVF using embryos frozen before the transplant.
“There is a good number of women coming forward saying, ‘I really would love to do this. I don’t have other options. We desperately want to have another child and we’d really love to be considered’,” Dr Deans told media.
“I’d love to be able to offer this to women in Australia.”
