Womb transplants are the new frontier of reproductive science. Richard Orange reports on the quest to produce the first healthy baby from a transplanted uterus.
Dr Mats Brannstrom’s phone begins to buzz and the words ”Donor 9” flash up on the screen. He apologises, picks up and then starts nodding patiently, answering the caller’s questions under his breath.
It’s now more than a year since Brannstrom and his team carried out nine pioneering womb transplants, five of them mother-to-daughter, in Gothenburg, Sweden. But Brannstrom and his colleagues are still on call for both donors and recipients 24 hours a day.
”They do ring me a lot,” he says, as he pads downstairs, still wearing surgical clothes and battered rubber hospital slip-ons, to show me the rooms at the Sahlgrenska Hospital where the operations took place.
Part of the reason for this 24-hour aftercare is that the surgery was unexpectedly difficult: the operation to remove the womb, which studies on baboons had indicated would take three to four hours, ended up taking between 10 and 13 hours in the theatre.
Brannstrom’s team transplanted not just the womb but also long veins and arteries, which were then attached directly to the large blood vessels deep in the recipient’s pelvis.
This will hopefully give a much better flow of blood to the foetus if the women succeed in getting pregnant, but it greatly complicated the surgery. Even Dr Andreas Tzakis, the eminent US transplant surgeon Brannstrom flew in to oversee the operations, was caught by surprise.
”He’s one of the absolute top transplant surgeons in the world, and he says that this is possibly the most difficult transplantation he has ever done,” Brannstrom says.
One of the recipients later suffered from a uterine infection, which meant the subsequent removal of the donated womb. Another woman’s womb was removed after she suffered thrombosis. But five women have already had their first embryos transplanted by IVF. This puts Brannstrom and Sahlgrenksa Institute in the lead in the race for the first healthy baby from a transplanted womb. And thousands of women without wombs around the world are watching every development.
”When I found out [about the transplants] I was so excited,” says Kristen Male, a 23-year-old tax worker from Adelaide.
Male has MRKH, a congenital disorder that affects one in 5000 women and prevents the womb from developing. Her mother Debbie has agreed to donate her womb if the operation becomes available in Australia.
”To me it doesn’t feel like getting somebody else’s body part, I feel like it’s my chance to have my own baby,” says Male. ”And the way my mum feels about it is that she’s giving a uterus to get a grandchild.”
A member of Brannstrom’s team, Queensland gynacologist Dr Ash Hanafy, says he has a database with the names of about 500 Australian women who have expressed preliminary interest in the procedure. One Melbourne woman, neonatal nurse Melinda Arnold, signed up to receive her mother’s womb several years ago. Hanafy says that if a healthy baby is born to one of the Swedish recipients, he hopes to begin the procedure in Australia in 2016.
But the process is ethically fraught. It’s not a transplant that’s about saving lives. And while Brannstrom and his team transfer wombs from live donors, others attempting the procedure around the world prefer to source them from deceased people, to minimise surgical risks.
Advocates for womb transplantation say it will enable women without wombs to have the actual experience of bearing a child (unlike surrogacy or adoption).
But Ruby Catsanos, a medical ethicist at Macquarie University, questions what kind of experience this will be.
”It will be a highly, highly medicalised birth, nothing like the highly romanticised idea of pregnancy that many young women have,” she argues. ”They can’t attach the nerves, so the womb itself will be numb. The women will have … IVF, a caesarean birth, and even between all that, there will be constant monitoring.”
When I speak to Brannstrom three months later, he is on the Gold Coast staying at Hanafy’s house ahead of a fertility conference. As the first embryo was transferred in mid-January, Brannstrom must now know if one of the five patients who have received IVF is pregnant. But he’s not going to reveal anything. Doing so would put unnecessary pressure on the women, the identities of whom he has kept a well-guarded secret.
The idea of trying to make womb transplants a reality actually came from one of Brannstrom and Hanafy’s former patients in Adelaide, a 26-year-old businesswoman they refer to as Angela, who lost her womb, and later her life, to cancer.
”While Mats was talking to her about the need for a hysterectomy and the fact that she wouldn’t be able to be a mother or to carry her own children, she came up with the idea,” Hanafy recalls.
”She said to Mats, ‘Well, why can’t you transplant a uterus? Surgeons do transplants all the time. Why can’t gynaecologists do uterus transplants?’
”The initial thought was, ‘What? This is crazy’,” Hanafy says. But when the two discussed the case later, they realised they had no idea why the operation was off the agenda.
They discovered there had been research programs with animals throughout the 1960s and ’70s, but these had stopped with the birth of Louise Brown, the first test-tube baby, in 1978. ”I think what happened basically is that IVF came in the late ’70s, and that’s how all gynaecologists basically dropped pursuing uterus transplantation because IVF sorted out 95 per cent or more of the problems of infertility,” Hanafy says.
After Brannstrom returned to Sweden in 1999, he managed to secure the first of a succession of grants from the Jane and Dan Olsson Foundation, a charity started by the family that owns Stena Line, the international ferry company. By a stroke of luck, Jane Olsson herself had previously worked as a fertility doctor at the Sahlgrenska Hospital.
”She really liked this project from the beginning, because she had treated a lot of patients with fibroids who could never get pregnant,” Brannstrom says. ”I told her that it was really difficult to get funding, because it’s not cancer, and it’s not heart disease, and because it’s ethically debatable.”
The money has given Brannstrom’s team the edge on rivals in the UK and the US. ”It is safe to say that the Swedish effort is monumental,” says Dr Giuseppe Del Priore, a US surgeon working with the UK uterine transplantation team. ”Although others may have started this effort … funding has limited our progress.”
It’s not just the emergence of IVF that put womb transplant out of the picture for nearly 30 years, however. The ethics are unusually problematic.
”This isn’t a life-saving transplant – it isn’t the same as a heart, lung, liver or kidney transplant,” argues Neil Huband, a spokesman for the Uterine Transplant UK, which is trying to raise money to carry out a similar trial in Britain.
Both the UK womb transplantation team and Turkish plastic surgeon Dr Omer Ozkan – who performed a transplant in 2011 on a woman whose foetus later miscarried – favour using deceased donors to minimise surgical risks. As deceased donors aren’t related to the recipients, this usually means heavier doses of immunosuppressant drugs, which are associated with lower birth weights and premature delivery.
But Huband points out that by putting the woman donating a womb through a major operation (as well as the woman receiving one), Brannstrom effectively doubles the risk. ”If we can find matched recently deceased donors, that is a big risk that we can remove,” he argues.
Live donors are also usually much older. As well as the five mothers, Brannstrom took one womb from a recipients’ older sister, another from an aunt, one from a mother-in-law and one from a family friend.
Brannstrom’s youngest donor, the sister, was 37. But the rest were all over 50, and the oldest was 62.
This has a less serious impact on the viability of the womb than you might think; all seven remaining wombs are now menstruating normally. But it does makes the donor less able to withstand such a serious operation.
One 58-year-old donor developed a ﬁstula between her ureter and her vagina, meaning she had to have a second round of surgery.
Then there is the impact on the pregnant women themselves, undergoing this highly medicalised pregnancy. ”They’ll feel morning sickness, they’ll feel their ankles swell, but they may or may not feel foetal movement, because the nerves won’t work as well,” says Kavita Shah Arora, an assistant professor of bioethics at the Case Western Reserve University in Ohio. ”My general take is that we should proceed with extreme caution. It can be justified, but we have to very carefully look at the risks and the benefits for all three parties.”
Still Brannstrom argues that for a novel procedure this involved, there were few complications.
”If you look at the first live liver transplantation, that took 24 hours, today they do the procedure in six to eight hours,” he says.
He predicts the removal part of the womb transplant operation will be reduced to as short as five to six hours as surgeons become more experienced, with a corresponding decrease in the risk. He acknowledges, however, that his results will for now make it difficult for rival teams to get regulatory permission to carry out womb transplants using live donors, as regulators are likely to rule that the risks for now outweigh the scientific benefits of further studies.
”My prediction is that if there are other studies launched, as they are doing in Britain, they will be a deceased donor concept, because what we have shown is that the surgery is more complicated than we thought.”
r Rebecca Deans, who works with MRKH patients at Sydney’s Royal Hospital for Women, doubts whether Kristen Male will be able to receive the operation as early as 2016, as she and Hanafy hope.
”I still think we’re a long way from this as a standard care for women,” she says. ”It’s not an operation we would take lightly, and it’s not an operation without risks. I think it’s very early days.”
She argues that even if one or more of the Swedish recipients manages to produce a healthy baby, it will take years before doctors will know if the blood flow to the foetus through the transplanted womb was good enough to ensure normal development, or what the long-term impacts of the immunosuppressant regime will be.
Hanafy says while the old immunosuppressant drugs given to transplant recipients could cause other health problems, the drugs being used now are so safe they are ”almost side-effect free”.
However, he acknowledges that women having babies after a womb transplant may experience more complications during their pregnancies than other women, and their babies may be smaller.
Studies of European women who have had babies after receiving organ transplants such as kidney and liver transplants, show that they have a slightly increased risk of complications, including pre-eclampsia (high blood pressure), premature birth and their babies being small for gestational age.
Still, Deans does not think any of these issues will deter any of the MRKH patients she treats from volunteering for the operation.
”They’re young, and they’re desperate and they want to have a baby,” she says. ”Young women who want to have a baby will do almost anything.”
Male wants to experience carrying a child in her own body, to feel it grow inside her. ”Giving a child life is one of the most amazing things that the female body is meant to do,” she says.
Indeed, Brannstrom argues that for the women who successfully received new wombs, the experience has already been life-changing. ”Some of them are 30 or 32 and they’ve never had a period before, and they think it’s so fantastic,” he says. ”They say, ‘Now I feel like a real woman’.”
With Julia Medew
Richard Orange is a journalist based in Sweden.