CLEVELAND — Six doctors swarmed around the body of the deceased organ donor and quickly started to operate.
The kidneys came out first. Then the team began another delicate dissection, to remove an organ that is rarely, if ever, taken from a donor. Ninety minutes later they had it, resting in the palm of a surgeon's hand: the uterus.
The operation was a practice run. Within the next few months, surgeons at the Cleveland Clinic expect to become the first in the United States to transplant a uterus into a woman who lacks one, so she can become pregnant and give birth. The recipients will be women who were either born without a uterus, had it removed or have uterine damage. The transplants will be temporary: each uterus will be removed after the recipient has had one or two babies, so she can stop taking transplant antirejection drugs.
Uterine transplantation is a new frontier, one that pairs specialists from two fields known for innovation and for pushing limits, medically and ethically: reproductive medicine and transplant surgery. If the procedure works, many women could benefit: an estimated 50,000 women in the United States do not have a uterus. But there are potential dangers.
The recipients, healthy women, will face the risks of surgery and antirejection drugs for a transplant that they, unlike someone with heart or liver failure, do not need to save their lives. Their pregnancies will be considered high-risk, with fetuses exposed to antirejection drugs and developing inside a womb taken from a dead woman.
Eight women from around the country have begun the screening process at the Cleveland Clinic, hoping to be selected for transplants. One, a 26-year-old with two adopted children, said she still wanted a chance to become pregnant and give birth.
"I crave that experience," she said. "I want the morning sickness, the backaches, the feet swelling. I want to feel the baby move. That is something I've wanted for as long as I can remember."
She traveled more than 1,000 miles to the clinic, paying her own way. She asked that her name and hometown be withheld to protect her family's privacy.
She was 16 when medical tests, performed because she had not begun menstruating, found that she had ovaries but no uterus — a syndrome that affects about 1 in 4,500 newborn girls. She comes from a large family, she said, and always assumed that she would have children. The test results were devastating.
Dr. Andreas G. Tzakis, the driving force behind the project, said, "There are women who won't adopt or have surrogates, for reasons that are personal, cultural or religious." Tzakis is the director of solid organ transplant surgery at a Cleveland Clinic hospital in Weston, Fla. "These women know exactly what this is about," he said. "They're informed of the risks and benefits. They have a lot of time to think about it, and think about it again. Our job is to make it as safe and successful as possible."
Laying the groundwork
The hospital plans to perform the procedure 10 times, as an experiment, and then decide whether to continue. Tzakis said he hoped to eventually make the operation readily available in the United States.
Sweden is the only country where uterine transplants have been completed successfully — all at the University of Gothenburg with a uterus from a live donor. Nine women have had them, and four have given birth, the first in September 2014. Another is due in January. Their babies were born healthy, though premature. Two transplants failed and had to be removed, one because of a blood clot and the other because of infection.
Two earlier attempts — one in Saudi Arabia, and one in Turkey — failed. Other hospitals in the United States, and in Britain, are also preparing to try the surgery, but are not as close as the team in Cleveland is.
Tzakis said the antirejection drugs were safe, noting that thousands of women with donor kidneys or livers, who must continue taking antirejection drugs during pregnancy, had given birth to healthy babies. Those women are more likely than others to have pre-eclampsia, a complication of pregnancy involving high blood pressure, and their babies tend to be smaller. But it is not known whether those problems are caused by the drugs, or by the underlying illnesses that led to the transplants. Because the women receiving uterine transplants would be healthy, Tzakis said, he was optimistic that complication rates would be very low.
A medical ethicist not connected with the research, Jeffrey Kahn, of Johns Hopkins University, said the procedure did not set off any alarms with him.
"We're doing lots of things to help people have babies in ways that were never done before," Kahn said. "It falls into that spectrum."
Dr. Eric Kodish, director of the clinic's ethics center, said that when organ transplantation started more than 50 years ago, the goal was purely to save lives, but has broadened to include improving quality of life, with for example, face and hand transplants.
Tzakis, 65, said he had performed 4,000 to 5,000 transplants of kidneys, livers and other abdominal organs. To prepare for the uterine surgery, he spent time with the Swedish team, practicing in miniature swine and baboons and observing all nine of the human transplants in the operating room.
He described transplantation as ethically superior to surrogacy. "You create a class of people who rent their uterus, rent their body, for reproduction," he said of surrogacy. "It has some gravity. It possibly exploits poor women."
A complicated rocess
The Swedish team used live donors, and showed that a uterus from a woman past menopause, transplanted into a young recipient, can still carry a pregnancy. In five cases, the donor was the recipient's mother, which raised the dizzying possibility of a woman giving birth from the same womb that produced her.
The Cleveland doctors will use deceased donors, to avoid putting healthy women at risk. For a live donor, the operation is far more complicated than a standard hysterectomy and takes much longer, seven to 11 hours, Tzakis said, adding, "You have to work near vital organs."
The surgeons have to remove part of the donor's vagina and other tissue needed to attach the uterus to the recipient. And they must tease away tiny blood vessels without harming the donor.
The uterine vessels are wound around the ureters, which carry urine from the kidneys to the bladder. "They're like worms wrapped around a tube," Tzakis said. "It's very tedious to separate them."
With deceased donors, there is no need to worry about injuries. The organ can be removed faster, and can survive outside the body for at least six to eight hours if kept cold.
For a prospective recipient of a uterus, the process is long and complicated. To be eligible, candidates must be in a stable relationship, because they will need help and support. They must also have ovaries. The initial phase includes screening for psychological disorders or relationship problems that could interfere with a candidate's ability to cope with a transplant and be part of a study. Candidates are also interviewed to make sure that they are not being pressured to have the transplant. Doctors use similar criteria for people receiving other types of organ transplants because the process is arduous, and patients with a strong social support system seem to fare better.
Finances matter, too, because during parts of the study, recipients will have to live in Cleveland, and those from out of town will have to pay for their food and lodging.
Because the fallopian tubes will not be connected to the transplanted uterus, a natural pregnancy will be impossible.
Instead the recipients will go through in vitro fertilization. Before the transplant, the woman will be given hormones to stimulate her ovaries to produce multiple eggs. Ten will be needed, so she may have to go through more than one cycle of hormone treatment. Doctors will collect the eggs, fertilize them with her partner's sperm and freeze them. Once there are 10 embryos in the freezer, the woman will be put on the waiting list for a transplant.
When a donor with matching blood and tissue type becomes available, the transplant will take place.
The transplant surgery is expected to take about five hours. It requires connecting an artery and a vein on either side of the uterus to the recipient's blood vessels. The organ will have part of the donor's vagina attached, and that will be stitched to the recipient's vagina. Supporting tissue attached to the uterus will be sewn into the recipient's pelvis to stabilize the transplant. No nerves have to be connected.
The woman will wait one year to heal from the surgery and adjust the doses of antirejection medicine before trying to become pregnant.
Then doctors will implant one embryo at a time in the uterus, until the recipient becomes pregnant. The baby will be delivered by cesarean section before the due date, to protect the transplanted uterus from the strain of labor.
After giving birth, the mother can either keep the uterus so she can try to have one more baby (two is the limit, for safety reasons), or have it removed so she can stop taking the antirejection drugs. If she does not want to have surgery to have it removed, doctors said it may be possible to quit the drugs and let the immune system reject the uterus, which should then gradually wither away.
One of the surgeons working with Tzakis will be Dr. Tommaso Falcone, the Cleveland Clinic's chairman of obstetrics and gynecology. Falcone said he first heard of uterus transplants about 10 years ago, in early research described at medical conferences. Initially, he was skeptical.
A trip to Sweden changed his mind. He went there in 2013 like a doubting Thomas, he said to see what the team was doing. He watched the surgery and spoke to several couples who wanted it.
"I almost cross-examined them," Falcone said. "I was thinking, 'There's got to be something wrong with these people.' "
But, he said, he came to understand how much pregnancy meant to them.
"It's a legitimate request," he said. "I got on the plane and knew I would be at the forefront of trying to make this program work at the Cleveland Clinic."
Dr. Alan Lichtin, chairman of the clinic's 15-member ethics board that evaluates research projects, said the medical team and the board went back and forth many times, and it took about a year to produce a plan that the board could approve. The final vote was overwhelmingly in favor of the project.
"I think our initial impression was, Wow. This is really pushing the envelope,'" Lichtin said. "But this is the way human progress occurs."
The 26-year-old candidate said that finding out she had no uterus had made her wonder if anyone would ever want to marry her. She did marry, and in addition to adopting children, she and her husband considered surrogacy, but could not afford it. Much of the transplant and pregnancy costs will be paid for by research money from the clinic and health insurance.
"I know the risks," she said. "It's a high-risk pregnancy. But I think we're in the best of hands. I think we can handle anything that comes our way."
She recently began the hormone treatments to stimulate egg production.
She belongs to a nondenominational Christian church, and members are praying she will have the transplant, she said.
"I know there will be people who don't understand or agree," she added. "But this is not a whim."