One day after Cleveland Clinic doctors hailed the first uterine transplant in the US a success last month, the prestigious medical center said the operation had, in fact, failed. At the time, the doctors didn't reveal the cause.
Now, the transplant recipient, a 26-year-old Texan named Lindsey McFarland, has shared the details of her experience. The cause of the sudden complication that caused her to have her new uterus removed was, she said, a simple yeast infection.
McFarland's tragedy — after much fanfare — raises the question about whether it's really worth continuing with the operation at all. Though the doctors in Cleveland have nine additional uterus transplants in the works as part of an ongoing study, the procedure remains hugely controversial.
I asked medical ethicists and doctors (including one of the authors of the global ethical guidelines for uterine transplants) for their opinion. They all pointed out that the uterine transplant is a supremely risky operation — but agreed that doctors and willing patients should continue experimenting with them anyway.
Uterine transplants involve at least four surgeries
Most of the routine organ transplants that occur now are done in an effort to save someone's life by replacing a failing vital organ, like a liver or kidney, with a new one. The uterine transplant is part of a newer wave of surgeries — think penile and face transplants — that are not lifesaving, but which give donor recipients potential they lost in an accident, disease, or birth defect.
In the case of a uterine transplant, explained the University of Montreal's Jacques Balayla, recipients may have either been born without the organ or had to have it removed due to a disease such as cancer. And, importantly, it's not just the ability to have a child that's at stake; it's the ability to carry one's own child in a pregnancy.
To appreciate why this particular transplant is so controversial, one needs to understand just how complicated the process is.
First, you need a candidate who doesn’t have a uterus but who would like to carry her own baby. Then the woman would need to find a compatible donor who is willing to give away her uterus. (Doctors, like the ones in the US, are also experimenting with using uteri from cadavers.)
Assuming there is a match, and both women agree to go through with the surgery, the patient who is going to receive the uterus has to then undergo in vitro fertilization. This means her eggs need to be retrieved, fertilized with the sperm of her partner, and frozen. (This assumes her own ovaries and eggs are viable. If they are not, the recipient can presumably use donor eggs in IVF.)
The donor's uterus is removed in an operation. Then, when the uterine recipient is ready to receive the transplant, she undergoes an operation, and her frozen embryos are transferred back into her body. She would also begin taking anti-rejection drugs to suppress her immune system so that it doesn't attack her new organ.
When she's ready to deliver the baby, another operation: She has to undergo a C-section. After she's finished with childbearing, there's a final operation to have the uterus removed. (That's so the woman doesn’t have to take anti-rejection drugs for the rest of her life.) The donor would go on without her uterus, having undergone what is essentially an early hysterectomy.
"If you are going to use living donors, it's a total of four operations," said New York University bioethicist Art Caplan. "That’s a lot of surgery to create the ability to carry a child, and obviously you have exposure to immunosuppressants, anesthesia, and a huge price tag." (Cleveland Clinic would not reveal the cost, but Stat reported an estimate of at least $100,000 and noted that insurance companies are unlikely to cover the procedure.)
There have been 12 uterine transplants worldwide, and about half have failed
With so much risk and potential for complication, it's no surprise that so many of the 12 uterine transplants that have been done in the world since the first in 2002 have failed.
In early 2014, when doctors announced the first successful birth from a uterine transplant in Sweden, they explained that they had had 10 potential recipients — but one didn't make it to the transplant stage, and two of the patients had to have their transplanted organs removed shortly after the surgery (like Lindsey McFarland). Of the seven transplants that proceeded, five resulted in births. Meanwhile, in Turkey, a uterine transplant recipient had to have her pregnancy terminated because of complications. Another such surgery failed in Saudi Arabia after the transplanted uterus started to deteriorate about three months after the procedure.
If a woman with a newly transplanted uterus does have a successful pregnancy, she faces a higher risk of premature birth — which carries its own mental and physical health risks. And though doctors prescribe anti-rejection drugs that have a lower risk of damaging the fetus, taking any medication during pregnancy can result in potential malformations.
The important dilemma here is that this transplant has to do with reproduction, not a vital organ. So women who get involved with the procedure undergo tremendous risk, some argue unnecessarily given other options like adoption and surrogacy.
"My concern for potential recipients is that the promotion of uterus transplantation as a form of reproductive technology obscures what it really is — an organ transplant," said medical ethicist Ruby Catsanos of Macquarie University in Sydney. "[It's] an invasive surgical procedure with significant risks associated with the surgery itself, issues of infection and organ rejection, and the adverse side effects of the anti-rejection drugs, including cancer and increased risk of opportunistic infection."
She continued: "For recipients of lifesaving transplants, these potential risks are outweighed by the health improvement gained from the transplant. For recipients of uterus transplants, the same risks exist but with no straightforward health benefits."
On the other hand, Dr. Jen Gunter, an OB-GYN based in San Francisco, pointed out, "We don't need hands to live, yet double hand transplants are applauded. Whether you can directly compare the two I'm not sure, but if transplanting a hand is okay, then why not a uterus?"
Why doctors think they should continue doing this operation anyway
According to ethical guidelines on uterine transplants that Balayla co-authored, a candidate for this surgery must intend to carry a child and have a "congenital or acquired uterine factor infertility," meaning she was either born without a uterus or lost her uterus to disease or accident. She must also have a "personal or legal contraindication to surrogacy and adoption measures."
In some parts of Europe and the Middle East (and in some states in the US), surrogacy is illegal. And adoption may be difficult or culturally problematic.
"It’s not a coincidence that [the first attempts at a transplant were] conducted in Islamic countries [like Saudi Arabia]," Mats Brännström, who led Sweden's uterine transplant efforts, told Popular Science in 2014. "It’s very important for a woman to become a mother, so surrogacy and adoption would not be approved by Islamic convention."
And even if surrogacy and adoption are easy to come by, they're not viable alternatives for some women, said Catsanos. "[There's] surrogacy and adoption as alternatives to uterus transplantation, but for a woman who wants a genetically related child, gestational surrogacy is the only alternative," she said. "Gestational surrogacy also raises many ethical concerns, so that it is a problematic alternative for many."
For this reason, there's a strong ethical argument for continuing with the experimentation. "[This could] truly grant women the ability to not only have a family but to carry a pregnancy when no other alternative exists for procreation," Balayla said.
As for the great risk of failure, Caplan said, it's a reality of experimentation that the patient presumably consented to. "Failure is a part of novel experimentation, and you have to be ready for it, willing to manage it, whether it's a face transplant or hand or uterus transplant."
In addition to the Cleveland Clinic's nine forthcoming uterus transplant attempts, three more US medical centers are planning their own experimental programs.
If the operation becomes more successful as experimentation continues, big questions remain for how commonly it should be used. "I wouldn't end research on uterus transplants because of this very sad failure," Caplan said. "But I think we in the US have to think very hard about this. Is it worth all the risk, surgery, simply to carry the pregnancy for some?"
Gunter was more hopeful. While the cost of a uterine transplant is enormous, she explained, "At one point in time people thought IVF was ridiculous and expensive and risky, and now it's commonplace — or at least it is for those who can afford it. It has enriched the lives of many. So who knows, maybe in 10 years we will think the same about uterine transplant."