Doctors are learning what to do if a pregnant woman's body rejects the uterus.
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There's no doubt that transplanted organs can help people live longer, better lives. But sometimes, those organs are rejected. It happens with 40 percent of hearts and a quarter of kidneys, because proteins in the new organ trigger an immune response in the recipient. If the organ in question is one for which medical treatments can't replace its function, such as the heart or the liver, a rejection may put the patient's life at risk; other organs, such as the kidney, can simply be removed (and replaced with dialysis) if it's not working properly.
Uterus transplantation is one of those procedures that isn't life-saving. And though doctors, patients, and sheer biology make rejection perhaps less likely than that in transplantations of other organs, a rejection of a uterus during pregnancy could be more complicated—it could threaten the lives of the fetus, and possibly the mother.
The uterus is just three inches long and two inches wide. "It's the smallest organ we've ever transplanted, with the smallest vessels," says Jiri Fronek, the head of the department of transplantation surgery at the Institute of Clinical and Experimental Medicine in Prague. Candidates for the transplant are women who are of reproductive age and were born without a uterus but are otherwise healthy. The donor can be either living (namely, an older woman who will not have more children) or deceased. The recipient will live with the transplant for a year before her doctors implant a fertilized embryo via in-vitro fertilization. Hopefully, the recipient will become pregnant; if all goes well, she will give birth, after which the uterus will be removed. "[The uterus is] the only temporary transplantation," Fronek says.
The first uterus transplant was done in 2000, in Saudi Arabia, but had to be removed after 99 days, before an embryo could be implanted. Subsequent efforts in Turkey, Sweden, and the United States have been more successful—the first baby that resulted from a transplanted uterus was born in 2014, in Sweden; five of the seven women in that trial have delivered babies, some more than one, says Michael Olausson, a professor and chief physician at the University of Gothenburg, where the trial was conducted. There have also been rejections and medical complications, most recently with the first American recipient, a 26-year-old woman, whose uterus had to be removed hours after a news conference declaring the transplant a success, because of an infection. But doctors and patients are undeterred, and more procedures are underway—the first Indian patient received a transplanted uterus in May, and 20 of Fronek's patients who are slated to undergo embryo transfers in July or August.
Everywhere uterus transplants have been performed, women have put their names on wait lists to undergo the procedure, though it's still experimental and, in some places, controversial: Critics point to the fact that uterus transplants are not necessary for a person's survival, and that the risks to the fetus and the mother courtesy of the necessary drugs, and risk of infection, might not be worth it. Others worry that encouraging women to go to such lengths to physically bear a child stands to perpetuate the idea that adopting or having a surrogate pregnancy aren't legitimate ways to become a "real" mother.
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Nonetheless, a transplanted uterus is, it seems, less likely than some other organs to succumb to rejection. That is in part because of the uterus's biological purpose. "The uterus is a very different organ...it seems like the uterus is less prone to [be] rejected," Olausson says. "During pregnancy, there are mechanisms activated by the regular hormones involved—estrogen and progesterone—that favor an anti-inflammatory path." Rejections are also more likely to occur if a patient isn't taking her immunosuppressant drugs, which doesn't tend to happen with uterus transplant patients who are so motivated to be mothers, Fronek says.
Still, as past cases show, rejection can happen. To avoid it, doctors carefully check potential transplant recipients for pre-formed antibodies that might make them more likely to reject a transplanted organ. After the surgery, doctors don't implant embryos until after the first year, when a rejection is much less likely. In typical organs, doctors would be able to check that it's functioning properly, but they can't do that with the uterus, so they take regular biopsies of the surface of the cervix, searching for molecules that could indicate inflammation, an early sign of rejection. If the results of the biopsy indicate that doctors should be concerned, the doctor can do a needle biopsy, which is more invasive.
Rejections can range from mild to severe, and the treatment for it can range from simple to invasive and aggressive. Doctors like Fronek and Olausson devise strategies to treat the rejection based on similar situations their colleagues have encountered with other types of organ rejections, transplant recipients who have been pregnant, or even other situations with other uterus transplant recipients.
If the rejection is caught while it's still mild, it can be treated simply with steroids (this happened with one of Olausson's patients, he says, late in her pregnancy; luckily, the drugs cleared the rejection right up). If that doesn't stop the rejection, doctors would then turn to anti-thymocyte globulin (ATG), antibodies from horses and rabbits infused into the patient's blood to block the patient's immune system from attacking the organ. If the rejection continues, doctors can try plasmapheresis, a process that exchanges a patient's plasma, the component of blood in which antibodies are concentrated, with new plasma to quiet the immune response. If none of these interventions work and it's late in the pregnancy, the doctors can deliver the baby prematurely; if it's early in the pregnancy, they may have to abort the fetus. "At some point we should just stop [treating the rejection] because you increase the risk of infection and other complications because of the treatment," Fronek says.
None of these interventions is itself life-threatening to the patient. But even a typical pregnancy can have its fair share of complications, including those that threaten the mother's well-being, and a pregnancy with a transplanted uterus is more complicated than most. Fronek and Olausson strive to make this sort of pregnancy just as safe as a conventional one, they say. They can't hope for 100 percent success—nothing is 100 percent in medicine, after all—but they believe they are moving in the right direction.
"You can only be so prepared," Olausson says. "We have to use our experience and knowledge to try to do the best we can and resolve the situation when it occurs."
Patients, of course, know about all these risks when they agree to the operation—Fronek spends more than an hour with each of his patients reviewing the informed consent form. "They are informed that rejection is part of [the risk]," Fronek says. But for most, the risk hasn't stopped them. According to Fronek, one of his patients, at the end of the informed consent conversation, said, "I fully understand all that, I'm just happy that we will be able to try. I understand all the bad bits, which may happen. I'm just grateful for the chance."
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