Uterus

An estimated 80,000 American women can never give birth because they lack one of pregnancy’s most basic requirements — a uterus. Until recently, their only options for having a family were through adoption or surrogacy. Uterus transplantation has opened the door to another.

The first successful uterus transplant took place in Sweden in 2014. To date, approximately 50 have been performed around the world, resulting in 16 live births. With the start of the UNTIL (Uterus Transplantation for Uterine Factor Infertility) trial in late 2017, Penn Medicine has brought this option to the East Coast … and is opening the door for further advances. “It’s an outstanding opportunity to take transplant into a new domain with a population never before served,” said Paige Porrett, MD, of the Penn Transplant Institute, and the trial’s co-principal investigator with Kate O’Neill, MD, a reproductive medical specialist in OB/GYN.

“These women want to carry their own child, to know what it feels like,” O’Neill said. And while this type of transplant isn’t life saving, “it enables a different kind of life.”

Uterus Transplant: What’s Involved?

Participants in Penn’s study suffer from uterine factor infertility (UFI), which means they were born without a uterus or had it removed for medical reasons. (Not included in the study are women with UFI who have a nonfunctioning uterus). All participants will first undergo IVF (in vitro fertilization) to retrieve and then fertilize their eggs with sperm in order to create embryos. About six months after a successful transplant, a single embryo will be implanted in the uterus. If that leads to a successful pregnancy, the baby will be delivered via C-section because women with UFI cannot delivery vaginally.

As with any other transplant, recipients must take immunosuppressive medicine to prevent organ rejection but, with uterus transplants, it’s temporary. After having one or two children, the recipient has a hysterectomy to remove the transplanted uterus, eliminating the need for anti-rejection medications.

All potential participants — and their partners — undergo a thorough education about the entire transplant process, which includes intense monitoring before, during and after pregnancy to help ensure the safety of both the mother and baby and the possible risks, for example, the recipient who gets pregnant and has a child undergoes three surgeries: the uterine transplant, a C-section, and the final hysterectomy to remove the organ.

Living Donors: Helping to Close the Gap

Similar to liver and kidney donation, uterus donors can be deceased or living, but as with most transplants, “there’s a discrepancy between supply and demand,” O’Neill said. Since Penn’s trial began, “over 200 individuals from 25 states have applied to receive the transplant. The wait could be two months… or over a year.” O’Neill hopes the Penn team will perform five uterus transplants by this summer.

Initially, Penn’s clinical trial focused on deceased donors, but they found that, although a vast majority of families of age-eligible organ donors were willing to donate the uterus (One young woman said, ‘My mom would have loved to know she was helping someone to eventually have a family’), most women who die that young have co-morbidities that preclude them from donating their uterus.

Living donors could help close the gap. In order to be eligible, a woman must be between the ages of 30 to 50, although “ideally the donor would be younger,” O’Neill said. “As blood vessels age, blood doesn’t flow as well. It could lead to complications in transplant and in pregnancy.” Donors must also have given birth, “to make sure the uterus is capable of carrying a pregnancy to term.”

A donor undergoes a hysterectomy to have her uterus removed but, unlike the standard procedure performed for medical reasons, a transplant hysterectomy removes not only the organ but also all of its surrounding blood vessels. “This includes the two main vessels on either side — the artery and vein — and as much of the ‘web’ of smaller vessels that travel from each,” she said. The surgery can take from four to eight hours. O’Neill stressed that only the uterus is removed, not the donor’s ovaries, so while the woman will no longer have periods (one potential donor considered that a distinct benefit), she will not immediately enter menopause or need to take any hormones.

While uterus transplants have not been available long enough to run long-time studies comparing living and deceased donors, there are distinct benefits of having a living donor. There is no clock ticking, as there is with a harvested organ from a deceased donor, and “there is more time to do a thorough assessment of the donated organ to make sure it is suitable,” O’Neill noted in a Scientific American article.

An Extensive Assessment

Not surprisingly, both potential donors and recipients undergo extensive, multidisciplinary assessments and evaluations to gauge their physical and psychological health. Discerning a person’s motivation for being a living donor — whether a directed donor (the uterus will be given to a specific recipient) or nondirected — is crucial. According to an article in the American Journal of Transplant, the greatest motivation for being a donor is to help another woman carry a child. One woman quoted in the article —a participant in the uterus transplant program at Baylor University Medical Center in Texas — said, “I know what it’s like to carry a baby for 9 months and I want to be part of letting someone else feel that.” The second most common reason was a desire to give back or help others. Potential donors are also screened to make sure they aren’t donating for a secondary gain, such as publicity or attention, and that they aren’t being coerced in any way.

In Baylor’s program, five of the nondirected living donors had nursing backgrounds. “We think health care providers have that tendency — an innate altruistic drive to help others, especially nurses,” said Penn clinical psychologist Lindsay Sortor, PsyD. “This is consistent with their core values and as such would find it emotionally satisfying and gratifying.”

In general, a woman’s motivation should align with either a history of medical altruism [e.g. regularly donates blood] or just altruistic behavior. For example, Jane Read, RDMS, a ultrasonographer in Penn Fertility Care who works with O’Neill, had offered to become a gestational carrier (i.e. surrogate) for a friend, but the plan fell through. Donating her uterus seemed to be a wonderful alternative. “It’s such an amazing gift to give to someone,” she said. Ultimately she decided not to donate due to the six-week recovery period after surgery and financial responsibilities, but “it may not be off the table completely.”

Also, “it’s crucial that donors maintain flexible and realistic expectations,” Sortor said. “How will they feel if the graft doesn’t take or pregnancy is not achieved or sustained? We want them to gain emotional gratification from the process and gesture but they need minimal expectations.”

In addition to helping women become pregnant and deliver babies, the trial also offers tremendous potential for research in the field, advancing knowledge of both transplantation and how the body handles pregnancy. Porrett, who researches interactions of the immune system between mom and baby, called the trial “an unparalleled opportunity.” In an article in Penn Medicine magazine, the publication for alumni from the Perelman School of Medicine, Porrett noted that research on the immunology of pregnancy could lead to being able to “someday trick the immune system to responding to any donor organ in the same way it responds to a newly developed fetus during a normal pregnancy.”

O’Neill said that, while the trial focuses on a specific patient population at this time, “if it’s successful, we might expand to include other individuals,” for example, women with nonfunctional uteri, recurrent pregnancy loss, and even potentially transgender individuals.

“The opportunity to help hundreds — or even thousands — of women is our motivation.”

Read more about Penn’s uterus transplant trial by clicking here and at PennMedicine.org/magazine/utx.

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