Ethical Considerations Paramount in Uterine Transplant

Cleveland Clinic’s first uterine transplant, performed last month, was the culmination of months of planning by a large, comprehensive, multidisciplinary team.

From the time initial discussions began, the team made ethical considerations a priority. Bioethicists have been instrumental in identifying ethical issues inherent in the procedure and deciding how to approach them. They played a central role in developing a protocol for this novel procedure, assist in counseling potential recipients and continue to help make decisions, as this research project evolves.

“Our goal is to minimize any risk to the recipient and family. Ultimately, we help participants understand the process and risks, so they can make an informed decision,” says Ruth Farrell, MD, MA (pictured at left), a Cleveland Clinic OB/GYN and the fellowship-trained bioethicist on the uterine transplant team.

Unique ethical challenges

Uterine transplantation shares several risks with other solid organ transplants, primarily bleeding, infection and rejection. But transplanting a uterus is new territory that may present risk to both the recipient and baby.

To fight rejection, transplant recipients must take anti-rejection medications. Fortunately, a large bank of data from solid organ (e.g. kidney or liver) transplantation confirms that the effect of immunosuppressant drugs on pregnant women and their fetuses is minimal.

Unlike hearts and kidneys, however, the uterus has a unique vascular system that allows it to grow from the size of a pear to the size of a watermelon during pregnancy. This posed questions as to how well the vascular connections would hold during the process. The team also considered the possibility a uterus could be rejected after an embryo is implanted, whether a fetus will grow normally in a graft uterus, and how fetal growth affects the graft organ.

Some of these questions are already being answered by the five Swedish transplants that have led to live births, the first of which was reported in The Lancet.

“Although uterine transplantation is new to us, there are decades of laboratory, animal and human research behind it,” says Dr. Farrell.

Beyond surgery

In additional to potential surgical complications, uterine transplantation offers new challenges by involving a series of procedures over time. Each has inherent ethical issues of its own.

The process starts with in vitro fertilization (IVF) to obtain embryos for implantation after the graft uterus has been accepted. The risks are similar to those of any IVF patient. However, the issue of what to do with extra embryos after the achievement of one or two pregnancies can be a struggle for transplant candidates.

“Some candidates find it very difficult to choose between donating their embryos to research, to another couple or freezing them,” says Dr. Farrell. “We found this can be a deal-breaker for some.”

After the baby is born, the transplant recipient faces another decision: remove the uterus, or take anti-rejection medication for life.

“It’s an ongoing risk-benefit analysis. The protocol calls for the uterus transplant to be ephemeral– temporary. Of course, the women’s input at this stage is a critical part of the final plan,” she says.

Transplantation and pregnancy: Not uncharted territory

Dr. Farrell emphasizes that pregnancy itself is not a contraindication to research. Rather, it is necessary to make scientific progress and to develop better therapies for use during pregnancy.

“When IVF was being developed, we didn’t know what the risks would be,” she says. “People were terrified it would cause injury to the woman or baby. It did not, and the procedure is widely accepted today.”

Careful consideration of all potential risks will be important to determining the success of uterine transplantation. That’s why the transplant team obtains institutional review board (IRB) guidance and approval for every step they take.

“We are fortunate because our IRB is used to thinking about innovative procedures — they approved the two face transplants performed at Cleveland Clinic to date,” she says. “They know what questions you have to ask when conducting scientific innovation.”

Why uterine transplantation?

With adoption and surrogacy acceptable options for parenthood, some question why Cleveland Clinic would put a woman and fetus through a procedure that may increase risk. To Dr. Farrell, the answer is clear.

“Uterine factor infertility can have a profound impact on every aspect of a woman’s life, from the time the diagnosis is made in adolescence onward,” she says. “It affects how a woman views herself and enters relationships. That’s why it’s important to allow this procedure to go forward. It’s not lifesaving, but it can be life-altering.”

“How a person wants to make a family is a very personal and private decision,” she continues. “Some women have no legal, religious or cultural access to adoption or surrogacy. Others have tried and failed, and don’t want to pursue the same path again. Uterine transplantation is not for everyone, but it should be an option.”