Uterus transplant offers a new path to parenthood

Uterine factor infertility (UFI) is a condition in which the lack of a functioning uterus makes pregnancy impossible. Now, promising results from the Uterine Transplantation for Uterine Factor Infertility (UNTIL) clinical trial at Penn Medicine offer new hope for pregnancy.

Women who experience UFI have historically relied on adoption or a gestational carrier (surrogate) to achieve parenthood. The condition affects as many as 5% of women worldwide, with Black women more likely to receive a UFI diagnosis (7.4% versus 3.1% for white women).

Six women were enrolled in the Penn Medicine UNTIL trial. Five babies have since been born to the first three study participants—all three of the remaining UNTIL trial participants have now had uterine transplants. Two are currently pregnant, and the other is presently undergoing embryo transfer.

“I want physicians to know that for patients with uterine factor infertility, uterus transplant is a viable treatment option,” says Kate O’Neill, MD, MTR, a Penn Medicine surgeon specializing in reproductive endocrinology and infertility and co-principal investigator of the UNTIL trial. “The data show it’s possible to have a healthy baby after uterus transplant and for the mother to stay healthy following transplant. It’s safe and effective, and patients with uterine factor infertility should know about this option.”

Causes of uterine factor infertility

Uterine factor infertility occurs when the uterus is absent as a result of surgical or biological factors) or is present but nonfunctional. A variety of congenital and acquired conditions—including a rare genetic disorder called Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, in which women are born without a uterus—can cause UFI.

Acquired UFI results from uterine damage from conditions including fibroids and endometriosis and from harm to the uterus from radiation therapy, physical or biological injury, and uterine scarring, among other sources.

Uterine transplant at Penn Medicine: Clinical expertise meets emerging science

A Swedish study published in 2014 marked the first successful uterus transplant, resulting in a subsequent pregnancy and live birth. In 2017, gynecological surgeons and transplant specialists at Penn Medicine launched the UNTIL trial to further demonstrate the efficacy of uterine transplants.

Some uterine transplant trials use only organs obtained from living donors, often a friend or family member. In the UNTIL trial, two of the first three trial participants received uteruses from deceased donors. One of those women delivered a baby in 2019. “One of these women gave birth in 2019, becoming only the second successful deceased donor uterus transplant in the United States,” Dr. O’Neill explains.

Managing risk with care

As with any organ transplant, managing the risk of rejection in uterine transplantation is critical.

Every uterus recipient in UNTIL required immunosuppressive medication. Because immunosuppressants pose toxic risks to the kidneys and the uterus, transplants are temporary. Participants are limited to two live births, after which the uterus is removed.

“Participants stay on anti-rejection drugs for the entire time the uterus is in place,” Dr. O’Neill says. “Once we remove the uterus, we stop the immunosuppressants.” But even with immunosuppressive regimens, rejection can occur, she adds. “We perform serial cervical biopsies to ensure that rejection isn’t occurring.”

All trial participants deliver their babies via cesarean section, which also creates risks that must be managed. “Every time you make an incision on the uterus, you increase the risk of placental abnormality in subsequent pregnancies,” Dr. O’Neill explains.

People who receive uterine transplants may also develop vaginal strictures. During transplant surgery, surgeons connect a portion of donated vaginal tissue to the top of the recipient’s vagina. “The area where the vaginas meet can become scarred and narrow,” Dr. O’Neill says. “That can be problematic because we need to view the cervix to both get biopsies and implant an embryo. This is a complication that may require dilation and follow-up surgery.”

Addressing racial disparities in infertility treatment

The UNTIL trial initially included four white patients and one Black Hispanic patient. A sixth participant, a Black non-Hispanic woman, was subsequently added.

These women are the second-and third-known Black uterine transplant recipients worldwide, according to Dr. O’Neill. This step is significant because Black women are more likely to report that their race is a barrier to getting fertility treatment.

“Access to fertility treatments has been limited for people of color,” Dr. O’Neill explains. “Access and equitable care are critically important to us at Penn. It was important to ensure we had Black patients represented in our cohort.”

In addition, differences in hysterectomy prevalence lead to higher rates of acquired UFI in Black women. Black women are more likely to undergo hysterectomy than white women (16.3% versus 15.6%), mainly before they’ve completed their families. Although Black women are more likely to experience anemia that results from heavy bleeding, including heavy menstrual bleeding (menorrhagia) and uncontrolled bleeding after childbirth, some studies suggest that differences in socioeconomic status, access to healthcare, and knowledge of treatment alternatives to hysterectomy may also be a factor in higher hysterectomy rates in Black women.

Dr. O’Neill stresses that all women, regardless of race, should be informed of all their options for starting a family. “I want Black women to know that they are also candidates for this procedure. I want them to know that there are people that look like them that have also had successful uterus transplants.”

The ideal uterine transplant candidate

An ideal candidate for uterine transplant is a patient with uterine factor infertility and normal kidney function who has not had multiple surgeries. “Most young women of reproductive age who have an absent uterus, for example, are good candidates for transplant,” Dr. O’Neill notes.

However, she adds, some women born without a uterus can have a single kidney or kidney abnormalities that make uterine transplants challenging because of the impact of immunosuppressants on the kidney. Generally, systemic health conditions such as hypertension, diabetes, or a history of clotting or vascular disease can also make successful uterine transplants less likely.

Next steps in uterine transplant at Penn Medicine

The UNTIL trial is no longer enrolling new patients. Still, the success of the trial, combined with Penn Medicine’s long history of pioneering innovative approaches to treating infertility, has encouraged Dr. O’Neill and the team to start working to ensure uterine transplant becomes an accessible option for treating UFI in all women.

“For patients with uterine factor infertility, I think it's important to mention that uterus transplant is an option, because options are the name of the game,” Dr. O’Neill says. “I think really providing patients with as many options as possible and then letting them decide what's best for them is critical. No longer should we be saying pregnancy is impossible for women with UFI.”