The first clinical trial of uterus transplantation in the United States has begun at Cleveland Clinic in Ohio, where the process of selecting women to participate in the study is now under way.

The ground-breaking study will include 10 women with uterine factor infertility (UFI), a condition in which a woman was born without a uterus, has lost her uterus, or has a uterus that no longer functions. For these women, traditional pregnancy is not possible.

Uterus transplantation may enable women with UFI to become pregnant and give birth. "Women who are coping with UFI have few existing options," Tommaso Falcone, MD, Ob/Gyn & Women's Health Institute Chair, said in an article published in Health Essentials, a Cleveland Clinic publication, on November 12. "Although adoption and surrogacy provide opportunities for parenthood, both pose logistical challenges and may not be acceptable due to personal, cultural or legal reasons."

"Many Years of Research"

"We are proud to have received approval to move forward with this novel study. It is a product of many years of research, the expertise of our medical teams and the support of our organization," Dr Falcone said.

The first two international attempts at uterus transplantation failed, largely because of organ rejection during pregnancy. Cleveland Clinic participated in research that eventually enabled a research team at the University of Gothenburg in Sweden to manage the mild organ rejection that sometimes occurs.

The Swedish research team accomplished its first birth in September 2014 and has performed a total of nine uterus transplants that have resulted in five pregnancies and four live births.

"Although there appears to be potential for treating UFI with uterine transplantation, it is still considered highly experimental," Dr Falcone explained. "Cleveland Clinic has a history of innovation in transplant and reproductive surgery and will explore the feasibility of this approach for women in the United States."

"The exciting work from the investigators in Sweden demonstrated that uterine transplantation can result in the successful delivery of healthy infants," Cleveland Clinic lead investigator Andreas Tzakis, MD, said in the publication.

Multidisciplinary Team

The clinical trial will use a multidisciplinary team of experts including reproductive and transplant surgeons, infertility and in vitro fertilization specialist Rebecca Flyckt, MD, and high-risk obstetrician Uma Perni, MD.

"Study participants will also benefit from the full support of a team of Cleveland Clinic doctors, psychologists, social workers, patient advocates and bioethicists," Dr Flyckt explained in the Cleveland Clinic story.

After approval from Cleveland Clinic's Institutional Review Board, the researchers began screening women aged 21 to 39 years with UFI in September.

Each woman must undergo extensive medical and psychological evaluations by a multidisciplinary team and receive unanimous approval of the transplant team to be included in the study.

Complex Protocol

After being approved for the trial, the woman follows a complicated protocol:

Clinicians begin the in vitro fertilization process by stimulating the woman's ovaries to produce multiple eggs.

After retrieval of the woman's eggs, they are fertilized with sperm in a laboratory and frozen.

After 10 embryos have been frozen, Lifebanc, an organ procurement agency, starts searching for a donor.

When a uterus donor has been found, that person's next-of-kin signs an informed consent for the organ donation.

The donor uterus is transplanted into the patient's pelvis within 6 to 8 hours after harvesting.

The transplanted uterus is allowed to fully heal over 12 months.

After 1 year, the woman's frozen embryos are thawed and implanted, one at a time, into the woman until she becomes pregnant.

The woman takes antirejection drugs during her pregnancy.

A high-risk obstetrics team monitors the woman throughout pregnancy and childbirth.

The woman undergoes a cervical biopsy each month to monitor for organ rejection.

An obstetrician delivers the baby by cesarean section.

After the woman has one to two babies, she undergoes a hysterectomy and stops taking antirejection drugs to reduce her long-term exposure to the medications.

Uterus transplants are unique because they are temporary. "Unlike any other transplants, they are 'ephemeral,'" Dr Tzakis explained. "They are not intended to last for the duration of the recipient's life, but will be maintained for only as long as is necessary to produce one or two children."