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The Uterus Transplant for Uterine Factor Infertility (UNTIL) Trial

Gobrechts with Newborn
Drew and Jennifer Gobrecht with son, Benjamin, in November 2019. Born without a uterus, Jennifer was the first to receive a uterus transplant at Penn Medicine.

Among the first institutions in the nation to offer access to uterus transplantation, Penn Medicine and the Perelman School of Medicine are advancing the field through an investigational clinical study, the Uterus Transplant for Uterine Factor Infertility (UNTIL) trial. The principal investigators for the trial are Kate O’Neill, MD, MTR, Medical Director of the Uterus Transplant Program, Paige Porrett, MD, PhD, the Program’s Surgical Director, and Nawar Latif, MD, Surgical Lead of the Living Donor Uterus Transplant Program.

Of the more than 6 million women in the United States who struggle with infertility, approximately 100,000 have uterine factor infertility (UFI), a condition characterized by the absence of a functional uterus and irreversible infertility. UFI is caused by congenital absence or surgical removal of the uterus, or uterine dysfunction as a result of trauma or disease. Until recently, women with UFI wishing to have children were limited to in-vitro fertilization (IVF) with a gestational carrier or adoption.

Today, transplant specialists at Penn Medicine are on the frontier of another option for those struggling with UFI—uterus transplant—through participation in the Uterus Transplant for Uterine Factor Infertility (UNTIL) trial. The purpose of UNTIL is to learn whether transplantation of a uterus from a living or deceased donor is a safe and effective way for a woman with UFI to achieve pregnancy.

A Unique Collaboration of Experts

UNTIL is a collaboration between Penn Medicine’s department of Obstetrics & Gynecology and the Penn Transplant Institute, a diverse team of experts consisting of more than 50 doctors, surgeons, nurses, psychologists, social workers, and bioethicists across multiple disciplines.

The effort to bring uterus transplant to Penn Medicine is being led by Drs. Porrett, O’Neill and Latif, as well as Eileen Wang, MD, of Penn Obstetrics and Gynecology. This team offers all of the elements in surgical expertise, scientific background and research to bring the program to fruition, and engages in knowledge sharing with other renowned institutions across the world doing similar research.

An attending surgeon specializing in reproductive endocrinology and reproductive infertility, Dr. O’Neill chose to be an UNTIL investigator to address the needs of her patients with UFI—an infertility population greatly underserved by current clinical research.

Gynecologic Oncology expertise has been essential since the inception of the program. Dr. Latif’s participation was prompted by his extensive experience in radical pelvic surgery as a gynecologic oncologist. Depth of experience in this area was critical to the success of uterine transplantation as well as to patient safety.

“Hysterectomy is a surgery complicated by the position of the uterus deep within the pelvis and its proximity to critical organs and vascular structures,” Dr. O’Neill explained in a recent interview. “What we’ve learned from other programs is that you need infertility, gynecology-oncology and transplant to have a successful program. You can’t do it without all three.”

“And this is what’s unique about the formula at Penn,” Dr. Latif adds. “We have Drs. O’Neill, Porrett and myself, all really passionate about this and willing to put in the time to execute the program.”

Dr. O’Neill was familiar with uterus transplant well before it entered the headlines, but was at a loss for answers early on when patients asked about the procedure.

“For many of my UFI patients, the use of a gestational carrier and adoption aren’t options,” Dr. O’Neill said. “Our goal is to help women build a family, and it was disappointing to have to tell my UFI patients that we couldn’t offer an option that allowed them to carry their pregnancy.”

Given the complexity of the surgeries involved, the peripheral patient experience was not a foremost consideration for Dr. Latif—but became so.

“At first, my interest was the surgical challenge,” Dr Latif says, “But as I began to talk to the patients and hear their stories, I realized that this was bigger than just a surgical challenge. This is about families and life itself.”

The advent of UNTIL means that uterus transplantation is now available at Penn Medicine, offering a new path to parenthood for women with UFI—outside of adoption and use of a gestational carrier—and the only option to carry and deliver a child.

Breaking News from The Penn Uterus Transplant Program

With the birth of son Benjamin at the Hospital of the University of Pennsylvania in November 2019, Jennifer Gobrecht became the first participant in UNTIL to give birth, and only the second woman in the US to give birth following a deceased-donor uterus transplant.

Born with a congenital condition characterized by the absence of a uterus and fallopian tubes, Jennifer, 33, received a donor uterus almost a year before the birth.

Uterus transplantation involves the temporary transplantation of a uterus from either a living or deceased donor to a woman with ovaries, but lacking a functional womb, who has thus no other options for child-bearing. Prior to transplantation, the recipient undergoes in-vitro fertilization (IVF) and cryopreservation of embryos, which will be transferred to the uterus 6-12 months after transplantation. At the time of transplantation, the recipient begins immunosuppressant drugs to prevent uterine graft rejection. At the completion of the transplant cycle, the uterus is explanted, and immunosuppression ceases.

The Gobrechts had previously had IVF while exploring the option of a gestational carrier, and had cryopreserved embryos available for transfer. However, IVF is a relatively simple procedure by comparison to uterus transplantation, an extensive and complex investigational procedure that involves both surgical and medical management.

Learning of UNTIL, Jennifer and her husband were enrolled only after completing an extensive evaluation by a study team that included not only clinicians, but specialists in bioethics, social work and psychology. This comprehensive approach to detail continued two years later when the Gobrechts welcomed their son via cesarean section in the presence of specialists in high risk obstetrics, transplant surgery, fertility, gynecologic surgery, neonatology, pediatrics, urology, nursing, and anesthesiology.

Since the launch of UNTIL, more than 1000 women have contacted the team. In addition to women with UFI seeking the opportunity to participate in the clinical trial, more than 70 women have expressed interest in donating a uterus so women with UFI may experience childbearing as they did.

“While there are still many unknowns about uterus transplantation, we know now — as evidenced by Jen and baby Benjamin — that this is potentially a viable option for some women,” Dr. O’Neill said. “Our collaboration with investigators at partnering institutions as well as with Jen and other brave patient pioneers in these clinical trials are helping us learn more about how to make uterus transplants safer, more effective and available to more women.”

The Future

Clinical research has been an intended goal of the Uterus Transplant Program at Penn Medicine from the outset. Among the most fascinating aspects of uterine transplantation is that it offers researchers the opportunity to investigate the endometrium, a tissue that remains little understood.

“Because there is mismatch between the donor and recipient, uterus transplant offers us a unique opportunity to study the endometrium,” says Dr. O’Neill. “This means that we can follow endometrial cells from their origin in the donor uterus and can then investigate where they travel to—giving us a window into the mystery of endometriosis, for example."

Another area of investigation involves minimally invasive robotic hysterectomy, a technique that Dr. Latif will introduce in the near future.

“This is a huge advantage for potential donors, because the recovery time for open hysterectomy can be six weeks,” Dr. Latif says. By shortening the timeframe for recovery and thus reducing the burden on donors and their families, he adds, minimally invasive surgery will make uterus transplantation a viable option for a wider population of patients—including women who’ve survived cancer.

“Uterus transplant is about providing a new choice,” Dr. O’Neill concludes. “It’s all about women and men creating families. This is not to diminish adoption or use of a gestational career, because these are great options, too, but I think that if there is the potential for a new treatment or option, we should offer women the choice and let them decide.”

About this Blog

The Penn Physician Blog is a resource for health care professionals featuring Penn Medicine physicians and their research, innovations, programs and events. 

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