Uterine Transplant for Uterine Factor Infertility

(UNTIL Trial)

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Pennsylvania

Must not be taking: Immunosuppressants, Heparin, Aspirin

Disqualifiers: Hypertension, Diabetes, Psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Options for childbearing are limited for the thousands of women in the United States who suffer from absolute uterine factor infertility. Uterine transplantation is an emerging treatment that provides hope for these individuals. In the Penn UNTIL trial, the investigators plan to perform uterus transplants on five women who will ultimately undergo embryo transfer, pregnancy, delivery, and then transplant hysterectomy. This trial is accepting women in need of a transplant and also women who are interested in being a live donor. For more information please visit: https://clinicalresearch.itmat.upenn.edu/clinicaltrial/4821/congenital-abnormalitiesfemale-infertility-penn-ut/

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you have allergies or intolerances to certain medications like immunosuppressive agents, you may not be eligible to participate.

How is uterine transplant different from other treatments for uterine factor infertility?

Uterine transplant is unique because it involves surgically replacing a non-functioning or absent uterus with a healthy one from a donor, allowing women with uterine factor infertility to potentially carry a pregnancy. Unlike other treatments, which may focus on assisted reproductive technologies, this approach directly addresses the lack of a functional uterus. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Uterine Transplant for Uterine Factor Infertility?

Research shows that uterine transplantation (UTx) is becoming a promising treatment for women with uterine-factor infertility, with initial trials reporting successful procedures and potential for healthy live births. ^{1 2 6 7 8}

Who Is on the Research Team?

Kathleen E O'Neill, MD, MTR

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for women aged 21-40 with uterine factor infertility (UFI) who have intact ovaries and live in the Philadelphia area. They must understand English, have a BMI under 35, adequate social support, and be willing to follow the trial procedures. Donors can be women aged 18-50 with compatible blood types and normal uterine anatomy who are also from the Philadelphia area.

Inclusion Criteria

Compatible blood type with recipient for Living Donor Participant

Negative flow cytometric crossmatch with recipient for Living Donor Participant

Has current health insurance for Living Donor Participant

Exclusion Criteria

I have not had a serious infection in the last 3 months.

I quit smoking at least 3 months ago and am considering a uterine transplant.

History of significant psychiatric illness for Uterine Transplant Recipient Participant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant Preparation

Participants undergo ovarian stimulation, oocyte retrieval, and create embryos for future use

4-6 weeks

Transplantation

Participants receive a donor uterus and are monitored for complications such as infection and rejection

12 months

Pregnancy Attempt

If the graft is stable, embryos are transferred to achieve pregnancy, monitored by a Maternal Fetal Medicine specialist

Up to 39 weeks per pregnancy

Follow-up

Participants are monitored for safety and effectiveness after delivery, including post-hysterectomy assessment

2 years post-hysterectomy

What Are the Treatments Tested in This Trial?

Interventions

• Uterine Transplant

Trial Overview The University of Pennsylvania UNTIL trial is testing uterus transplants as a treatment for absolute uterine factor infertility. Women will receive a transplant, undergo embryo transfer leading to pregnancy and delivery, followed by removal of the transplanted uterus.

How Is the Trial Designed?

Group I: Uterine Transplantation Experimental Treatment 1 Intervention

Women will undergo extensive medical and psychological screening. Five women that meet all inclusion and exclusion criteria will undergo ovarian stimulation, oocyte retrieval and will create embryos that will be stored for future use. Women will then undergo uterine transplantation from a donor. Following transplant women will be closely monitored for complications (including infection and rejection). If no complications arise, or complications that do arise can be treated, attempts at pregnancy will begin approximately 6 months after transplant. Pregnancy in the setting of uterine transplant requires directly placing embryos directly into the uterus.

Uterine Transplant is already approved in United States, European Union for the following indications:

Approved in United States as Uterus Transplantation for:

• Absolute Uterine Factor Infertility (AUFI)

Approved in European Union as Uterus Transplantation for:

• Absolute Uterine Factor Infertility (AUFI)

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

In a study of 10 uterus transplant procedures (5 from live donors and 5 from deceased donors), the graft survival rate was 70% at one year, indicating a promising mid-term viability for this treatment of uterine-factor infertility.

The study resulted in three live births, demonstrating the potential effectiveness of both live and deceased donor uterus transplants, while also highlighting challenges such as a 63% incidence of vaginal anastomotic stenosis and cases of severe acute rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Uterus Transplantation from Living and Deceased Donors: The Interim Results of the First 10 Cases of the Czech Trial. Fronek, J., Kristek, J., Chlupac, J., et al.[2021]

Uterine transplantation (UTx) is a promising treatment for women with uterine factor infertility, aiming to replace a non-functioning or absent uterus.

Since the first human UTx attempt 10 years ago, extensive research has focused on improving surgical techniques, understanding ischaemia-reperfusion injury, managing immunosuppression, and enhancing fertility outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uterine transplantation: one human case followed by a decade of experimental research in animal models. Hanafy, A., Diaz-Garcia, C., Olausson, M., et al.[2022]

The first clinical uterus transplantation trial showed that after 6 months, 7 out of 9 transplanted uteri remained viable and allowed for regular menstrual cycles, indicating the procedure's potential effectiveness for treating absolute uterine-factor infertility.

No immediate complications were reported during surgery, and mild rejection episodes in four patients were successfully managed with corticosteroids, demonstrating the safety of the low-dose immunosuppression protocol used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First clinical uterus transplantation trial: a six-month report. Brännström, M., Johannesson, L., Dahm-Kähler, P., et al.[2022]

Uterus transplantation (UTx) is evolving into a clinical treatment for absolute uterine factor infertility (AUFI), with a focus on developing standardized protocols for selecting donors and recipients to maximize the chances of a healthy live birth.

Current eligibility criteria for recipients are limited to healthy women of childbearing age with AUFI who can undergo in-vitro fertilization (IVF), while donor selection requires a history of term birth and a healthy uterus, indicating a thorough evaluation process to minimize risks and improve success rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uterus transplantation - donor and recipient work-up. Johannesson, L., Wall, A.[2021]

Uterine transplantation (UTx) has successfully resulted in the birth of 12 healthy babies from over 40 procedures conducted between 2014 and 2018, demonstrating its potential as a treatment for absolute uterine factor infertility (AUFI).

While the surgical procedure for UTx is feasible and no uteri have been lost due to rejection, complications such as posttransplant partial stenosis can occur, affecting embryo transfer and menstrual flow, highlighting the need for careful donor selection and surgical optimization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uterine transplantation in an era of successful childbirths from living and deceased donor uteri: Current challenges. Chmel, R., Pastor, Z., Matecha, J., et al.[2021]

Uterine transplantation (UTx) in cynomolgus monkeys showed potential for temporary recovery of uterine function, including menstruation, when using a three-drug immunosuppressive regimen.

In contrast, a two-drug regimen led to uterine atrophy due to ischemia, indicating that the choice of immunosuppressants is critical for the success of UTx and recovery of uterine function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uterus allotransplantation in cynomolgus macaque: a preliminary experience with non-human primate models. Kisu, I., Mihara, M., Banno, K., et al.[2014]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Human Uterus Transplantation from Living and Deceased Donors: The Interim Results of the First 10 Cases of the Czech Trial. [2021]

2. Australia pubmed.ncbi.nlm.nih.gov

Uterine transplantation: one human case followed by a decade of experimental research in animal models. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

First clinical uterus transplantation trial: a six-month report. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Human uterus transplantation in focus. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Uterus transplantation - donor and recipient work-up. [2021]

6. Czech Republic pubmed.ncbi.nlm.nih.gov

Uterine transplantation in an era of successful childbirths from living and deceased donor uteri: Current challenges. [2021]

7. Australia pubmed.ncbi.nlm.nih.gov

Uterus allotransplantation in cynomolgus macaque: a preliminary experience with non-human primate models. [2014]

8. United States pubmed.ncbi.nlm.nih.gov

Psychological Issues Associated With Absolute Uterine Factor Infertility and Attitudes of Patients Toward Uterine Transplantation. [2016]