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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist women who cannot have children due to uterine issues. The treatment involves transplanting a healthy uterus from a donor into the recipient, aiming to enable these women to carry a pregnancy to term. Women who have been told they cannot have children due to uterine problems and have frozen embryos are ideal candidates. The trial also seeks women who have completed their own families and are interested in donating their uterus. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could transform fertility options for women with uterine issues.

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.

What prior data suggests that uterine transplantation is safe for women with uterine factor infertility?

Research has shown that uterine transplants are generally safe and well-tolerated. Studies indicate that about 74% of these transplants succeed, meaning most women who receive a uterine transplant do well. However, complications such as infection or rejection of the transplanted uterus can occur.

Long-term studies have demonstrated that uterine transplants can lead to successful pregnancies. Approximately 36.3% of embryo transfers result in pregnancy, and around 22% lead to a live birth per embryo transfer.

Overall, while this treatment offers hope for those unable to conceive due to uterine issues, potential participants should be aware of both the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Uterine transplantation is unique because it offers a groundbreaking solution for women with uterine factor infertility, a condition where the uterus is absent or non-functional. Unlike traditional treatments like surrogacy or adoption, this method allows women to carry and give birth to their own biological children. Researchers are excited about this approach because it directly addresses the root cause of infertility by providing a functional uterus, potentially transforming the lives of women who previously had limited options for having children.

What evidence suggests that uterine transplant might be an effective treatment for uterine factor infertility?

Research has shown that uterine transplants, the treatment under study in this trial, can be a promising option for women unable to have children due to uterine issues. Studies indicate a success rate of about 70-74% for these transplants, often enabling women to attempt pregnancy. Among those with a successful transplant, approximately 83% have had a live birth. The chance of having a baby per embryo transfer ranges from 22-36%, suggesting a good possibility of pregnancy through this method. Overall, these findings suggest that uterine transplants could offer hope to women unable to carry a pregnancy otherwise. ^{1 2 4 6 7}

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

Has current health insurance for Living Donor Participant

Compatible blood type with recipient for Living Donor Participant

Negative flow cytometric crossmatch with recipient 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

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12109914/

Uterine Transplantation: Advances, Challenges, and ... The UTx success rate was 74.0%; clinical pregnancy rate (CPR) and live birth rates (LBR) per embryo transfer (ET) were 36.3% and 22.0%, ...

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2822479

Uterus Transplant in Women With Absolute Uterine-Factor ... Findings In this series of 20 participants, uterus allograft was successful in 70% of recipients and was associated with at least 1 live birth ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02573415

Study Details | NCT02573415 | Uterine Transplantation for ... Framing the diagnosis and treatment of absolute uterine factor infertility: Insights from in-depth interviews with uterus transplant trial participants.

4. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/the-first-five-years-of-uterus-transplantation-in-the-united-states

The First Five Years of Uterus Transplantation in the United ... Study results and the impact of collaboration · A one-year graft survival of 74% · A live-birth rate of 83% among recipients with a viable graft ...

5. southcarolinablues.com southcarolinablues.com/web/public/brands/medicalpolicyhb/external-policies/uterus-transplantation-for-absolute-uterine-factor-infertility/

Uterus Transplantation for Absolute Uterine Factor Infertility Two systematic reviews of interim trial data have reported live birth success estimates exceeding 60% overall and 80% among transplant attempts with surgical ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34636769/

Uterus transplantation worldwide: clinical activities and ... Summary: UTx has proven to be a successful treatment for uterine factor infertility at several centers around the world. The modest success rate ...

7. eujtransplantation.com eujtransplantation.com/article/view/533

Uterus transplantation: current status in 2024 Abstract. Uterus transplantation (UTx) has evolved as an effective treatment for women with absolute uterine-factor infertility (AUFI).