Uterus Transplant for Infertility

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Must be taking: Immunosuppressive medications

Disqualifiers: Hypertension, Diabetes, Heart disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help women unable to have children due to uterine issues. It involves transplanting a uterus from a deceased donor to determine if it can enable pregnancy and childbirth. The trial includes several steps, such as IVF (creating embryos in a lab) and the transplant surgery itself. Suitable candidates have either undergone a hysterectomy or were born without a properly functioning uterus. Participants must also be willing to undergo major surgeries and take medications that help the body accept the new uterus. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could transform fertility options for women worldwide.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must be willing to take immunosuppressive medications and follow infection prevention protocols, which might affect your current medication regimen.

What prior data suggests that this uterus transplant is safe for infertility?

Research has shown that uterus transplants are generally safe. In one study, a year after the transplant, 74% of patients had a successful transplant, meaning the new uterus was still functioning well. Among those with a healthy transplant, 83% were able to have a baby.

However, challenges can arise. Some women may experience transplant failure, where the new uterus stops functioning. Others might not be able to carry a pregnancy to term, even if the transplant succeeds.

Overall, earlier studies suggest that while the procedure carries risks, many women have managed it well and have been able to have a child. It's important to consider these factors when thinking about participating. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about uterus transplantation for infertility because it offers a groundbreaking solution for women who cannot conceive due to the absence or dysfunction of a uterus. While traditional options like surrogacy and adoption allow for parenthood, they don't provide the opportunity for a woman to carry and deliver her own child. Uterus transplantation, especially from deceased donors, could enable women to experience pregnancy and childbirth firsthand, which is a significant advancement in reproductive medicine. This approach is particularly promising as it could expand the possibilities of parenthood for women with uterine factor infertility.

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

Research has shown that uterus transplants, the focus of this trial, can assist women unable to have children due to uterine issues. One study found that 74% of transplanted uteruses functioned after one year, with 83% of these women experiencing a successful birth. Another study reported that 36.3% of women became pregnant, and 22% had a successful birth per embryo transfer. These results offer promise for women considering this procedure. ^{1 2 3 5 6}

Who Is on the Research Team?

Koji Hashimoto, MD, PhD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for women aged 21-45 with uterine factor infertility, who've had a hysterectomy or have congenital absence/malformation of the uterus. Participants must be willing to undergo extensive medical procedures including IVF, major surgery, and high-risk pregnancy. They should agree to psychiatric evaluation and take immunosuppressive drugs post-transplant.

Inclusion Criteria

Some women are born without a uterus, while others may have a uterus that is malformed or damaged, preventing pregnancy

You have a specific type of infertility called uterine factor infertility.

Must be willing to undergo a psychiatric and social work pre-transplant evaluation

Exclusion Criteria

I have a history of high blood pressure, diabetes, or major heart, liver, kidney, or brain disease.

I quit smoking more than 3 months ago.

You have a body mass index (BMI) higher than 30, which means you are overweight.

Timeline for a Trial Participant

Primary and Secondary Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits (in-person)

Medical Evaluation

Comprehensive medical evaluation to assess suitability for uterine transplantation

4 weeks

Multiple visits (in-person)

IVF

In vitro fertilization to produce viable embryos prior to uterine transplantation

6-8 weeks

Multiple visits (in-person)

Transplantation

Deceased donor uterine transplantation procedure

1 week

Hospital stay

Embryo Transfer

Transfer of embryos into the transplanted uterus to achieve pregnancy

1-2 weeks

Multiple visits (in-person)

Pregnancy/Delivery

Monitoring of pregnancy and delivery of the child

9 months

Regular prenatal visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Uterus Transplant

Trial Overview The study tests the feasibility of deceased donor uterine transplantation in women unable to carry a pregnancy due to lack of a functional uterus. It involves screening candidates, IVF treatment before transplant, monitoring through potential pregnancy after embryo transfer, and follow-up care.

How Is the Trial Designed?

Group I: Uterus Transplantation Experimental Treatment 1 Intervention

Women will undergo deceased donor uterine transplantation after IVF.

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

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]

In a study of 796 women undergoing reproductive surgery, the overall rate of adverse events (AEs) was 6%, with 12 of these events deemed preventable, highlighting the importance of monitoring for safety in surgical settings.

The duration of surgery was identified as a significant risk factor for AEs, with longer surgeries increasing the likelihood of complications, suggesting that surgical time management could improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome monitoring in a reproductive surgery unit: a prospective cohort study in 796 patients. Bentz, EK., Imhof, M., Pateisky, N., et al.[2009]

An automated search algorithm was developed to effectively identify complications related to urogynecologic mesh surgeries, matching 93% of cases found through manual review of 2874 records.

This method successfully identified complications in 380 of the cases, demonstrating that automated surveillance can enhance the tracking of device-related adverse events in healthcare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harnessing a health information exchange to identify surgical device adverse events for urogynecologic mesh. Ballard, J., Rosenman, M., Weiner, M.[2021]

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 MAUDE database has significant limitations in capturing and standardizing adverse events related to transvaginal mesh, with issues like missing and duplicated reports affecting data quality.

Nearly half of the reports did not identify a source, and at least 28% of the devices reported are no longer available on the market, highlighting the need for improved reporting systems to better assess device safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of the Manufacturer And User Facility Device Experience database that inspired the United States Food and Drug Administration's Reclassification of transvaginal mesh. Sandberg, JM., Gray, I., Pearlman, A., et al.[2019]

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]

Citations

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

Uterus Transplant in Women With Absolute Uterine-Factor ... National US data for infertility treatment in women younger than 35 years using their own ova describe a live birth rate of 68.9% following any ...

2. 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%, ...

3. 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 ...

4. 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.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11327905/

Uterus Transplant in Women With Absolute Uterine-Factor ... National US data for infertility treatment in women younger than 35 years using their own ova describe a live birth rate of 68.9% following any ...

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

Uterus transplantation worldwide: clinical activities and ... The different outcomes of transplanted women include graft failure, as well as graft survival with failure to achieve livebirth, or livebirth(s) ...