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

10 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Uterus Transplant for Infertility?

Research shows that uterus transplantation is being explored as a treatment for women with uterine-factor infertility, allowing them to potentially carry and give birth to their own children. Initial trials, including the first 10 cases in the Czech trial, indicate that this treatment is progressing and may become a viable option for those affected by this type of infertility. ^{1 2 3 4 5}

Is uterus transplant generally safe for humans?

The available research does not specifically address the safety of uterus transplants, but it does highlight that adverse events can occur in gynecological procedures, with some being avoidable and often minor. The risk of complications may increase with age and existing health conditions. ^{6 7 8 9 10}

How is uterus transplant different from other treatments for infertility?

Uterus transplant is unique because it is the first treatment that allows women with absolute uterine infertility (absence or severe dysfunction of the uterus) to potentially carry and give birth to their own biological children. Unlike other options like surrogacy or adoption, it involves transplanting a uterus from a donor, which is a complex and experimental procedure. ^{1 11 12 13 14}

What is the purpose of this trial?

This feasibility study aims to enroll ten subjects who will undergo deceased donor uterine transplantation at Cleveland Clinic. We estimate that fifty to one hundred patients with uterine factor infertility will need to be screened to identify 10 appropriate subjects. There are seven phases involved in this study: Primary and Secondary Screening, Medical Evaluation, IVF, Transplantation, Embryo Transfer, Pregnancy/Delivery and Follow up

Research Team

Koji Hashimoto, MD, PhD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

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

3. England pubmed.ncbi.nlm.nih.gov

Human uterus transplantation in focus. [2017]

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

Uterine Transplantation: A Survey of Perceptions and Attitudes of American Reproductive Endocrinologists and Gynecologic Surgeons. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Uterus transplantation: ethical and regulatory challenges. [2014]

6. England pubmed.ncbi.nlm.nih.gov

Adverse events in gynaecology at King Edward VIII Hospital, Durban, South Africa. [2015]

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

Clinical outcome monitoring in a reproductive surgery unit: a prospective cohort study in 796 patients. [2009]

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

Harnessing a health information exchange to identify surgical device adverse events for urogynecologic mesh. [2021]

9. Korea (South) 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. [2019]

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

Hysteroscopic morcellation: review of the manufacturer and user facility device experience (MAUDE) database. [2022]

11. France pubmed.ncbi.nlm.nih.gov

[Uterine transplantation: a treatment for absolute uterine infertility]. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Livebirth after uterus transplantation. [2022]

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

Uterus transplantation in the treatment of female infertility: the pathologists perspective. [2022]

14. Australia pubmed.ncbi.nlm.nih.gov

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