Uterine Transplant for Infertility

Overseen By Becky M Johnson

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: John Goss

Must not be taking: Tacrolimus, Thymoglobulin, Everolimus

Disqualifiers: Diabetes, Hypertension, Cancer, 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

Trial Summary

What is the purpose of this trial?

This trial aims to help women by transplanting a donor uterus. These women cannot carry a pregnancy because their uterus is either missing or not working properly. The transplanted uterus allows them to try to become pregnant. This method has been successfully introduced as a treatment option for women with this condition.

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, if you have a known hypersensitivity to certain medications like Tacrolimus, Thymoglobulin, or Everolimus, you may be excluded from the trial.

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

Research shows that uterine transplantation (UTx) is being developed as a treatment for women who cannot have children due to problems with their uterus. Early results from trials and studies, including animal models, suggest that UTx can lead to successful pregnancies and healthy births. ^{1 2 3 4 5}

Is uterine transplantation generally safe for humans?

The available research does not provide specific safety data on uterine transplantation, but it highlights the importance of adverse event reporting systems in organ and tissue transplantation to ensure safety and quality. ^{6 7 8 9 10}

How is uterine transplant different from other treatments for 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 infertility treatments, which often focus on assisting conception, this procedure addresses the root cause by providing a functional uterus. ^{2 4 11 12 13}

Research Team

John Goss, M.D.

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for women aged 20-40 with Absolute Uterine Factor Infertility (AUFI) due to a missing or nonfunctional uterus, who have at least one working ovary and are willing to undergo in-vitro fertilization. They must not smoke, abuse substances, or have recent cancer history. Women over 65, those with significant health risks like diabetes or hypertension, and anyone unable to meet study requirements are excluded.

Inclusion Criteria

I have tested negative for Gonorrhea, Chlamydia, Syphilis, and do not have active bacterial vaginosis or a yeast infection.

I am a woman with AUFI and have at least one working ovary.

Subjects meeting psychological recipient criteria

Exclusion Criteria

Subjects seropositive for HIV, HBV, HCV

I cannot have in-vitro fertilization or am not approved for a transplant.

Subjects with alcohol or drug abuse within 12 months of screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4-8 weeks

Multiple visits for consultations and evaluations

Pre-transplant Evaluation

Consultations, tests, and procedures to evaluate if the recipient is prepared for uterine transplant

4-6 weeks

Multiple visits for evaluations and procedures

Uterine Transplantation

Uterine transplantation from a living or deceased donor, followed by monitoring for infection, rejection, and other complications

3 months

Frequent monitoring visits post-operative

Embryo Transfer and Pregnancy Monitoring

Preparation of the uterus for embryo transfer, followed by monitoring for pregnancy establishment and progression

11 weeks

Regular visits for hormone monitoring and ultrasound evaluations

Follow-up

Participants are monitored for safety and effectiveness after delivery, with the option to discuss a second pregnancy or explant

60 days post-delivery

Follow-up visits to evaluate health of the newborn and mother's candidacy for second pregnancy

Treatment Details

Interventions

• Uterine Transplant

Trial Overview The trial is testing uterine transplants from living or deceased donors as a treatment for AUFI in women who wish to give birth. The goal is successful pregnancy and live birth post-transplantation. Ten participants will receive transplants after ensuring they have viable embryos through IVF.

Participant Groups

Group I: Uterine Transplant Experimental Treatment 1 Intervention

uterus transplantation from living or deceased donor.

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?

John Goss

Lead Sponsor

Trials

1

Recruited

10+

Findings from Research

This study successfully achieved pregnancy in a rabbit following allogeneic uterine transplantation (UTx), marking a significant step in exploring UTx as a treatment for absolute uterine factor infertility.

Despite initial signs of pregnancy, the study observed fetal resorption, indicating that while UTx can lead to conception, challenges remain in sustaining a viable pregnancy, as evidenced by the reduction in gestation sac size and eventual loss of the fetus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achieving an early pregnancy following allogeneic uterine transplantation in a rabbit model. Saso, S., Petts, G., David, AL., et al.[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 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]

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]

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]

The study successfully mapped 11 different adverse event reporting systems related to the donation and transplantation of cells, organs, and tissues, providing a comprehensive overview of the terminology used in each system.

This scoping review, which analyzed 24 articles and materials, aims to improve future reporting systems by highlighting key features and terms, ultimately enhancing safety and efficacy in transplantation practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Reporting Systems in Cells, Organs, and Tissues Donation and Transplantation: Scoping Review. Schuantes-Paim, SM., Wachholz, LF., Knihs, NDS., et al.[2023]

In the UK, a robust system for reporting and analyzing serious adverse events related to ocular tissue transplantation has been established, ensuring safety and quality in accordance with EU regulations.

The most significant adverse reactions identified in this system are endophthalmitis (0.58%) and primary graft failure (0.3%), highlighting the importance of ongoing monitoring and analysis to improve transplantation services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A UK scheme for reporting serious adverse events and reactions associated with ocular tissue transplantation. Kaye, S., Baddon, A., Jones, M., et al.[2016]

Patient safety incidents occur in about 10% of hospital admissions in the UK, and assisted conception may be equally vulnerable to such incidents, highlighting the need for improved safety measures in this field.

To enhance patient safety in assisted conception, established methodologies like root cause analysis and failure mode effects analysis should be implemented, along with process mapping to better understand and mitigate risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk management in IVF. Kennedy, CR., Mortimer, D.[2007]

Assisted reproduction techniques (A.R.T.) are associated with higher rates of complications such as preterm birth, low birthweight, and perinatal mortality compared to the general population, highlighting the need for thorough evaluation.

To ensure the long-term safety of A.R.T., it is crucial for centers to maintain standardized records of all procedures and outcomes, which can facilitate future studies on potential risks, including ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Assisted reproduction vigilance]. Bréart, G., de Mouzon, J.[2006]

Frozen embryo transfer (FET) during an artificial cycle (AC) is associated with a higher risk of ectopic pregnancy and lower live birth rates compared to natural cycles with luteal phase support (NC-LPS), based on a retrospective study of FET cycles from 2013 to 2016.

Obstetric outcomes also showed that AC-FET increased the risk of hypertension disorders and cesarean sections, while multiples born from NC-LPS had better birth weights and gestational ages compared to those from AC-FET.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased pregnancy complications following frozen-thawed embryo transfer during an artificial cycle. Jing, S., Li, XF., Zhang, S., et al.[2020]

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]

The registry has documented 45 uterus transplantation (UTx) procedures, primarily from live donors (78%), with a notable live birth rate of 35.8% per embryo transfer, indicating the potential efficacy of UTx in treating infertility.

Postoperative complications were observed in 20% of live donors and 24% of recipients, with rejection episodes being more common in the early months after transplantation, highlighting the importance of monitoring and managing these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Registry of the International Society of Uterus Transplantation: First Report. Brännström, M., Tullius, SG., Brucker, S., et al.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Achieving an early pregnancy following allogeneic uterine transplantation in a rabbit model. [2021]

2. 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]

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

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

4. Australia pubmed.ncbi.nlm.nih.gov

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

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

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

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

Adverse Events Reporting Systems in Cells, Organs, and Tissues Donation and Transplantation: Scoping Review. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

A UK scheme for reporting serious adverse events and reactions associated with ocular tissue transplantation. [2016]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Risk management in IVF. [2007]

9. Netherlands pubmed.ncbi.nlm.nih.gov

[Assisted reproduction vigilance]. [2006]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Increased pregnancy complications following frozen-thawed embryo transfer during an artificial cycle. [2020]

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

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

12. Australia pubmed.ncbi.nlm.nih.gov

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

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

Registry of the International Society of Uterus Transplantation: First Report. [2023]