Uterine Transplant for Infertility

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Baylor Research Institute

Must not be taking: Tacrolimus, Thymoglobulin, CellCept

Disqualifiers: Diabetes, Hypertension, Cancer, Obesity, 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 help women unable to conceive due to a nonfunctioning uterus. The plan involves performing a uterine transplant (also known as uterus transplantation or UTx) from a donor, either living or deceased, followed by in-vitro fertilization (IVF) to achieve pregnancy. Interested women should have functioning ovaries but lack a uterus or have a nonfunctioning one. Participants must be free from certain infections and willing to undergo IVF. The goal is to determine if this approach can result in a successful pregnancy and birth. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could transform fertility options for women without a working uterus.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have a known hypersensitivity to certain medications like Tacrolimus, Thymoglobulin, or CellCept, you may not be eligible to participate.

What prior data suggests that uterine transplantation is safe for treating absolute uterine infertility?

Research has shown that uterine transplants have been somewhat successful. In one study, 67% of 9 patients who underwent the procedure gave birth. However, not all transplants worked as hoped. Two patients experienced graft failure, meaning the transplanted uterus didn't function properly.

Further findings indicate that about 74% of uterine transplants remained functional one year after surgery. Among those whose transplants lasted, 83% resulted in a live birth.

While these results are encouraging, complications like graft failure can occur. This happens when the transplanted organ doesn't work as expected. Prospective participants should consider the potential risks and benefits and stay informed about ongoing research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about uterine transplants for infertility because they offer a groundbreaking option for women who cannot carry a pregnancy due to uterine factor infertility. Unlike traditional methods such as surrogacy or adoption, a uterine transplant allows a woman to potentially experience pregnancy and childbirth herself. This procedure involves transplanting a uterus from either a living or deceased donor, which is not only innovative but also opens up new possibilities for women who previously had limited options. Additionally, it taps into the body’s own reproductive system post-transplant, offering a more natural approach compared to existing alternatives.

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

Research has shown that uterine transplantation, the treatment under study in this trial, offers a promising option for women unable to have children due to uterine issues. In one study with 20 participants, 70% of the women who received a transplant had at least one successful birth. Another report found that 74% of the transplants were successful, with 36.3% of women becoming pregnant and 22% having a baby per embryo transfer. Uterine transplantation has been successfully used worldwide, aiding women who cannot conceive due to a non-functioning uterus. This procedure offers hope to those wishing to experience pregnancy and childbirth. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for women aged 20-35 with absolute uterine infertility, who have functioning ovaries but no uterus due to congenital absence or surgical removal. Participants must be HPV negative, free from certain STIs, and able to fund assisted reproduction services. They should not have a BMI over 30, any substance abuse history in the past year, diabetes, uncontrolled hypertension, active infections or other medical conditions that increase risk.

Inclusion Criteria

A subject who is negative for Gonorrhea, Chlamydia, and Syphilis

Willing to undergo in-vitro fertilization and medically cleared for in-vitro fertilization

Evaluated by a fertility specialist and determined to have good ovarian reproductive potential and ability to carry fetus to term

Exclusion Criteria

Subject who has alcohol or drug abuse within 12 months of screening

Subject who is seropositive for HIV, HBV, HCV

Subject with technical obstacles as per anatomical malformations, which pose a high surgical risk in the judgment of the investigator

Timeline for a Trial Participant

Pre-transplant/Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplant/Recovery

Participants undergo uterine transplantation and recovery from the procedure

6-12 weeks

Embryo transfer/Pregnancy

Embryo transfer is performed and participants are monitored for pregnancy

Up to 2 years

Delivery/Explant

Participants undergo delivery via cesarean section and potential explant of the uterus

Varies based on pregnancy outcome

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years post-transplant

What Are the Treatments Tested in This Trial?

Interventions

• Uterine Transplant

Trial Overview The study tests uterine transplants from living or deceased donors in women with absolute uterine infertility aiming for a successful pregnancy and live birth. It follows a model based on previous Swedish research and involves subsequent in-vitro fertilization procedures after transplantation.

How Is the Trial Designed?

Group I: Uterine Transplant Experimental Treatment 1 Intervention

Women will undergo uterine transplantation after IVF. Donor uterus will be from either a living donor or cadaveric.

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?

Baylor Research Institute

Lead Sponsor

Trials

210

Recruited

205,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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) 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]

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]

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]

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. 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 ...

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. 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).

6. 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 ...