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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for women unable to have children due to Absolute Uterine Factor Infertility (AUFI), which involves a uterine transplant. In this procedure, a uterus from a living or deceased donor is transplanted to a woman with AUFI. The goal is to enable these women to experience pregnancy and childbirth. Women with AUFI who have at least one functioning ovary and are open to in-vitro fertilization may be suitable candidates for this study. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could transform fertility options for women with AUFI.

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 prior data suggests that this uterine transplant technique is safe for treating AUFI?

Research shows that uterine transplants can be a promising option for women unable to have children due to Absolute Uterine Factor Infertility (AUFI). Studies indicate that about 74% of transplanted uteruses function well in the recipient's body. However, not every transplant results in a live birth.

One study found a live birth rate of 67%, while another reported an 83% live birth rate among women whose transplanted uterus remained healthy. This indicates that while the procedure is often successful, difficulties can still arise. Some women experience graft failure, where the transplanted uterus does not function as expected.

Overall, uterine transplants have been successfully performed for many women worldwide, resulting in the birth of more than 30 children. While the procedure is promising, potential participants should consider these factors and discuss them with their healthcare providers. ^{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 conceive due to uterine factor infertility, a condition where the uterus is either absent or non-functional. Unlike traditional options like surrogacy or adoption, uterine transplants provide the opportunity for a woman to carry and give birth to her own child. This procedure involves transplanting a uterus from either a living or deceased donor, which is a remarkable advancement in reproductive medicine. The potential for women to experience pregnancy and childbirth themselves, despite previous infertility, is what makes this treatment truly unique and promising.

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

Studies have shown that uterine transplants can successfully help women unable to have children due to Absolute Uterine Factor Infertility (AUFI). Research indicates that about 70-74% of these transplants are successful. After a successful transplant, approximately 36.3% of embryo transfers result in pregnancy, and about 22% lead to a live birth. To date, 34 children have been born to mothers who received a uterine transplant from a living donor. This treatment, offered in this trial, provides hope for women who previously only had the options of adoption or using a surrogate. ^{1 2 3 4 6}

Who Is on the Research Team?

John Goss, M.D.

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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. 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. 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).

5. 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.

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 ...