Initiation of a Deceased Donor Uterine Transplantation Program at the University of Nebraska Medical Center

NCT02409147 | Withdrawn DMC

• 1 other identifier: 0138-15-FB
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will explore the feasibility of initiating a uterine transplant program at UNMC. Using the procedural templates established by a successful Swedish team, the investigators will identify emotionally and socially stable females of reproductive age with intact ovaries who are unable to gestate a child due to congenital or acquired uterine factor infertility (UFI). Women will be 21 to 35 years of age upon entry into the protocol, with normal ovarian reserve and otherwise healthy for pregnancy. After careful screening, participants will undergo egg harvest, in-vitro fertilization, and embryo cryopreservation using standard methods. Women who successfully complete in vitro fertilization and cryopreservation of at least six embryos will be eligible to receive implantation of a deceased donor uterus. After a period of observation to ensure normal menstrual cycling and graft viability, embryo implantation will be undertaken. Gestations will be carefully monitored by our high-risk pregnancy specialists. Medical research interventions include uterine harvest from a deceased donor, surgical implantation of the organ utilizing standard transplant techniques, careful post-transplant follow-up including immune suppression therapy tailored to minimize fetal compromise, and careful management of pregnancy. After childbearing is complete (at most two gestations), the donor uterus will be removed. In addition, open-ended interviews and written surveys will be conducted to elicit ethical and psychosocial concerns arising from the experience of subjects and their families, health care providers, and the wider community. The investigators intent is to monitor outcomes lifelong for transplant recipients and live-born infants.

Conditions

Uterus Transplant

Outcome Measures

Primary Outcomes (1)

• Successful Uterine Transplant

  A successful uterine transplant surgery will be obtained by deceased-donor graft implantation and take (without rejection) and successful menstruation for a set period. Once stability is achieved, IVF will be performed and close monitoring of a pregnancy will be done. Finally, a successful healthy baby will be delivered via C-section. A successful uterine transplant will accomplish all the previously described metrics

  2 years

Study Arms (1)

Patients

EXPERIMENTAL

Healthy female volunteers wishing to have a childbirth via uterine transplantation

Procedure: Uterine Transplant

Interventions

Uterine Transplant PROCEDURE

Surgical implantation of a deceased donor uterus, induction therapy with thymoglobulin or basiliximab, maintenance immunosuppression with Prograf, Cellcept, and Prednisone. Anti-infective treatment with Bactrim and Valcyte and Nystatin. Anti-platelet therapy with aspirin. IVF per standard protocol. At time of birth: ceasarean section. Ultimately, transplant hysterectomy.

Also known as: Thymoglobulin, Basiliximab, Prograf, Cellcept, Prednisone, Bactrim, Valcyte, Aspirin, Nystatin

Patients

Eligibility Criteria

• Age: 21 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For transplantation, the criteria are as follows:
• Female of reproductive age with intact native ovaries and no medical contraindication to transplantation, including surgical procedure and subsequent immunosuppression, and no medical contraindication to reproduction and gestation in a transplanted uterus. Evaluation for a medical contraindication will be determined by a maternal-fetal medicine specialist at UNMC.
• Diagnosed with either congenital or acquired uterine factor infertility (UFI) and counseled about alternate options for family building including gestational surrogacy and/or adoption and provided access to these alternate services. Acquired circumstances may include nonfunctional uterus and hysterectomy due to benign disease (uterine fibroids, Asherman's syndrome, pelvic infection, postpartum hemorrhage) or gynecologic malignancy of the uterus or cervix. Additionally, UFI may be a result of congenital anomaly of the uterus and uterine agenesis.
• If uterine removal was for uterine or cervical cancer a minimum 5 year recurrence-free time period will be required.
• If MRKH Syndrome (Mayer-Rokitansky-Kuster-Hauser) or Mullerian agenesis is present, the patient has a negative evaluation for other relevant congenital abnormalities (such as a pelvic kidney). Additionally, women with Mulllerian agenesis who have absence of the vagina must have had neovaginal creation surgery prior to uterine transplant in order to allow for embryo transplantation and monitoring of the organ after transplant.
• Ovaries are intact with adequate ovarian reserve as determined by accepted markers including anti-Mullerian hormone level (AMH), astral follicle count and/or early follicular follicle stimulating hormone (FSH) levels.
• Desires a biological child and is unable or unwilling to consider gestational surrogacy, and / or seeks uterine transplantation as a means to experience gestation, with an understanding of the limitations provided by the uterine transplant in this respect.
• Meets psychological evaluation criteria, e.g.,stable, committed relationship with an individual who supports uterine transplant and intends to co-parent; emotionally mature with good coping skills and no significantly adverse mental health history; normal intellect allowing careful analysis of risks and benefits; no evidence of coercion; no significant evidence of previous noncompliance with medical care; no evidence of frank unsuitability for motherhood (e.g., previous conviction for child abuse).
• Likely to comply with medical management, including antirejection immune suppression, frequent follow-up with surgical team, time-sensitive reproductive endocrinology management, high-risk pregnancy management, possible high-risk neonatal management.
• Likely to be able to accommodate potential adverse outcomes such as loss of graft, inability to conceive, loss of pregnancy, adverse fetal or neonatal outcome.
• Willing to consider transplant hysterectomy or termination of pregnancy if medically necessary.
• Willing to undergo oocyte harvest and in-vitro fertilization prior to transplantation, with at least six viable embryos cryopreserved in anticipation of post-transplant implantation.
• Financially able to cover anticipated expenses of assisted reproductive services, either through third party coverage or through personal assets.

Sponsors & Collaborators

• University of Nebraska: lead

MeSH Terms

Interventions

thymoglobulin; Basiliximab; Tacrolimus; Mycophenolic Acid; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination; Valganciclovir; Aspirin; Nystatin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols

Study Officials

• Alexander T Maskin, MD

  UNMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2015
• First Posted: April 6, 2015
• Study Start: January 1, 2016
• Primary Completion: July 24, 2018
• Study Completion: July 24, 2018
• Last Updated: August 15, 2023

Record last verified: 2023-08