Uterus transplantation to help women with infertility

OPRTUNTI: Offering Potential for Reproduction Through Transplantation of Uterus iN the Treatment of Infertility

This study is testing if transplanting a uterus from a living donor can help women who don't have a uterus become pregnant and have healthy babies.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 38 Years
• Sex: Female
• Sponsor: Johns Hopkins University (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT05646992 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to treat uterine factor infertility through uterus transplantation from living donors to women who lack a uterus. The study involves multiple stages, including screening, in vitro fertilization (IVF), and embryo cryopreservation, followed by the surgical transplantation of the uterus. Participants will take immunosuppressive medications to maintain the health of the transplanted uterus, which is intended to be temporary, lasting about five years, after which the uterus will be removed following childbirth. The ultimate goal is to enable successful pregnancies and the birth of healthy children.

Who should consider this trial

Good fit: Ideal candidates are genotypic females aged 18-38 with uterine factor infertility who have a strong desire to become pregnant and have or are willing to create cryopreserved embryos.

Not a fit: Patients who do not have uterine factor infertility or those who are outside the age range of 18-38 years may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide women with uterine factor infertility the opportunity to experience pregnancy and childbirth.

How similar studies have performed: Other studies on uterus transplantation have shown promising results, indicating that this approach is gaining traction in the medical field.

Eligibility criteria

INCLUSION CRITERIA -

Recipient Inclusion Criteria:

* Genotypic female of any race, color, or ethnicity.
* Uterine factor infertility.
* Aged 18-38 years at time of egg retrieval.
* Strong desire to undergo uterus transplant in order to become pregnant and give birth to a child.
* Embryo cryopreservation with embryos located at Johns Hopkins:

  * Has a minimum of 4-8 cryopreserved normal embryos following Preimplantation Genetic Screening (PGS-screening).

OR o Is willing to undergo egg retrieval, in vitro fertilization, and PGS-screening to cryopreserve a minimum of 4-8 normal embryos.

* Willingness to undergo embryo implantation after uterus transplantation to achieve pregnancy.
* In the opinion of the study team, makes a reasonable effort to identify and refer her own potential uterus donor to the study team.
* Completes the protocol informed consent form.
* Non-smoker, defined by having never smoked or having quit \>6 consecutive months prior to screening.
* No co-existing medical condition which, in the opinion of the study team, could affect the immunosuppression protocol, surgical procedure, or ability to be pregnant or bear a child. (See Donor and Recipient Exclusion Criteria below. If the condition is amenable to treatment, the study team must agree that said condition should not significantly enhance the surgical risks of uterus transplantation.)
* Negative serum pregnancy test.
* Blood type compatible with donor.
* Negative crossmatch with donor.
* Patient agrees to comply with the protocol and states a dedication to the treatment regime.
* Agrees to uterus explanation following birth of a child and or 5 years without successful pregnancy.

Donor Inclusion Criteria:

* Genotypic female with an intact uterus.
* Medical history includes known successful pregnancy (e.g., gravid uterus).
* Aged 25 - 65 years.
* Consents to uterus donation and required pre-donation screening.
* For females of child-bearing potential: Negative serum pregnancy test.
* Blood type compatible with recipient.
* Negative crossmatch with recipient.

Donor and Recipient Inclusion Criteria:

* USA citizen or equivalent.
* No co-existing psycho-social problems (i.e., alcoholism, drug abuse).
* BMI ≤35

  o A higher BMI may be accepted at the discretion of the study team.
* Negative for HIV at transplant.
* Negative for malignancy for past 5 years.

EXCLUSION CRITERIA-

Donor and Recipient Exclusion Criteria:

* Positive for any of the following conditions:

  * Insulin-dependent diabetes mellitus.
  * Untreated sepsis.
  * HIV (active or seropositive).
  * Active tuberculosis.
  * Active Hepatitis B infection.
  * Active Hepatitis C infection.
  * Viral encephalitis.
  * Toxoplasmosis.
  * Current/recent (within 3 months of donation/screening consent) IV drug abuse.
  * Significant cardiac disease
  * Significant vascular disease o
* Sensitized recipients with high levels (50%) of panel-reactive Human Leukocyte Antigens (HLA) antibodies.
* Conditions that may impact the success of the surgical procedure or increase the risk of postoperative complications including inherited coagulopathies like Hemophilia, Von-Willebrand's disease, Protein C and S deficiency, Thrombocythemias, Thalassemias, Sickle Cell disease, etc.
* Mixed connective tissue diseases and collagen diseases that can result in poor wound healing after surgery.
* Severe neurologic deficits.
* Patients considered unsuitable per the consulted Psychiatric/Psychologic appraisal.
* A history of medical non-compliance.

Donor Only Exclusion Criteria:

* Previous injury to the uterus including giving birth by Cesarean section.
* History of radiation therapy to the abdominal area.
* Other medical conditions, as determined by the study physicians, that would preclude donation.

Recipient Only Exclusion Criteria:

• Conditions that, in the opinion of the study team, may expose the recipient to unacceptable risks under immunosuppressive treatment.

Where this trial is running

Baltimore, Maryland

• Johns Hopkins University School of Medicine — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Richard J Redett, MD — Johns Hopkins University
• Study coordinator: Jane Littleton, CRNP, MSN

Conditions Uterine Factor Infertility; Uterus/Transplantation; Uterus/Surgery; Vascularized Composite Allotransplantation; Immunosuppression; Mayer-Rokitansky-Küster-Hauser; Allotransplantation; Humans