Uterus Transplantation From Live Donors and From Deceased Donors - Clinical Study (UTxLD/DBD)

February 25, 2019 updated by: Jiri Fronek, Institute for Clinical and Experimental Medicine
Uterus transplantation (UTx) is the only causative treatment for congenital or acquired uterus absence. Individual cases of UTx from a live donor (LD UTx) with healthy child birth performed so far showed favourable outcomes. The present study will include both LD UTx and UTx from deceased donors after brain death (DBD UTx). The aim is treatment of uterine infertility by UTx. It is is an ethically justifiable life-promoting transplantation. Twenty UTx will be performed in 2 parallel arms: 10 LD UTx and 10 DBD UTx. Immunosuppression will be administered. Phases of the UTx procedure are: in vitro fertilization - cryopreservation of embryos - uterus retrieval - UTx - follow up - embryo transfer - pregnancy - child birth - later graft hysterectomy - life long follow up. Introduction of UTx into clinical practice may enable women with uterine infertility to have their own children.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Introduction: Uterus transplantation (UTx) is the only causative treatment for congenital or acquired uterus absence, i.e. absolute uterine factor infertility (AUFI). Feasibility of uterus transplantation from o live donor and possibility of healthy child birth have been proven in previous clinical study in Sweden. The present study is supposed to extend the swedish experience by including UTx from both live donors and from deceased donors after brain death.

Aim: Treatment of absolute uterine factor infertility that has no other therapy option by uterus transplantation. Extending basic knowledge on UTx. Possible introduction of UTx into clinical practice.

Indications: UTx can be offered to patients with congenital uterus absence - aplasia uteri et vaginae, also called Mullerian aplasia or Rokitansky-Mayer-Kuster-Hauser syndrome (RMKH), in whom previous neo-vagina was created. UTx can be performed also in women with acquired uterus absence on the basis of previous hysterectomy e.g. for myomas, endometriosis, post-partum bleeding, cervical cancer, uterus malformations or intrauterine adhesions. Ovarian function must be preserved and stable male partner is required for in vitro fertilization (IVF).

Ethics: Uterus retrieval from a deceased brain-dead donor does not endanger retrieval of other life-saving organs. Live donor does not loose a vitally important organ. The only alternative is adoption of a child. Surrogacy is illegal in many european countries. UTx is the only causative treatment of AUFI. It is is an ethically justifiable life-promoting transplantation. UTx improves quality of live of both the recipient and the live donor by giving an opportunity to have an own child. Board certification for this study was obtained from the Ministry of Health of the Czech Republic and from the local Ethics Committee.

Methods: Twenty UTx will be performed in total in 2 parallel arms: 10 UTx from a live donor (LD UTx) and 10 UTx from a deceased brain-dead donor (DBD UTx). Patients who have no suitable live donor will be wait-listed for a deceased donor. Compatible blood group and negative cross-match test is required. AB0 incompatible or pair exchange transplantations are also possible. Donors and recipients will be examined by clinical, laboratory and imaging methods. All diagnostic and therapeutic procedures will be performed according to a protocol. Risk and benefit will be assessed by a multi-disciplinary team. Informed consent will be signed. Time period between UTx and embryo transfer is supposed to be about 1 year depending on condition of the recipient and the graft, e.g. level of immunosuppression, rejection or infection episodes. Adverse events will be monitored and addressed. Number of possible pregnancies and child births is estimated to be up to 2. The uterus graft will be removed in the end. Overall time interval of keeping the uterus graft in situ and exposure to immunosuppressive therapy is estimated to be up to 5 years.

Immunosuppression: Induction immunosuppression is based on thymoglobuline and corticosteroids. Maintenance immunosuppression is based on tacrolimus, mycophenolate and corticosteroids. Temporary anti-infective prophylaxis will be administered. Minimalization of immunosuppression is needed before pregnancy (monotherapy with tacrolimus). Protocol cervix biopsies to look for possible rejection will be performed. Immunosuppression will be discontinued after graft hysterectomy.

Phases of the UTx procedure: in vitro fertilization (IVF phase I) - cryopreservation of embryos - uterus retrieval from a live donor or from a deceased donor - orthotopic uterus transplantation with open technique - follow up period - embryo transfer (IVF phase II) - pregnancy - child birth via Cesarian section - later graft hysterectomy - life long follow up.

Merit: Individual cases of uterus transplantation performed so far showed favourable outcomes. Introduction of UTx into clinical practice may enable women with uterine infertility to have their own children.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jiri Fronek, Assoc Prof
  • Phone Number: +420 26 136 4105
  • Email: jifr@ikem.cz

Study Contact Backup

  • Name: Renata Zamecnikova, Bc
  • Phone Number: +420 26 136 4105, 5300
  • Email: zamr@ikem.cz

Study Locations

  • Czechia
      • Prague, Czechia, 14021
        • Recruiting
        • Institute for Clinical and Experimental Medicine
        • Contact:
          • Jiri Fronek, Assoc Prof
          • Phone Number: +420 26 136 4105
          • Email: jifr@ikem.cz
        • Contact:
          • Renata Zamecnikova, Bc
          • Phone Number: +420 26 136 4105
          • Email: zamr@ikem.cz
        • Principal Investigator:
          • Jiri Fronek, Assoc Prof
        • Sub-Investigator:
          • Roman Chmel, MD PhD
        • Sub-Investigator:
          • Michael Olausson, Prof

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria for UTx recipient:

  • 18 - 40 years of age
  • good general health
  • congenital or acquired uterus absence
  • desire for a child

Exclusion Criteria for UTx recipient:

  • age over 40
  • serious comorbidity

Inclusion Criteria for a live uterus donor:

  • female
  • 18 - 60 years of age
  • maximum 4 child births
  • maximum 1 Cesarian section
  • good general health

Exclusion Criteria for a live uterus donor:

  • age over 60
  • hypertension with organ damage
  • diabetes mellitus
  • other serious comorbidity

Inclusion Criteria for a deceased brain-dead uterus donor:

  • female
  • age under 60
  • no previous hysterectomy
  • no previous uterus malignancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Live donor uterus transplantation
Transplantation of uterus from a living donor. Immunosuppression with tacrolimus.
Procedure: Live donor uterus transplantation
Transplantation of uterus from a living donor.
Drug: Tacrolimus
Maintenance immunosuppression in UTx recipient will be reduced to tacrolimus monotherapy to minimalize fetal compromise.
Other Names:
  • FK506
Experimental: Deceased donor uterus transplantation
Transplantation of uterus from a deceased brain-dead donor. Immunosuppression with tacrolimus.
Procedure: Deceased donor uterus transplantation
Transplantation of uterus from a deceased brain-dead donor.
Drug: Tacrolimus
Maintenance immunosuppression in UTx recipient will be reduced to tacrolimus monotherapy to minimalize fetal compromise.
Other Names:
  • FK506

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of uterus transplantation.
Time Frame: Until 10 live donor and 10 deceased donor uterus transplants have been performed plus approximately 5 years.
Number of successful uterus transplantations and healthy child births. Treatment of absolute uterine factor infertility that has no other therapy option by uterus transplantation that includes in vitro fertilization and cryopreservation, uterus transplantation from a live donor or from a deceased donor, graft survival on immunosuppression, embryo transfer, pregnancy and child birth, final graft hysterectomy.
Until 10 live donor and 10 deceased donor uterus transplants have been performed plus approximately 5 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of efficacy of uterus transplantation from live donors versus deceased donors.
Time Frame: Until 10 live donor and 10 deceased donor uterus transplants have been performed plus approximately 5 years.
Number of successful uterus transplantations and healthy child births from live donors versus deceased donors.
Until 10 live donor and 10 deceased donor uterus transplants have been performed plus approximately 5 years.
Rate of adverse events after uterus transplantation
Time Frame: Until 10 live donor and 10 deceased donor uterus transplants have been performed plus approximately 5 years.
Number of recipients of uterus transplantation with adverse events.
Until 10 live donor and 10 deceased donor uterus transplants have been performed plus approximately 5 years.
Rate of adverse events after live uterus donation
Time Frame: Until 10 live donor transplants have been performed plus approximately 5 years.
Number of live donor participants after uterus retrieval with adverse events.
Until 10 live donor transplants have been performed plus approximately 5 years.
Rate of adverse events during pregnancy and child birth after uterus transplantation
Time Frame: Until 10 live donor and 10 deceased donor uterus transplants have been performed plus approximately 5 years.
Number of children conceived and born from transplanted uterus with adverse events.
Until 10 live donor and 10 deceased donor uterus transplants have been performed plus approximately 5 years.
Verification of technique of uterus retrieval
Time Frame: Until 10 live donor and 10 deceased donor uterus transplants have been performed plus approximately 5 years.
Verification of surgical technique of uterus retrieval from a live donor and from a deceased donor.
Until 10 live donor and 10 deceased donor uterus transplants have been performed plus approximately 5 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute for Clinical and Experimental Medicine

Collaborators

Sahlgrenska University Hospital, Sweden
University Hospital, Motol

Investigators

  • Principal Investigator: Jiri Fronek, Assoc Prof, Transplant Surgery Department, Institute of Clinical and Experimental Medicine, Prague, Czech Republic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 9, 2015

Primary Completion (Anticipated)

December 31, 2020

Study Completion (Anticipated)

December 31, 2025

Study Registration Dates

First Submitted

September 4, 2017

First Submitted That Met QC Criteria

September 6, 2017

First Posted (Actual)

September 11, 2017

Study Record Updates

Last Update Posted (Actual)

February 27, 2019

Last Update Submitted That Met QC Criteria

February 25, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2044/15 (NM-15-01)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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