Uterus Transplantation From Live Donors and From Deceased Donors - Clinical Study

NCT ID: NCT03277430

Last Updated: 2019-02-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-09

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Mayer Rokitansky Kuster Hauser Syndrome Mullerian Aplasia Uterus; Absence, Congenital Infertility, Female Uterus Absence, Acquired Absolute Uterine Factor Infertility

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Live donor uterus transplantation

Transplantation of uterus from a living donor. Immunosuppression with tacrolimus.

Group Type EXPERIMENTAL

Live donor uterus transplantation

Intervention Type PROCEDURE

Transplantation of uterus from a living donor.

Tacrolimus

Intervention Type DRUG

Maintenance immunosuppression in UTx recipient will be reduced to tacrolimus monotherapy to minimalize fetal compromise.

Deceased donor uterus transplantation

Transplantation of uterus from a deceased brain-dead donor. Immunosuppression with tacrolimus.

Group Type EXPERIMENTAL

Deceased donor uterus transplantation

Intervention Type PROCEDURE

Transplantation of uterus from a deceased brain-dead donor.

Tacrolimus

Intervention Type DRUG

Maintenance immunosuppression in UTx recipient will be reduced to tacrolimus monotherapy to minimalize fetal compromise.

Interventions

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Live donor uterus transplantation

Transplantation of uterus from a living donor.

Intervention Type PROCEDURE

Deceased donor uterus transplantation

Transplantation of uterus from a deceased brain-dead donor.

Intervention Type PROCEDURE

Tacrolimus

Maintenance immunosuppression in UTx recipient will be reduced to tacrolimus monotherapy to minimalize fetal compromise.

Intervention Type DRUG

Other Intervention Names

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FK506

Eligibility Criteria

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Inclusion Criteria

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


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


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

Exclusion Criteria

* age over 40
* serious comorbidity


* age over 60
* hypertension with organ damage
* diabetes mellitus
* other serious comorbidity
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Motol

OTHER

Sponsor Role collaborator

Sahlgrenska University Hospital

OTHER

Sponsor Role collaborator

Institute for Clinical and Experimental Medicine

OTHER_GOV

Sponsor Role lead

Responsible Party

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Jiri Fronek

MD PhD Assoc Prof

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jiri Fronek, Assoc Prof

Role: PRINCIPAL_INVESTIGATOR

Transplant Surgery Department, Institute of Clinical and Experimental Medicine, Prague, Czech Republic

Locations

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Institute for Clinical and Experimental Medicine

Prague, , Czechia

Site Status RECRUITING

Countries

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Czechia

Central Contacts

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Jiri Fronek, Assoc Prof

Role: CONTACT

+420 26 136 4105

Renata Zamecnikova, Bc

Role: CONTACT

+420 26 136 4105, 5300

Facility Contacts

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Jiri Fronek, Assoc Prof

Role: primary

+420 26 136 4105

Renata Zamecnikova, Bc

Role: backup

+420 26 136 4105

References

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Erman Akar M, Ozekinci M, Alper O, Demir D, Cevikol C, Meric Bilekdemir A, Daloglu A, Ongut G, Senol Y, Ozdem S, Uzun G, Luleci G, Suleymanlar G. Assessment of women who applied for the uterine transplant project as potential candidates for uterus transplantation. J Obstet Gynaecol Res. 2015 Jan;41(1):12-6. doi: 10.1111/jog.12486. Epub 2014 Sep 17.

Reference Type BACKGROUND
PMID: 25226847 (View on PubMed)

Olausson M, Johannesson L, Brattgard D, Diaz-Garcia C, Lundmark C, Groth K, Marcickiewizc J, Enskog A, Akouri R, Tzakis A, Rogiers X, Janson PO, Brannstrom M. Ethics of uterus transplantation with live donors. Fertil Steril. 2014 Jul;102(1):40-3. doi: 10.1016/j.fertnstert.2014.03.048. Epub 2014 Apr 28. No abstract available.

Reference Type BACKGROUND
PMID: 24784936 (View on PubMed)

Johannesson L, Dahm-Kahler P, Eklind S, Brannstrom M. The future of human uterus transplantation. Womens Health (Lond). 2014 Jul;10(4):455-67. doi: 10.2217/whe.14.22.

Reference Type BACKGROUND
PMID: 25259905 (View on PubMed)

Farrell RM, Falcone T. Uterine transplantation. Fertil Steril. 2014 May;101(5):1244-5. doi: 10.1016/j.fertnstert.2014.03.022. Epub 2014 Apr 13. No abstract available.

Reference Type BACKGROUND
PMID: 24726215 (View on PubMed)

Brannstrom M, Johannesson L, Dahm-Kahler P, Enskog A, Molne J, Kvarnstrom N, Diaz-Garcia C, Hanafy A, Lundmark C, Marcickiewicz J, Gabel M, Groth K, Akouri R, Eklind S, Holgersson J, Tzakis A, Olausson M. First clinical uterus transplantation trial: a six-month report. Fertil Steril. 2014 May;101(5):1228-36. doi: 10.1016/j.fertnstert.2014.02.024. Epub 2014 Feb 27.

Reference Type BACKGROUND
PMID: 24582522 (View on PubMed)

Ozturk H. How real is the uterine transplantation? Ann Transplant. 2014 Feb 14;19:82-3. doi: 10.12659/AOT.889973. No abstract available.

Reference Type BACKGROUND
PMID: 24535028 (View on PubMed)

Akar ME, Ozkan O, Ozekinci M, Sindel M, Yildirim F, Oguz N. Uterus retrieval in cadaver: technical aspects. Clin Exp Obstet Gynecol. 2014;41(3):293-5.

Reference Type BACKGROUND
PMID: 24992779 (View on PubMed)

Fronek J, Janousek L, Kristek J, Chlupac J, Pluta M, Novotny R, Maluskova J, Olausson M. Live Birth Following Uterine Transplantation From a Nulliparous Deceased Donor. Transplantation. 2021 May 1;105(5):1077-1081. doi: 10.1097/TP.0000000000003346.

Reference Type DERIVED
PMID: 32541565 (View on PubMed)

Related Links

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Other Identifiers

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2044/15 (NM-15-01)

Identifier Type: -

Identifier Source: org_study_id

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