TULIPE: Transplantation of Uterus for Uterine infertiLIty From Living Donor or Deceased Donor
Study Details
Study Description
Brief Summary
Patients with absolute Uterine Factor Infertility (AUFI) are infertile due to the absence of a uterus. The absence of a uterus can be either iatrogenic (hysterectomy for gynecological pathology such as cancer or for obstetric pathology such as postpartum hemorrhage with hysterectomy for hemostasis), or congenital with utero-vaginal agenesis including Mayer Rokitansky Küster Hauser syndrome (MRKH) is the most common syndrome of uterine agenesis.
Alongside the AUFI, there is Non-Absolute Uterine Factor Infertility (NAUFI) which corresponds to patients with a uterus in place but which is altered by different pathologies, most often acquired, making it unsuitable for embryonic implantation and preventing the patient to get pregnant.
Uterus Transplantation (UT) represents an interesting alternative to the treatment of AUFI and potentially NAUFI (in the event of a uterus present but unsuitable for implantation) to access parenthood, especially since it is the only proposal that allows the patient to be both the surrogate mother, the biological mother (in case of simple donation) and the legal mother.
Many animal experiments have been accelerated since the beginning of the 21st century demonstrating that uterus transplantation was technically feasible and that pregnancy was possible.
In humans, several teams have recently performed several uterus transplants and have shown that this procedure is possible whether the donor is alive or dead (state of brain death).
In France, two teams (Foch and Limoges) have developed a uterus transplantation program. One in the context of living donors and the other of a deceased donors.
At the University Hospital of Rennes, we want to offer a TU program allowing access to a living or deceased donor.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Methods: Sixteen UT will be performed in total in 2 parallel arms: 8 UT from a live donor and 8 UT from a deceased brain-dead donor. Patients who have no suitable live donor will be wait-listed for a deceased donor.
Phases of the UT procedure: selection, in vitro fertilization and cryopreservation of embryos, uterus retrieval from a live donor or from a deceased donor, orthotopic uterus transplantation , follow up period (12 months), embryo transfer, pregnancy, child birth via Cesarian section (2 children maximum), later graft hysterectomy.
Study Design
Arms and Interventions
| 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.
|
| 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.
|
Outcome Measures
Primary Outcome Measures
- Efficacy of uterus transplantation [6 months after uterus transplantation]
Show a functional uterus validated by a return of menses in the recipient within 6 months after transplantation
Eligibility Criteria
Criteria
Inclusion Criteria for UT recepient:
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Patient aged 18 to 40 at the time of the UT;
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BMI ≤ 30 kg/m²;
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With AUFI or with an untreatable NAUFI;
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Compatibility with the donor (ABO group, HLA typing);
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Vaginal cup longer than 7 cm.
Inclusion Criteria for a deceased brain-dead uterus donor:
- Any person who is brain dead and who has been duly diagnosed with the following criteria: Female gender;Age ≤ 42 years;Compatibility with the recipient (ABO group, HLA typing).
Inclusion Criteria for a live uterus donor:
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Patient belonging to the family of the recipient (mother, sister, aunt, mother-in-law...) or any person who can prove a stable emotional relationship for more than 2 years with the recipient (paragraphs 1 and 2 of Article L.1231-1 of the Public Health Code);
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Age ≥ 40 years;
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BMI ≤ 30 kg/m²;
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Having completed all her parenthood plans and no longer having any plans of pregnancy;
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Having had at least one live-born child at term (i.e. after 37 weeks of of amenorrhea);
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If the patient is menopausal: maximum 6 years after the age of menopause (or the end of hormone replacement therapy) at the supposed date of the uterine uterine sampling;
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Compatibility with the recipient (ABO group, HLA typing);
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Normal suprapubic and/or endovaginal ultrasound or pelvic MRI, including uterine (no uterine abnormalities);
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Satisfactory uterine vessels assessed by MRI angio.
Exclusion Criteria for UT recepient:
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Non-stable psychological state defined by a clinical psychologist after a qualitative interview;
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Severe co-morbidity;
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Association of severe abnormality with MRKH syndrome other than renal such as a cardiac malformation;
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A single pelvic kidney (urinary malformation that can be associated with MRKH syndrome);
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Anomaly on the GREB1L gene (MRKH patient);
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Diabetes (HbA1c > 6%);
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Disorders of hemostasis: Prothrombin rate <70%;
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Hemoglobin abnormality;
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HTA treated by more than 2 antihypertensive drugs;
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Vaginal reconstruction (neovagina) by digestive segment (colonic plastic surgery or other);
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History of major abdominal or pelvic surgery;
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Known thrombophilia (acquired or constitutional);
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HIV, HCV, HBV, HAV, HTLV serology positive;
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Signs of chronic renal disease;
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Drug addiction or alcoholism not weaned for more than 2 years or drug addiction or excessive alcohol consumption (> 30 g/day of alcohol) current;
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History of cancer less than 5 years old, cancer under treatment (except in the cancer in situ, or basal cell skin lesion) or diagnosed during the selection process;
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Known psychiatric pathology that is not stable;
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Active tuberculosis (i.e. under treatment);
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History of smoking for more than 2 years or active smoker.
Exclusion Criteria for a deceased brain-dead uterus donor:
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Initial circulatory arrest of more than 10 minutes;
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Opposition to organ donation (register of refusals) or to uterine removal by a relative of the deceased;
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Chronic and uncontrolled hypertension;
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Absence of uterus (history of hysterectomy or uterine agenesis);
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Presence of uterine pathology;
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Delivery less than 3 months ago or ongoing pregnancy;
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History of several caesarean sections (multi-scarred uterus: more than 2);
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History of major abdominal or pelvic surgery;
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Infection of the sepsis type or uncontrolled infection (bacterial, viral viral, parasitic fungal, active Chagas disease);
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Encephalitis of viral origin or febrile of uncertain origin or meningoencephalitis of unknown origin;
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Risk of Prion disease transmission;
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Presence of an infectious disease: HIV, HCV, HBV, HTLV;
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Carrying of human Papilloma Virus High Risk (hPV-HR) class 1 positive in the genital tract if known before transplantation;
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Positive EBV serology in the donor if the recipient is EBV negative for EBV ;
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Positive pre-transplant virtual crossmatch;
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Donor/recipient ABO final check in the operating room before transplantation positive;
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Drug addiction or alcoholism not weaned for more than 2 years or drug addiction or excessive alcohol consumption (> 30 g/day of alcohol) current;
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History of cancer less than 5 years old, cancer under treatment (except in the cancer in situ, or basal cell skin lesion) ;
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Active tuberculosis (i.e. under treatment);
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History of smoking for more than 2 years or active smoker.
Exclusion Criteria for a live uterus donor:
-
Non-stable psychological state defined by a clinical psychologist clinician after a qualitative interview;
-
Severe co-morbidity;
-
Diabetes (HbA1c > 6%);
-
Hemostasis disorders: Prothrombin rate <70%;
-
Hemoglobin abnormality;
-
hypertension treated with more than 2 antihypertensive drugs;
-
Delivery less than 3 months ago or ongoing pregnancy;
-
History of cervical pathology;
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History of recurrent miscarriage syndrome (defined as 3 consecutive consecutive miscarriages);
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History of premature delivery before 36 weeks of amenorrhea;
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History of pre-eclampsia;
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History of several caesarean sections (multi-scarred uterus: more than 2);
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History of major uterine surgery;
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History of major abdominal or pelvic surgery;
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Endometrial biopsy and diagnostic hysteroscopy showing an abnormality of the endometrium;
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Known thrombophilia (acquired or constitutional);
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HIV, HCV, HBV, HTLV serology positive;
-
Signs of chronic kidney disease;
-
Risks of Prion disease transmission;
-
Drug addiction or alcoholism not weaned for more than 2 years or drug addiction or excessive alcohol consumption (> 30 g/day of alcohol) current;
-
History of cancer less than 5 years old, cancer under treatment (except in the cancer in situ, or basal cell skin lesion) or diagnosed during the selection process;
-
Known psychiatric pathology that is not stable;
-
Active tuberculosis (i.e. under treatment);
-
History of smoking for more than 2 years or active smoker.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vincent LAVOUE | Rennes | France |
Sponsors and Collaborators
- Rennes University Hospital
Investigators
- Principal Investigator: Vincent LAVOUE, Rennes University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 35RC20_9902_TULIPE