Transplantation of Uterus for Uterine infertiLIty From Living Donor or Deceased Donor

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.

Inclusion criteria

for UT recipient:

• Patient aged 18 to 40 at the time of the UT;
• BMI (Body Mass Index) ≤ 30 kg/m²;
• With AUFI (type 1 or 2 MRKH syndrome and hysterectomy);
• Informed about the possibility of adoption;
• Compatibility with the donor (ABO group, Human Leukocyte Antigen (HLA) typing);
• Up-to-date vaccinations;
• Able to reach the transplant center in less than 11 hours (applicable only for the "deceased donor" arm);
• Having a parental project that is formulated by a heterosexual couple, by a couple of women or by a single woman;
• Vaginal cup of length greater than or equal to 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:

• 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);
• Age ≥ 37 years and ≤ 62 years ;
• BMI ≤ 30 kg/m²;
• Having completed all her parenthood plans and no longer having any plans of pregnancy;
• Having had at least one live-born child at term (i.e. after 37 weeks of of amenorrhea);
• Compatibility with the recipient (ABO group, HLA typing);
• Normal suprapubic and/or endovaginal ultrasound or pelvic Magnetic Resonance Imaging (MRI), including uterine (no uterine abnormalities);
• Satisfactory uterine vessels assessed by MRI angio.

Exclusion criteria

for UT recipient:

• Patient with acquired uterine infertility and having had one or more children;
• Non-stable psychological state defined by a clinical psychologist after a qualitative interview;
• Severe co-morbidity;
• Association of severe abnormality with MRKH syndrome other than renal such as a cardiac malformation;
• A single pelvic kidney (urinary malformation that can be associated with MRKH syndrome);
• Pathogenic parental genetic anomaly which may lead to medical termination of pregnancy in the current state of knowledge;
• Diabetes (HbA1c > 6%);
• Disorders of hemostasis: Prothrombin rate <70%;
• Hemoglobin abnormality;
• Existence of hypertension;
• Vaginal reconstruction (neovagina) by digestive segment (colonic plastic surgery or other);
• History of major abdominal or pelvic surgery;
• Known thrombophilia (acquired or constitutional);
• HIV (Human Immunodeficiency Virus), HCV (Hepatitis C Virus), HBV (Hepatitis B Virus), HAV (Hepatitis A Virus), HTLV (Human T-Lymphotropic Virus) serology positive and presence of irreversible communicable infectious diseases;
• Positive vaginal hPV-HR (human Papilloma Virus High Risk) test;
• Signs of chronic renal disease;
• 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 10 years old, cancer under treatment (except in the cancer in situ, or basal cell skin lesion) or diagnosed during the selection process;
• History of pelvic radiotherapy or vaginal brachytherapy regardless of when this irradiation was performed;
• Known psychiatric pathology;
• Active tuberculosis (i.e. under treatment);
• Known or suspected contraindications to one or more of the treatments (active substance or excipient(s)) to be administered for the purposes of the study and/or essential treatment having an interaction/impact with one of the treatments planned by the research;
• Existence of organ dysfunction not compatible with the uterine transplantation protocol;
• History of smoking (defined as consumption greater than 20 packs/year) not weaned for more than 2 years or active smoker.

Exclusion criteria

for a deceased brain-dead uterus donor:

• Initial circulatory arrest of more than 10 minutes;
• Opposition to organ donation (register of refusals) or to uterine removal by a relative of the deceased;
• Chronic and uncontrolled hypertension;
• Absence of uterus (history of hysterectomy or uterine agenesis);
• Presence of uterine pathology;
• Delivery less than 6 months ago or ongoing pregnancy;
• History of several caesarean sections (multi-scarred uterus: more than 2);
• History of major abdominal or pelvic surgery;
• Infection of the sepsis type or uncontrolled infection (bacterial, viral viral, parasitic fungal, active Chagas disease);
• Encephalitis of viral origin or febrile of uncertain origin or meningoencephalitis of unknown origin;
• Risk of Prion disease transmission;
• Presence of an infectious disease: HIV, HCV, HBV, HTLV and presence of irreversible communicable infectious diseases;
• Carrying of human Papilloma Virus High Risk (hPV-HR) class 1 positive in the genital tract if known before transplantation;
• Positive EBV (Epstein-Barr Virus) serology in the donor if the recipient is EBV negative for EBV ;
• Positive pre-transplant virtual crossmatch;
• Donor/recipient ABO final check in the operating room before transplantation positive;
• 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) ;
• Active tuberculosis (i.e. under treatment);
• History of smoking (defined as consumption greater than 20 packs/year) not weaned 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 6 months ago or ongoing pregnancy;
• History of cervical pathology;
• History of recurrent miscarriage syndrome (defined as 3 consecutive consecutive miscarriages);
• History of premature delivery before 36 weeks of amenorrhea;
• History of pre-eclampsia;
• History of caesarean sections;
• History of major uterine surgery;
• History of major abdominal or pelvic surgery;
• Endometrial biopsy and diagnostic hysteroscopy showing an abnormality of the endometrium;
• Known thrombophilia (acquired or constitutional);
• HIV, HCV, HBV, HTLV serology positive and presence of irreversible communicable infectious diseases;
• Positive vaginal hPV-HR (human Papilloma Virus High Risk) test;
• PCR (Polymerase Chain reaction) on HSV (Herpes Simplex Virus) 1/2 positive sample;
• Abnormal vaginal swab;
• 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 10 years old, cancer under treatment (except in the cancer in situ, or basal cell skin lesion) or diagnosed during the selection process;
• History of pelvic radiotherapy or vaginal brachytherapy regardless of when this irradiation was performed;
• Known psychiatric pathology;
• Active tuberculosis (i.e. under treatment);
• Presence of a known thromboembolic risk factor;
• Angio-MRI, CT angiography and/or arteriography revealing an anomaly incompatible with uterine transplantation;
• History of smoking (defined as consumption greater than 20 packs/year) not weaned for more than 2 years or active smoker.