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

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.