The University of Pennsylvania Uterus Transplant for Uterine Factor Infertility Trial (UNTIL)

This is an interventional treatment trial for Mayer Rokitansky Kuster Hauser Syndrome focused on measuring Uterine Transplant, MRKH Read More

Uterine Transplant Recipient Participant Inclusion Criteria:

1. XX-bearing individual diagnosed with Uterine Factor Infertility (UFI) a
2. Age 21-40
3. Lives in Philadelphia region for the duration of the trial
4. Received counseling regarding alternatives to uterine transplant such as adoption or surrogacy
5. Intact ovaries
6. Vaginal length >6 cm (average vaginal length established with dilators)
7. Body mass index <35 kg/m2
8. Fluent in the English Language
9. If cervix present/previously present, human papillomavirus (HPV)) negative or received vaccination for HPV
10. Willing to comply with screening, protocol and all required procedures
11. Has adequate social support
12. Has undergone controlled ovarian hyperstimulation, egg retrieval, in vitro fertilization, and embryo freezing and has frozen embryos of sufficient embryo quality/quantity (≥2 high quality blastocysts); (Required for Transplant Phase, not Screening or Evaluation Phases)

Uterine Transplant Recipient Participant Exclusion Criteria:

1. Previous multiple major abdominal/pelvic surgery
2. Severe endometriosis
3. History of hypertension, diabetes mellitus, thrombophilia or other clotting or bleeding disorders, significant heart, liver, kidney or central nervous system disease
4. History of prior malignancy except for cervical cancer in stage 1a or 1b (must be in remission for 3 years)
5. History of significant psychiatric illness
6. Allergy, hypersensitivity, or intolerance of expected immunosuppressive agents (i.e. Thymoglobulin®, tacrolimus, etc.)
7. Allergy, hypersensitivity, or intolerance of heparin or aspirin
8. Presence of active documented systemic infection or recent systemic infection within the past 3 months
9. Seropositivity for HIV, HBV core antibody or antigen, HCV
10. Current smoker (smoking cessation must have occurred 3 months prior to enrollment)
11. Chemical and/or alcohol dependency or abuse
12. Psychosocial problems (including alcoholism, drug abuse, documented behavioral disorders)
13. Renal abnormalities, specifically single kidney or pelvic kidneys (imaging confirmation of 2 normal kidneys is required for MRKH subjects)
14. Contraindications to pregnancy
15. Unwilling to receive a transfusion of blood or blood products

Living Donor Participant Inclusion Criteria:

1. Age 30-50
2. Has definitively completed childbearing
3. Live birth to miscarriage ratio ≥1
4. Body mass index <35 kg/m2
5. Normal uterine anatomy
6. Normal pap test and Human papillomavirus (HPV) negative
7. Negative infection screen (HIV, HepB, HepC, Syphilis, gonorrhea, chlamydia)
8. Received counseling regarding alternatives to uterus donation such as adoption and gestational surrogacy
9. Fluent in the English Language
10. Willing to comply with screening, protocol and all required procedures
11. Has adequate social support
12. Compatible blood type with recipient
13. Negative flow cytometric crossmatch with recipient
14. Has current health insurance
15. Able to stay in the Philadelphia region for 3 weeks following uterus donation

Living Donor Participant Exclusion Criteria:

1. Previous multiple major abdominal/pelvic surgery
2. Severe endometriosis
3. History of hypertension, diabetes mellitus, thrombophilia or other clotting or bleeding disorders, significant heart, liver, kidney or central nervous system disease
4. History or obvious evidence of previous multiple/significant uterine surgery. Defined as >1 cesarean delivery and/or myomectomy
5. History of previous cervical surgery (cone biopsy or loop electrosurgical excision procedure)
6. Significant systemic disease (diabetes or systemic lupus erythematosus)
7. Previous obstetric problem including delivery <34 weeks and abnormal placental location (i.e. placenta Previa/accreta/increta/percreta)
8. Pregnancy
9. Abnormal uterine cavity
10. Vascular calcification on imaging tests
11. History of significant psychiatric illness
12. Current smoker (smoking cessation must have occurred 3 months prior to enrollment)
13. Chemical and/or alcohol dependency or abuse
14. Psychosocial problems (including alcoholism, drug abuse, documented behavioral disorders)
15. Unwilling to receive a transfusion of blood or blood products
16. Evidence of coercion or exchange of money or goods for donating the organ

Deceased Donor Inclusion Criteria:

1. Hemodynamically stable donor
2. Age between 18 to 50 years
3. Compatible blood type with recipient
4. Negative flow cytometric crossmatch with recipient
5. Live birth to miscarriage ratio ≥1
6. Normal gross uterine anatomy (as visually assessed by gynecologic surgeon at time of organ procurement)
7. Macroscopically normal cervix (polyp acceptable)
8. Negative infection screen (HIV, HepB, HepC, Syphilis)
9. Cytomegalovirus (CMV)- matched based on rapid donor screening. A CMV positive donor may be used in a CMV negative recipient. A CMV negative donor may be used in either a CMV positive or negative recipient.
10. Donates after brain death

Deceased Donor Exclusion Criteria:

1. Current malignancy or history of malignancy active within the past 5 years (Except adequately treated localized basal or squamous cell carcinoma of skin without evidence of recurrence)
2. No history or obvious evidence of previous multiple/significant uterine surgery. Defined as >1 cesarean delivery and/or myomectomy
3. No history or obvious evidence of previous cervical surgery (cone biopsy or loop electrosurgical excision procedure)
4. Significant systemic disease (i.e. diabetes, peripheral vascular or cardiovascular disease, autoimmune disease, renal or liver failure, etc.)
5. Previous obstetric problem including delivery <34 weeks and abnormal placental location (i.e. placenta Previa/accreta/increta/percreta)
6. Pregnancy
7. BMI >35 kg/m2
8. Donates after cardiac death (DCD)