Clinical trial NCT04026893: Deceased Uterine Transplant in Absolute Uterine Infertility (AUIF)
Official title: Deceased Uterine Transplant in Absolute Uterine Infertility (AUIF)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Infertility of Uterine Origin
Keywords: AUFI
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2019-07-19
Enrollment: 250
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Our study will explore the feasibility of initiating a deceased donor uterine transplant program in addition to the existing living donor IRB at BWH.

Using the template established by teams around the world, we will identify emotionally and socially stable females of reproductive age with intact ovaries who are unable to gestate a child due to congenital or acquired uterine factor infertility. After careful screening, participants will undergo egg harvest, in vitro fertilization, and embryo cryopreservation using standard methods. Women who successfully complete the fertilization of at least six euploid embryos will be eligible to be placed on the waitlist for a deceased donor uterus transplant. After a successful transplant and a period of observation to ensure normal menstrual cycle and graft viability (anticipate six months), embryo implantation will be undertaken.

Following an embryo transfer, gestation will be carefully monitored by our high-risk pregnancy specialists. Medical research interventions include the surgical implantation of a uterus utilizing techniques by teams that have applied this approach successfully, close post-transplant follow up including immunosuppression therapy tailored to established standards during pregnancy minimizing fetal risks, and careful management of pregnancy. After childbearing is complete (at most two gestations), the donor uterus will be removed either during Cesarean or during an elective procedure. In addition, open ended interviews and surveys will be conducted to elicit ethical and psychosocial concerns arising from the experience of subjects and their families, health care providers, and the wider community. The investigator's intent is to monitor outcomes for transplant recipients as well as the live born infants for 30 days after removal of the transplanted uterus.

It is estimated that the time from screening to a potential live birth will be a minimum of 22 months, but likely between 24 - 36 months depending on organ availability.


Eligibility criteria: Inclusion Criteria:

* Evidence of AUFI diagnosed by BWH gynecologist
* Ability to produce at least 6 euploid embryos for cryopreservation
* BMI ≤ 30
* GFR 60 or greater in any patient including those with a single kidney
* PRA 20% or less
* Deemed stable and capable of undergoing transplant by the transplant team to include psychiatry, social work, and transplant coordinator and study doctors to assure compliance with treatment
* Evidence to be compliant with follow-up and immunosuppression
* Partner willing to undergo psychological evaluation and receive immunizations as recommended
* Stable home environment to support a child

Exclusion Criteria:

* Active smoking, alcohol use or use of illicit drugs
* Inability to follow a strict medication dosing schedule post-transplant and adhere to required follow-up appointments.
* Any co-morbidities which would increase surgical risk, risk of pregnancy or the risk of taking anti-rejection medications as determined by the Maternal Fetal Specialist and Transplant Surgeon.
* Active infection: HIV, Hepatitis B, Hepatitis C
* Inadequate blood vessels to support the transplanted uterus.
* Prior extensive abdominal or pelvic surgery
* Presence of pelvic kidney
* History of abnormal PAP
* HPV related vulvar, vaginal or cervical dysplasia
* Evidence of genital condylomata
* History of PID
* One or more living biological children

Primary outcomes:
measure: Number of Live Births Following Uterus Transplant
timeFrame: Within 5 years of transplant
measure: Number of Surgically Successful Uterus Transplants
timeFrame: Within 3 months of transplant
Secondary outcomes:
measure: Financial impact of deceased donor uterus transplantation
timeFrame: Through Study completion, up to 5 years post transplant
measure: Quality of life impact of deceased donor uterus transplantation
timeFrame: Through study completion, up to 5 years post transplant
Other outcomes:
Locations:
Study officials:
affiliation: Brigham and Women's Hospital
name: Stefan G Tullius, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Tullius SG, Rudolf JA, Malek SK. Moving boundaries--the Nightingale twins and transplantation science. N Engl J Med. 2012 Apr 26;366(17):1564-5. doi: 10.1056/NEJMp1114193. No abstract available.
citation: Lefkowitz A, Edwards M, Balayla J. The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation. Transpl Int. 2012 Apr;25(4):439-47. doi: 10.1111/j.1432-2277.2012.01438.x. Epub 2012 Feb 23.
citation: Del Priore G, Saso S, Meslin EM, Tzakis A, Brannstrom M, Clarke A, Vianna R, Sawyer R, Smith JR. Uterine transplantation--a real possibility? The Indianapolis consensus. Hum Reprod. 2013 Feb;28(2):288-91. doi: 10.1093/humrep/des406. Epub 2012 Nov 30.
citation: McKay DB, Josephson MA. Pregnancy in recipients of solid organs--effects on mother and child. N Engl J Med. 2006 Mar 23;354(12):1281-93. doi: 10.1056/NEJMra050431. No abstract available.