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Uterine Transplant in Absolute Uterine Infertility (AUIF)

Not Applicable
Conditions
Female Infertility
Interventions
Procedure: Uterine Transplant
Registration Number
NCT02741102
Lead Sponsor
Brigham and Women's Hospital
Brief Summary

This study will examine the feasibility of initiating a uterine transplant program for Absolute Uterine Factor Infertility (AUFI) at Brigham and Women's Hospital. The investigators plan to screen 30 patients with a goal of enrolling 10 patients. (5 donors and 5 recipients) After careful screening, appropriate candidates will undergo IVF, Uterine Transplantation, Embryo Transfer, Pregnancy and Delivery. Once the uterus is explanted, five years of follow-up is planned.

Detailed Description

There are approximately 9.5 million women in the United States with Absolute Uterine Factor Infertility (AUFI).Congenital uterine infertility in women is linked to a malformed or absent mullerian system termed MRKH - Rokitansky's or Mayer-Rokitansky-Kuster-Hauser Syndrome). Additional causes of acquired uterine infertility include a hysterectomy subsequent to life-threatening hemorrhage during childbirth or as a consequence to a hysterectomy related to cervical cancer or for large symptomatic fibroids. Additional causes may include intrauterine adhesions subsequent to surgical abortion or infection.

Uterine transplantation will provide a much needed medical option for many women in the U.S. and overseas who are unable to carry their own children based on uterine infertility. Centers outside of the US have initiated uterus transplant programs. Initial attempts were reported from Saudi Arabia. While the deceased donor transplant had been successful, successful pregnancies were not achieved. Another deceased donor transplant had been performed in Turkey with a uterus procured from a deceased donor. Although several IVF attempts had been performed, they had not resulted in live births.

Uterus transplants from live donors have been successful. In October 2014, Swedish doctors treating a woman born without a uterus, announced the world's first live birth of a healthy baby boy after a live donor uterine transplantation. Since then, an additional three babies have been born in Sweden to mothers who received live donor uterus transplants. A fifth baby is at term and a 6th pregnancy has been reported.

For this study, the investigators plan to screen 30 patients in order to enroll 10 patients, 5 recipients and their respective donors. Prospective recipients will undergo comprehensive medical and psychological evaluation. If deemed an appropriate candidate, In Vitro Fertilization would be started with the goal of obtaining 6 normal embryos for implantation. The uterus of a suitable live donor would then transplanted into the recipient. The recipient would need to take potent anti-rejection drugs and undergo regular assessments for rejection. After one year, embryo transfer to the transplanted uterus would be tried. Up to 6 cycles would be attempted hopefully resulting in pregnancy. If pregnancy results, the recipient would be followed by the high risk pregnancy team. Delivery will be by Caesarian Section. A woman may have up to 2 pregnancies with the transplanted uterus. The uterus is later removed so the recipient no longer has to take anti-rejection drugs.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
10
Inclusion Criteria

Not provided

Exclusion Criteria
  • Active smoking, alcohol use or use of illicit drugs
  • Psychiatric illness
  • Cervical or endometrial polyps (growths) or tumors in the uterus muscle
  • History of more than 1 Caesarean section
  • History of abnormal PAP smear or genital warts
  • Internal scarring from extensive abdominal or pelvic surgery
  • Hypertension, Coronary artery disease, Chronic Obstructive Lung disease (emphysema) and Diabetes
  • Active cancer or incompletely treated cancer
  • Active infection including Human Immunodeficiency Disease (HIV) , Tuberculosis, Hepatitis B or Hepatitis C
  • Significant history of either blood clots or bleeding tendencies
  • Evidence of coercion or exchange of money or goods for donating the organ

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Women with AUFIUterine TransplantWomen with AUFI must meet criteria for uterine transplant. In vitro fertilization to obtain 6 (screened) healthy embryos for cryo-preservation precedes uterine transplant from an appropriate donor The recipient will be required to take potent anti rejection medications including Thymoglobulin, Prednisone, Tacrolimus, Mycophenolate Mofetil (MMF) , later substituted with Azathioprine to avoid birth defects. One year later, up to 6 attempts using 1 screened embryo at a time will be tried to achieve pregnancy. During pregnancy, the high risk pregnancy and transplant teams will follow the recipient. The goal is a full term baby and delivery will be by Caesarian section. A second pregnancy may be attempted. Afterward, the uterus will be explanted.
Primary Outcome Measures
NameTimeMethod
Number of successful live births following uterus transplant/embryo transfer2 years after uterine transplant

Full term live birth by caesarian section after uterus transplant and IVF

Secondary Outcome Measures
NameTimeMethod
Cost comparison for uterine transplant vs. surrogacy vs adoptionUp to 5 years after uterine transplant

At the end of the study, investigators will calculate average cost of each modality, i.e. transplant vs surrogacy vs adoption to compare the three alternatives to infertility

Impact of uterine donation on donor quality of lifeUp to 2 years post donation

Measured by serial SF 36 QOL survey by psychiatrist at pre-donation and at follow-up appointments

Impact of uterine transplant on quality of lifeUp to 5 years after uterine transplant

Measured by serial SF 36 QOL survey by psychiatrist pre-transplant and at follow-up appointments..

Rate of complications following uterine donationUp to 2 years post donation

Monitoring for excessive bleeding , infection and bladder dysfunction

Rate of complications during pregnancy in uterus transplant recipient9 months after pregnancy achieved by embryo transfer

Monitoring for pre-eclampsia, hypertension, pre-term delivery

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