RecruitingEarly Phase 1ACTRN12619000808145

Is a uterine transplant a safe and effective option for women who do not have a uterus (for various reasons) to achieve pregnancy and gain parenthood.

Uterus Transplantation and Pregnancy Induction in Women affected by Absolute Uterine Factor Infertility


Sponsor

Sydney Local Health district

Enrollment

20 participants

Start Date

Feb 10, 2023

Study Type

Interventional

Conditions

Summary

Absolute uterus factor infertility (AUFI) affects 1-5% of reproductive-aged infertile women AUFI may result from: - Major congenital anomaly e.g. MRKH syndrome where the woman is born without a uterus; - Hysterectomy for benign or malignant reasons; - Acquired condition rendering the uterus non-functional e.g. Asherman syndrome (intra-uterine adhesions). Traditionally, women with AUFI could only obtain parenthood through gestational surrogacy or adoption. However, these options may not be acceptable for some women and their partners due to legal, religious, financial or ethical concerns. Furthermore, achieving a pregnancy and delivering a baby is a basic human right. Recently, Uterus Transplantation (UT) has become an alternative option for women of reproductive age with AUFI to bear children. As of January 2019, UT has been successfully performed, with 13 reported live births worldwide – 8 in Sweden, 2 in the United States, and 1 in Brazil, China, and India . Of the 13 live births, all have been from a living donor UT, except the 1 in Brazil which used the uterus from a deceased donor Once the results of the initial trial demonstrate efficacy, safety and operational viability, we intend on providing a nation-wide tertiary referral service offering UT as a viable option for women with AUFI through RPAH. In order to achieve this, we need to create a multi-disciplinary team with adequate infrastructure for the selection, assessment, and management of appropriate patients as donors and recipients.


Eligibility

Sex: FemalesMin Age: 40 YearssMax Age: 65 Yearss

Plain Language Summary

Simplified for easier understanding

Some women are born without a uterus, or lose their uterus due to surgery or disease, making pregnancy impossible through conventional means. This condition is called absolute uterine factor infertility (AUFI). While surrogacy and adoption are options, they are not acceptable or accessible to everyone. Uterus transplantation — receiving a healthy uterus from a living or deceased donor — has now resulted in more than 13 live births worldwide. This Australian trial aims to establish whether this procedure is safe and feasible in Australia. The study involves two participants for each case: a donor (a woman aged 40–65 who has given birth before and has a healthy uterus) and a recipient (a woman aged 18–45 with AUFI who has functioning ovaries and is willing to undergo IVF). After the transplant, recipients will attempt pregnancy through IVF. The uterus is removed after one or two successful pregnancies, as lifelong immunosuppression would be needed to keep it. Both donors and recipients must meet detailed medical and psychological criteria. Key exclusions include HIV, active infections, BMI over 30, and recent smoking. This is a pioneering study that could establish the foundation for uterus transplantation as a recognised fertility treatment across Australia, offering hope to women who currently have no path to carrying their own pregnancy.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

This is a prospective cohort study whose primary objective is to assess the outcomes of UT as a treatment for AUFI. There are seven distinct clinical stages as detailed below. 1. Screening/pre-transp

This is a prospective cohort study whose primary objective is to assess the outcomes of UT as a treatment for AUFI. There are seven distinct clinical stages as detailed below. 1. Screening/pre-transplant assessment - The donor and recipient will undergo a series of assessments/tests to determine suitability into the study. Assessments include: past medical history, CT/MRI scans, appointments with gynaecology/vascular surgery, psychiatry and fertility counsellor, neonatology, and maternal fetal medicine. After the multi disciplinary team decides the donor/recipient are suitable for the study consent is them taken from the patients. 2. Creation of embryos via IVF - The prospective recipient will begin the in vitro fertilisation process. This involves: * superovulation - medications to stimulate the growth of the follicles * Egg retrieval - One or more eggs to be taken from the ovaries by follicle aspiration under ultrasound guidance * Fertilisation/Insemination - In the laboratory the eggs that have matured will be fertilised by standard IVF or inserting a single sperm into each egg * Embryo transfer - After day 5 of developing the embryo will be assessed by the embryologist and suitable embryos are frozen until it is time to transfer into the recipient under ultra sound guidance. 3. Transplant - Donor will undergo an abdominal hysterectomy, the recipient will receive a midline incision between the pubis and umbilicus. The uterus will be placed in its normal position in the pelvis. 4. Recovery with immunosuppression- The recipient will be placed on up to 3 immunosuppressive drugs to avoid graft rejection. Doses and length of therapy vary and the decision will be made by transplant team. 5. Embryo transfer - On the day of transfer the embryo will be thawed and transferred into the uterus by means of a sterile catheter system under ultrasound. 9-12 days later a blood test will be done to detect pregnancy. 6. Pregnancy care and delivery - The recipient will undergo many tests to ensure graft survival including: gynaecological assessments, lab tests (bloods every 2-4 weeks), ultrasounds every 2-4 weeks, biopsy of the cervix at each trimester. High risks obstetrics will be involved with visits every 2-4 weeks or as needed. 7. Post delivery, potential second pregnancy, and explant with follow-up. - The infant will be cared for by neonatal team and visits to the infant will be: 2-5 days, 6 weeks, then monthly. 6 months after the first birth, a second pregnancy can be discussed with the option of on explant if the recipient does not wish to have a second child. Counselling will be provided heavily at this stage. For the initial study, we intend on recruiting 10 females of reproductive age with AUFI. These patients will have intact ovarian function or are willing to use a donor oocyte(s). They will then go on to receive a UT from a living donor. A corresponding number of live female donors who are prepared to undergo an abdominal hysterectomy in order to assist women with AUFI achieve a live birth will be recruited. Donor: total abdominal hysterectomy and upper vaginectomy with preservation of the major feeding arteries and veins to the uterus of the donor. The ovaries are not removed. This surgery will take between 4-6 hours. The donor will then be transferred to recovery then to a standard hospital room. Recipient: implantation of the donor uterus in the pelvis of the recipient. Vascular anastomosis between the 2 major uterine arteries and uterine veins or ovarian veins is performed to the external iliac vessels using transplant microvascular techniques. Finally, the vaginal rim of the transplanted uterus is anastomosed to the recipient’s vaginal vault. This surgery will take between 4-8 hours. The recipient will be transferred to ICU for 24-48 hours then to a standard room. To monitor adherence to the intervention we have data collection forms for both the donor and recipient where routine pre op, intra op, and post op observations are recorded as either "between the flags" (within normal parameters) or not "between the flags"(abnormal and documented as an adverse event). This ensures auditing is done on every patient as part of standard of care. Pre-transplantation, the recipient will require IVF in order to cryostore embryos. Post-transplantation, the recipient will then require immunosuppression, embryo transfer, Caesarean section (for 1-2 pregnancies), and then removal of the donor uterus (explant). Multi-Disciplinary Team Transplant Research Nurse Coordinator provides education and support during all phases of the study as described above. They also serve as the primary contact should the donor or recipient have concerns. Reproductive Endocrinology and Infertility (REI) Specialists will serve as lead clinicians for this study. Prospective recipients and their partners will be thoroughly counselled about all of their options to gain parenthood. The REI specialist will manage the in-vitro fertilization process. Prospective donors and recipients will be counselled about the research nature of the trial. Transplant Surgeon and Vascular Surgeon will discuss and manage the surgical aspects of UT for the prospective donor and recipients. This will include consenting for the surgical procedures after discussing the risks of surgery and potential complications. The transplant surgeon will act as a donor ‘advocate’. This process has worked well in overseas centres – Gothenburg, Sweden. Radiologist will be involved in the pre-operative assessment of the potential donor and recipient in order to determine suitability. Transplant Physician will meet with the prospective recipient to discuss the type of immunosuppression needed after the transplant, the side effects and potential complications. They are also responsible for the administration and monitoring of the immunosuppression. Psychiatrist and Fertility Counsellor are responsible for the psychosocial assessment and management of the prospective donor and recipient. Maternal-Fetal Medicine Specialists will be responsible for the pre-transplant obstetric counselling and subsequent management of any ongoing pregnancy. They are also responsible for all sonographic imaging. Neonatologist will be responsible for the pre-transplant counselling of the prospective recipient (and her partner) regarding potential issues affecting the neonate. They will also be the primary carers of the neonate. Pathologist will be responsible for the pre- and post-transplant assessment of histopathology. This will include looking for histological features suggestive of allograft rejection. Recruitment Women will be self-referred or referred by a medical practitioner. The study investigators will be liaising with various support groups e.g. ‘Sisters for Love’ – MRKH support group in Australia. At this stage, we anticipate that all donors will be known to the recipient. Donation must be altruistic in nature.


Locations(1)

Royal Prince Alfred Hospital - Camperdown

ACT,NSW,NT,QLD,SA,TAS,WA,VIC, Australia

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ACTRN12619000808145