Uterine Allotransplantations Using Uterine Grafts From Brain-dead Female Donors
试验速览
- 阶段
- 不适用
- 状态
- 暂停
- 发起方
- 入组人数
- 10
- 试验地点
- 8
- 主要终点
- Successful uterus transplant
研究概览
简要总结
Uterus transplantation may enable women with uterine factor infertility to become pregnant and give birth.
This study will explore the feasibility of a uterine transplant and eight subjects will undergo deceased donor uterine transplantation at CHU de Limoges.
There phases involved in this study: Primary, Secondary and Tertiary Screening, Medical Evaluation, IVF, Transplantation, Embryo Transfer, Pregnancy/Delivery and Follow up.
详细描述
It is estimated that 1 in 500 women of reproductive age have congenital or acquired uterine factor infertility (UFI).
The solution for such patients who wish to have a child is either to adopt or use a surrogate. The latter is illegal in France .Uterine transplantation (UT) could be a beneficial medical alternative.
Over the last 13 years, about 30 experimental studies have been conducted on rodents, rabbits, pigs, sheeps and monkeys. They have shown TU to be feasible, with a number of births achieved after uterus auto-transplantation, syngeneic transplantation and allotransplantation. However, animal experiments are not able to provide a definitive answer to the question of the feasibility of UT in women due to the specific characteristics of each species and a lower degree of control of immunosuppression and in vitro fertilisation techniques in animals. Thus, the information from animal experiments and the present knowledge on immunosuppression in women, based on experiments in other solid organ transplantation, explain the willingness to take the step of undergoing clinical UT. The recent human data and the first births after UT obtained by a Swedish team are reassuring and confirmed the feasibility of the procedure. The data gathered over 50 years of pregnancies in patients who have received kidney, liver or heart transplants is reassuring, with over 20,000 births recorded and recommendations for the start of the pregnancy, patient follow-up and immunosuppressive drugs (ISD) handling are currently relatively well-established.
As compared to other solid organ transplantations, UT is particular in being temporary (the graft will be removed once the child is born or in case of safety issue) and the period of exposure to immunosuppressants is thus reduced.
Our team has recognised experience in the field of female fertility preservation and ovarian grafting. Work begun in animals at the end of the 1990s led to the first pregnancies in France after an ovarian autograft in 2010. With regard to uterus grafting, the investigators have published work on uterine allotransplantation involving ewes and the evaluation of the graft by magnetic resonance imaging (MRI). Clinically, the investigator began by working on cadavers and conducted a study in 2012-2013, which was supported by the French Biomedical Agency (Agence de la biomédecine), on the feasibility of uterus retrieving as part of a multi-organ retrieval (MOR) procedure. In this preliminary clinical study, the investigators were able to show that the technique of uterus retrieval in brain-dead donors can be reproduced. Acceptance of the retrieval by the relatives of the brain-dead patient was good (no refusal).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 36 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Recipients :
- •Primary selection criteria
- •Patients with uterine factor infertility defined as followed :
- •A history of hysterectomy for benign pathology or postpartum haemorrhage
- •Total or partial uterine agenesis
- •Age ≥ 25 and < 35 years
- •couple living together for at least two years
- •BMI ≤ 30 kg/m2
- •At least 12 months from colpoplasty surgery
- •At least 12 months from diagnosis of uterine infertility
- •Nulliparous
- •Compliance with the legal criteria of medically assisted procreation Acceptance to take part of NEHAVI cohort
- •Acceptance of the protocol constraints
- •Coverage by the French national Health service
- •Secondary selection criteria
- •Signed informed consent by the patient and spouse
- •Prior psychological evaluation not contraindicating participation in the study
- •Normal ovarian function and satisfactory ovarian reserve
- •Compliance with primary selection criteria.
- •Tertiary selection criteria
- •At least 10 embryos obtained by IVF
- •Compliance with primary and secondary selection criteria
- •Brain dead female ≥ 18 years old and ≤ 50 years old.
排除标准
- •Recipients Primary criteria for non-selection
- •• Previous major abdomino-pelvic surgery
- •Previous ileal or sigmoid colpoplasty
- •History of cancer
- •Active tobacco consumption
- •Hypertension (HT), including treated HT
- •Type 1 or 2 diabetes
- •Chronic kidney disease
- •Evolving cardiovascular pathology
- •Psychiatric disease
- •Under guardianship or conservatorship
- •Contraindication to one of the treatments used in the study
- •Contraindication to ovarian stimulation treatment except uterine infertility
- •Secondary criteria for non-selection
- •Prior psychological evaluation contraindicating participation in the study
- •Rare blood group AB or B, for the purpose of reducing the waiting time for a graft. Groups A and O combined constitute over 85% of donors (see appendix)
- •Positive irregular agglutinin test (IAT)
- •Ovarian insufficiency according to laboratory norms
- •Presence of anti-HLA antibodies
- •Negative Epstein-Barr virus serology
- •HIV or hepatitis C infection,
- •Hepatitis B (acute, chronic, treated)
- •Presence of a single kidney
- •Detected cardiac pathology
- •Contraindication to participation into the trial detected at the anaesthetic assessment
- •Dermatological, stomatological and/or ear, nose, and throat (ENT) pathology/ies contraindicating treatment with ISDs
- •Thoracic-abdominal-pelvic CT scan anomalies contraindicating UT and the use of treatment with ISDs
- •Increased risk of miscarriage (thrombophilia, anormal karyotype)
- •Separation of the couple.
- •Tertiary criteria for non-selection
- •Spouse/partner with azoospermia
- •Less than 10 frozen embryos obtained
- •Separation of the couple.
- •Previous uterine transplantation
- •Length of no flow > 10 min
- •Pregnancy at the time of brain death
- •Time from delivery < 3 months
- •Positive oncogen human papillomavirus (HPV )test (16 and 18)
- •Myomas > 3 cm and/or endoluminal fibroid and/or endometrial polyps and/or heterogenous annexial cyst seen in a pelvic ultrasound or CT scan
- •Multi-scarred uterus ( ≥ 2 uterine scars)
- •Registered in the national registry of persons who refuse to donate any organ.
- •Opposition to the uterine retrieval from the donor's relatives.
- •Uterine agenesis and uterine malformation
- •Criteria usually seen as contraindicating retrieval (HIV+, evolutive neoplasia, etc.)
研究组 & 干预措施
Uterus Transplantation
Women will undergo deceased donor uterine transplantation after IVF
干预措施: Uterus Transplant (Procedure)
结局指标
主要结局
Successful uterus transplant
时间窗: 12 month after each transplantation
Success will be measured by by the occurrence of at least two spontaneous menstrual cycles during the first year following the UT.
次要结局
- UT complications(up to 41 after transplantation)
- Pregnancy complications after UT(up to 39 months after transplantation)
- Successful of pregnancies achieved(up to 30 months after transplantation)
- Successful of births achieved(up to 39 months after transplantation)