The Danish TURNER Cryopreservation Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Number of miscarriages in pregnant Turner syndrome women
研究概览
简要总结
The goal of this clinical trial is to investigate if cryopreservation of ovarian tissue in girls with Turner syndrome can improve their fertility and lead to increased number of liveborn babies of Turner syndrome mothers. Women with Turner syndrome suffer from premature ovarian insufficiency which leads to infertility and lack of estrogen.
The main questions it aims to answer are:
- Does the number of pregnancies and liveborn children increase after cryopreservation of ovarian tissue in turner syndrome?
- Is the possible to predict when a girl with Turner syndrome reach menopause using monitoring of sex hormones?
- Is it possible to identify any genes causing ovarian failure in Turner syndrome females?
Participants between 2-18 years old will be asked to participate in a laparoscopic surgery and removal of one ovary in order to cryopreserve the tissue until adulthood. The the cortical tissue will be autotransplanted in order to preserve fertility. The participant will during the study period be monitored using sex hormones.
Furthermore, the investigators wish to investigate the ovarian tissue using RNA sequencing and DNA methylation analysis.
No comparison group is present.
详细描述
Hypothesis:
The majority of patients with Turner Syndrome (TS) lose their ovarian germ cells early in life. The primary hypothesis is that some patients with TS can become pregnant with their own oocytes after undergoing cryopreservation of one ovary during childhood, followed by auto-transplantation in adulthood.
Introduction Hypergonadotropic hypogonadism is a consistent trait in Turner syndrome (TS) affecting up to 95%. Through decades, a TS diagnosis was equivalent to a life with infertility. Despite a broad range of several other comorbidities, dealing with infertility is one of the most detrimental factors affecting quality of life in TS.
Most girls and women with TS undergo premature ovarian failure or insufficiency (POI) during childhood or early adolescence, before sufficient pubertal maturation. Spontaneous menarche is only present in 4-12% of 45,X females, although more frequent among mosaic karyotypes. Only a minority continue to have regular menstrual cycles (3-9%, depending on karyotype).
According to international guidelines, TS girls should be treated with estrogen from the age of 11-12 years old and later progesterone is added to ensure breakthrough bleedings. Besides ensuring uterine growth, estrogen has a wide range of beneficial effects across the entire body and receptors are present in most tissues. Estrogen therapy is essential in order to obtain optimal uterine growth and endometrial development ideal for embryo transfer during adult life.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •45,X karyotype or other Turner variant karyotypes (45,X/46,XX mosaicism, ring X mosaicism, isochromosome X)
- •Age 2-17 years old
- •Ability to participate in a physical examination including a cardiac examination.
- •Signed consent from both parents.
排除标准
- •Severe cardiac disease which inhibits safe surgery and pregnancy.
- •Karyotype with Y chromosome material
- •Mental retardation
结局指标
主要结局
Number of miscarriages in pregnant Turner syndrome women
时间窗: 20 to 30 years after cryopreservation
The number of miscarriages
Number of pregnancies in Turner syndrome women
时间窗: 20 to 30 years after cryopreservation
The number of pregnancies
Number of liveborn children birthed by Turner syndrome women
时间窗: 20 to 30 years after cryopreservation
The number of liveborn children
次要结局
- Number of ovarian follicles.(2-5 days after surgery)
- TGF-β signaling in follicular fluid(At ovarian cryopreservation. Timeframe can be 1 to 15 years, an average of 3 years.)
- DNA methylation, RNA expression and proteome profile in oocytes.(At ovarian cryopreservation. Timeframe can be 1 to 15 years, an average of 3 years.)
- Evaluation of uterine growth after OTC.(From the date of inclusion in study until fertility treatment/pregnancy. Timeframe can be up to 35 years.)
- DNA Methylation in leukocytes before and after menopause(From the date of inclusion in study until autotransplantation. Timeframe can be up to 35 years.)
- Maturation of follicles in vitro.(At ovarian cryopreservation. Timeframe can be 1 to 15 years, an average of 3 years.)
- To examine somatic mosaicism in peripheral lymphocytes(At ovarian cryopreservation. Timeframe can be 1 to 15 years, an average of 3 years.)
- To examine bone mineralization and body composition after OTC.(From the date of inclusion in study until autotransplantation. Timeframe can be up to 35 years.)
- To examine somatic mosaicism in epithelial cells in the mouth.(At ovarian cryopreservation. Timeframe can be 1 to 15 years, an average of 3 years.)
- To examine quality of life (QoL) among participants.(At inclusion)
- To examine somatic mosaicism in germ cells.(At ovarian cryopreservation. Timeframe can be 1 to 15 years, an average of 3 years.)
- To evaluate predictors of premature ovarian failure in Turner syndrome under 18 years after ovarian cryopreservation.(From the date of inclusion in study until autotransplantation. Timeframe can be up to 30 years)
- To examine occurrence of surgical complications after OTC.(At ovarian cryopreservation. Timeframe can be 1 to 15 years, an average of 3 years.)