Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Single cell/nucleus RNA sequencing
研究概览
简要总结
Background:
Turner Syndrome, galactosemia, and premature ovarian insufficiency are all conditions that may make it very hard or impossible for a person to become pregnant and have their own child. Researchers want to learn more about why this happens and if freezing Gonadal tissue allows for fertility preservation.
Objective:
To find out why people with certain conditions have can have premature ovarian insufficiency (POI or early menopause) and individuals with variations in sex characteristics have trouble getting pregnant and if freezing the gonads tissue from them will help to have their own child in the future.
Eligibility:
Individuals aged 2-21 who have Turner Syndrome or galactosemia. Also, females aged 13-21 with premature ovarian insufficiency, individuals with variations in sex characteristics, and individuals 2-35 receiving high-risk gonadotoxic therapy
Design:
Participants will be screened with a medical history.
Participants may have a physical exam and blood tests. Their body measurements may be taken. These include weight, height, arm span, skin fold, and sitting height. They may fill out surveys about their quality of life, body image, and health.
Participants may have a transabdominal pelvic ultrasound. A probe will be placed on their belly and will take pictures of the organs in the pelvis. They may have a transvaginal pelvic ultrasound performed while asleep in the operating room if needed.
Participants may have surgery to remove an gonads and skin biopsy. The removed tissue will be frozen and stored. The tissue will have to be stored for many years. NIH will pay to store the tissue for 1 year. After that, participants will have to pay for storage.
A piece of the gonads (no more than 20%) will be used for research
Travel, lodging and meals for participants traveling greater than 50 miles will be reimbursed based off the government rate. Local participants will not be reimbursed.
Participants will have a checkup 6 weeks after surgery one or more follow-up visits 6-18 months after surgery. They may have phone follow-up every 12-24 months after surgery.
Participation will last 30 years.
详细描述
Study Description:
Gonadal tissue cryopreservation will be evaluated in individuals with Turner Syndrome, galactosemia, post-menarcheal adolescents with recent premature ovarian insufficiency, and children/adolescents conditions associated with POI and with diminished ovarian reserve (DOR) who have contraindication to ovarian stimulation as well as those with diminished ovarian reserve who did not respond to ovarian stimulation, and individuals with variations in sex characteristics (VSD or differences in sex development, DSD) including those with Turner syndrome with Y chromosome material and those with conditions that require high risk gonadotoxic therapy.
Objectives:
Primary Objectives: After initial evaluation of number and quality of follicles/gametes, the remaining tissue will be utilized to perform research regarding mechanisms of follicle/gametes loss in the included conditions.
a. We will perform next generation sequencing on the tissue collected from study participants and ovaries from cadaveric organ donors on cardiopulmonary support. Additionally, some ovarian tissue from patients undergoing gonadotoxic therapy will function as controls.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 2 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •Individuals with Turner Syndrome prior to menarche aged 2 years to 12 years whose families seek to store ovarian tissue for possible future use.
- •Individuals with galactosemia (age 2-21)
- •Adolescent females up to age 21 years old, who have undergone menarche and are subsequently diagnosed with premature ovarian insufficiency and their last menstrual period occurred within 2 years of presentation. Diagnosis of POI is based on 2 elevated FSH concentrations obtained over 1 month apart.
- •Children or adolescents aged 2-24 years old who have diminished ovarian reserve based on laboratory findings or who respond poorly to ovarian stimulation for egg freezing.
- •Individuals with variations in sex characteristics (or differences in sex development, DSD) including Turner syndrome with Y chromosome material who undergo prophylactic gonadectomy for clinical indications.
- •Individuals (2-35 years) receiving high-risk gonadotoxic therapy at the NIH Clinical Center who are at high risk for developing premature ovarian insufficiency and infertility.
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •Ability of subject, parents, or guardian to understand and the willingness to sign a written informed consent document.
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Individuals older than 7 years with psychological, psychiatric, or other conditions which prevent giving fully informed consent or assent.
- •Individuals with a pelvic mass tumor noted on pre-operative ultrasound, will undergo usual care for the underlying condition and will not undergo oophorectomy for ovarian tissue cryopreservation.
- •Individuals whose underlying medical condition significantly increases their risk of complications from anesthesia and surgery.
- •Females with POI due to chemotherapy or radiation treatment
- •Pregnancy or lactation
- •Individuals with VSC who choose to retain gonads after clinical consulting.
- •Individuals with Turner Syndrome who have an undetectable AMH based on testing laboratory reference range.
研究组 & 干预措施
Turner Syndrome with Y material
Children and adolescents who have Turner syndrome with Y material and undergo prophylactic gonadectomy.
Adolescents with DOR
Adolescents with diminished ovarian reserve (DOR) who respond poorly to ovarian stimulation for egg freezing.
Individuals receiving high-risk gonadotoxic therapy
Individuals (2-35 years) receiving high-risk gonadotoxic therapy at the NIH Clinical Center who are at high risk for developing premature ovarian insufficiency and infertility.
Individuals with variations in sex characteristics (or differences in sex development, DSD)
Individuals with variations in sex characteristics (or differences in sex development, DSD) who undergo gonadectomy for clinical indications.
Turner Syndrome and galactosemia
Individuals with Turner Syndrome prior to menarche aged 2 years to 12 years, who have not previously demonstrated signs of premature ovarian insufficiency (FSH>25 IU/L).
Adolescents with POI
Adolescent females up to age 21 years old, who have undergone menarche and are subsequently diagnosed with POI and their last menstrual period occurred within 2 years of presentation.
结局指标
主要结局
Single cell/nucleus RNA sequencing
时间窗: before and after cryopreservation
Single cell/nucleus RNA sequencing on fresh compared to frozen and thawed tissue. This will assess what transcription changed occur due to the freezing process.
Tissue for research
时间窗: before and after cryopreservation
initial evaluation of number and quality of follicles before and after cryopreservation
次要结局
- Compare hormone levels(before and after cryopreservation)
- density and quality of follicles in the ovaries(before and after cryopreservation)
- Evaluate gonadal tissue(before and after cryopreservation)
- Evaluate changes in single cell/nucleus RNA sequencing(before and after cryopreservation)
- Correlation of follicle density and quality with markers such as age, AMH, condition.(before and after cryopreservation)