Identifying Genome Variants and Evaluating PRDM9 and piRNA Clusters as Candidates for Infertility in a Cohort of Individuals With Non-Obstructive Azoospermia (NOA) or Primary Ovarian Insufficiency (POI)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 500
- 试验地点
- 2
- 主要终点
- Genetic associations with infertility (primary ovarian insufficiency, oligospermia, non obstructive azoospermia)
研究概览
简要总结
Background:
Infertility affects 1 in 6 people. Often, the causes of infertility are unknown. Treatments are successful in only about 50% of cases. Infertility caused by non obstructive azoospermia in males and primary ovarian insufficiency in females can have genetic causes. Researchers want to learn more about these genes.
Objective:
To identify genes that may cause infertility.
Eligibility:
Adult men and women with non-obstructive azoospermia (NOA) or primary ovarian insufficiency (POI) of unknown cause.
Design:
Participants will provide a saliva sample. A kit will be sent to their home. The kit will contain a collection tube and a cotton swab. They will swirl the swab inside their mouth and then seal it in the tube. They will mail the tube back to the researchers.
Male participants who are having a procedure done to collect tissue from their testes may opt to have leftover tissue provided to study researchers. This tissue would otherwise have been discarded. No new procedures will be performed just for this study.
Data may be collected from participants medical records.
详细描述
Study Description:
PRDM9 and the piRNA pathway have well established roles in meiosis and are known to cause infertility in mouse, yet have not been systematically evaluated for a role in human infertility. We will utilize a combination of genome sequencing, targeted PacBio sequencing, and in vitro assays to evaluate these compelling candidates as causative for human infertility. All participants will be asked to provide saliva or blood samples as a source of genomic DNA for sequencing. A small subset of participants who undergo surgery as part of their diagnosis and treatment plan will be asked to consent to research use of leftover testicular biopsies from these procedures.
Objectives:
Primary Objective:
To determine the sequence of PRDM9 and noncoding piRNA clusters in a cohort of individuals with infertility. These loci are inherently unstable in the genome, and we hypothesize that sequence variants in these loci are causative for infertility.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older 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:
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Adult male or female, of reproductive age
- •Clinical diagnosis of NOA, oligospermia, or POI.
- •In good general health with no medical history suspected as the cause of infertility.
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Current use of medications that may cause infertility (chemotherapy, etc.)
- •Pregnant or lactating
- •Medical history indicating known common cause of infertility such as karyotype anomalies, Y-chromosome microdeletions, known monogenic causes, or other medical history affecting gamete production (i.e. injuries, surgical operations, infections, radiation, or chemotherapy).
研究组 & 干预措施
Non obstructive azoospermia
Men aged 18 and older who have no semen in the ejaculate with no evidence of pathologic transport of sperm
Oligospermia
Men aged 18 or older who have a concentration less than 5 million/mL in ejaculate with no other known cause of oligospermia.
Primary ovarian insufficiency
Women who have been diagnosed with primary ovarian insufficiency
结局指标
主要结局
Genetic associations with infertility (primary ovarian insufficiency, oligospermia, non obstructive azoospermia)
时间窗: 5 years
Across 5 years we will sequence patients with POI and NOA to determine genetic associations with infertility
次要结局
未报告次要终点