Fragile X Premutations Among Women Diagnosed with Diminished Ovarian Reserve

诊断为卵巢储备功能减退的女性中的脆性 X 前突变

• 批准号: 7195967
• 负责人: LISA M PASTORE
• 金额: $ 8.3万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-05 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7195967
• 关键词: Academic Medical Centers; Address; Adult; Age; Aging; Blood Tests; Blood specimen; Child; Clinical; Communication; Conceptions; Condition; Decision Making; Development; Diagnosis; Disclosure; Disease; Educational workshop; Enrollment; Estrogens; Etiology; Extramural Activities; FMR1 Gene; Failure; Family history of; Female; Female infertility; Fertility; Fertility Agents; Fertilization in Vitro; Follicle Stimulating Hormone; Fragile X Gene; Fragile X Premutation; Fragile X Syndrome; Functional disorder; Future; Genetic Counseling; Genetic Risk; Genetic screening method; Hormonal; Individual; Infertility; Lead; Learning; Linear Models; Linear Regressions; Logistic Regressions; Measures; Medical; Medical center; Menopause; Modality; Modeling; Mutation; National Institute of Child Health and Human Development; Neonatal Screening; North Carolina; Numbers; Ovarian; Ovarian hormone; Ovary; Participant; Patient currently pregnant; Patients; Phenotype; Physiological; Population; Premature Menopause; Premature Ovarian Failure; Prevalence; Private Practice; Protocols documentation; Purpose; Questionnaires; Rate; Reaction; Relative (related person); Reproduction; Research; Risk; Risk Factors; Sample Size; Screening procedure; Second Degree Relative; Societies; Son; Test Result; Testing; Twin Multiple Birth; United States National Institutes of Health; Virginia; Visit; Woman; X Chromosome; cohort; day; experience; improved; prospective; racial/ethnic difference; reproductive; size; success; tool

DESCRIPTION (provided by applicant): About 10% of women who are unable to get pregnant are diagnosed with diminished ovarian reserve (DOR). DOR describes a reduction in ovarian function. Few women (<5%) with this diagnosis will become pregnant spontaneously and they do not respond normally to fertility drugs. There are no effective treatments to reverse this condition. Women with DOR may have a premutation alteration of the Fragile X gene ("carriers"). Carriers of this premutation are also at increased risk for premature ovarian failure (POF), which is a greater degree of ovarian dysfunction than DOR. About 5-6% of the women with POF are premutation carriers (14% if she has a family history of premature menopause; 2% otherwise). It is unknown what percentage of women with DOR are premutation carriers. We will extend the current Fragile X research on POF to the DOR population. Specific aims of this study are: (1) to determine the prevalence of the Fragile X premutation among DOR women; (2) to determine if the prevalence varies with a family history of early menopause and/or infertility; and (3) to determine if there is a relationship between patient age, follicle stimulating hormone level, and the "size" of the premutation. In this prospective cohort, 65 eligible DOR patients will be enrolled from three academic medical centers (Virginia, North Carolina) and one private practice. The protocol includes pretest genetic counseling, a blood sample for Fragile X testing, and questionnaires. No blood test results will be filed in the medical charts, and women will have the option of learning their Fragile X test results or not. Post test genetic counseling will be provided to all carriers. We are currently pilot-testing this study; among our first 16 participants, one is a carrier and 15 have wanted to learn their test results. The statistical analysis will consist of proportions with binomial testing, logistic regression models, and linear regression models. This research may identify a new phenotype from Fragile X premutations, begin the development of a clinical tool to predict age-at-infertility among carriers, and enhance reproductive planning and decision-making by carriers. The implications of fertility treatment to Fragile X carriers is notable in terms of transmitting Fragile X Syndrome to the children born via fertility treatment; therefore, this research also has applications to the greater issue of the impact on society and individuals from unanticipated genetic testing.

描述（由申请人提供）：约有10％无法怀孕的妇女被诊断出患有卵巢储量减少（DOR）。 DOR描述了卵巢功能的降低。很少有女性（<5％）可以自发怀孕，并且对生育药物的反应不正常。没有有效的治疗方法可以扭转这种情况。患有DOR的妇女可能会对脆弱的X基因（“载体”）进行预先改变。该预先享受的载体也有增加卵巢衰竭（POF）的风险，这比DOR更大程度。大约5-6％的POF妇女是招聘携带者（如果她有更年期的家族史，则为14％；否则为2％）。尚不清楚有多数百分比有DOR的妇女。我们将将当前对POF的脆弱X研究扩展到DOR人群。这项研究的具体目的是：（1）确定DOR妇女脆弱的X extrience的患病率； （2）确定患病率是否随早期和/或不孕症的家族史而变化； （3）确定患者年龄之间的关系，卵泡刺激激素水平和预告的“大小”。在这个潜在的队列中，将有65名合格的DOR患者从三个学术医疗中心（弗吉尼亚州，北卡罗来纳州）和一名私人执业中入学。该方案包括预测的遗传咨询，用于脆弱X检测的血液样本和问卷。医疗图表中不会提交血液检查结果，女性将可以选择学习脆弱的X测试结果。测试后的遗传咨询将向所有承运人提供。我们目前正在对这项研究进行试点测试；在我们的前16名参与者中，有15个是载体，而15位则想学习他们的测试结果。统计分析将包括具有二项式测试，逻辑回归模型和线性回归模型的比例。这项研究可能会从脆弱的X预言中确定一种新的表型，开始开发一种临床工具，以预测载体之间的年龄，并增强载体的生殖计划和决策。生育治疗对脆弱的X载体的影响在将脆弱的X综合征传递给通过生育治疗而出生的孩子而言是值得注意的。因此，这项研究还适用于对社会和意外基因测试对个人的影响更大的问题。