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）：大约 10% 无法怀孕的女性被诊断患有卵巢储备功能减退 (DOR)。 DOR 描述了卵巢功能的下降。很少有患有此诊断的女性（<5%）会自然怀孕，并且她们对生育药物没有正常反应。没有有效的治疗方法可以逆转这种情况。患有 DOR 的女性可能存在脆性 X 基因（“携带者”）的前突变改变。这种前突变的携带者患卵巢早衰 (POF) 的风险也增加，这是一种比 DOR 更严重的卵巢功能障碍。大约 5-6% 的 POF 女性是前突变携带者（如果有过早绝经家族史，则为 14%；否则为 2%）。目前尚不清楚患有 DOR 的女性中有多少比例是前突变携带者。我们将把目前针对 POF 的 Fragile X 研究扩展到 DOR 人群。本研究的具体目的是： (1) 确定 DOR 女性中脆性 X 前突变的患病率； (2) 确定患病率是否随早期绝经和/或不孕不育的家族史而变化； (3)确定患者年龄、卵泡刺激素水平和前突变的“大小”之间是否存在关系。在这一前瞻性队列中，将从三个学术医疗中心（弗吉尼亚州、北卡罗来纳州）和一个私人诊所招募 65 名符合条件的 DOR 患者。该协议包括预测试遗传咨询、用于脆性 X 细胞测试的血液样本和问卷。医疗图表中不会记录血液检测结果，女性可以选择是否了解脆性 X 检测结果。将为所有携带者提供测试后遗传咨询。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，一名是携带者，另外 15 名希望了解他们的测试结果。统计分析将包括二项式检验、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性 X 前突变中识别出一种新的表型，开始开发一种临床工具来预测携带者的不孕年龄，并增强携带者的生殖计划和决策。生育治疗对脆性 X 染色体携带者的影响值得注意，因为将脆性 X 染色体综合征传播给通过生育治疗出生的孩子；因此，这项研究也适用于更大的问题，即意外基因检测对社会和个人的影响。