Evaluation of ovarian reserve, aging and fertility preservation in women with sickle cell disease

镰状细胞病女性卵巢储备、衰老和生育力保存的评估

• 批准号: 10217221
• 负责人: Bo Yu
• 金额: $ 23.66万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217221
• 关键词: Acceleration; Acute; Address; Adult; Adverse event; Affect; African; African American; Age; Aging; Assisted Reproductive Technology; Biological; Birth; Caring; Cells; Child; Childhood; Chronic; Chronic Disease; Clinical; Clinical Research; Collaborations; Counseling; Cryopreservation; DNA Methylation; Data; Disease; Eligibility Determination; Embryo; Erythrocyte Transfusion; Evaluation; Female; Female Adolescents; Fertility; Follicular Fluid; Foundations; Functional disorder; Future; Gene Expression; Goals; Grant; Head; Health; Health Personnel; Hematological Disease; Hematologist; Hypoxia; Immunization; Impairment; Infertility; Inflammation; Inflammatory; Intervention; Investigation; Knowledge; Life; Measures; Mendelian disorder; Methods; Modality; Molecular; Morbidity - disease rate; Neonatal Screening; Observational Study; Oocytes; Organ; Outcome; Ovarian; Ovarian Granulosa Cell; Ovarian aging; Pathology; Patients; Penicillins; Physiology; Pilot Projects; Population; Procedures; Prophylactic treatment; Protocols documentation; Recommendation; Recurrence; Registries; Reproduction; Reproductive Endocrinology; Reproductive Health; Research Personnel; Risk; Severity of illness; Sickle Cell Anemia; Solid; Specialist; Streptococcus pneumoniae; Testing; Therapeutic; Time; Tissues; United States; Universities; Washington; Woman; Work; age related; aged; base; cohort; diminished ovarian reserve; disorder control; embryo cryopreservation; female fertility; fertility preservation; granulosa cell; high risk; hydroxyurea; improved; insight; male fertility; offspring; oocyte cryopreservation; ovarian reserve; programs; reproductive; safety study; subfertility; success; treatment strategy

PROJECT SUMMARY/ABSTRACT Sickle cell disease (SCD) is one of the most common monogenic diseases affecting over 300,000 births worldwide and 1 in 400 of African descent. In the last few decades, SCD has evolved from a life-threatening disease of childhood to a chronic disease in adults. With improved survival and reduced disease-related morbidity, reproductive health is emerging as a priority in SCD care. However, appropriate fertility counseling and treatment recommendations are limited by our lack of understanding of the impact of SCD and disease- modifying therapies on reproduction. There is an urgent need to evaluate the fertility and to optimize fertility preservation options in women affected by SCD. The objectives of this proposal are to evaluate how SCD affects ovarian reserve and female fertility, and to determine what the best timing and methods to preserve fertility are in these women. The central hypothesis is that SCD leads to accelerated ovarian aging through chronic tissue hypoxia and inflammation, which adversely affects the fertility of women with SCD. Utilizing our complementary expertise and an existing adult SCD clinical research program, we propose the following studies to achieve our objectives: Aim 1. Measure ovarian reserve in adult women with SCD and follow longitudinally over two years. Aim 2. Establish optimal fertility preservation protocol in a pilot cohort of women with SCD and optimize the management of any adverse events that occur during their assisted reproductive treatments. Aim 3. Assess ovarian aging acceleration and inflammation in the ovarian granulosa cells obtained from women with SCD, as compared with age-matched non-SCD controls. These studies will the first to systematically evaluate the impact of SCD on ovarian aging and female fertility from both clinical and molecular levels. This work will significantly improve our ability to counsel women with SCD on their risks of infertility and how these risks are modified by age and disease severity. This grant will lay important groundwork for a more comprehensive study on ovarian pathophysiology in adolescent females with SCD, with the goal of optimizing fertility preservation prior to onset of end-organ damage in this younger population. The preliminary data obtained from this study will also serve as the basis for establishing a national registry to surveil fertility preservation approaches and long-term outcomes in women with SCD seeking fertility evaluation and treatments. These investigations will increase our understanding of how SCD impacts female fertility and serve the unmet reproductive health needs of all women with SCD.

项目摘要/摘要 镰状细胞疾病（SCD）是影响超过300,000个出生的最常见的单基因疾病之一 全球，非洲血统中有1个。在过去的几十年中，SCD源于威胁生命的 成人慢性病的儿童疾病。随着生存率提高并降低了与疾病相关的 发病率，生殖健康正在成为SCD护理的优先事项。但是，适当的生育咨询 以及治疗建议受到我们对SCD和疾病影响的不了解的限制。 修改繁殖疗法。迫切需要评估生育能力并优化生育能力 受SCD影响的妇女的保存选择。该提案的目标是评估SCD 影响卵巢储备和女性生育能力，并确定保存的最佳时机和方法 这些妇女的生育能力。中心假设是SCD导致通过 慢性组织缺氧和炎症，会对SCD女性的生育产生不利影响。利用我们的 补充专业知识和现有的成人SCD临床研究计划，我们提出以下内容 实现我们目标的研究：目标1。衡量SCD成年女性的卵巢储备并遵循 纵向两年。目标2。在妇女的飞行员队列中建立最佳的生育能力保护方案 使用SCD并优化对辅助生殖期间发生的任何不良事件的管理 治疗。 AIM 3。评估获得的卵巢衰老加速度和炎症 与年龄匹配的非SCD对照相比，来自SCD的女性。这些研究将首先 系统地评估SCD对临床和分子的卵巢衰老和女性生育的影响 水平。这项工作将大大提高我们为SCD咨询妇女的不孕风险和 这些风险如何通过年龄和疾病的严重程度来改变。这笔赠款将为更多的基础奠定重要的基础 SCD青春期女性卵巢病理生理学的全面研究，目的是优化 在这个年轻人口的最终器官损害发作之前，生育力保存。初步数据 从这项研究获得 SCD寻求生育评估的女性的保存方法和长期结局 治疗。这些调查将增加我们对SCD如何影响女性生育能力的理解并服务 所有SCD女性的未满足的生殖健康需求。

项目成果

Preconception paternal comorbidities and offspring birth defects: Analysis of a large national data set.

孕前父亲合并症和后代出生缺陷：大型国家数据集的分析。

• DOI: 10.1002/bdr2.2082
• 发表时间: 2023
• 期刊: Birth defects research
• 影响因子: 2.1
• 作者: Yu,Bo;Zhang,ChiyuanAmy;Li,Shufeng;Chen,Tony;Mulloy,Evan;Shaw,GaryM;Eisenberg,MichaelL
• 通讯作者: Eisenberg,MichaelL