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: 10307488
• 负责人: Bo Yu
• 金额: $ 19.71万
• 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 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10307488
• 关键词: Evaluation; ovarian; reserve; aging; fertility

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.

项目概要/摘要 镰状细胞病 (SCD) 是最常见的单基因疾病之一，影响超过 300,000 名新生儿 全世界每 400 人中就有 1 人是非洲人后裔。在过去的几十年里，SCD 已经从威胁生命的疾病演变为 儿童时期的疾病到成人的慢性疾病。提高生存率并减少疾病相关 发病率、生殖健康正在成为 SCD 护理的优先事项。然而，适当的生育咨询 由于我们对 SCD 和疾病的影响缺乏了解，治疗建议受到限制 - 修改生殖疗法。迫切需要评估生育能力并优化生育能力 受 SCD 影响的女性的保存选择。本提案的目标是评估 SCD 如何 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 这些女性具有生育能力。核心假设是 SCD 通过以下方式导致卵巢加速老化： 慢性组织缺氧和炎症，对患有 SCD 的女性的生育能力产生不利影响。利用我们的 互补的专业知识和现有的成人 SCD 临床研究计划，我们提出以下建议 为实现我们的目标而进行的研究： 目标 1. 测量患有 SCD 的成年女性的卵巢储备并遵循 纵向超过两年。目标 2. 在女性试点队列中建立最佳的生育力保存方案 进行 SCD 并优化辅助生殖期间发生的任何不良事件的管理 治疗。目标 3. 评估获得的卵巢颗粒细胞的卵巢老化加速和炎症 患有 SCD 的女性与年龄匹配的非 SCD 对照相比。这些研究将首先 从临床和分子水平系统评价SCD对卵巢衰老和女性生育能力的影响 水平。这项工作将显着提高我们为患有 SCD 的女性提供有关不孕和不孕风险的咨询的能力 这些风险如何随年龄和疾病严重程度而改变。这笔赠款将为更多的项目奠定重要基础 青春期女性 SCD 卵巢病理生理学的综合研究，目标是优化 在这一年轻人群中，在终末器官损伤发生之前保留生育能力。初步数据 从这项研究中获得的数据也将作为建立国家登记处以监测生育率的基础 寻求生育力评估的 SCD 女性的保存方法和长期结果 治疗。这些调查将加深我们对 SCD 如何影响女性生育力的了解并服务 所有患有 SCD 的妇女未得到满足的生殖健康需求。