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 镰状细胞病（SCD）是最常见的单基因疾病之一，影响30多万新生儿 全世界每400人中就有一人是非洲人后裔。在过去的几十年里，SCD已经从一种危及生命的疾病发展成为一种 从儿童期的疾病转变为成人的慢性疾病。提高了生存率，减少了与疾病相关的 在发病率方面，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 和治疗建议是有限的，因为我们缺乏对SCD和疾病的影响的了解- 修改生殖疗法。迫切需要对生育率进行评估并优化生育率 在患有SCD的女性中的保存选择。本提案的目的是评估SCD如何 影响卵巢储备和女性生育能力，并确定什么是最佳的时间和方法来保存 生育能力在这些女性身上。核心假设是SCD通过以下途径导致卵巢加速老化： 慢性组织缺氧和炎症，这对患有SCD的女性的生育能力产生不利影响。利用我们 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。SCD成年女性卵巢储备功能的测定及随访 纵向超过两年。目标2.在一个试点妇女队列中建立最佳生育力保存方案 与SCD和优化管理的任何不良事件发生在他们的辅助生殖 治疗。目标3.评估卵巢老化加速和卵巢颗粒细胞中的炎症， 与年龄匹配的非SCD对照组相比。这些研究将首次 从临床和分子水平系统评价SCD对卵巢衰老和女性生育力的影响 程度.这项工作将显著提高我们为SCD妇女提供不孕风险咨询的能力， 这些风险是如何被年龄和疾病严重程度所改变的。这笔赠款将为一个更重要的基础， 对患有SCD的青春期女性卵巢病理生理学进行全面研究，目标是优化 在这个年轻人群中，在终末器官损伤发生之前保持生育能力。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册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局， 治疗。这些调查将增加我们对SCD如何影响女性生育力的理解， 所有SCD妇女的生殖健康需求未得到满足。

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