OVARIAN RESERVE IN POST-MENARCHAL FEMALES WITH SICKLE CELL ANEMIA

摘要 镰状细胞性贫血（SCA）是一种先天性溶血性贫血， 导致多器官损伤和早期死亡的贫血，由于缺乏数据， 避孕选择、妊娠管理或生育风险。在SCA中，卵巢可能 氧化损伤和缺氧缺血损伤。羟基脲（HU），用于治疗 SCA早在9个月大时，可能会对生育能力产生负面影响。在一项研究中， 在用HU治疗的SCA女孩中，33例HU治疗的受试者中有8例卵巢储备减少， 储备，这与年龄较大和使用HU的时间较长有关。该数据支持 卵巢储备功能在某些患者中受损，但SCA，SCA 并发症或SCA治疗未知。 为了优化SCA患者护理并更好地了解这种生殖生物学， 需要对卵巢储备功能进行设计性研究，以评估疾病表型和治疗。 本研究的目的是对卵巢储备功能进行严格的方法学评估 在患有SCA的女性中，评估SCA或其治疗是否与减少 卵巢储备这一证据将有助于临床医生管理患者， 未治疗的SCA与SCA治疗的已知和理论风险之间的关系。 拟议的研究将调查SCA的临床特征或其主要治疗， 通过进行（1）横断面研究， 一项需要收集SCA女性卵巢储备测量数据的研究 和匹配的对照，以及（2）是否HU治疗，临床和实验室研究 SCA的生物标志物与卵巢储备减少有关。由于这些信息将 纳入以病人为中心的决策，我们还将（3）探索病人的知识， 关于生育和SCA疗法的经验和偏好。 这项研究对于理解SCA和HU对卵巢储备功能的影响至关重要， SCA的女性，将通过高级培训培养主要研究者， 流行病学和生物统计学，定性研究方法和生殖医学， SCA。很少有血液学家有这样的专业知识，首席研究员将泰然自若 在SCA的生殖健康前沿建立一个独立的研究计划。

ABSTRACT Reproductive health decisions for women with sickle cell anemia (SCA) a congenital hemolytic anemia that causes multi-organ injury and early death, are limited by a lack of data to inform contraception choices, pregnancy management or fertility risks. In SCA, the ovaries may be injured by oxidative and hypoxic-ischemic injury. Hydroxyurea (HU), a medication used to treat SCA as early as 9 months of age, may affect fertility negatively. In a study evaluating ovarian reserve in girls with SCA treated with HU, 8 of 33 HU-treated subjects had diminished ovarian reserve, which was associated with older age and longer duration of HU use. This data supports that ovarian reserve is compromised in some patients, but the contributions of SCA, SCA complications or SCA treatments are unknown. To optimize SCA patient care and to better understand this reproductive biology, carefully designed studies of ovarian reserve that assess disease phenotype and treatment are needed. The goal of this research is to conduct a methodologically rigorous evaluation of ovarian reserve in women with SCA to assess whether SCA or its treatments are associated with diminished ovarian reserve. This evidence will help clinicians manage patients considering the risks of untreated SCA against the known and theorized risks of SCA therapies. The proposed study will investigate whether clinical features of SCA or its primary treatment, hydroxyurea, are associated with ovarian reserve in SCA by conducting (1) a cross-sectional study that entails primary data collection of measures of ovarian reserve in women with SCA and matched controls, and (2) a study of whether HU treatment, clinical and laboratory biomarkers of SCA are associated with reduced ovarian reserve. As this information will be incorporated into patient-centered decision making, we will also (3) explore patient knowledge, experiences and preferences about fertility and SCA therapies. This research, critical for understanding the effects of SCA and HU on ovarian reserve in women with SCA, will develop the principal investigator through advanced training in epidemiology and biostatistics, qualitative research methods and reproductive medicine and SCA. Few hematologists have this kind of expertise and the principal investigator will be poised to build an independent research program at the forefront of reproductive health in SCA.