OVARIAN RESERVE IN POST-MENARCHAL FEMALES WITH SICKLE CELL ANEMIA

摘要 先天性溶血性镰状细胞性贫血(SCA)妇女的生殖健康决策 导致多器官损伤和过早死亡的贫血，由于缺乏数据而受到限制 避孕选择、怀孕管理或生育风险。在SCA中，卵巢可能是 氧化损伤和缺氧缺血损伤。羟基脲(HU)，一种用于治疗 SCA早在9个月龄时，可能会对生育能力产生负面影响。在一项评估卵巢的研究中 接受HU治疗的SCA女孩中，33名接受HU治疗的受试者中有8人卵巢储备减少 储备，这与较高的年龄和较长的HU使用时间有关。该数据支持 有些患者的卵巢储备受损，但SCA、SCA 并发症或SCA治疗方法尚不清楚。 为了优化SCA患者的护理，并更好地了解这种生殖生物学，请仔细 需要对卵巢储备进行设计研究，以评估疾病表型和治疗。 这项研究的目标是对卵巢储备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 卵巢储备。这一证据将有助于临床医生考虑到 未经治疗的SCA对抗已知和理论上的SCA疗法的风险。 拟议的研究将调查SCA的临床特征或其主要治疗方法， 羟基脲通过以下途径与SCA的卵巢储备有关：(1)横断面 一项需要收集SCA女性卵巢储备指标的初步数据的研究 和配对对照，以及(2)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。因为这一信息将是 融入以患者为中心的决策，我们还将(3)探索患者知识， 关于生育和SCA治疗的经验和偏好。 这项研究对于了解SCA和HU对卵巢储备的影响至关重要 患有SCA的妇女将通过以下高级培训培养首席调查员 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，首席研究员将泰然处之 在SCA建立生殖健康前沿的独立研究计划。

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.