Risk factors as predictors of ectopic pregnancy

描述（由申请人提供）：背景：异位妊娠（EP）是妊娠早期妊娠相关死亡的主要原因，也是孕产妇发病的主要原因。随着输卵管妊娠的进展，它会侵蚀血管，并可能导致大量腹腔内出血。目前用于诊断EP的策略存在局限性。即使使用诊断算法系统地评估所有有EP风险的女性，也只有50%的EP女性可以在就诊时被诊断出来。其余50%的诊断代表了临床难题，可能需要长达6周的时间。如果EP的诊断是迟发性潜在破裂，导致发病率和死亡率的风险更大，可发生。此外，大尺寸的EP不适合药物治疗，可能需要大手术（剖腹手术）而不是腹腔镜检查，并且即使在破裂之前治疗，也可能对输卵管造成更大的损伤（以及更大的生育能力损害）。此应用程序是ROI（异位妊娠预测的风险因素）的竞争性持续更新。我们已经取得了实质性的进展，包括划定的风险因素作为预测因子的关联强度，临床预测规则的发展，以帮助诊断介绍，并初步发展的血清分子诊断使用蛋白质组学方法。我们还重新定义了使用系列hCG测定来诊断那些在就诊时诊断不确定的有EP风险的妇女。最后，我们已经建立了一个新的医疗管理方案的异位妊娠妇女的安全性。本申请的目的是在更大、多样化和独立的人群中进一步开发和验证这些发现。具体目标和方法：我们计划扩大对有异位妊娠风险的妇女的系统评估，并收集血清，从宾夕法尼亚大学医学中心到其他两个中心（迈阿密和南加州大学）使用修改后的现有电子数据库，该数据库记录了临床过程，并包含用于明确诊断有EP风险但未在演示文稿.我们计划使用这些数据：1）优化（和验证）一个简单的，准确的，非侵入性的，诊断危及生命的条件异位妊娠使用a）临床因素，B）潜在的新的血清标志物和c）这两种方法的组合。2)鉴定构成我们候选分子标志物的蛋白质：3）验证基于系列hCG值的决策规则，该规则适用于在就诊时诊断不明确的女性。4)创建一个潜在的测试，以预测那些谁将有最佳的成功与异位妊娠的医疗管理。这一应用代表了一个独特的机会，联合收割机结合流行病学和基础科学的方法，以了解和改善我们的能力，诊断生殖疾病的重大公共卫生后果的重要限制。我们认为，我们的转化研究的继续有希望提高我们对早期妊娠丢失科学的理解，并优化临床护理，降低发病率和死亡率，因此非常适合NIH路线图战略，以帮助跨学科的开创性研究，以帮助从实验室到床边和床边到实践的翻译。

DESCRIPTION (provided by applicant): Background: Ectopic pregnancy (EP) is the leading pregnancy - related cause of death in the first trimester of pregnancy and a major contributor to maternal morbidity. As the tubal pregnancy progresses, it erodes into blood vessels and can cause massive intra-abdominal bleeding. There are limitations in the strategies currently employed to diagnose EP. Even with the use of diagnostic algorithms that systematically evaluate all women at risk for an EP, only 50 percent of women with an EP can be diagnosed upon presentation. Diagnosis in the remaining 50 percent represents a clinical conundrum and can take up to 6 weeks. If the diagnosis of EP is delayed potential rupture, resulting in greater risks of morbidity and mortality, can occur. Moreover, an EP of large size is not amenable to medical therapy, may require major surgery (laparotomy) instead of laparoscopy and can cause greater damage to fallopian tube (and greater impairment of fertility), even if treated before rupture. This application is a competitive continuing renewal of an ROI (Risk Factors as Predictors of Ectopic pregnancy). We have made substantial progress including delineation of the strength of association of risk factors as predictors, development of a clinical prediction rule to aid in diagnosis upon presentations, and preliminary development of a serum molecular diagnosis using a proteomic approach. We have also redefined the use of serial hCG determinations to diagnosis women at risk for EP whose diagnosis was uncertain at presentation. Finally we have established the safety of a novel medical management regimen for women with ectopic pregnancy. The goals of this application focus on further develop and validation of these finding in a larger, diverse and separate population from which they were developed. Specific Aims and Methods: We plan to extend the systematic evaluation of women at risk for ectopic pregnancy, and collection of serum, form The University of Pennsylvania Medical Center to include to two other centers (The Universities of Miami and Southern California) using a modified existing electronic database that chronicles the clinical course and contains the results of the diagnostic tests used to definitively diagnose women at risk for EP but not diagnosed upon presentation. We plan to use these data to: 1) optimize (and validate) a simple, accurate, non-invasive, diagnosis for the life-threatening condition of ectopic pregnancy using a) clinical factors, b) potential novel serum markers and c) the combination of the two approaches. 2) Identify the proteins that comprise our candidate molecular markers: 3) to validate a decision rule based on serial hCG values for women whose diagnosis was not definitive upon presentation. 4) create a potential test to predict those who will have optimal success with medical management of ectopic pregnancy. This application represents a unique opportunity to combine epidemiologic and basic science methodologies to understand and improve upon important limitations in our ability to diagnose a reproductive disorder with significant public health consequences. We feel that continuation of our translational research has promise to both enhance our understanding of the science of early pregnancy loss as well as to optimize clinical care with potential reduction of morbidity and mortality and therefore fits well into the NIH roadmap strategy to aide interdisciplinary pioneering research to aid in translation from bench to bedside and bedside to practice.