MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
PLoS One. 2012;7(8):e41442. doi: 10.1371/journal.pone.0041442. Epub 2012 Aug 21.
Ectopic pregnancy (EP) remains the most life-threatening acute condition in modern gynaecology. It remains difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a 'pregnancy of unknown location' (PUL) and diagnosis/exclusion of EP is challenging due to a lack of reliable biomarkers. Recent studies suggest that serum levels of a disintegrin and metalloprotease protein-12 (ADAM-12) can be used differentiate EP from viable intrauterine pregnancy (VIUP). Here we describe a prospective study evaluating the performance of ADAM-12 in differentiating EP from the full spectrum of alternative PUL outcomes in an independent patient cohort.
METHODOLOGY/PRINCIPAL FINDINGS: Sera were collected from 120 patients at their first clinical presentation with a PUL and assayed for ADAM-12 by ELISA. Patients were categorized according to final pregnancy outcomes. Serum ADAM-12 concentrations were increased in women with histologically-confirmed EP (median 442 pg/mL; 25%-75% percentile 232-783 pg/mL) compared to women with VIUP (256 pg/mL; 168-442 pg/mL) or miscarriage (192 pg/mL; 133-476 pg/mL). Serum ADAM-12 did not differentiate histologically-confirmed EP from spontaneously resolving PUL (srPUL) (416 pg/mL; 154-608 pg/mL). The diagnostic potential of ADAM-12 was only significant when 'ambiguous' PUL outcomes were excluded from the analysis (AROC = 0.6633; P = 0.03901).
CONCLUSIONS/SIGNIFICANCE: When measured in isolation, ADAM-12 levels had limited value as a diagnostic biomarker for EP in our patient cohort. The development of a reliable serum biomarker-based test for EP remains an ongoing challenge.
宫外孕（EP）仍然是现代妇科中最具威胁生命的急性病症。早期准确诊断仍然具有挑战性。由于缺乏可靠的生物标志物，女性在早孕时常因“位置不明的妊娠”（PUL）就诊于急诊科，因此诊断/排除 EP 具有挑战性。最近的研究表明，解整合素和金属蛋白酶 12（ADAM-12）的血清水平可用于区分 EP 与有活力的宫内妊娠（VIUP）。在这里，我们描述了一项前瞻性研究，该研究评估了 ADAM-12 在区分 EP 与独立患者队列中替代 PUL 结果的全谱方面的性能。
方法/主要发现：从 120 名首次出现 PUL 的患者的血清中采集血清，并通过 ELISA 测定 ADAM-12。根据最终妊娠结局对患者进行分类。与 VIUP（256pg/ml；168-442pg/ml）或流产（192pg/ml；133-476pg/ml）相比，组织学证实的 EP 患者血清 ADAM-12 浓度升高（中位数 442pg/ml；25%-75%百分位数 232-783pg/ml）。血清 ADAM-12 不能区分组织学证实的 EP 与自发消退的 PUL（srPUL）（416pg/ml；154-608pg/ml）。当排除“模糊”PUL 结局时，ADAM-12 的诊断潜力仅具有统计学意义（AUC=0.6633；P=0.03901）。
结论/意义：在我们的患者队列中，单独测量时，ADAM-12 水平作为 EP 的诊断生物标志物的价值有限。开发基于可靠血清生物标志物的 EP 测试仍然是一个持续的挑战。
