Abstract
BackgroundEctopic pregnancy (EP) occurs in 1–2% of pregnancies, but is over-represented as a leading cause of maternal death in early pregnancy. It remains a challenge to diagnose early and accurately. Women often present in early pregnancy with a ‘pregnancy of unknown location’ (PUL) and the diagnosis and exclusion of EP is difficult due to a lack of reliable biomarkers. A serum biomarker able to clearly distinguish between EP and other pregnancy outcomes would greatly assist clinicians in diagnosing and safely managing PULs. This study evaluates the ability of maternal serum macrophage inhibitory cytokine-1 (MIC-1) levels to differentiate between EP and other pregnancy outcomes in women with a PUL.MethodsSera were collected from 120 women with a PUL at first clinical presentation and assayed for MIC-1 by ELISA. Results were classified according to ultimate pregnancy outcome and the discriminatory ability of MIC-1 to diagnose EP was assessed.ResultsSerum MIC-1 levels were lower in women with histologically confirmed (definite) EP (dEP) (median 552 ng/mL; interquartile range (IQR) 414–693 ng/mL) compared to women with definite viable intra-uterine pregnancies (dVIUPs) (722 ng/mL; IQR 412–1122 ng/mL), and higher when compared to women with definite non-viable intra-uterine pregnancies (dNVIUPs) (465 ng/mL; IQR 341–675 ng/mL). MIC-1 levels were significantly higher in women with dEP compared to women whose PULs resolved without medical intervention (srPUL) (401 ng/mL; IQR 315–475 ng/mL) (p<0.003). There were no women with an ectopic pregnancy where serum MIC-1>1000 ng/mL.ConclusionSerum MIC-1 levels in PUL were not able to categorically diagnose EP, however, MIC-1 could distinguish women with an EP that required medical intervention and those women whose PULs spontaneously resolved. A single serum MIC-1 measurement also excluded EP at levels above 1000 ng/mL. MIC-1 may play a role in the development of a combined assay of biomarkers for the diagnosis of EP.
Highlights
Ectopic pregnancy (EP) occurs in 1–2% of pregnancies and remains a leading cause of maternal death in early pregnancy [1,2]
Serum macrophage inhibitory cytokine-1 (MIC-1) levels were lower in women with histologically confirmed EP compared to women with definite viable intrauterine pregnancies (722 ng/mL; interquartile range (IQR) 412–1122 ng/mL), and higher compared to women with definite non-viable intrauterine pregnancies (465 ng/mL; IQR 341–675 ng/mL) and treated pregnancy of unknown location’ (PUL) (400 ng/mL; IQR 388–473 ng/mL)
Levels were higher in women with dEP than in women who were medically managed for probable EPs (434 ng/mL; IQR 315–541 ng/mL)
Summary
Ectopic pregnancy (EP) occurs in 1–2% of pregnancies and remains a leading cause of maternal death in early pregnancy [1,2]. The challenge for the clinician is to be able to accurately distinguish between pregnancy outcomes in order to safely manage any woman presenting with these symptoms. When neither an intrauterine nor an EP can be visualized by TVUS, the woman is classified as having a pregnancy of unknown location (PUL) [4] This requires further time and resource intensive follow-up, including serial serum human chorionic gonadotrophin (hCG) levels and repeat TVUS to determine pregnancy location and appropriate management [5,6]. A serum biomarker able to clearly distinguish between EP and other pregnancy outcomes would greatly assist clinicians in diagnosing and safely managing PULs. This study evaluates the ability of maternal serum macrophage inhibitory cytokine-1 (MIC-1) levels to differentiate between EP and other pregnancy outcomes in women with a PUL
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