Placental mRNA in maternal plasma as a predictor of ectopic pregnancy

Abstract

Objective To measure and compare placental mRNA expression in the maternal circulation among women with intrauterine and ectopic pregnancies. Methods Plasma was collected from patients in early pregnancy at risk of ectopic pregnancy. Clinical information was prospectively collected and entered into a dedicated database. mRNA was isolated from maternal plasma and quantitative RT-PCR was performed to measure mRNA for human gonadotropin (hCG) and human placental lactogen (hPL). GAPDH mRNA expression was used as an internal control. Results Twelve women with ectopic pregnancy and 13 women with intrauterine pregnancy were enrolled. Patients with ectopic pregnancy were 6 times more likely to have undetectable levels of hPL mRNA (relative risk [RR] 6.36; 95% confidence interval [CI], 1.70–23.20; P<0.01). They were also 8 times more likely to have undetectable levels of hCG mRNA (RR 8.64, 95% CI, 1.30–57.10; P<0.01). mRNA copy numbers for hPL and hCG (normalized by GAPDH) were significantly lower in the ectopic group than in the intrauterine group. Conclusion Placental mRNA is present in the maternal circulation in significantly lower copies in cases of ectopic pregnancy compared with cases of intrauterine pregnancy. Measurement of placental mRNA in the maternal circulation may help to distinguish between intrauterine and ectopic pregnancies.

Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies: a review

“…These potential proteins include, but are not limited to: Inhibin A, which is produced by the corpus luteum; activin A, pregnancy-associated plasma protein-A (PAPP-A) and A Disintegrin and Metalloprotease-12 (ADAM-12) which are generated by the placenta; and vascular endothelial growth factor (VEGF), which, produced by a variety of cell types, is crucial for angiogenesis and may be upregulated in EP [ 75 ]. Various messenger and micro-RNA—regulators of downstream gene expression—may also be differentially expressed by an EP [ 81 , 82 ].…”

Measuring circulating placental RNAs to non-invasively assess the placental transcriptome and to predict pregnancy complications

“…Serum human chorionic gonadotrophin (HCG) levels are often used to discriminate between intra‐uterine and ectopic pregnancies but are poor predictors of outcome. Takacs et al found that circulating HPL and HCG RNA were significantly lower or undetectable in ectopic compared with intra‐uterine pregnancies, allowing earlier discrimination and, therefore, intervention . In intra‐uterine pregnancies, Farina et al also noted lower levels of placental‐specific 1 gene in pregnancies complicated by vaginal bleeding compared with healthy controls, although this did not predict miscarriage .…”

Biomarkers of Ectopic Pregnancy-Present and Future

“…Placental mRNAs secreted by trophoblasts can be altered in early pregnancy failure, and therefore have been studied recently for their diagnostic potential in EP. A recent case-control study conducted by Takacs et al demonstrated that patients with EP have significantly lower copy numbers of hCG and hPL mRNA in plasma compared to viable IUP [54]. Placental mRNA have also been studied for viability and chromosomal aneuploidy [55,56].…”