Comparison of the diagnostic values of circulating steroid hormones, VEGF-A, PIGF, and ADAM12 in women with ectopic pregnancy

Abstract

BackgroundSeveral peripheral proteins that might be useful for detecting the presence of ectopic pregnancy (EP) have been evaluated, but none have been proven entirely useful in the clinic. We investigated the presence and the possible changes in circulating molecules that distinguish between normal intrauterine pregnancy (IUP) and tubal ectopic pregnancy.MethodsNon-pregnant women during the menstrual cycle, women with IUP, and women with tubal EP after informed consent. Serum levels of 17β-estradiol (E2), progesterone (P4), testosterone (T), beta-human chorionic gonadotropin (β-hCG), vascular endothelial growth factor-A (VEGF-A), placental growth factor (PIGF), and a distintegrin and metalloprotease protein 12 (ADAM12) were analyzed. Receiver operating characteristic analysis was used to assess the diagnostic discrimination of EP and gestational age-matched IUP.ResultsE2, P4, PIGF, and ADAM12 levels increased and β-hCG decreased throughout IUP. E2 and VEGF-A levels were significantly different between women with tubal EP and IUP. However, using a serum β-hCG cut-off of less than 1000 mIU/mL, P4 was significantly lower in women with tubal EP compared to IUP. Although E2 was inversely correlated with VEGF-A in women in the early stages of IUP, E2 was not correlated with VEGF-A in women with EP prior to tubal surgery. There were no significant differences in either PIGF or ADAM12 alone between women with tubal EP or IUP. Although no significant correlations were seen between E2 and PIGF or P4 and ADAM12 in women in the early stages of IUP, E2 was positively correlated with PIGF and P4 was positively correlated with ADAM12 in women with EP prior to tubal surgery. Our studies defined associations but not causality.ConclusionsIndividual measurements of serum E2 or VEGF-A levels are strongly related to early pregnancy outcomes for women with IUP and EP, and pregnancy-associated E2 and VEGF-A levels provide diagnostic accuracy for the presence of tubal EP. This study demonstrates that correlation analysis of E2/VEGF-A and E2/PIGF serum levels may be able to distinguish a tubal EP from a normal IUP.

Effect of progesterone on nitric oxide/cyclic guanosine monophosphate signaling and contraction in gastric smooth muscle cells

“…For this reason, all experiments in the present study were performed on single gastric muscle cells to avoid the effect of other non-muscle cell types. Indeed, the relatively high concentration of progesterone (1 µM) required to produce relaxation of gastric smooth muscle in the present experiments was considerably greater than the picomolar-nanomolar levels of circulating steroids in the plasma under normal (non-pregnant) physiological conditions (43). However, the concentration tested here agrees with the micromolar (0.1-10 µM) concentrations of progesterone required to elicit significant relaxation in smooth muscle of the GI tract in vitro (25,26).…”

Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications

“…Accordingly, different biomarkers have been proposed in order to increase accuracy of EP diagnosis, which would allow a rapid triage of pregnancies at risk of extra-uterine location. These putative markers may include circulating levels of progesterone, estradiol, vascular-endothelial Kisspeptin and miR-324-3p in Ectopic Pregnancy growth factor-A (VEGF-A), inhibin-A and activin-A (6)(7)(8)(9)(10)(11). Yet, despite promising results (11), there is little pathogenic information emerging from these studies, and no diagnostic test based on these markers is currently available in clinical practice for accurate biochemical identification of EP.…”

Efficacy of combined medication of nifedipine and magnesium sulfate on gestational hypertension and the effect on PAPP-A, VEGF, NO, Hcy and vWF

“…Gestational hypertension, with an incidence rate of 10%, is a kind of stenosis in lumen caused by the spasm in small arteries, manifesting obstruction in blood circulation and injuries to the endothelial cells, thereby evolving into the multi-organ lesions. The clinical characteristics of gestational hypertension include hypertension, urinary proteins, coma and edema or even failure of multiple organs, and due to the high incidence, gestational hypertension, in some severe cases, can cause death of puerpera or perinatal infant (Goeschen et al, 2003, Zou et al, 2013). However, symptoms usually emerge after 20 weeks of gestation, and, at that time, puerpera and fetus have been injured somehow.…”