Serum soluble FMS-like tyrosine kinase-1 in ectopic pregnancy

Abstract

CONTEXT: The diagnosis of an ectopic pregnancy (EP) requires the usage of serial beta-human chorionic gonadotropin (hCG) measurements and ultrasonography to locate the gestational sac. With the rising trends in its incidence, a rapid, noninvasive biomarker to detect this condition at the earliest can aid in decreasing the morbidity and mortality linked with EP. AIMS: This study was performed to determine the serum level of soluble FMS-like tyrosine kinase-1 (sFLT-1) at 4–10-week gestation in EP and normal pregnancy and to identify whether it can be used as a biomarker to distinguish an EP from a normal intrauterine pregnancy. SETTINGS AND DESIGN: This was a prospective case–control study conducted over 2 years from 2015 to 2017 in 280 women between the age groups of 19 and 38 years at a tertiary level hospital. SUBJECTS AND METHODS: Levels of sFLT-1 in sera of 140 women with EP and 140 women with normal pregnancy were assayed by a sandwich enzyme-linked immunosorbent assay at Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India. STATISTICAL ANALYSIS USED: Statistical analyses were performed with SPSS software version 16.0, and P ≤ 0.05 was considered statistically significant. RESULTS: The median sFLT-1 level in EP was 419 pg/ml. This was significantly lower than the value of 898 pg/ml in normal pregnancy. Receiver operating characteristic curve analysis showed that at a cutoff of 623 pg/ml, sFLT-1 was able to distinguish an EP from a normal intrauterine pregnancy with a sensitivity of 98.6% and a specificity of 90.7%. CONCLUSIONS: The present study showed the significant early lowering of sFLT-1 in EP and may be considered as an effective biomarker compared to beta-hCG.

Evaluation of Serum Soluble fms-like Tyrosine Kinase-1 as a Biomarker in Ectopic Pregnancy

“…The mechanism behind the reduction in the level of sFLt-1 in EP may be related to increased consumption due to the subsequent binding of the sFLt1 receptor to the excessively expressed VEGF, or a decrease in sFLt-1 production or both. This was in line with other studies finding that showed the level of sFLt-1 level was significantly lower in ectopic pregnancy and miscarriage compared to normal pregnancy, such as Daponte et al [9] study in which the mean value of sFLt-1 was significantly lower in EP (178.16 ±76.03 pg/ml) and miscarriage (399.42 ± 337.54 pg/ml) compared to women with viable IUP (1390.32 ± 655.37pg/ml) and in the Selvarajan et al [10] study that reported that the sFLt-1 level is significantly lower in the ectopic group (419 pg/ml) compared to IUP( 898 pg/ml). The differences in the mean sFLt-1 reported in our study with studies of Selvarjan et al and Daponate et al [9,10].…”

“…Serum soluble FMS-like tyrosine kinase-1 has been studied extensively for diagnosis and prediction of many gynecological conditions like preeclampsia, preterm birth, growth restriction, stillbirth, and miscarriage [16,18,19]. However, studies on its role in ectopic pregnancy are still spared [10] In the current study, the mean βhCG was significantly higher among IUP group (24851.07 IU/L) in comparison to ectopic pregnancy (6270.87 IU/L) and miscarriage (9783.67 IU/L),…”

“…Soluble FMS-like tyrosine kinase1 (sFLt1) is the soluble variant of the vascular endothelial growth factor (VEGF) recep-tor1 acts as markers of normal vascularization [9]. (sFLt 1) ensnares VEGF with excessive affinity, inhibiting its mitogenic activity in vascular endothelial cells, and may personate an imperative role in down regulating angiogenesis [10]. In the placenta, sFlt-1 is expressed in trophoblast cells.…”

“…Monitoring sFLt-1 levels in the early first trimester, especially during the first 4 to 10 weeks, helps determine the normal development and functioning of the placenta, which is the prerequisite for normal embryonic development [12]. Previous reports suggested that serum measurements of angiogenic factors can be used as markers to identify cases of early pregnancy failure (ectopic or miscarriage) [13].…”

Efficacy of Methotrexate Treatment, Nonsurgical Treatment of Ectopic Pregnancy (EP)

“…A disaster in human reproduction is ectopic pregnancy in which fetus implants outside the uterine cavity and inevitably results in the death of the fetus. 1 Although ectopic pregnancy has been recognized for many years, it is a growing problem, affecting approximately 2% of all pregnancies. 2 There are also regional differences in its incidence, 18/1000 in India, 7.4/1000 births in Bangladesh, and 1:128 to 1:130 pregnancies in Pakistan.…”