Maternal serum vascular endothelial growth factor (VEGF) levels discriminate between ectopic and intrauterine pregnancies following IVF treatment

Abstract

Objective: To determine serum levels of VEGF in women with normal intrauterine pregnancy (IUP), abnormal IUP (SAB), biochemical pregnancy (BC) and ectopic pregnancy (EP) following IVF therapy and evaluate the capacity of VEGF to serve as a marker for the diagnosis of ectopic pregnancy. Design: Retrospective analysis. Materials and Methods: During the period from January 1999 to December 2002, all patients who had IVF therapy in our center leading to the establishment of a pregnancy underwent blood sampling at 11 days after a 3-day embryo transfer for possible serum VEGF measurements. These patients were asymptomatic. Samples were centrifuged and the supernatants were stored at -80°C until assayed. VEGF concentrations were measured collectively from 108 women who subsequently were diagnosed to have an EP, a BC, an abnormal IUP and a normal IUP (27 women in each category). All patients were matched by age and stimulation results. SAB and BC were diagnosed by means of serial β-hCG measurements and transvaginal sonography. EP was confirmed by laparoscopy or by sonographic visualization. Serum VEGF was measured in duplicate by commercial ELISA. The sensitivity of the assay was < 9 pg/ml. In addition to VEGF, serum β-hCG and progesterone levels were also measured for all patients. The data were analyzed using analysis of variance with the Bonferroni post hoc test, non-parametric testing and Chi-square testing where appropriate. P < 0.05 was considered statistically significant. Data are presented as mean ± standard error of the mean. Results: Serum β-hCG and progesterone levels were significantly higher in women with normal and abnormal IUP than the other two groups. The serum concentrations of VEGF among women with EP and BC were higher than in those with normal IUP and SAB, but did not reach statistical significance (Table I). VEGF levels were higher in ectopic gestations than in known intra-uterine gestations (604.4±73.4 pg/ml vs. 455.4±27.7 pg/ml; P= 0.02). Furthermore, when a cut-off concentration of > 700 pg/ml for VEGF was used, an EP could be distinguished from an IUP with a specificity of 93%, and a positive predictive value of 63%. Tabled 1 Conclusion: Maternal serum levels of VEGF are higher in women with ectopic than intrauterine IVF pregnancies, as early as 11 days following embryo transfer. This difference in VEGF concentrations provides the ability to discriminate ectopic from intrauterine IVF pregnancies, and thus may be used as an additional potential marker for an ectopic pregnancy.