Department of Obstetrics and Gynecology, McGill University, 687 Pine Avenue West, Montreal, Quebec, Canada
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: arrested pregnancy/ectopic pregnancy/pregnancy/VEGF
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Another serum marker is progesterone (McCord et al., 1996; Mol. et al., 1998
; Perkins et al., 2000
). Its concentrations are higher in women with normal IUP, but its use to distinguish between EP and arrested IUP is also not reliable. Accordingly, investigators are looking for other markers for EP. One of the promising markers is vascular endothelial growth factor (VEGF; Daniel et al., 1999
). VEGF is a potent angiogenic factor and angiogenesis is needed for successful reproduction. Its levels in women with polycystic ovarian syndrome are higher than in those with normal ovaries (Tulandi et al., 2000
) and it may play a role in the pathophysiology of ovarian hyperstimulation syndrome (Lee et al., 1997
).
The purpose of our study was to evaluate serum VEGF concentrations in women with normal and arrested IUP, and EP.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
VEGF concentrations were measured collectively from the first 45 samples from women who subsequently were diagnosed to have an EP, a normal IUP and an arrested IUP (15 women in each category). The diagnosis was made by serial transvaginal ultrasound examinations. Following our standard practice, serum ß-HCG concentrations were also measured. All blood samples were from singleton pregnancies at 5 weeks gestation. An arrested IUP was defined as an intrauterine sac without fetal tissue or fetal cardiac activity.
Serum VEGF was measured in duplicate by commercial ELISA (human VEGF165; RandD system, Minneapolis, MN, USA) specific for the human molecule. The sensitivity of the assay was <5 pg/ml. The inter-assay coefficient of variation for the VEGF assays ranged from 5.0 to 8.8%.
The data were analysed using analysis of variance with the Bonferroni post hoc test. P < 0.05 was considered statistically significant (two-tailed).
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In agreement with a previous study (Daniel et al., 1999), it was found that the serum VEGF concentrations in women with EP are higher than in those with normal IUP and arrested IUP. The finding that VEGF concentrations in women with EP are different from those in arrested IUP is important. Unlike progesterone and HCG concentratons, it seems that by using serum VEGF concentrations, it might be possible to distinguish between EP and arrested IUP.
All serum concentrations of VEGF in women with normal IUP were <200 pg/ml. With this cut-off point, a normal IUP could be distinguished from an EP with a sensitivity of 88%, a specificity of 100% and a positive predictive value of 100%. Combining serum VEGF and progesterone has been shown to increase the specificity and positive predictive value of the test (Daniel et al., 1999). In our study, we did not measure progesterone concentrations.
If our results can be confirmed in a larger study, VEGF may be useful in detecting an early EP. This will allow early and successful medical treatment. Indeed, the most important factor associated with the failure of medical treatment with methotrexate is a high serum HCG concentration (Tulandi and Sammour, 2000).
We conclude that there is a difference in the concentrations of serum VEGF in women with EP, arrested IUP and normal IUP. The potential use of VEGF as a marker for EP should be investigated further in a larger trial.
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Daniel, Y., Geva, E., Lerner-Geva, L. et al. (1999) Levels of vascular endothelial growth factor are elevated in patients with ectopic pregnancy: is this a novel marker? Fertil. Steril., 72, 10131017.[ISI][Medline]
Evans, P.W., Wheeler, T., Anthony, F.W. and Osmond, C. (1998) A longitudinal study of maternal serum vascular endothelial growth factor in early pregnancy. Hum. Reprod., 13, 10571062.[Abstract]
Jauniaux, E., Watson, A. and Burton, G. (2001) Evaluation of respiratory gases and acidbase gradients in human fetal fluids and uteroplacental tissue between 7 and 16 weeks' gestation. Am. J. Obstet. Gynecol., 184, 9981003.[ISI][Medline]
Kadar, N., DeCherney, A.H. and Romero, R. (1982) Receiver operating characteristics (ROC) curve analysis of the relative efficacy of single and serial chorionic gonadotropin determinations in the early diagnosis of ectopic pregnancy. Fertil. Steril., 37, 542547.[ISI][Medline]
Lee, A., Christenson, L.K., Stouffer, R.L. et al. (1997) Vascular endothelial growth factor levels in serum and follicular fluid of patients undergoing in vitro fertilization. Fertil. Steril., 68, 305311.[ISI][Medline]
McCord, M.L., Muram, D., Buster, J.E. et al. (1996). Single serum progesterone as a screen for ectopic pregnancy; exchanging specificity and sensitivity to obtain optimal test performance. Fertil. Steril., 66, 513516.[ISI][Medline]
Mol, B.W., Lijmer, J.G., Ankum, W.M. et al. (1998) The accuracy of single serum progesterone measurement in the diagnosis of ectopic pregnancy: a meta-analysis. Hum. Reprod., 13, 32203227.[Abstract]
Perkins, S.L., Al-Ramahi, M. and Claman, P. (2000) Comparison of serum progesterone as an indicator of pregnancy non-viability in spontaneously pregnant emergency room and infertility clinic patient populations. Fertil. Steril., 73, 499504.[ISI][Medline]
Torry, D.S. and Torry, R.J. (1997) Angiogenesis and the expression of vascular endothelial growth factor in endometrium and placenta. Am. J. Reprod. Immunol., 37, 2129.[ISI][Medline]
Tulandi, T. and Sammour, A. (2000) Evidence based management of ectopic pregnancy. Curr. Opin. Obstet. Gynecol., 12, 289292.[ISI][Medline]
Tulandi, T., Saleh, A., Morris, D. et al. (2000) Effects of laparoscopic ovarian drilling on serum vascular endothelial growth factor (VEGF) and on insulin responses to oral glucose tolerance test in women with polycystic ovarian syndrome. Fertil. Steril., 74, 585588.[ISI][Medline]
Yao, M. and Tulandi, T. (1997) Current status of surgical and non-surgical management of ectopic pregnancy. Fertil. Steril., 67, 421433.[ISI][Medline]
accepted on September 29, 2001.