Peripheral levels of vascular endothelial growth factor (VEGF) are higher in gonadotropin stimulated as compared to natural ovarian cycles

Summary:

The purpose of the present study was to investigate the stability of vascular endothelial growth factor (VEGF) in plasma samples and the influence of ovarian hyperstimulation on systemic levels of VEGF. Stability assays for VEGF in plasma samples revealed significant increases following even short incubations of samples at room temperature (≤ 2 h, p < 0.001). To investigate a possible impact of controlled ovarian hyperstimulation (COH) on peripheral VEGF levels, serial blood collection over one menstrual cycle was performed in unstimulated as well as in gonadotropin-stimulated cycles for in vitro fertilisation / embryo transfer (IVF/ET) (10 women each). Peripheral levels for VEGF were significantly higher in gonadotropin stimulated cycles as compared to non-stimulated cycles (p < 0.001). There was no significant difference between follicular phase and luteal phase levels in either group. VEGF levels tended to correlate with the number of follicles detected by vaginal sonography prior to oocyte aspiration (p = 0.051). In conclusion, VEGF levels are elevated in gonadotropin-stimulated IVF/ET cycles as compared to natural cycles.

VEGF - gonadotropins - ovarian hyperstimulation - IVF

References

• 1 Agrawal R, Conway G, Sladkevicius P, Tan S L, Engmann L, Payne N, Bekir J, Campbell S, Jacobs H. Serum vascular endothelial growth factor and doppler flow velocities in in vitro fertilization: relevance to ovarian hyperstimulation syndrome and polycystic ovaries.  Fertil Steril. 70 651-658 1998; 
• 2 Agrawal R, Conway G, Sladkevicius P, Payne N, Bekir J, Campbell S, Tan S L, Jacobs H. Serum vascular endothelial growth factor (VEGF) in the normal menstrual cycle: association with changes in ovarian and uterine Doppler blood flow.  Clin Endocrinol (Oxf). 50 101-106 1999; 
• 3 Asch R H, Balmeceda J P. et al . Severe ovarian hyperstimulation syndrome in assisted reproduction technology: definition of high risk groups.  Hum Reprod. 6 1395-1399 1991; 
• 4 Golan A, Ron-El R, Herman A, Soffer Y, Weinraub Z, Capsi E. Ovarian hyperstimulation syndrome: an updated review.  Obstet Gynecol. 44 430-440 1989; 
• 5 Knox G E. Antihistamine blockage of the ovarian hyperstimulation syndrome.  Am J Obstet Gynecol. 118 992-994 1974; 
• 6 Lee A, Christenson L K, Patton K A, Stouffer R L. Vascular endothelial growth factor production by human luteinized granulosa cells in vitro.  Hum Reprod. 12 2756-2761 1997a; 
• 7 Lee A, Christenson L K, Stouffer R L, Burry K A, Patton P E. Vascular endothelial growth factor levels in serum and follicular fluid of patients undergoing in vitro fertilisation.  Fertil Steril. 68 305-311 1997b; 
• 8 Ludwig M, Bauer O, Lopens A, Jelkmann W, Diedrich K. Serum concentrations of vascular endothelial growth factor cannot predict the course of severe ovarian hyperstimulation syndrome.  Hum Reprod. 13 30-32 1998; 
• 9 Maloney J P, Silliman C C, Ambruso D R, Wang J, Tuder R M, Voelkel N F. In vitro release of vascular endothelial growth factor during platelet aggregation.  Am J Physiol. 275 H1054-H1061 1998; 
• 10 McClure N, Healy D L, Rogers P AW, Sullivan J, Beaton L, Haning R V, Connolly D T, Robertson D M. Vascular endothelial growth factor as capillary permeability agent in ovarian hyperstimulation syndrome.  Lancet. 344 235-236 1994; 
• 11 Navot D, Margalioth E, Laufer M. Direct correlation between plasma renin activity and severity of the ovarian hyperstimulation syndrome.  Fertil Steril. 48 57-61 1987; 
• 12 Neulen J, Yan Z, Raczek S, Weindel K, Keck C, Weich H A, Marme D, Breckwoldt M. HCG-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulosa cells.  J Clin Endocrinol Metab. 80 1967-1971 1995; 
• 13 Neulen J, Wenzel D, Hornig C, Wunsch E, Weissenborn U, Grunwald K, Buttner R, Weich H. Poor responder - high responder: the importance of soluble vascular endothelial growth factor receptor 1 in ovarian stimulation protocols.  Hum Reprod. 16 621-626 2001; 
• 14 Olson T A, Mohanraj D, Carson L F, Ramakrishnan S. Vascular endothelial growth factor gene expression in normal and neoplastic human ovaries.  Cancer Res. 54 276-280 1994; 
• 15 Phillips H S, Hains J, Leung D W, Ferrara N. Vascular endothelial growth factor is expressed in rat corpus luteum.  Endocrinology. 127 965-967 1990; 
• 16 Redmer D A, Dai Y, Charnock-Jones D S, Smith S K, Reynolds L P, Moor R M. Characterization and expression o vascular endothelial growth factor (VEGF) in the ovine corpus luteum.  J Reprod Fertil. 108 157-165 1996; 
• 17 Rizk B, Aboulghar M, Smitz J, Ron-El R. The role of vascular endothelial growth factor and interleukins in the pathogenesis of severe ovarian hyperstimulation syndrome.  Hum Reprod Update. 3 255-266 1997; 
• 18 Robertson D, Selleck K, Suikkari A M, Hurley V, Moohan J, Healy D. Urinary vascular endothelial growth factor concentrations in women undergoing gonadotropin treatment.  Hum Reprod. 10 2478-2482 1995; 
• 19 Sealey J E, Atlas S A, Gloriosi N. et al . Cyclic secretion of prorenin during the menstrual cycle : synchronization with luteinizing hormone and progesterone.  Proc Natl Acad Sci USA. 82 8705-8709 1985; 
• 20 Todorow S, Schricker S T, Siebzehnruebl E R, Neidhardt B, Wildt L, Lang N. Von Willebrand factor: an endothelial marker to monitor in vitro-fertilization patients with ovarian hyperstimulation syndrome.  Hum Reprod. 8 2039-2046 1993; 
• 21 Toth P, Xi L, Rao C V, Lincoln S R, Sanfilippo J S, Spinnato J A, Yussman M A. Expression of functional human chorionic gonadotropin/human luteinizing hormone receptor gene in human uterine arteries.  J Clin Endocrinol Metab. 79 307-315 1994; 
• 22 Unkila-Kallio L, Vuorela-Vepsalainen P, Tiitinen A, Halmesmaki E, Ylikorkala O. No cyclicity in serum vascular endothelial growth factor durino normal menstrual cycle but significant luteal phase elevation durino an in vitro fertilization program.  Am J Reprod Immunol. 43 25-30 2000; 
• 23 Yan Z, Weich H A, Bernart W, Breckwoldt M, Neulen J. Vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) expression in luteinized human granulosa cells in vitro.  J Clin Endocrinol Metab. 77 1723-1725 1993; 
• 24 Zar J H. Biostatistical analysis. 2nd edition. pp. Prentice Hall, Englewood Cliffs, N.J., U.S.A.; 1984