Follicular fluid levels of vascular endothelial growth factor and early corpus luteum function during assisted reproductive technology cycles
The relation between vascular endothelial growth factor (VEGF) and early luteal function has rarely been proven in humans. The purpose of this study was to define the relation between follicular fluid concentrations of VEGF (FF VEGF) and early luteal function at the preimplantation stage during assisted reproductive technology (ART) cycles.
71 women were divided into two groups, based on reproductive outcome: women who became pregnant after embryo transfer (ET) (n = 18, Group A) and non-pregnant women (n = 53, Group B). Serum progesterone (Se P) and inhibin A on ET day, and FF VEGF levels were measured in all women. Data were expressed as mean ± standard deviation. Statistical analysis was performed using Excel Office 98 for Student's t-test, linear regression test and chi-square test. A p value of < 0.05 was considered statistically significant.
The groups were comparable for age, ovarian reserve, number and quality of the oocytes retrieved and of the embryos obtained and transferred. FF VEGF levels were increased (4235 ± 1433 vs 3432 ± 1231 pg/ml), while Se P and inhibin A levels were significantly reduced (83.1 ± 34.1 vs 112.0 ± 58.8 ng/ml and 397.4 ± 223 vs 533.5 ± 283 pg/ml, respectively) in the non-pregnant group and were negatively correlated with FF VEGF (r = -0.482, p < 0.05; r = -0.468, p < 0.05) only in pregnant women.
Much has to be learned about the regulation and role of VEGF during the early luteal phase. We advance the hypothesis that the existence of a negative correlation between FF VEGF/Se P and FF VEGF/inhibin A in pregnant women might indicate the existence of a normal VEGF-mediated paracrine response when Se P and inhibin A levels are decreased. Excess production of FF VEGF and the absence of a correlation between FF VEGF/Se P and FF VEGF/inhibin A in non-pregnant women may be a paracrine reaction to immature luteal vasculature, resulting in luteal dysfunction.
The authors would like to acknowledge Mario Rossi, L.T., Rinaldo Spallanzani L.T., Maria Grazia Ziveri B.Sc., and medical student Manuela Calabrese for their precious assistance in data collection.
- 7.Treetampinich C, O'Connor AE, MacLachlan V, Groome NP, de Kretser DM: Maternal serum inhibin A concentrations in early pregnancy after IVF and embryo transfer reflect the corpus luteum contribution and pregnancy outcome. Hum Reprod. 2000, 15: 2029-2032. 10.1093/humrep/15.9.2028.CrossRefGoogle Scholar
- 9.Rombauts L, Verhoven G, Meuleman C, Koninckx PR, Poncelet E, Franchimont P: Dimeric inhibin A and alpha-subunit immunoreactive material in maternal serum during spontaneous and in-vitro fertilization pregnancies. J Clin Endocrinol Metab. 1996, 81: 985-989. 10.1210/jc.81.3.985.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Yohkaichiya T, Polson DW, Hughes EG, MacLachlan V, Robertson DM, Healy DL, de Kretser DM: Serum immunoreactive inhibin concentrations in early pregnancy after in vitro fertilization and embryo transfer: evidence for an ovarian source of inhibin and assessment of the inhibin measurements in predicting outcome of pregnancy. Fertil Steril. 1993, 5: 1081-1089.CrossRefGoogle Scholar
- 15.Friedman CI, Danforth DR, Herbosa-Encarnación C, Arbogast L, Alak BM, Seifer DB: Follicular fluid vascular endothelial growth factor concentrations are elevated in women of advanced reproductive age undergoing ovulation induction. Fertil Steril. 1997, 68: 607-12. 10.1016/S0015-0282(97)00278-1.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Koga K, Osuga Y, Tsutsumi O, Momoeda M, Suenaga A, Kugu K, et al: Evidence for the presence of angiogenin in human follicular fluid and the up-regulation of its production by human chorionic gonadotropin and hypoxia. J Clin Endocrinol Metab. 2000, 85: 3352-55. 10.1210/jc.85.9.3352.CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Van Blerkom J, Antczak M, Schrader R: The developmental potential of the human oocyte is related to the dissolved oxygen content of follicular fluid: association with vascular endothelial growth factor levels and perifollicular blood flow characteristics. Hum Reprod. 1997, 12: 1047-55. 10.1093/humrep/12.5.1047.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Stouffer RL: Corpus luteum formation and demise. Reproductive Endocrinology, Surgery, and Technology. Edited by: Adash EY, Rock JA, Rosenwaks Z. 1996, Lippincott – Raven Philadelphia, 1: 251-269.Google Scholar
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