angiogenin and Ovarian-Hyperstimulation-Syndrome

In a prospective study we measured circulating levels of vasoactive factors and their soluble receptors in women undergoing controlled ovarian stimulation (COS) for IVF who were at risk for ovarian hyperstimulation syndrome (OHSS), and compared them to those in a primate model, the rhesus monkey.. A total of 23 women were enrolled in the study and serum vascular endothelial growth factor (VEGF)-A (free and total), soluble (s)VEGF-R1 and -R2, and angiogenin levels were compared in pregnant and non-pregnant women, and in monkeys, during follicular stimulation, the luteal phase and early pregnancy.. VEGF levels were similar during the period of follicular stimulation in pregnant and non-pregnant women, but a significant rise in both free and total VEGF occurred in pregnant women during the luteal phase (P < 0.05). The level of sVEGF-R1 (but not -R2) increased (P < 0.05) following implantation, and the rise in sVEGF-R1 corresponded to an abrupt fall in free (but not total) VEGF. In contrast, total VEGF levels remained similar to those observed on the day of hCG injection. Angiogenin levels tended to decline during follicular stimulation, then increased marginally during the luteal phase and were unchanged in early pregnancy. In contrast to women, free VEGF levels were non-detectable and total levels remained constant through the natural menstrual cycle and COS protocols in monkeys.. The levels of circulating angiogenic factors and soluble receptors demonstrate significant changes during COS cycles and early pregnancy in women. Thus, the systemic effect of these agents is influenced by ligand-receptor protein-binding interactions, and these relationships may exhibit dynamic changes during COS cycles and early pregnancy, and could contribute to the development of OHSS.

Topics: Animals; Chlorocebus aethiops; COS Cells; Estradiol; Female; Fertilization in Vitro; Humans; Macaca mulatta; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Progesterone; Ribonuclease, Pancreatic; Solubility; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2

The studies reported investigated the concentrations of angiogenic, proliferative, and apoptotic factors in the follicular fluid (FF) of individual follicles, aspirated from women undergoing controlled ovarian hyperstimulation using a long protocol for IVF treatment. Furthermore, the association of the concentrations of the preceding factors with oocyte maturity was studied. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin, tissue polypeptide specific antigen (TPS), and soluble Fas (sFas) were all found in the FF of all follicles examined. Moreover, from the angiogenic factors only angiogenin concentrations, and from the apoptotic factors sFas concentrations (the soluble form expressing rather an antiapoptotic function), were positively associated with oocyte maturity, possibly indicating angiogenin's biological role beyond neovascularization and a lower apoptotic rate allowing oocytes to mature. Last, the abundant expression of TPS in FF may be indicative of intense cell proliferation, in cases of ovarian stimulation.

Topics: Adult; Apoptosis; Case-Control Studies; Female; Fertilization in Vitro; Fibroblast Growth Factor 2; Follicular Fluid; Humans; Maternal Age; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Peptides; Pregnancy; Pregnancy, High-Risk; Reference Values; Ribonuclease, Pancreatic; Risk Assessment; Sampling Studies; Sensitivity and Specificity; Vascular Endothelial Growth Factor A

This study was conducted to investigate the possible role of angiogenin in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). The study group consisted of 10 healthy women who developed severe OHSS (group A) following ovarian stimulation by a long protocol of gonadotrophin-releasing hormone analogues/human menopausal gonadotrophin for in-vitro fertilization. A control group B (n = 10) underwent stimulation by the same protocol and did not develop OHSS. Blood samples were taken from group A on day of admission to hospital for treatment of OHSS and, in group B, 1 week after oocyte retrieval. In group A, ascitic fluid was routinely aspirated as a treatment for severe OHSS, and a peritoneal fluid sample was aspirated transvaginally before oocyte retrieval in group B. In group A, the mean serum angiogenin, the mean ascitic fluid angiogenin, the mean serum oestradiol concentration on day of human chorionic gonadotrophin and the mean haematocrit were 8390 +/- 6836 ng/ml, 2794 +/- 1024 ng/ml, 6300 +/- 2450 pg/ml and 46.6 +/- 4.4 respectively, as compared with 234 +/- 91 ng/ml, 254 +/- 105 ng/ml, 1850 +/- 1100 pg/ml and 36.8 +/- 4.6 in group B respectively. The differences between groups were highly significant for all parameters. Angiogenin seems to be strongly associated with the formation of neovascularization responsible for the development of OHSS.

Topics: Adult; Angiogenesis Inducing Agents; Ascitic Fluid; Capillary Permeability; Case-Control Studies; Estradiol; Female; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Proteins; Ribonuclease, Pancreatic