ACTA ENDOCRINOLOGICA (BUC)

Background and aims. Severe Ovarian Hyperstimulation Syndrome (OHSS) forms with very aggressive clinical evolution are still common, despite prophylactic measures. Besides the Vascular Endothelial Growth Factor (VEGF), there are other angiogenic factors, like Renin-Angiotensin-Aldosterone System (RAS), that might be associated with this disorder. Our study aims to evaluate the role of VEGF and Angiotensin II (ANG II) in the development of early severe OHSS, in high risk patients under prophylactic Cabergoline therapy. Material and Methods. We recruited 192 patients undergoing in vitro fertilization (IVF) procedures with high risk for OHSS development. Out of these, 106 patients with OHSS were enrolled in the study, of which 28 subjects had a severe form of disease (group I), and 78 patients had a mild/ moderate form (group II). We collected blood and follicular fluid from our study participants and determined serum and follicular VEGF and ANG II levels using Enzyme-Linked Immunosorbent Assay (ELISA) technique. Results. Follicular VEGF, ANG II, and serum VEGF levels were significantly higher in group I versus group II. Serum VEGF titers were 645.97 versus 548.62 (p = 0.0008), follicular VEGF titers were 2919.52 versus 1093.68 (p < 0.0001), and follicular ANG II levels were 281.64 versus 65.76 (p < 0.0001). No significant differences have been shown between the two groups for serum ANG II levels. Conclusion. Our study results provide evidence of a OHSS phenotype that is more prone to undergo severe clinical forms of disease, despite treatments with VEGF receptor blockers, and show that ANG II appears to play a major role alongside VEGF, in the development of these severe forms of disease.

The debates on the quality of oocytes in PCOS patients are still heated and controversy is very intense, with a wide\r\nspectrum of variations proposed. The present study aims at analyzing the main factors altered in the economy of PCOS\r\npathogenesis, mainly those involved in the folliculogenesis dysfunction, and, also, to evaluate their potentially detrimental role upon oocyte quality.\r\nIndividual elimination of the more prominent follicular factors, at least through deviation from the normal, as compared to the degree of oocyte maturation did not manage to be cleared in unequivocal terms for any of them. Most interestingly, the spectrum of answers varied from\r\nprofoundly modified values to the absence of any differences whatsoever, inevitably leading, as sole functional conclusion, to assuming the extremely heterogeneous\r\ncharacter of this affection.

Background. Polycystic ovarian syndrome (PCOS) involves various changes within folliculogenesis. Aside from its systemic action, metformin seems to exert a local direct effect independent of insulinemia. The IGF system appears to be an important local target for metformin although the evidence we possess is circumstantial. Objective. The aim of this study was to evaluate the impact of metformin on insulin growth factor (IGF) system proteins and steroids production in PCOS patients and to analyze potential involvement in oocyte quality. Material and methods. This prospective study was performed on 86 in vitro fertilization (IVF) patients who were categorized into three groups as follows: Group 1 formed of PCOS patients who received metformin (n=27); Group 2 with PCOS patients who did not receive metformin (n=29) and Group 3 with controls (n=30). Interventions. Interventions included controlled ovarian stimulation for IVF and metformin (at least 16 weeks prior to the time of ovarian puncture). Main Outcome Measures.Follicular fluid analysis was performed using radioimmunoassay with specific kits (estradiol, testosterone, progesterone, IGF I, IGF II, IGF binding protein 1 - IGFBP1, IGFBP2, IGFBP3, IGFBP4). Results. Important differences were measured for the three types of steroids among the three studied groups (PCOS treated, PCOS not treated, controls) estradiol (538 vs. 466 vs. 688 ng/mL p < 0.0001), testosterone (6.7 vs. 7.6 vs. 5.1 ng/mL p<0.01), progesterone (8899 vs. 7878 vs. 9755 pg/mL p<0.0001) while for IGF system proteins important differences were noted only regarding IGFBP1 (114 vs. 107 vs. 121 p<0.002) IGFBP2 (263 vs. 268 vs. 252 ng/mL p<0.04), and IGFBP4 (128 vs. 138 vs. 118 p<0001). Correlations were also established between fertilization rate and estradiol (R: 0.53 p<0.5), testosterone (R: -0.39 p<0.05), IGFBP1 (R: 0.48 p< 0.05), IGFBP4 (R: 0.39, p<0.05). Conclusions. Patients with PCOS and hyperinsulinemia have the greatest benefit from metformin treatment. However, metformin action surpasses correction of systemic differences having a direct action at the level of follicular structures. Alteration of IGF system proteins does not concern only hyperinsulinic patients and can be partially amended by metformin administration.