Relationship Between Etiology of Sterility of Patients Undergoing Controlled Ovarian Hyperstimulation (COH) and Serum, Follicular Fluid Concentration of Leukaemia Inhibitory Factor (LIF), Vascular Endothelial Growth Factor (VEGF), Nitic Oxide (NO) and Their Influence on ICSI Outcome

Abstract

The aim of this study was to determine the concentration of LIF, VEGF and NO concentration in serum and follicular fluid of tubar, endometriosis and male factor infertility patients who undergoing COH for intracytoplasmatic sperm injection (ICSI) and to find out (i) the difference between the FF and serum concentration, (ii) the relationship between the etiology of sterility and these growth factors concentrations, (iii) the influence of these investigated growth factor on ICSI outcome. Prospective study. 75 women undergoing ICSI therapy were included in this study. Tubar sterility (G.1=17), endometriosis (G.2 = 15) and male factor infertility (G.3. 43). After pituitary down regulation using Gn-RH a, the women underwent COH either with rFSH or HMG/FSH. Serum and FF were collected at the time of oocytes retrieval and were frozen at -80°C until the measurement of LIF; VEGF and NO concentration. LIF and VEGF concentration was determined by using enzyme-linked immunosorbent assay (ELISA). Whereas, the NO was measured using the Griess reaction as an indirect assessment of NO activity. LIF concentrations in FF of patients with tubal sterility, endometriosis, male factor sterility were (43.20±12.10, 43.6±18.9 and 50.0±23.70 pg/ml respectively) and the corresponding values in serum were (1.60±0.90; 1.50±0.96 and 2.30±2.4 pg/ml). VEGF concentrations in FF of the first, second and third groups were (3247.8±931.9; 3546.3±893.40 and 3358.1±894.3 pg/ml) and in serum as follows (375.3±180.5; 354.3±160.5 and 374.8±182.4). NO concentrations were at the same level in FF and serum in the first group (42.3±9.50 vs. 39.190± 15.52, p=0, 26; 41.5±8.99vs.36.3±13.6 p= 0.18) in the second group and 40.1±12.5 vs. 35.96±18.9 p= 0.059 μmol/l in the third group. LIF concentration in FF was 43.2±12.1 and in 1.6±0.9 pg/ml in serum (p<0.001). VEGF in FF was 3247.8±931.9 and in serum 375.3±180.5 pg/m (p<0.001). NO concentrations in FF and serum were similar (42.3±9.5 vs. 39.19.52μmol/l; p=0.26). The main number of retrieved, fertilized and transferred oocytes in the first group was (8.2±5.3; 4.7±3.7 and 2.0±0.8) the corresponding value in the second group was (5.0±3.6; 3.7±3.1 and 1.9±0.9) and in the third group (5.9±4.1; 3.4±2.7 and 1.7±0.9). No significance difference was shown between the groups in respect of the age of the patient (p=0.31), the main number of retrieved (p=0.132), fertilized (p=0.29) and transferred oocytes (p=0.73). Moreover, the fertilization rate, in all three investigated groups (64.0±2.9%, 81.0±3.1% and 60.0±4.5%, p=0.42), cleavage (60. 0±3.1%; 69.0±2.9% and 65.0±2.8%; p=0.73) and ongoing pregnancy rates (17.6%; 46.7%; 20.9% p=0.19) were similar. The concentration of NO and LIF in FF correlate negatively with fertilization (-0.012; -0.218) and cleavage rate (-0.10; -0.067) of the oocytes. The concentration of LIF, VEGF and NO in the investigated groups was similar. LIF and VEGF concentration was significantly higher in FF in comparison to serum, which indicated that these growth factors synthesised in the ovary and play an important role in ovarian physiology. Whereas, NO concentration was at the same levels in FF and serum. Besides, a negative correlation was shown between NO concentration in FF, serum and fertilization and cleavage rates of the fertilized oocytes.