Effect of GnRH antagonist on vascular endothelial growth factor (VEGF) during ovarian stimulation cycle

Abstract

Objective: VEGF is produced and released by granulosa-theca and endotelial cells. This factor is related to increase the vascular permeability and has also been related to ovarian response to ovarian stimulation(COH). The purpose of the present study was to compare the concentration of VEGF in the serum and follicular fluid from women undergoing controlled ovarian hyperstimulation treated with GnRH antagonist or agonist. Design: Prospective study. Materials/Methods: Twenty women with primary infertility undergoing IVF were included. Patients were randomized to two different COH protocols: (1): long mid luteal suppression with GnRH agonist, Triptorelin (Decapeptyl®0.1, Ipsen-Pharma) or (2) multiple doses of GnRH antagonist (Cetrotide® 0.25; Serono) with recombinant FSH (Gonal F®, Serono). In both groups ovarian stimulation was started on day 3 with 225 UI for 4 days, then individual dosage was adjusted according the follicular growth. Antagonist was started on day 6 until the day HCG administration. Blood samples were obtained in the first day of ovarian stimulation and daily after day 5 up to HCG administration. The day of ovum pick up, follicular fluid (FF) of 5 mature follicles (>16 mm diameter) was polled and also blood was withdrawn for analysis. VEGF was determined in serum and FF by ELISA (Quantikine®R&DSystens). Results: No significant differences were found between both groups in age (25.5 ± 6.1 vs 27.0 ± 4.0), length of stimulation days (7.8 ± 1.4 vs 9.1 ± 1.7), total FSH dose (1339 ± 226 vs 1596 ± 279), number of oocytes obtained (12 ± 6.7 vs 17.2 ± 5.7), number of metaphase II oocytes (10.2 ± 5.7 vs 15.4 ± 4.8) and fertilization rate (78.3% vs 81.4%). Conclusions: VEGF serum levels are stimulated by gonadotropins and down-regulated by both, agonists and antagonists of GnRH. However, FF VEGF levels are higher in antagonist cycles, suggesting that the process of angiogenesis may be less affected under this regimen of ovarian stimulation. Table TableVEGF serum and follicular fluid levels (pg/ml)Day 2–3Day 5Day 6Day 7Day HCGVEGF Follicular Fluid (pg/ml)Antagonist0,36 ± 0,20,57 ± 0,1†p < 0,050,51 ± 0,2†p < 0,050,37 ± 0,010,40 ± 0,190,46 ± 0,25Agonist0,28 ± 0,10,33 ± 0,1†p < 0,050,25 ± 0,1†p < 0,050,23 ± 0,060,30 ± 0,070,37 ± 0,17† p < 0,05 Open table in a new tab