Hum. Reprod. Advance Access originally published online on May 20, 2004
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Human Reproduction, Vol. 19, No. 7, 1530-1538,
July 2004
© 2004 European Society of Human Reproduction and Embryology
Coasting acts through downregulation of VEGF gene expression and protein secretion
1 IVI-Madrid, Rey Juan Carlos University, Madrid, Spain and 2 IVI Foundation, Valencia, Spain
3 To whom correspondence should be addressed at: IVI-Madrid, Santiago de Compostela 88, 28035 Madrid, Spain. e-mail: jgvelasco{at}ivi.es
BACKGROUND: This study was conducted to investigate the mechanisms by which coasting may be effective in decreasing the incidence of ovarian hyperstimulation syndrome (OHSS). METHODS: A total of 160 women (patients and oocyte donors) undergoing coasting and 116 controls were included in the study. Serum, follicular fluid and granulosa cells were collected on the day of oocyte retrieval. Vascular endothelial growth factor (VEGF) concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Real-time PCR was performed to evaluate VEGF gene expression in granulosa cells. Cell death was studied by flow cytometry using annexin V–fluorescein isothiocyanate (FITC) and counterstaining by propidium iodide, and double staining with CD45 monoclonal antibody was performed to distinguish the contamination of apoptotic leukocytes. RESULTS: Follicular cells aspirated from coasted patients showed a ratio in favour of apoptosis, especially in smaller follicles (48 versus 26%, P < 0.05). Follicular fluid determinations confirmed that coasting reduces VEGF protein secretion (1413 versus 3538 pg/ml, P < 0.001) and gene expression (2-fold decrease) in granulosa cells. Follicular fluid VEGF protein levels positively correlated with follicular size (r = 0.594, P = 0.001) and estradiol production (r = 0.558, P = 0.038). Women who underwent coasting showed a comparable IVF cycle outcome; however, a higher cancellation rate was found in cycles that were coasted. CONCLUSIONS: Coasting affects all follicles through apoptosis, especially immature follicles, without affecting oocyte/endometrial quality. The significant decrease found in VEGF expression and secretion explains why coasting is clinically effective in reducing the incidence and severity of OHSS.
Key words: coasting/ovarian hyperstimulation syndrome/VEGF
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