Smoking impairs angiogenesis during maturation of human oocytes

Objective: This study determines whether smoking influences ovarian vascularization which thus may impair follicular development. Design: Prospective laboratory study of follicular fluids and granulosa, cells from patients undergoing in vitro fertilization. Setting: University Hospital Aachen, Germany. Patient(s): Fifty smoking women and 50 nonsmoking women. Intervention(s): Cultivation of human granulosa cells. Cultivation of human umbilical vein endothelial cells (HUVECs) with either granulosa cell-conditioned medium or follicular fluid. Determination of clinical parameters. Main Outcome Measure(s): Quantification of soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) and cotinine. Result(s): Mean sVEGFR-1 concentration in follicular fluid of smokers was 499.6 pg/mL, compared with 159.2 pg/mL in nonsmokers. Correspondingly, supernatant of HUVECs cultured with follicular fluid from smoking and nonsmoking women showed, respectively, 1,74.1 pg/mL versus 794.2 pg/mL sVEGFR-1. The HUVECs incubated with conditioned medium from smokers' granulosa cells at culturing days 5, 9, 13, and 17 secreted, 1,712.4, 1,560.6, 1,619.0, and 1,635.0 pg/mL sVEGFR 1, whereas nonsmokers showed, respectively 1,147.6, 1,067.2, 1,135.9 and 1,206.3 sVEGFR-1. Mean cotinine concentration in smoking women was 83.9 ng/mL and in nonsmoking was 2.8 ng/mL. In all four comparisons, differences between groups reached statistical significance. Conclusion(s): This study showed that smokers secrete significantly higher amounts of sVEGFR-1 than non-smokers, which may result in decreased ovarian vascularization and reduced oocyte maturation.