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Smoking impairs angiogenesis during maturation of human oocytes.

Motejlek K, Palluch F, Neulen J, Grümmer R

Clinic of Gynecologic Endocrinology and Reproductive Medicine, University Hospital Aachen, Aachen, Germany. kmotejlek@ukaachen.de

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, 1,174.1 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, respectively, 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 pg/mL 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 nonsmokers, which may result in decreased ovarian vascularization and reduced oocyte maturation.

Published 4 July 2006 in Fertil Steril, 86(1): 186-91.
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