Vaginal lubricants are commonly used for symptomatic relief of dyspareunia. When mixed with human semen during intercourse, lubricants may impact sperm integrity and function thereby decreasing its fertilization potential. The objective of our study was to evaluate the sperm motility and chromatin integrity following contact with vaginal lubricants, including two claiming to not harm sperm: FemGlide® (FG) and Pre-Seed® (PS); as well as two previously reported to harm sperm, but still often recommended to fertility patients: Astroglide® (AG) and Replens® (R). Prospective-controlled study using normozoospermic donors Sperm samples from normal donors were collected, analyzed (WHO, 1999), and diluted to 20 - 40 x 106/ mL using human tubal fluid media (HTF) with 10% human serum albumin. For experiment 1, sperm samples from 13 subjects were incubated at 370 C in HTF controls or 10% (v/v) lubricant treatments of AG, FG, PS and R. After 30 minutes of culture, progressive motility (% a + b) was assessed for sperm in each treatment. For experiment 2 (12 donors), spermatozoa were processed as above and placed in positive control (HTF); 10% v/v FG or PS; or negative control (10% KY®) and cultured for 4 hours to evaluate sperm chromatin integrity after longer exposure to lubricants. After culture, spermatozoa were flash frozen and analyzed for the percent damaged chromatin (% DNA fragmentation index, DFI) using the acridine orange-based sperm chromatin structure assay (SCSA®). Repeated measures analysis of variance (ANOVA) was used to evaluate outcomes, and Bonferonni’s correction when comparing percent change in treated versus control sperm. Data are expressed as mean (SD). In experiment 1, mean percentage (%) of progressively motile sperm did not differ between HTF controls or PS following the incubation period, while other treatments (FG, R and AG) showed a significant decrease in motility (p<0.01). Tabled 1 In experiment 2, there was no difference in %DFI between the HTF control and PS (p=0.23), but a decline in sperm chromatin quality was noted after exposure to FG (p=0.02) and KY (p=0.04). Tabled 1 Pre-Seed does not cause a significant decrease in progressive sperm motility or chromatin integrity, whereas other lubricants used by fertility patients do. Pre-Seed may be an appropriate vaginal dryness relief product for couples trying to conceive.