Objective: To evaluate the changes in cervical mucus within the first hours or days after depot medroxyprogesterone acetate (MPA) injection so as to estimate the time at which cervical mucus becomes hostile enough to prevent pregnancy. Design: Multicenter, clinical descriptive study. Setting: Family planning clinic. Patient(s): Thirty women who were between days 8 and 13 of their menstrual cycle and who had requested Depo-Provera were enrolled in the study. Intervention(s): Cervical mucus and blood samples were obtained; transvaginal ultrasonography was performed. Main Outcome Measure(s): Cervical mucus scores, sperm penetration distances, ovarian follicular size, and serum levels of progesterone and estradiol. Result(s): From 6 to 24 hours after injection, there was a sharp decline in the cervical mucus score for most of the subjects. All subjects exhibited poor mucus on day 3 after injection, and by day 7, all subjects had zero scores, with the exception of two outliers on each day. Sperm penetration, as measured by the vanguard sperm distance, was already poor (<1 cm) in 7 of the 30 subjects at the time of injection and was reduced progressively up to 24 hours after injection, when only four subjects had a sperm penetration of >1 cm. A rapid decline in the estimated number of sperm was observed at 12 hours and more so at 24 hours in the majority of subjects. Conclusion(s): The data presented in this report confirm that depot MPA causes profound changes in cervical mucus after injection. Although very little change was seen at 6 hours, alterations were observed subsequently, with 90% of the subjects showing a poor cervical mucus score 24 hours after administration of the progestin. No reliable clinical marker is available to identify in which women depot MPA might exert its effect on cervical mucus within 3 days. Thus, we believe that at present, women should be informed of this uncertainty and should use a backup method of contraception for 7 days when the first injection of depot MPA is provided after the seventh day of the menstrual cycle. (C) 1998 by American Society for Reproductive Medicine.692252257