Vaginal versus oral indomethacin in a rabbit model for non-infection-mediated preterm birth: An alternate tocolytic approach

Objective: We examined the hypotheses that vaginal indomethacin is more effective for prolonging gestation, and mediates its tocolytic actions via changes in cervical matrix metalloproteinase (MMP) activity, compared to oral. Study design: Pregnant rabbits induced with mifepristone received oral or vaginal indomethacin; or oral or vaginal vehicle once daily for 2 days. Premature delivery, fetal ductus arteriosus, and cervical MMP activity were assessed. Results: Vaginal indomethacin delayed delivery >72 hours in 100% of the rabbits, extending gestation to 28.2 ± 0.5 (P < .01) versus 26.4 ± 0.3, 25.8 ± 0.5, and 26.5 ± 0.3 days, for vaginal placebo, oral indomethacin, and oral vehicle, respectively. Fetal ductus arteriosus was patent in all groups. Vaginal indomethacin decreased MMP-1, -8, and -9 activities and increased TIMP-1 levels in the cervix. Conclusion: Vaginal indomethacin is more effective than oral for prolonging gestation in the rabbit. Its tocolytic effects may be mediated, in part, by alterations in cervical MMP activity.