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.