Inhibition of cervical ripening by local application of cyclooxygenase 2 inhibitor

OBJECTIVE: Our goal was to test the hypothesis that the previously demonstr ated progesterone-independent prolongation of pregnancy in rats treated wit h cervical application of the cyclooxygenase 2 inhibitor nimesulide is the result of inhibition of cervical ripening. STUDY DESIGN: Timed-pregnant Sprague-Dawley rats were randomly allocated to treatment with 50 mg nimesulide or vehicle, applied daily on the cervix fo r 5 days (days 14-18). On day 19 the animals were humanely killed and the c ervices were removed. In the first series of experiments the cervices of an imals treated with nimesulide (n = 10) or vehicle (n = 10) were examined wi th a cervimeter, which stretches the cervical tissues in incremental steps of 0.2 mm at 1-minute intervals. A steeper slope through the linear portion of the resulting force-versus-displacement curve indicates more resistance to stretch. In the second series of experiments the cervices of animals tr eated with nimesulide (n = 11) or vehicle (n = 11) were examined with the C ollascope optical device. The cervical content of cross-linked collagen was measured with light-induced fluorescence. The fluorescence spectrum at 390 nm (peak wavelength of the collagen spectrum) was determined. For standard ization, the ratio of counts of collagen peak over reference counts was use d in the final analyses as an indicator of cross-linked collagen content. RESULTS: Animals treated with cervical application of nimesulide had signif icantly higher resistance to stretch than controls (slope: 0.2564 +/- 0.121 3 vs 0.1387 +/- 0.0652; P = 0.019). The cervical content of crosslinked col lagen was not significantly different between nimesulide-treated animals an d controls (light-induced fluorescence ratios: 3.2134 +/- 0.7390 vs 2.7892 +/- 0.8518; P = .227). CONCLUSIONS: Treatment with cervical application of the cyclooxygenase 2 in hibitor nimesulide prevents the physiologic process of cervical ripening in late pregnancy. The inhibition is not the result of changes in cross-linke d collagen content. Inhibition of cervical ripening with locally administer ed cyclooxygenase 2 inhibitor may be a potentially valuable treatment for p atients at risk for preterm delivery.