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12: Pharmacological actions of progesterone (P4) or 17-alpha-hydroxyprogesterone caproate (17P) to inhibit cervical ripening or prevent term delivery depend upon the route of administration and effects on the myometrium

      Objective

      Recent clinical reports indicate that progestins, P4 or 17P applied vaginally or parenterally, might be useful to treat recurrent preterm labor. Our objectives were to evaluate the cervix throughout pregnancy and estimate the effects of P4 (vaginal application and injection), 17P and the P4 antagonist RU-486 on cervical ripening and delivery in pregnant rats.

      Study Design

      The cervices of timed-pregnant rats (normal delivery on day 22) were followed with LIF (collagen light-induced fluroescence). Daily treatments consisted of: (1) P4 (4mg s.c.) (2) P4 (2mg to 15 mg, vaginally bid) (3) 17P (10 mg s.c) or (4) vehicle (n=6 for each group) from day 13 of pregnancy until delivery. Some rats were also treated with a single injection of RU-486 (3 mg s.c.) on day 16 .Cervical ripening was assessed every second day in vivo by LIF using a collascope instrument by placing the probe on the cervix. Statistics were assessed by ANOVA and the Student′s t-test (P<.05).

      Results

      LIF is significantly higher in the P4-injection group and in the 17P treated group (until day 19 only for the 17P) compared with vehicle controls. There is no significant difference between the vaginal P4 group and vehicle controls at any time in gestation. Only injection of P4 delays delivery. LIF is significantly lower in the RU-486 treated rats during preterm delivery compared to controls.

      Conclusion

      The cervix progressively softens during pregnancy and reverts to a rigid state postpartum. Parenteral treatment with P4 delays and reduces softening and completely blocks delivery. Vaginal P4, even at very high dose, has no effect on cervical softening or delivery. Injections of 17P also delays and reduces cervical softening until term but it does not inhibit delivery. Parenteral P4 treatment may be the preferred treatment to prevent preterm cervical ripening and prevent delivery as it also inhibits uterine contractility.