Does projesteron helps in maintaining cervical length in twin pregnancy
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Progesterone is a key hormone for pregnancy maintenance, and a decline in progesterone action is considered to be central to the initiation of parturition in most mammalian species, including primates.This hormone acts in all components of the common pathway of parturition and promotes myometrial quiescence, inhibits cervical ripening, and down-regulates the production of chemokines [such as interleukin by the chorioamniotic membranes. Importantly, the administration of progesterone receptor antagonists [i.e. mifepristone (RU486) or onapristone (ZK98299)] to pregnant women, non-human primates and guinea pigs can induce the onset of labor and cervical ripening. Thus, it is not surprising that many investigators have explored the use of progesterone for the prevention of preterm birth.
Two compounds with progestational action have been used in clinical trials: progesterone, the bioequivalent of the natural hormone, and 17-alpha-hydroxyprogesterone caproate (17OHP-C), a synthetic ester, in which the caproate is added to prolong the half-life of the compound.5 The two molecules have different physiologic properties6 and clinical effectiveness in the prevention of preterm birth (i.e. vaginal progesterone prevents preterm birth in women with a short cervix and singleton gestation,7, 8 but there is no evidence that 17OHP-C does9). Trials of 17OHP-C in twin10, 11 and triplet12, 13 gestations have indicated that this compound does not prevent preterm birth in multiple pregnancies. Three trials have explored the effects of vaginal progesterone in the prevention of preterm birth in twins. Two have used vaginal progesterone (90mg daily in a bioadhesive gel), and one has used 200mg. All trials have been negative. A logical question is whether twin gestations require a larger dose of progesterone for the prevention of preterm birth.
In this issue of the Journal, Serra et al report the results of an important randomized clinical trial which addressed this question. Women with dichorionic, diamniotic twin pregnancies, conceiving largely through assisted reproductive technologies (ART; ovarian stimulation, in vitro fertilization or intracytoplasmic sperm injection), were randomized to either placebo or two different doses of vaginal progesterone daily in pessaries (one group received 200mg, and another, 400mg). The primary endpoint of the study was preterm birth (<37 weeks). Eligible women were recruited at 11-13 weeks of gestation, but randomized at 20 weeks. If patients had been treated with vaginal progesterone during the first trimester for corpus luteum support, that treatment was stopped at the time of recruitment. The study was conducted in 5 centers in Spain and included 290 women (with complete follow-up data). The rate of preterm birth at <37, <34, <32 and <28 weeks was not significantly different among the 3 groups (placebo, 200mg of progesterone, or 400 mg of progesterone). The frequency of a sonographic short cervix (<25mm) in the trial of Serra et al.17 was low (1.7%; 5/290), and this may be one explanation for the negative results (see below for the relationship between a short cervix and response to progesterone).