Progesterone appears to reduce the rate of preterm delivery in asymptomatic women found to have a short cervix on transvaginal ultrasound performed midway through gestation.
However, progesterone does not reduce the rate of preterm delivery in another group of high-risk women–those carrying twins, researchers in two separate randomized clinical trials reported
Since the 2003 publication of a report that weekly injections of 17 α-hydroxyprogesterone (17P) decreased the rate of recurrent preterm birth, numerous studies have been undertaken to assess the hormone's potential benefit in different high-risk populations. Now, Dr. Eduardo B. Fonseca of King's College Hospital, London, and his associates have evaluated the effect of 200-mg vaginal capsules of micronized progesterone in women who were found at routine midtrimester ultrasound screening to have a short cervix (15 mm or less).
The researchers tested the vaginal formulation of progesterone because of its enhanced bioavailability and reduced incidence of adverse effects, compared with the oral formulation. They chose a high dose rather than the 100-mg dose used in previous studies, because they considered women with a short cervix to be at very high risk for preterm delivery.
The study subjects were 250 women treated at maternity hospitals in London, Santiago (Chile), and São Paulo (Brazil). The rate of spontaneous preterm delivery was 19% in those who had been randomly assigned to use progesterone capsules from 24 weeks' gestation until delivery, compared with 34% in those who had used placebo capsules.
This finding demonstrates that daily vaginal administration of progesterone significantly decreases the rate of preterm delivery in women with a short cervix, Dr. Fonseca and his associates said (N. Engl. J. Med. 2007;357:462-9).
Similar results were seen across most subgroups of subjects, including those who had previously delivered prematurely. However, in the small number of twin pregnancies (24) included in this study, the progesterone treatment was associated with only a nonsignificant reduction in preterm delivery.
In the second study, Dr. Dwight J. Rouse of the University of Alabama, Birmingham, and his associates assessed weekly 250-mg IM injections of 17P in 661 women pregnant with twins. The study population was drawn from a broad geographic area and was racially and ethnically diverse. Two-thirds of the women had conceived spontaneously.
The subjects were randomly assigned to receive either active injections or placebo beginning at 20 weeks' gestation and were followed at 14 sites across the United States.
The rates of preterm delivery or fetal death did not differ significantly between the group receiving 17P (42%) and those receiving placebo (37%). The mean gestational age at delivery also did not differ significantly, nor did the proportion of deliveries that occurred at 28 weeks, 32 weeks, or 36 weeks.
The rates of obstetric interventions such as tocolysis, cervical cerclage, and cesarean section also were similar between the two groups, as were the rates of adverse neonatal outcomes such as major congenital malformations. The composite outcome of serious adverse events including respiratory distress syndrome, severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, bronchopulmonary dysplasia, severe retinopathy of prematurity, and sepsis also was similar between the two groups.
Side effects from the injections were frequent in both groups, and three women discontinued injections because of intense local reactions.
The findings, which “are generalizable to most women in the United States who are pregnant with twins,” demonstrate that 17P doesn't lower the rate of preterm birth, prolong gestation, or improve fetal or neonatal outcomes in twin pregnancies, Dr. Rouse and his associates said (N. Engl. J. Med. 2007:357:454-61).
In an editorial comment accompanying these reports, Dr. Jim G. Thornton of the University of Nottingham (England) said that much more information is needed if progesterone is to be used widely to curtail preterm delivery in women found to have a short cervix. In particular, the possible risks associated with daily vaginal administration of medication must be rigorously evaluated in women who are already susceptible to preterm delivery.
“Even if progesterone therapy is effective for some women who are at risk of preterm labor, reliable evidence is needed about long-term effects on the children before it could be widely recommended,” he noted (N. Engl. J. Med. 2007;357:499-501).
“There are at least 14 ongoing trials involving women with high-risk pregnancies (both singleton and twin) that aim to recruit a total of more than 5,000 women, and I am aware of at least 2 more currently awaiting funding decisions. These should have ample power to test the effect of progesterone on important fetal outcomes as well as any differential effect in twin gestations, and long-term follow-up of the surviving children will provide important additional information,” Dr. Thornton added.