Intramuscular progesterone in women with twins and a prior singleton spontaneous preterm birth

Although the use of 17-alpha-hydroxyprogesterone caproate is one of the most commonly used strategies to reduce the risk of preterm birth since its approval by the Food and Drug Administration in 2011, there has been controversy recently that there may be no benefit associated with its use in singleton pregnancies in women with a prior history of spontaneous preterm birth. However, very few of these investigations evaluated the use of intramuscular progesterone in twin pregnancies. A few studies that used 17-alpha-hydroxyprogesterone caproate in twin pregnancies had mainly included unselected twin pregnancies. Although a twin pregnancy is independently associated with an increased likelihood of preterm birth, the primary indication for the use of supplemental progesterone in pregnancy is prior history of spontaneous preterm birth. Therefore, our investigation of weekly intramuscular progesterone in twin pregnancies with this birth history best addresses this question using a selected cohort.

To assess whether weekly 17-alpha-hydroxyprogesterone caproate prevents recurrent preterm birth in women with a current twin pregnancy and a prior singleton spontaneous preterm birth.

This was a retrospective cohort study of women with twin pregnancy and a prior singleton spontaneous preterm birth in 2 institutions between January 2005 and December 2016. One group (intervention group) consisted of women who received weekly 17-alpha-hydroxyprogesterone caproate, whereas the other (control group) did not. The primary outcome was twin spontaneous preterm birth <34 weeks compared with odds ratio and adjusted odds ratio, adjusting for potential confounders. Secondary outcomes included composite neonatal morbidity such as respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, admission to the neonatal intensive care nursery, and fetal or neonatal death before hospital discharge.

A total of 79 patients were included; 27 women received weekly 17-alpha-hydroxyprogesterone caproate and 52 did not. There were no statistically significant differences in maternal demographics except for age. Spontaneous preterm birth <34 weeks occurred in 16 patients (59%) in the intervention group vs 24 (46%) in the control group (odds ratio, 1.69; 95% confidence interval, 0.68-4.54). Composite neonatal morbidity occurred in 20 pregnancies (74%) in the intervention group and 41 pregnancies (79%) in the control group (odds ratio, 0.76; 95% confidence interval, 0.27-2.12). There remained no differences in outcomes after adjusting for potential confounders.

In our study, weekly 17-alpha-hydroxyprogesterone caproate did not prevent spontaneous preterm birth or neonatal morbidity in women with twins and a prior singleton spontaneous preterm birth; however, further research with larger numbers and prospective design is needed.