lthough somewhat efective in reducing recurrent preterm birth in women with a singleton pregnancy, weekly injections of 17 alpha-hydroxyprogesterone caproate (17 -OHP-C) are not efective for multifetal gestations (Caritis, 2009; Rouse, 2007). hese results were corroborated in a randomized trial of 240 twin pregnancies (Combs, 2011). Moreover, women carrying twins and having a cervical length <36 mm (25th percentile) did not beneit despite their greater risk for preterm birth (Durnwald, 2010). Senat and colleagues (2013) assigned 165 asymptomatic women with twins and a cervical length <25 mm to 17-0HP-C and also found no reduction in delivery rate before 37 weeks. Last, in an evaluation of plasma drug concentrations, higher concentrations of 17 -OHP-C were associated with earlier gestational age at delivery (Caritis, 2012). he authors concluded that 17-0HP-C may adversely lower the gestational age at delivery in women with twin gestations. In sum, administration of intramuscular 17 -OHP-C to women with twin pregnancies, even to those with a shortened cervix, does not lower the preterm birth risk.
Micronized progesterone administered vaginally to women with twins to prevent preterm birth has provided conlicting results.
Cetingoz and coworkers (2011) gave 100 mg of micronized progesterone intravaginally daily from 24 to 34 weeks' gestation. his practice reduced rates of delivery before 37 weeks from 79 to 51 percent in 67 women with twins. In contrast, several studies have failed to demonstrate any preterm birth rate reduction in women receiving various formulations of vaginal progesterone. In the Prevention of Preterm Delivery in Twin Gestations (PREDICT) trial, 677 women with twins were randomly assigned to receive prophylactic, 200-mg progesterone pessaries or placebo pessaries (Rode, 2011). Progesterone failed to reduce delivery rates before 34 weeks. In a subgroup analysis that included only women with a short cervix or a history of prior preterm birth, also no benefit was found (Klein, 2011). Norman and colleagues (2009) also noted no lower rates of delivery before 34 weeks with progesterone gel treatment.
Romero and colleagues (2017) performed a metaanalysis of individual patient data for 303 women with twin gestation and a short cervix randomized to receive either vaginal progesterone or no treatment. They reported a significantly reduced risk of preterm birth before 30 weeks' gestation and improved composite perinatal outcomes in the treated women. Currently at Parkland Hospital, management of women with multifetal gestations does not typically include progestetone in any formulation.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently enrolling patients into a randomized, placebo-controlled trial to further evaluate the use of micronized vaginal progesterone or the Arabin pessary, describe subsequently (PROSPECT, 2015). The primary outcome is delivery prior to 35 weeks or fetal loss.
Prophylactic cerclage does not improve perinatal outcome in women with multifetal pregnancies. Studies have included women who were not specially selected but also those who were selected because of a shortened cervix that was identified sonographically (Houlihan, 2016; Newman, 2002; Rebarber, 2005). Indeed, in the latter group, cerclage may actually worsen outcomes (Berghella, 2005; Roman, 2013).
Rescue cerclage in women with a second-trimester twin gestation and a dilated cervix may be beneficial. Roman and coworkers (2016) reported a retrospective cohort study in which women undergoing rescue cerclage had significantly better neonatal outcomes than those without cerclage.