Prophylactic Progesterone May Be Harmful in Twin Pregnancies

The use of prophylactic 17 alpha-hydroxyprogesterone caproate (17P) is not effective for the prevention of preterm delivery, and may even be harmful in women with an asymptomatic twin pregnancy and short cervix, concluded the authors of a new study.¹
   
Studies in singleton pregnancies have shown that prenatal progesterone significantly reduces the rate of preterm delivery in high-risk women, explained the study authors.¹ Similar trials in unselected twin pregnancies have shown that prophylactic progesterone does not offer the benefit of a reduced rate of preterm delivery that it does in singleton pregnancies. The use of cervical ultrasonography seems to allow clinicians to better predict which twin pregnancies are at especially high risk for preterm birth. Using selected asymptomatic twin pregnancies, the study authors sought to determine whether prophylactic progesterone reduces preterm delivery in women with a short cervix (cervical length of 25 millimeters or less) and a gestational age of 24+0 to 31+6 weeks.
   
In the study, 165 women were randomized to receive either 500 mg of intramuscular 17P, repeated twice weekly, or no treatment with 17P (control group). Treatment with 17P continued until 36 weeks’ gestation or preterm delivery. The primary outcome was time from randomization to delivery. If preterm labor occurred before 34 weeks, standard management for all women was hospital admission, tocolysis, and a course of betamethasone, 12 mg IM, which was repeated after 24 hours.
   
The median time to delivery between the 17P group and the control group was not significantly different (45 days vs 51 days, respectively). After the study authors adjusted for gestational age at randomization, the mean time to delivery was 7.3 days shorter in the 17P group, but this difference remained insignificant. Interestingly, preterm delivery before 32 weeks’ gestation occurred significantly more often in the 17P group than in the control group (29% vs 12%, respectively; P=0.007). Although the rates of premature delivery remained higher for the 17P group than for the control group at 34 weeks’ gestation (80% vs 77%, respectively; P=0.70) and 37 weeks’ gestation (44% vs 28%, respectively; P=0.10), the differences did not reach statistical significance.
   
“These negative results of prophylactic progesterone on twins suggest that some interventions useful for singletons might possibly be harmful for twins,” wrote the study authors.¹

Pertinent Points:
- Twice-weekly prophylactic injections of 17 alpha-hydroxyprogesterone caproate (17P) did not prolong the pregnancy of women with asymptomatic twin pregnancy and short cervix.
- The rate of preterm delivery before 32 weeks’ gestation was significantly increased in women treated with 17P compared with women in the control group.
 

References:

1. Senat M-V, Porcher R, Winer N, et al. Prevention of preterm delivery by 17 alpha-hydroxyprogesterone caproate in asymptomatic twin pregnancies with a short cervix: a randomized controlled trial. Am J Obstet Gynecol. 2013;208:e1-8.