Vaginal Progesterone Ineffective for Arrested Preterm Labor, Yet Promising in Twin Pregnancies: JAMA

"In a randomized clinical trial involving 129 women experiencing arrested preterm labor between 24 and 34 weeks of gestation, vaginal progesterone (VMP) did not extend pregnancy duration or prevent spontaneous preterm delivery when compared to no treatment. However, in a subgroup of 27 pairs of twins, VMP significantly prolonged pregnancy by an average of 26 to 44 days," the researchers reported in JAMA Network Open.

Women with APTL are noted to be at very high risk for spontaneous preterm delivery (SPTD), which is the leading cause of neonatal morbidity and mortality. So far, no maintenance therapy has proven effective for prolonging pregnancy. However, some clinical trials, despite notable methodological limitations, have shown some efficacy for 400 mg of VMP in women with arrested preterm labor.

Against the above background, Zohar Nachum, Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel, and colleagues sought to investigate the effectiveness of daily 400 mg VMP for prolonging pregnancy after APTL.

For this purpose, the researchers conducted a randomized clinical trial between 2018 and 2023 in three university-affiliated medical centers in Israel. Participants were women with singleton and twin pregnancies after APTL following tocolysis at 24 weeks 0 days to 34 weeks 0 days gestation. They excluded women with a history of preterm delivery or asymptomatic cervical shortening in the current pregnancy.

Participants were randomly assigned to receive either 200 mg of vaginal micronized progesterone twice daily or no treatment until 36 weeks and six days of gestation.

The primary endpoints were the mean number of days from study enrollment to delivery and the SPTD rate before 37 weeks gestation.

The study led to the following findings:

• The study enrolled 129 participants (65 in the VMP group and 64 in the no-treatment group). The mean age was 27.6 years.
• Between the VMP and no-treatment groups, there was no difference in pregnancy prolongation (mean, 40.0 versus 37.4 days) and the rate of SPTD (25% versus 30%; relative risk, 0.8).
• In twin pregnancies, including 12 and 15 pairs in the VMP and no-treatment groups, respectively, VMP prolonged pregnancy (mean, 43.7 versus 26.1 days), postponed the delivery week (36.5 versus 34.7 weeks), shortened the length of stay in the neonatal intensive care unit (4.9 versus 13.2 days) and overall hospital stay (8.3 versus 15.1 days), and was associated with a higher birth weight (2444 versus 2018 g).

"These findings indicate that administering 200 mg of vaginal micronized progesterone twice daily after arrested preterm labor is not effective for prolonging pregnancy or preventing spontaneous preterm delivery. However, VMP showed positive effects in twin pregnancies, suggesting the need for further investigation," the researchers concluded.

Reference:

Nachum Z, Ganor Paz Y, Massalha M, Wated M, Harel N, Yefet E. Vaginal Progesterone for Pregnancy Prolongation After Arrested Preterm Labor: A Randomized Clinical Trial. JAMA Netw Open. 2024;7(7):e2419894. doi:10.1001/jamanetworkopen.2024.19894