Vaginal micronized progesterone (VMP) 200 mg administration twice a day is not effective following arrested preterm labor (APTL) for preventing spontaneous preterm delivery (SPTD), but may be effective in twin pregnancies, according to a recent study published in JAMA Network Open.
Takeaways
- Vaginal micronized progesterone (VMP) 200 mg twice daily is not effective in preventing spontaneous preterm delivery (SPTD) following arrested preterm labor in singleton pregnancies.
- VMP may have potential benefits for twin pregnancies, including shorter neonatal intensive care unit stays, shorter overall hospital stays, and higher birth weights.
- The mean number of days from enrollment to delivery did not significantly differ between the VMP group and the no treatment group.
- The rates of SPTD were similar between the VMP group and the no treatment group, with relative risk showing no significant difference.
- Investigators recommend further studies to explore the potential efficacy of VMP in twin pregnancies.
As preterm delivery is the leading source of neonatal morbidity and mortality, a tocolytic treatment is often given to patients diagnosed with preterm labor (PTL). However, the efficacy of tocolytic treatment has not been proven in randomized clinical trials (RCTs).
Progestins have been considered for preventing SPTD, with vaginal progesterone being the only intervention with consistent efficacy data. However, this efficacy data has methodological limitations, and research about the efficacy in twin pregnancies is needed.
Investigators conducted a multicenter RCT to determine the efficacy of daily 400 mg VMP for prolonging pregnancy after APTL in singleton and twin pregnancies. Participants included women aged at least 18 years with PTL arrested by tocolytic treatment.
Women with 3 or more uterine contractions of 30 seconds or longer per 30 minutes were considered in preterm labor. This was confirmed by a short cervix or a cervical dilation of 1 to 4 cm and cervical effacement of at least 50%.
Tocolytic treatment was initiated between 24 weeks’ and 34 weeks’ gestation and included atosiban, ifedipine, or indomethacin. PTL arrest was determined by a stable condition without progress to active labor.
Participants were randomized 1:1 to receive either VMP, 200 mg twice daily or no treatment. The first VMP dose was taken at least 24 hours after the initial tocolytic treatment and lasted up to 3 days after completed tocolytic treatment.
Follow-up occurred every 3 to 5 weeks, during which adverse effects and patient compliance were reported. The final visits were at 36- or 37-weeks’ gestation.
The mean number of days from enrollment to delivery and the rate of SPTD were reported as primary outcomes. Secondary outcomes included the number of days from recruitment to repeated PTL episode, pregnancy prolongation over 1 week, need for repeated tocolysis, and number of hospitalizations.
There were 129 participants included in the final analysis, aged a mean 27.6 years. Of the VMP group, 81% of participants took more than 80% of the tablets, while overall compliance in the no treatment group was 90%. Comparable patient characteristics were found between groups.
The VMP group had 12 pairs of twins while the no treatment group had 15 pairs. The mean number of days between enrollment and delivery did not significantly differ between the VMP and no treatment groups, at 40 vs 37.4 days, respectively.
Similarly, the rate of SPTD did not significantly differ at 25% vs 30%, respectively, for a relative risk of 0.8. For overall PTDs, rates were 28% vs 44%, for a relative risk of 0.7. There were also no significant differences between groups observed for other endpoints.
Similar characteristics were observed between groups for twin pregnancies, but the mean time to enrollment was longer in the VMP group at 43.7 days vs 26.1 days for the no treatment group. Among twin pregnancies, the VMP group also had a shorter neonatal intensive care unit stay, shorter overall hospital stay, and higher birth weight.
These results indicate VMP given as 200 mg twice per day is not effective for prolonging pregnancy or preventing SPTD after APTL. Investigators recommended further investigation about potential efficacy in twin pregnancies.
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
