American Journal of Obstetrics and Gynecology, included 30 patients at 8 centers. The investigators stopped the trial early because perinatal mortality occurred more often in the group that did not receive the intervention.according to a randomized controlled trial. The trial, which was published in the
The research suggests that a combination of physical exam–indicated cerclage, indomethacin, and antibiotics decreased the incidence of spontaneous preterm birth and prolonged the period from diagnosis to delivery by an average of 5.6 weeks, compared with no cerclage.
“We’ve already incorporated this cerclage into our practice and have been able to offer this to pregnant mothers with twins with great success,” senior author Vincenzo Berghella, MD, said in a news release.
“These results have the potential to change practice and help many more women have healthy twin babies,” said Dr. Berghella, director of the division of maternal fetal medicine at Thomas Jefferson University in Philadelphia.
A shift in perspective
More research is needed to establish a standardized approach, but the trial should “open physicians’ perspectives to think about how, in selected cases and with the proper approach, cerclage can work well,” said Ozhan M. Turan, MD, PhD, director of the division of maternal and fetal medicine and director of fetal therapy and complex obstetric surgery at University of Maryland in Baltimore.
Although many physicians use cerclage for twin pregnancies in select situations, the practice is not well established. “If you look at the guidelines or books, mostly everyone thinks that doing a cerclage in twins is not a good idea,” Dr. Turan said in an interview.
In the present trial, the researchers controlled for many factors and carefully selected patients with no signs of preterm labor or infection. It is not simply a matter of saying, “Do the stitch,” he said. “But it is proven: if you select patients well and use the appropriate approach, then you could improve the outcome.”
The study is the first randomized controlled trial of physical exam–indicated cerclage focused on twins, according to its authors. It enrolled patients between July 2015 and July 2019. In the end, the researchers analyzed data from 30 pregnancies, rather than the originally intended 52. They stopped the trial after a data and safety monitoring board considered it “unethical to continue the study due to the considerable perinatal mortality in one of the arms ... and requested to unmask the arms of the study,” the researchers said.
Perinatal mortality occurred in 18% of neonates in the cerclage group (6 of 34), compared with 77% in the group without cerclage (20 of 26). All perinatal mortality cases were associated with delivery before 24 weeks.
“The small number of participants reflects how rare this condition is among all pregnancies,” first author Amanda Roman, MD, of the division of maternal fetal medicine at Thomas Jefferson University, Philadelphia, said in the news release. “But because women were randomized to treatment and nontreatment groups, the results are strong, as confirmed by the independent data and safety monitoring board.”
The researchers enrolled women with twin pregnancies and asymptomatic cervical dilation from 1 to 4 cm before 24 weeks. Exclusion criteria included monochorionic-monoamniotic pregnancy, selective fetal growth restriction, twin-twin transfusion syndrome, major fetal malformation, known genetic anomaly, placenta previa, signs of labor, or clinical chorioamnionitis.
In all, 17 women were randomized to cerclage and 13 to the no-cerclage group. Both groups had similar patient characteristics. About 93% of the twin gestations were diamniotic-dichorionic. Assisted reproductive technology was used by about 36% of the participants, and 20% had a history of singleton preterm birth. Four women assigned to cerclage did not undergo the procedure but were included in the intention-to-treat analysis. Two of the four patients had contraindications that occurred soon after randomization (rupture of amniotic membranes and vaginal bleeding), one had a friable cervix, and one declined cerclage after being randomized.
Spontaneous preterm birth before 34 weeks of gestation, the primary outcome, occurred in 12 of 17 women in the cerclage group and in all 13 women in the no-cerclage group (70% vs. 100%).
Trial to assess ultrasound indicated cerclage
“Expectant management with no cerclage is the current standard of care for these women,” Dr. Roman and coauthors wrote. “Despite small sample size, we were able to show a significant benefit to physical exam–indicated cerclage.”
Inability to place the cerclage in one patient due to friable cervix was the only intraoperative complication. “Larger cohorts in singleton pregnancies have informed a 10%-20% risk of intraoperative rupture of the membranes, cervical laceration, and bleeding during the procedure,” the researchers noted.
All women who received cerclage also received indomethacin and antibiotics, although these elements of management were not prespecified. Given the relatively small sample size, it is unclear what role factors such as indomethacin, which was administered to 82% of the cerclage group versus 31% of the no-cerclage group, and antibiotics may have played, said Dr. Turan.
Prospective studies may help clarify how the degree of cervical dilation, gestational age, use of progesterone, or surgical techniques may influence outcomes. In addition, the researchers are enrolling patients in another trial. That study aims to assess whether cerclage reduces the incidence of spontaneous preterm birth in asymptomatic women with twin gestations and cervical length of 15 mm or less diagnosed by transvaginal ultrasound between 16 and 24 weeks of gestation.
The study had no external financial support. The authors had no conflicts of interest. Dr. Turan said he had no relevant financial disclosures.
SOURCE: Roman A et al. Am J Obstet Gynecol. 2020 Jun. doi: 10.1016/j.ajog.2020.06.047.