Physical Examination—Indicated Cerclage in Twin Pregnancy: A Randomized Controlled Trial

Abstract

Twin pregnancies in the United States represent a small proportion of births each year, but they are associated with increased risks of preterm birth (PTB), low birthweight, and perinatal mortality. In the setting of cervical dilation in the second trimester, the risks for complications in a twin pregnancy are even higher. In singleton pregnancies, physical examinationindicated cerclage has been shown to decrease PTB and loss of pregnancy. However, the data for this procedure in twin pregnancies are limited. There has been 1 prior randomized controlled trial (RCT) to examine cerclage for cervical dilation in pregnant women. The RCT compared 13 women who received cerclage, indomethacin, and bed rest with 10 women on bed-rest only. Although the RCT included some twin pregnancies (3 in the cerclage group and 4 in the bed-rest only group), these data were not reported separately. In addition, 3 retrospective, case-controlled studies on twin pregnancies with and without cerclage found decreases in spontaneous PTBs and perinatal mortality. The aim of this study is to assess whether physical examination-indicated cerclage could reduce the rate of PTBs in women with twin pregnancies and cervical dilation in the second trimester.This was a parallel-group, open-label RCT conducted between July 2015 and July 2019 at 8 clinical centers. Included were 18-to 50-year-old women with twin pregnancies and asymptomatic cervical dilation of 1 cm to 5 cm between 16 weeks' gestation and 23 weeks, 6/7 days' gestation. Excluded were women with monochorionic gestations, selective fetal growth restriction, known genetic anomaly or fetal malformation, twin-twin transfusion syndrome, placenta previa, and indications of labor. Women were randomly assigned to either the cerclage group or no-cerclage group. Although the use of indomethacin and antibiotics were at the discretion of the physician, all women who underwent cerclage received them. During interim analysis, the study was stopped due to significant decreases in the rate of perinatal death in the cerclage group.Of the 30 women included in the analysis, 17 were in the cerclage group and 13 in the no-cerclage group. At <34 weeks' gestation, spontaneous PTBs occurred in 12 women in the cerclage group and 13 in the no-cerclage group (70.6% vs 100%, respectively; risk ratio [RR], 0.7; 95% confidence interval [CI], 0.46-0.96; P = 0.05). Significant decreases in PTBs were also observed at <32, <28, and <24 weeks' gestation in the cerclage group versus no-cerclage group (64.

Efficacy of long‐term indomethacin therapy in prolonging pregnancy after fetoscopic laser surgery for twin‐to‐twin transfusion syndrome: a collaborative cohort study

“…Effective PTB prevention measures in multiple gestations, in general, and, more specifically, in monochorionic diamniotic twin pregnancies complicated with TTTS undergoing FLS, have not yet been defined. In multiple gestation with a normal or short cervix, interventions such as other forms of tocolytics, cerclage, progesterone, pessary, routine hospitalisation, or bed rest have not been proven to prolong pregnancy or improve neonatal morbidity and mortality 10,28–40 . In the setting of TTTS treated with FLS with short preoperative CL, cervical cerclage did not prolong pregnancy in a retrospective, multicentre cohort study 41 .…”

“…In multiple gestation with a normal or short cervix, interventions such as other forms of tocolytics, cerclage, progesterone, pessary, routine hospitalisation, or bed rest have not been proven to prolong pregnancy or improve neonatal morbidity and mortality. 10,[28][29][30][31][32][33][34][35][36][37][38][39][40] In the setting of TTTS treated with FLS with short preoperative CL, cervical cerclage did not prolong pregnancy in a retrospective, multicentre cohort study. 41 Our study showed that LIT use significantly increased the FLS-to-delivery interval regardless of the length of the cervix and gestational age of the surgery.…”

Challenges in Interpreting Obstetrics and Gynecology Literature

“…When we interpret study results on approaches to cerclage for cervical insufficiency (beyond cerclage vs. no-cerclage), wide variation exists in most study interventions for management, including surgical approach (eg, McDonald vs. Shirodkar cerclage, suture type) and adjunct interventions (eg, antibiotics, tocolytics, amniocentesis, bed rest) 59. Roman et al60 performed a multicenter RCT and found that use of a physical examination-indicated cerclage reduced the rate of spontaneous preterm birth for twin pregnancies with asymptomatic cervical dilation before 24 weeks when compared with no cerclage (relative risk: 0.7, 95% confidence interval: 0.46-0.96). However, 82% of those in the cerclage intervention arm also received tocolytic and antibiotics periprocedure.…”

Outstanding clinical and research questions in complex twin and multiple pregnancy

“…16 There is, however, now high-quality evidence supporting the use of physician examination indicated cerclage in twin pregnancies. 17,18 Areas for further investigation include the use of progesterone in twin pregnancies with a short cervix, the role of the microbiome and inflammation in preterm birth in multiple pregnancy. 19 A key knowledge gap highlighted in the recent MBRRACE Special Report on perinatal mortality in twins is the best management of delivery of the second twin in a diamniotic pregnancy where the first twin has delivered spontaneously at an extremely preterm gestation and the second sac remains intact and there is no spontaneous labour or maternal compromise.…”

“…There is no benefit with the Arabin pessary 15 in the management of twin pregnancies with a short (<35 mm) cervix, or in the use of vaginal progesterone in unselected twin pregnancies 16 . There is, however, now high‐quality evidence supporting the use of physician examination indicated cerclage in twin pregnancies 17,18 . Areas for further investigation include the use of progesterone in twin pregnancies with a short cervix, the role of the microbiome and inflammation in preterm birth in multiple pregnancy 19 .…”