By John C. Hobbins, MD
Professor, Department of Obstetrics & Gynecology, University of Colorado School of Medicine, Aurora
Dr. Hobbins reports no financial relationships relevant to this field of study.
SYNOPSIS: The largest multicenter, randomized, controlled trial so far has found no significant benefit of pessaries to prevent preterm birth or to decrease neonatal morbidity in patients with short cervices.
SOURCE: Nicolaides KH, Syngelaki A, Poon LC, et al. A randomized trial of cervical pessary to prevent preterm singleton birth. N Eng J Med 2016;374:1044-1052.
Previous Alerts have been devoted to preterm birth (PTB) because it remains one of our biggest obstetrical problems. After many years of a frustrating inability to put a dent in the rate of PTB, the good news is that recently there has been a trend downward from our peak rate of 12.8% in 2006 to 9.6% in 2014.1
Possible reasons for this heartening change might include the use of progesterone, screening with cervical length (CL), judicious use of cerclage, or simply an increased awareness of its possible presence. While looking for yet another treatment option, practitioners have been awaiting more news on the newest method for prevention of PTB: the pessary.
An article in the March New England Journal of Medicine may help in decision-making by clinicians for patients noted to have short cervices in the mid trimester. Nicolaides et al undertook a randomized clinical trial (RCT) involving patients with singleton pregnancies with CLs < 2.5 cm between 20 and 24 weeks.2 A total of 935 patients were recruited from hospitals in 16 countries, although most (n = 746) were from England. The authors randomly assigned 467 patients to have an insertion of an Arabin pessary and 465 patients were designated as controls. If the cervix was < 1.5 cm, both groups were given vaginal progesterone daily. The pessary was removed empirically at 34 weeks.
Delivery at less than 34 weeks occurred in 55 controls (12.0%) vs. 50 in the pessary group (10.8%) (odds ratio [OR], 1.12; 95% confidence interval [CI], 0.77-1.65). After adjusting for various confounding factors, such as “iatrogenic intervention” (antibiotics, progesterone, and past obstetrical history), significance was still not attained (OR, 1.09; 95% CI, 0.73-1.61). There were no differences in neonatal outcomes between the two groups.
Adverse outcomes included vaginal discharge (46.8% vs. 13.8%) and pelvic discomfort (11.4% vs. 3.4%). Although 24.5% had the pessary removed because of premature rupture of membranes, preterm labor, and indicated early deliveries, another 10% of patients were bothered by the pessaries enough to request that they be removed.
This study represents the largest of only three RCTs that have addressed pessary use in singletons whose mothers have short cervices. One study3 has suggested benefit and another4 has not, so this study represents a “tiebreaker” of sorts, which will have to sit until new information surfaces. It is interesting that while two out of three studies showed no benefit of pessaries in singletons, the same mixed bag of results are popping up with pessaries in twins, where there is a desperate need for prevention of PTB. Although a very recent small case control study in the Green Journal5 showed a significant benefit from pessaries in patients with twins whose CL < 2.0 cm, other studies, including another RCT from Nicolaides et al,6 found no difference in PTB prior to 34 weeks with pessaries. Another RCT showed no difference in neonatal outcomes in twins when pessaries were empirically placed.7 Secondary analysis in this study, however, showed some improvement in outcome in patients with CL < 3.8 cm. Nevertheless, the predominance of evidence points toward no benefit from pessaries in twins.
The following is a summary of information to date on various methods to prevent PTB:
- The original, and largest, study shows 17 alpha-hydroxyprogesterone caproate (17P) to be effective in preventing recurrent PTB in patients with a past history.8
- Meta-analysis shows vaginal progesterone to be useful in patients with short cervices, irrespective of history, but the weakest effect occurred in patients with CL < 1.0 cm.9
- Two RCTs show vaginal progesterone to outperform IM progesterone in decreasing PTB.10,11
- Meta-analysis shows that cerclage decreases PTB in patients with short cervices (< 2.5 cm) who have a history of PTB, with its greatest effect in patients with CL < 1.5 cm. However, significant benefit was not seen in those without a history.12
- Two out of three studies show that pessaries are not effective in preventing PTB in singletons with short cervices.2,3,4
- Twins: While waiting for more data to be published, thus far there is no compelling evidence that progesterone, cerclage, or pessary are useful in preventing PTB in twins.
- Schoen CN, Tabbah S, Iams JD, et al. Why the United States preterm birth rate is declining. Am J Obstet Gynecol 2015;213:175-180.
- Nicolaides KH, Syngelaki A, Poon LC, et al. A randomized trial of cervical pessary to prevent preterm singleton birth. N Eng J Med 2016;374:1044-1052.
- Goya M, Pratcorona L, Merced C, et al. Cervical pessary in pregnant women with a short cervix (PECEP): An open label randomized controlled trial. Lancet 2012;379:1800-1806.
- Hui SY, Chor CM, Lau TK, et al. Cerclage pessary for preventing preterm birth in women with singleton pregnancy and a short cervix at 20 to 24 weeks: A randomized controlled trial. Am J Perinatol 2013;30:283-288.
- Fox NS, Gupta S, Lam-Rachlin J, et al. Cervical pessary and vaginal progesterone in twin pregnancies with a short cervix. Obstet Gynecol 2016;127:625-630.
- Nicolaides KH, Syngelaki A, Poon LC, et al. Cervical pessary placement for prevention of preterm birth in unselected twin pregnancies: A randomized clinical trial. Am J Obstet Gynecol 2016;214:3.e1-9.
- Liem S, Schuit E, Hegeman M, et al. Cervical pessaries for prevention of preterm birth in women with multiple pregnancy (ProTWIN): A multicenter open label randomized controlled trial. Lancet 2013;382:1341-1349.
- Meiss RJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med 2003;384:2379-2385.
- Romero R, Nicolaides K, Conde-Agudelo A, et al. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the mid trimester decreases preterm delivery and neonatal morbidity: A systematic review and meta-analysis of individual patient-level data. Am J Obstet Gynecol 2012;206:124.e1-19.
- Maher MA, Abdelaziz A, Ellithy M, et al. Prevention of preterm birth a randomized trial of vaginal compared with intramuscular progesterone. Acta Obstet Gynecol Scandinavica 2013;92:215-222.
- El-Gharib MN, El-Hawary TM. Matched sample comparison of intramuscular versus vaginal micronized progesterone for prevention of preterm birth. J Matern Fetal Neonatal Med 2013;26:716-719.
- Berghella V, Rafael TJ, Szychowski JM, et al. Cerclage for short cervix on ultrasonography in women with singleton gestations in previous preterm birth: A meta-analysis. Obstet Gynecol 2011;117:663-671.