Am J Perinatol 2022; 39(16): 1719-1725
DOI: 10.1055/a-1877-9078
SMFM Fellows Research Series

Adjunct Therapy at Time of Examination-Indicated Cervical Cerclage in Singleton Pregnancies: A Systematic Review and Meta-analysis

Ann M. Bruno
1   Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah
2   Department of Obstetrics and Gynecology, Intermountain Healthcare, Murray, Utah
,
Ashley E. Benson
1   Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah
2   Department of Obstetrics and Gynecology, Intermountain Healthcare, Murray, Utah
,
Torri D. Metz
1   Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah
2   Department of Obstetrics and Gynecology, Intermountain Healthcare, Murray, Utah
,
Nathan R. Blue
1   Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah
2   Department of Obstetrics and Gynecology, Intermountain Healthcare, Murray, Utah
› Author Affiliations
Funding This work was funded in part by the U.S. Department of Health and Human Services, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, grant no.: K12 HD085816.

Abstract

Objective Physical examination–indicated cerclage for cervical insufficiency prolongs gestation, but evidence on the addition of adjuncts to further prolong latency is limited. The aim of this systematic review and meta-analysis was to compare gestational latency between those who did and did not receive adjunct antibiotic or tocolytic therapy at the time of examination-indicated cerclage.

Study Design Electronic databases (1966–2020) were searched for randomized controlled trials (RCTs) and cohort studies comparing adjunct antibiotic or tocolytic use versus nonuse at time of examination-indicated cerclage, defined as placement for cervical dilation ≥1 cm, in a current singleton pregnancy. Studies including individuals with intra-amniotic infection, cerclage in place, nonviable gestation, or ruptured membranes were excluded. The primary outcome was latency from cerclage placement to delivery. Secondary outcomes included preterm birth, preterm premature rupture of membranes, birth weight, and neonatal survival. Risk of bias was assessed using standardized tools. Heterogeneity was assessed using χ 2 and I 2 tests. Results were pooled and analyzed using a random-effects model. This study is registered with The International Prospective Register of Systematic Reviews (PROSPERO) with registration no.: CRD42021216370.

Results Of 923 unique records, 163 were reviewed in full. Three met inclusion criteria: one RCT and two retrospective cohorts. The included RCT (n = 50) and one cohort (n = 142) compared outcomes with and without adjunct use of antibiotic and tocolytic, while the second cohort (n = 150) compared outcomes with and without adjunct tocolytic, with a subpopulation also receiving antibiotics. The RCT was nested within one of the cohorts, and therefore only one of these two studies was utilized for any given outcome to eliminate counting individuals twice. Risk of bias was “critical” for one cohort study, “moderate” for the other cohort study, and “some concerns” for the RCT. Gestational latency could not be pooled and meta-analyzed. Adjunct tocolytic-antibiotic therapy was not associated with a decrease in risk of preterm delivery <28 weeks (relative risk [RR] = 0.90, 95% confidence interval [CI]: 0.65–1.26; χ 2 = 0.0, I 2 = 0.0%) or neonatal survival to discharge (RR = 1.11, 95% CI: 0.91–1.35; χ 2 = 0.05, I 2 = 0.0%).

Conclusion There is not enough evidence to robustly evaluate the use of adjunct tocolytics or antibiotics at time of examination-indicated cerclage to prolong latency.

Key Points

  • Limited data on adjunct antibiotic tocolytics at cerclage.

  • Widely variable practices at time of cerclage identified.

  • Role of adjunct therapies at time of examination-indicated cerclage remains unclear.

Note

This study was presented as a poster at the Society for Reproductive Investigation (SRI) Annual Meeting (virtual) from July 6–9, 2021.


Supplementary Material



Publication History

Received: 20 June 2021

Accepted: 02 June 2022

Accepted Manuscript online:
16 June 2022

Article published online:
08 September 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 ACOG practice bulletin no.142: cerclage for the management of cervical insufficiency. Obstet Gynecol 2014; 123 (2, pt. 1): 372-379
  • 2 Roman A, Suhag A, Berghella V. Overview of cervical insufficiency: diagnosis, etiologies, and risk factors. Clin Obstet Gynecol 2016; 59 (02) 237-240
  • 3 Shirodkar VN. A new method of operative treatment for habitual abortions in the second trimester of pregnancy. Antiseptic 1955; 52: 299-300
  • 4 McDonald IA. Suture of the cervix for inevitable miscarriage. J Obstet Gynaecol Br Emp 1957; 64 (03) 346-350
  • 5 Harger JH. Comparison of success and morbidity in cervical cerclage procedures. Obstet Gynecol 1980; 56 (05) 543-548
  • 6 Novy MJ, Gupta A, Wothe DD, Gupta S, Kennedy KA, Gravett MG. Cervical cerclage in the second trimester of pregnancy: a historical cohort study. Am J Obstet Gynecol 2001; 184 (07) 1447-1454 , discussion 1454–1456
  • 7 Barth Jr. WH, Yeomans ER, Hankins GD. Emergent cerclage. Surg Gynecol Obstet 1990; 170 (04) 323-326
  • 8 Lipitz S, Libshitz A, Oelsner G. et al. Outcome of second-trimester, emergency cervical cerclage in patients with no history of cervical incompetence. Am J Perinatol 1996; 13 (07) 419-422
  • 9 Olatunbosun OA, al-Nuaim L, Turnell RW. Emergency cerclage compared with bed rest for advanced cervical dilatation in pregnancy. Int Surg 1995; 80 (02) 170-174
  • 10 Ehsanipoor RM, Seligman NS, Saccone G. et al. Physical examination-indicated cerclage: a systematic review and meta-analysis. Obstet Gynecol 2015; 126 (01) 125-135
  • 11 Terkildsen MF, Parilla BV, Kumar P, Grobman WA. Factors associated with success of emergent second-trimester cerclage. Obstet Gynecol 2003; 101 (03) 565-569
  • 12 Althuisius SM, Dekker GA, Hummel P, van Geijn HP. Cervical incompetence prevention randomized cerclage trial. Cervical incompetence prevention randomized cerclage trial: emergency cerclage with bed rest versus bed rest alone. Am J Obstet Gynecol 2003; 189 (04) 907-910
  • 13 Berghella V, Ludmir J, Simonazzi G, Owen J. Transvaginal cervical cerclage: evidence for perioperative management strategies. Am J Obstet Gynecol 2013; 209 (03) 181-192
  • 14 Smith J, DeFranco EA. Tocolytics used as adjunctive therapy at the time of cerclage placement: a systematic review. J Perinatol 2015; 35 (08) 561-565
  • 15 Practice bulletin no. 199: use of prophylactic antibiotics in labor and delivery: correction. Obstet Gynecol 2019; 134 (04) 883-884
  • 16 Alfirevic Z, Stampalija T, Medley N. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. Cochrane Database Syst Rev 2017; 6: CD008991
  • 17 Cochrane Handbook for Systematic Reviews of Interventions. . 2nd ed. Chichester, United Kingdom: John Wiley & Sons; 2019
  • 18 McMaster University. Search Filters for MEDLINE in Ovid Syntax and the PubMed translation. Accessed September 29, 2020 at: https://hiru.mcmaster.ca/hiru/HIRU_Hedges_MEDLINE_Strategies.aspx
  • 19 Lee E, Dobbins M, Decorby K, McRae L, Tirilis D, Husson H. An optimal search filter for retrieving systematic reviews and meta-analyses. BMC Med Res Methodol 2012; 12 (01) 51
  • 20 Sterne JAC, Savović J, Page MJ. et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898
  • 21 Sterne JA, Hernán MA, Reeves BC. et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016; 355: i4919
  • 22 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21 (11) 1539-1558
  • 23 Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22 (04) 719-748
  • 24 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7 (03) 177-188
  • 25 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315 (7109): 629-634
  • 26 Moher D, Shamseer L, Clarke M. et al; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4 (01) 1
  • 27 Miller ES, Grobman WA, Fonseca L, Robinson BK. Indomethacin and antibiotics in examination-indicated cerclage: a randomized controlled trial. Obstet Gynecol 2014; 123 (06) 1311-1316
  • 28 Premkumar A, Sinha N, Miller ES, Peaceman AM. Perioperative use of cefazolin and indomethacin for physical examination-indicated cerclages to improve gestational latency. Obstet Gynecol 2020; 135 (06) 1409-1416
  • 29 Berghella V, Prasertcharoensuk W, Cotter A. et al. Does indomethacin prevent preterm birth in women with cervical dilatation in the second trimester?. Am J Perinatol 2009; 26 (01) 13-19
  • 30 Berghella V, Seibel-Seamon J. Contemporary use of cervical cerclage. Clin Obstet Gynecol 2007; 50 (02) 468-477
  • 31 Novy MJ, Ducsay CA, Stanczyk FZ. Plasma concentrations of prostaglandin F2 alpha and prostaglandin E2 metabolites after transabdominal and transvaginal cervical cerclage. Am J Obstet Gynecol 1987; 156 (06) 1543-1552
  • 32 Hanley M, Sayres L, Reiff ES, Wood A, Grotegut CA, Kuller JA. Tocolysis: a review of the literature. Obstet Gynecol Surv 2019; 74 (01) 50-55
  • 33 Eleje GU, Eke AC, Ikechebelu JI, Ezebialu IU, Okam PC, Ilika CP. Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies. Cochrane Database Syst Rev 2020; 9: CD012871