Authors' objectives: Second trimester miscarriage and preterm birth is a significant global problem. Surgical cervical cerclage is performed to prevent pregnancy loss and preterm birth. It utilises either a monofilament or braided suture. It is hypothesised that a braided material becomes colonised with pathogenic bacteria that causes vaginal dysbiosis, infection and cerclage failure. The primary objective of the study was to examine the effectiveness of using a monofilament suture material as opposed to a braided suture material on pregnancy loss in women requiring a vaginal cervical cerclage. Preterm birth and second trimester miscarriage is a significant cause of worldwide neonatal morbidity and mortality. The aetiology is complex and multifactorial with a number of causes, including cervical insufficiency. One treatment to prevent preterm birth and second trimester miscarriage caused by cervical insufficiency is the placement of a vaginal cervical cerclage (CC). A CC is the placement of a purse string suture thread around the cervix aiming to prevent pregnancy loss and preterm birth. A CC can be performed with either a monofilament suture thread or a braided suture thread. The choice of thread used during surgical operations is dependent on the properties of the thread, with braided threads being multifilament in nature with lots of single strands woven together, which predisposes it to potentially becoming colonised with pathogenic bacteria. A prior feasibility study suggested a difference in pregnancy loss outcomes between monofilament and braided suture threads and the acceptability of either thread for clinicians and women. Therefore, a randomised controlled trial was designed to explore this discrepancy, aiming to reduce pregnancy loss for women at high risk of preterm birth. The primary objective of the study was to examine the effectiveness of using a monofilament suture material compared to a braided suture material on minimising the risk of pregnancy loss in women requiring a vaginal CC. The secondary objectives of the study included exploring the impact of suture material on maternal and neonatal outcomes.

Authors' results and conclusions: A total of 2049 women were randomised, after withdrawals and loss to follow-up, data on 1005 women in the monofilament group and 993 women in the braided group were included. The baseline demographics between the groups were similar. There was no evidence of a difference in pregnancy loss rates between the monofilament and braided groups (80/1003 vs. 75/993; adjusted risk ratio: 1.05, 95% confidence interval: 0.79 to 1.40; adjusted risk difference: 0.002, 95% confidence interval: −0.02 to 0.03). There was no evidence of a difference in pregnancy loss between a monofilament suture and a braided suture. The trial opened for recruitment in August 2015 and completed recruitment in January 2021. A total of 2049 women were randomised into the trial and data for analysis was available for 1003 women in the monofilament group and 993 women in the braided group. The baseline demographic characteristics of women in the monofilament and braided group were similar. There was no evidence of a difference in pregnancy loss rates between the monofilament and braided groups [80/1003 vs. 75/993; adjusted risk ratio (RR) 1.05, 95% confidence interval (CI) 0.79 to 1.40; adjusted risk difference 0.002, 95% CI −0.02 to 0.03]. There was no difference in conception to pregnancy end (median time to pregnancy end: 37.9 weeks vs. 38.0 weeks; adjusted hazard ratio 1.04, 95% CI 0.95 to 1.14). Regarding maternal outcomes there was a decrease in maternal sepsis in the monofilament group (4%) compared to the braided group (7%) (RR 0.58, 95% CI 0.40 to 0.82) and a decreased risk of chorioamnionitis in the monofilament group (3%) compared to the braided group (6%) (RR 0.45, 95% CI 0.29 to 0.71). There was no difference in any neonatal outcomes. CC removal complications showed an increase in the monofilament group (56% vs. 42%, RR 1.25, 95% CI 1.15 to 1.36), with increased difficulty of removal and an increased need for anaesthetic for removal being the most common complications. There was no evidence of a difference between a monofilament suture thread and a braided suture for pregnancy outcomes. We can be relatively confident that using a monofilament suture is unlikely to have a substantial impact on pregnancy loss compared to a braided suture. The uncertainty around our comparative estimate for this outcome is at most 2% in favour of the monofilament in absolute terms. While this margin may not completely rule out missing a clinically important difference, we consider this scenario to be unlikely. Therefore, clinicians should consider the relative merits and disadvantages of the physical suture properties when selecting the material to perform a vaginal CC. The trial was robustly conducted with minimal limitations. An important strength of the study is the recognition early in the trial that the event rate was lower than anticipated and, therefore, the sample size was increased allowing the effectiveness of a monofilament versus braided suture thread to be fully evaluated.

Authors' methods: Superiority open randomised controlled trial. Seventy-five maternity sites across the UK. Women experiencing a singleton pregnancy requiring a cervical cerclage. Monofilament suture or braided suture. The primary outcome was pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life). Secondary outcomes included the core outcome set for preterm birth. Women were randomised on a 1 : 1 basis to monofilament or braided cerclage utilising a bespoke randomisation service with minimisation dependent on the site, indication for cerclage, intention to use progesterone and planned surgical technique. The inclusion criteria were three or more previous mid-trimester losses or preterm births, insertion of a cerclage in a previous pregnancy, a history of a mid-trimester loss or preterm birth with a shortened cervical length in the current pregnancy or in women who clinicians deemed at risk of preterm birth. The exclusion criteria were an emergency or rescue cerclage, age of < 18 years, being unable to give informed consent or the cerclage having to be placed abdominally. The original sample size was calculated based on a relative risk reduction of 41% from a pregnancy loss rate of 19% in the braided group to 11% in the monofilament group with 90% power and alpha at p = 0.05. The independent data monitoring committee noted a lower-than-anticipated pooled event rate within the trial and recommended an increase in sample size to 2050. The outcome data were collected using clinical record forms from the maternal and neonatal medical records and reported to Birmingham Clinical Trials Unit. The trial did not collect long-term paediatric outcomes. There were no safety concerns. A pragmatic open, parallel, multicentre, randomised superiority trial of monofilament versus braided suture type during CC to prevent pregnancy loss. The study was conducted in hospital settings across the UK (75 sites) between 2015 and 2022. Women were eligible for the trial if they required a vaginal CC as part of their routine care within their current pregnancy and they fulfilled the following eligibility criteria: Inclusion Singleton pregnancy. Indication for CC for either: a history of three or more previous mid-term losses or premature births (≤ 28 weeks), OR insertion of cervical sutures in previous pregnancies, OR a history of mid-trimester loss or premature birth with a shortened (≤ 25 mm) cervix, OR women whom clinicians deemed to be at risk of preterm birth either because of their history or because of the results of an ultrasound scan. Exclusion Had taken part in C-STICH previously. Aged < 18 years old at the time of presentation. Requiring a rescue cerclage. Unwilling or unable to give informed consent. Those in whom a cerclage was to be placed by any route other than vaginally (e.g. via an abdominal route). Immediate need for insertion of a suture. Membranes that had ruptured or were surfacing. Women were randomised at a 1 : 1 ratio via a secure internet facility to have their CC performed using either a monofilament or braided suture thread. Minimisation was employed to balance for the following: indication for cerclage, planned bladder dissection, intention to commence patient on progesterone and recruiting site.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/13/04/107

Year Published: 2024

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/YKTW8402

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/YKTW8402

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk