Introduction

Preterm birth

Preterm birth (before 37 weeks) is a significant global problem, contributing to worldwide excess neonatal mortality and morbidity.1 Office for National Statistics data demonstrate the contribution of preterm birth to excess neonatal mortality and morbidity, with over 51,000 preterm births per year in England and Wales.2 Second trimester miscarriage is the delivery of a baby between 14 and 24 weeks without signs of life, a devastating event for women and their families. The number of women experiencing a second trimester miscarriage is harder to quantify as these losses are not registered through national reporting systems. The aetiology of second trimester miscarriage and preterm birth are complex and multifactorial and the conditions are often unrecognised as a continuum.3 Romero et al. described the complex underlying mechanism of preterm birth as a pathological activation of the labour pathway, with a range of aetiologies.4 The pathological processes potentially involved in preterm labour are infection/inflammation, cervical insufficiency, vascular disorders, decidual failure, uterine over distension (twins/polyhydramnios), decline in progesterone action, stress and breakdown of maternal–fetal tolerance.4

Risk factors for second trimester miscarriage and preterm birth

There are several risk factors that can that predispose women to an increased risk of second trimester miscarriage and preterm birth. Previous history is the strongest predictor of recurrence; a systematic review and meta-analysis of 32 studies including 55,109 women identified a recurrence risk of 30%.5 Additionally, previous preterm prelabour rupture of membranes (PPROM) is also associated with a risk of recurrence of approximately 7%, with previous early PPROM conferring a higher risk.5 These risk factors when identified in a subsequent pregnancy enable increased surveillance, screening and interventions to help reduce the risk of recurrence. Previous early birth and PPROM have mixed aetiologies and can result from multiple underlying pathological processes. One of these pathological processes is cervical insufficiency, which is a condition of unknown aetiology but involves cervical shortening [which can be diagnosed by transvaginal ultrasound scanning (TVUS) measuring cervical length] and loss of cervical integrity. Cervical cerclage (CC) is one of several interventions proposed to treat cervical insufficiency.6 Previous cervical surgery, often for premalignant cervical changes also predisposes to cervical insufficiency and early birth, with the risk of early delivery being directly proportionate to the depth of cervical excision.7

Cervical cerclage

Vaginal CC is one treatment option for the prevention of second trimester miscarriage and preterm birth. A vaginal CC was first described in the literature over 70 years ago. The surgical procedure involves the placement of a purse string stitch around the cervix to close the cervix, provide mechanical support and potentially prevent ascending infection. There remains uncertainty regarding the surgical technique for performing the cerclage, the magnitude of effect and the population in which to offer CC. One of the largest trials evaluating the efficacy of CC was a joint collaboration between the Medical Research Council (MRC) and the Royal College of Obstetricians and Gynaecologists (RCOG), randomising women to CC or standard care (no intervention/standard care). Eligible women were defined as those women where clinicians felt there was uncertainty regarding the benefit of cerclage, and the trial demonstrated no significant benefit of CC.8 The trial did not potentially recruit women at the highest risk of second trimester miscarriage and preterm birth, additionally it was conducted before the use of routine transvaginal cervical length scanning. Thus, the trial has significant limitations related to the population risk. However, it did offer important insights into the potential risks of cerclage, including maternal infection.8 Prior to commencing this trial, a Cochrane review also did not conclusively demonstrate a benefit of CC.9 At the same time as C-STICH (cerclage suture type for an insufficient cervix and its effects on health outcomes) opened for recruitment, the National Institute for Health and Care Excellence (NICE) 2015 preterm birth guideline identified two groups of women who should be offered a vaginal CC:10 women with a previous preterm birth and a short cervix on transvaginal scanning and women with previous PPROM and short cervical length.10 A subsequent updated Cochrane review identified a benefit in reducing preterm birth in women at high risk based on their history (second trimester miscarriage and preterm birth) and a short cervical length, supporting the recommendations of the NICE guideline.11 Vaginal CC is an appropriate treatment option for some, but not all, women, and care must be taken to ensure that background risk is carefully assessed to determine the potential benefit of a CC.

Cerclage technique

There are two main surgical techniques for performing a vaginal CC. A Shirodkar cerclage, which involves a bladder dissection and is placed at the levels of cardinal ligaments, or a McDonald cerclage, which is placed lower in the cervix without a bladder dissection (see Figure 1).

FIGURE 1 Illustration of cerclage technique. (Figure not reproduced here; see the original article.)

There are no randomised controlled trials (RCTs) comparing these two surgical techniques; a systematic review of the Shirodkar versus the McDonald technique suggests that there is no clear benefit of a bladder-dissected cerclage, and the authors suggest that if using a McDonald technique it should be placed as high as possible.12

Current practice in the UK to prevent preterm birth

Preterm birth and second trimester prevention is an integral part of the Saving Babies Lives Care Bundle version 2. This bundle details a national approach to reducing stillbirth and neonatal death. Women are screened at booking for risk factors for preterm term birth and identified as either high risk or intermediate risk as per Table 1.

Women who are at high risk should be counselled regarding the risks and benefits of screening and treatment options, including CC, progesterone and Arabin pessaries. The majority of women will follow a screening pathway and will have a TVUS assessment of their cervix to measure the cervical length. In high-risk women, a cervical length measurement is recommended at least every 4 weeks from 16 weeks until 24 weeks. Women at intermediate risk of preterm birth should be offered at least one cervical assessment between 18 and 22 weeks.

Properties of suture threads

There are different types of suture thread used in surgical practice related to their properties: synthetic versus natural, monofilament versus braided and absorbable versus non-absorbable. Sutures are selected for different procedures based on the required characteristics, for example strength, diameter of suture, type of needle size, handling, ability to remove suture (anatomical location), absorption time. Surgeon preference also plays a role.

In the context of vaginal CC there are two main suture types: a thin, monofilament synthetic, non-absorbable suture and a thicker, multifilament, synthetic, non-absorbable braided tape. Braided suture materials, due to the multifilament threads woven together, have the potential to harbour bacteria.13 In the context of a vaginal CC, this has the potential to cause vaginal dysbiosis which can predispose the area to infection and cerclage failure.14 Microbiome studies have identified stability in the lactobacillus vaginal microbiome with a monofilament cerclage and a loss of microbiome stability (vaginal dysbiosis) with the use of a braided thread.14 Yet, single-stranded monofilament sutures have been shown not to confer the same risk of vaginal dysbiosis.14

Cerclage outcome by the type of suture material

Prior to C-STICH a feasibility study, cerclage outcome by the type of suture material (COTS), was performed. This study consisted of a literature review, a survey of optimal practice and the development of a protocol and trial documentation which then underwent feasibility-for-recruitment testing with women.15–17

The survey of practice revealed that 87% of clinicians had a preference for a braided suture thread and 13% had a preference for a monofilament thread.17 When exploring the decision-making process, the majority of clinicians did not consider suture-thread properties when making a choice, but instead utilised the thread that they were taught to perform the procedure with. Some clinicians, particularly those clinicians who had experience of mesh/woven type sutures within urogynaecology, considered that bacteria could penetrate the thread and potentially cause vaginal dysbiosis and predispose the area to infection.17 Others felt that a braided tape could offer additional strength and support to a weak cervix.17

As part of the COTS feasibility study, a literature review was performed which identified that there were limited data to inform suture-thread choice when performing a vaginal CC, with no RCTs. Additionally, most cerclage trials did not report the suture thread utilised during the procedure. Therefore, a retrospective cohort study in the authors’ units was performed and a non-randomised meta-analysis identified a potential difference in pregnancy loss between the different suture materials used for CC.15–17

The meta-analysis is graphically represented in Figure 2 and identifies a reduction in pregnancy loss of up to 7% in the monofilament group compared with 18% in the braided group. The limitations of these data include the retrospective nature and the potential bias from the operator choice of suture thread, with a suggestion from the survey that those with high levels of experience preferentially choose monofilament suture threads. In view of the potential benefit of a monofilament suture thread and the lack of robust evidence, there was a need for a trial. Therefore, the concluding part of the COTS study included the development of a proposed protocol for a randomised trial and patient information leaflet that was evaluated by women undergoing a CC and demonstrated the willingness of women to be recruited and randomised.16

FIGURE 2 Non-randomised meta-analysis of pregnancy loss with monofilament vs. braided suture thread at CC.18 (Figure not reproduced here; see the original article.)

Hypothesis

Multifilament braided suture threads are susceptible to colonisation by bacteria due to the nature of the woven threads. This colonisation increases the risk of CC failure and pregnancy loss through an infective mechanism which will be reduced by using a monofilament single-stranded thread when performing a CC.

Specific objectives

Primary objective

The primary objective of the study was to examine the effectiveness of using monofilament suture material as opposed to braided suture material on pregnancy loss in women requiring a vaginal CC.

Secondary objectives

The secondary objectives of the study include exploring the effectiveness of suture material on maternal and neonatal outcomes, exploring the variation of effect with regard to surgical technique (with or without bladder dissection) and exploring the variation of effect between indications for cerclage.