Efficiency of cervical cerclage and pessary in addition to vaginal progesterone to prevent preterm birth in twin pregnancies: a case-control study from a tertiary center

TL;DR

This study found that adding cervical cerclage or pessary to vaginal progesterone does not improve outcomes for twin pregnancies at risk of preterm birth.

Contribution

The study provides clinical evidence that cervical cerclage or pessary offer no additional benefit over vaginal progesterone in twin pregnancies.

Findings

Cervical cerclage or pessary added to vaginal progesterone did not improve delivery after 34 weeks.

Intraamniotic sludge was a negative independent factor for delivery after 34 weeks.

No significant differences in effectiveness were found between treatment groups.

Abstract

This study evaluated the efficiency of cervical cerclage and pessary in addition to vaginal progesterone to prevent preterm birth in twin pregnancies.

This retrospective case-control study included 46 cases of twin pregnancy with cervical insufficiency delivered at Ankara Bilkent City Hospital between January 2022 and January 2024. Patients were grouped as those receiving cervical cerclage in addition to vaginal progesterone (n = 10), cervical pessary in addition to vaginal progesterone (n = 11), and only vaginal progesterone (n = 25). Patients’ data were obtained from the hospital’s database. Obstetric parameters (gravidity, parity, abortion, artificial reproductive technologies, second-trimester abortion) and ultrasound parameters (cervical length, intraamniotic sludge) were recorded. Gestational week at birth, latency period (diagnosis to delivery), and delivery after 34 weeks were evaluated for effectiveness. All parameters were compared between groups and evaluated for effectiveness as an independent factor for preterm birth.

The primary effectiveness parameters of latency period, birth week, and delivery after 34 weeks did not differ statistically between groups. When the parameters were evaluated independently of treatment groups for their effects on delivery after 34 weeks with multivariate regression analysis, the presence of intraamniotic sludge was found to be a negative independent factor for delivery after 34 weeks (p = 0.03).

Cervical cerclage or pessary in addition to vaginal progesterone had no additional benefit for achieving birth after 34 gestational weeks. The only factor that had a negative effect on birth after 34 gestational weeks was the presence of intraamniotic sludge. Our clinical experience with twin pregnancies may provide insight into treatment options for clinicians.

Full text

1. Introduction

Cervical insufficiency (CI) is a condition characterized by the inability of the cervix to maintain a pregnancy in the second or early third trimester with painless cervical shortening, dilatation, and delivery. While the diagnosis is primarily made based on ultrasound results with cervical length of less than 25 mm measured by transvaginal ultrasound incidentally, history-based diagnoses can also be made in cases of recurrent second-trimester abortion/delivery [1,2]. The incidence of CI is approximately 1% among all pregnancies [3,4].

While multiple pregnancies alone are a determining risk factor for preterm birth, accompanying CI increases the risk of preterm delivery. Premature birth is one of the most important health problems in terms of neonatal mortality and morbidity [5].

Prophylactic and therapeutic treatment algorithms are more specific in singleton pregnancies and the treatment methods that may be effective in multiple pregnancies are not as clear. There are conflicting publications in the literature regarding the effectiveness of vaginal progesterone, cerclage, and pessary application, which are possible treatment methods in cases of singleton pregnancies.

In the literature, the use of cervical pessary was reported to be associated with the prolongation of twin pregnancies with cervical length of <15 mm [6]. Although there are some reports on the effectiveness of pessaries, cervical pessaries are generally not accepted as typical therapies in the literature and their therapeutic effects are unclear even for singleton pregnancies [5,7]. In a metaanalysis, ultrasound results indicated that cerclage was associated with an increase in the risk of preterm birth before 34 weeks of gestation in twin pregnancies [8]. On the contrary, in a few studies, cerclage before 24 weeks of gestation in twin pregnancies was found to be effective in reducing the risk of preterm birth [5,9]. There are difficulties in treatment selection and patient management in this high-risk patient group due to the conflicting results in the literature.

The aim of this study was to compare the effectiveness of different treatment modalities to prevent preterm delivery and to evaluate the factors that may affect premature birth in cases of twin pregnancies with CI.

2. Materials and methods

This case-control study was retrospectively conducted with the cases of women with dichorionic-diamniotic twin pregnancies diagnosed with CI who delivered in Ankara Bilkent City Hospital’s Department of Perinatology between January 2022 and January 2024. Patients who had cervical cerclage in addition to vaginal progesterone or used a cervical pessary in addition to vaginal progesterone to prevent preterm delivery constituted the case groups. All patients diagnosed with CI received vaginal progesterone treatment. Patients who refused any cervical interventions and used only vaginal progesterone constituted the control group used to compare cervical intervention efficiencies. The McDonald cerclage procedure was performed in all cerclage cases. All patients were informed about the procedures, therapy options, and treatment decisions. Patients’ data were obtained retrospectively from the hospital’s database and patient files.

The eligibility criteria for the study included having a dichorionic-diamniotic twin pregnancy, having no systemic chronic diseases, not using any medications, and having intact membranes at the time of diagnosis and cervical length data. Eligible patients were consecutively included in the study. For standardization of the groups, monochorionic-diamniotic twin pregnancies and other multiple pregnancies were excluded from the study. Patients with missing data and those with comorbidities, unclear diagnosis, or birth indications other than preterm labor were excluded from the study. Written informed consent was obtained from all participants. The study was approved by the Institutional Review Board of the University of Health Sciences Ankara Bilkent City Hospital Ethics Committee (Approval Number: E2-24-6139).

Maternal age and obstetric data (gravidity, parity, abortion and living children, history of artificial reproductive technologies, second-trimester abortion/delivery in previous pregnancies, and abortus imminens in present pregnancy) were recorded for all analyzed cases. Transvaginal sonographic cervical length at the time of diagnosis, diagnosis week, and indications (ultrasound-based/shortening, physical examination-based/dilatation, and history-based) were also evaluated. Gestational week at delivery, latency period (from diagnosis to delivery), and delivery after 34 weeks were analyzed to determine the effectiveness of cervical interventions in addition to vaginal progesterone use. Possible confounding parameters such as invasive procedures, tocolysis, early membrane rupture (24 h before delivery), and the presence of intraamniotic sludge at any time during the pregnancy were also noted for all analyzed cases. All parameters were compared between treatment groups and evaluated for their effectiveness as independent factors for preterm delivery. Antibiotic treatment was not given in cases of pregnancies with sludge in our clinic because there are conflicting results in the literature regarding the effectiveness of antibiotic treatment in such cases [10,11]. Patients who underwent cerclage were hospitalized for 3–5 days, and all patients were followed as outpatients weekly or every 2 weeks until delivery.

Statistical analyses were conducted using IBM SPSS Statistics 23 (IBM Corp., Armonk, NY, USA). Normality analyses were performed for the parameters of interest based on the Shapiro–Wilk test. Due to a lack of normal distribution, descriptive statistics were presented as median and minimum–maximum values. The Kruskal–Wallis test was used to compare parameters between groups. Categorical variables were given as numbers and percentages. The chi-square test was used to compare independent variables between groups. Multivariate regression analysis was used to investigate independent parameters. Statistical significance was defined as a two-tailed p-value of 0.05 with a 95% confidence interval.

3. Results

Ten patients were treated with cerclage in addition to progesterone, 11 were treated with a pessary in addition to progesterone, and 25 were treated with progesterone alone. Maternal age and obstetric parameters were similar between the groups. Use of artificial reproductive technology, second-trimester abortion/delivery history, cervical length, and week of diagnosis did not differ. Two of the cerclage cases entailed emergent rescue cerclage. One of 17 patients with abortus imminens history was in the cerclage group. All obstetric parameters are given in Table 1 with p-values.

Although the rate of delivery after 34 weeks was higher in the cerclage group than in the other groups, the primary effectiveness parameters of latency period, birth week, and delivery after 34 weeks did not differ statistically between the groups. Rates of the possible confounding factors of intraamniotic sludge and early membrane rupture were similar among the groups. These parameters are given with p-values in Table 2.

In the second part of the analysis, the parameters of interest were evaluated independently of treatment groups to determine their effects on delivery after 34 gestational weeks with multivariate regression analysis. The presence of intraamniotic sludge was found to be a negative independent factor for delivery after 34 weeks (p = 0.03). The results of multivariate regression analysis performed to investigate independent predictors of birth after 34 weeks are shown in Table 3.

4. Discussion

In this study, the effects of cervical pessary and cerclage applied in addition to vaginal progesterone on preterm birth in cases of dichorionic-diamniotic twin pregnancies with CI were investigated. It was found that neither cerclage nor pessary usage had any additional positive effect on birth after 34 weeks of gestation. Gestational weeks at birth and the latency period between week of diagnosis and birth were similar among the groups.

A recent metanalysis reported that vaginal progesterone in cases of twin gestation with short cervix length reduced the risk of preterm birth before 34 gestational weeks [12]. In a randomized controlled trial of twin pregnancies, the use of a cervical pessary was reported to be associated with a decrease in preterm birth in cases of short cervixes. On the contrary, in other studies, researchers did not demonstrate any benefits of using a cervical pessary in twin pregnancies [13,14], which is in line with the present results.

In previous metaanalyses, cerclage was found to be associated with a higher risk of preterm birth in twin pregnancies [8,15]. On the other hand, recent studies reported that cerclage in twin pregnancies was beneficial, especially in cases of cervical dilatation [16,17]. In the present study, cervical cerclage was ineffective in decreasing the preterm birth rate. A possible explanation for this result might be that patients in the present study were mostly ultrasound-indicated rather than dilatation-indicated, in contrast to previous studies.

In the present study, possible factors affecting preterm birth were examined independently of the treatment groups and the presence of intraamniotic sludge was found to be a risk factor for birth before 34 gestational weeks, similar to previous studies in the literature. In one previous study, the presence of intraamniotic sludge in twin pregnancies with short cervixes was found to be a risk factor for extreme prematurity [18]. In a different retrospective study, intraamniotic sludge was an independent risk factor for preterm birth in twin pregnancies [19].

The rates of history of artificial reproductive technology usage, abortus imminens, and second-trimester birth, evaluated as factors that may have affected patients’ treatment choices or gestational birth weeks, were similar among the groups analyzed in the present study. Transvaginal cervical lengths and gestational weeks at the time of diagnosis did not differ between groups. The diagnosis was most often made incidentally during a detailed ultrasound or at an outpatient clinic visit due to abortus imminens. In previous studies, short cervical length in combination with positive fetal fibronectin was reported to be associated with preterm birth in cases of twin pregnancies [19]. In the present study, fetal fibronectin was not evaluated together with cervical length measurements, and this difference in study design or the limited patient numbers may explain the discrepancies in results compared to previous studies in the literature.

This study was a comprehensive study examining the effectiveness of cervical treatment options in cases of dichorionic-diamniotic twin pregnancies with CI together with all other possible preterm birth risk factors. It is anticipated that this study may provide guidance for clinicians considering treatment options for twin pregnancies. Future studies with larger numbers of patients are needed to confirm the effectiveness of cervical interventions applied together with vaginal progesterone.

The possible limitations of this study include its retrospective design, limited patient numbers, and inability to evaluate fetal fibronectin. The strengths of the study were its comprehensive design, groups being carefully standardized compared to similar studies, and evaluation of the effects of parameters that could be confounding, which were evaluated independently of the treatment groups.

In conclusion, twin pregnancies diagnosed with CI constitute a high-risk group of patients, and preventing premature birth is of critical importance in terms of reducing neonatal morbidity and mortality. In this study, vaginal cerclage or pessary application in addition to vaginal progesterone did not have any negative effects other than increasing vaginal discharge. However, pessary and cerclage applications were found to have no additional benefits over progesterone treatment in achieving births after 34 weeks of gestation. The only factor that affected birth before 34 gestational weeks was the presence of intraamniotic sludge. Our clinical experience with twin pregnancies may provide insight into treatment options for clinicians in this field. More comprehensive studies are needed to guide clinical treatment selection in cases of twin pregnancies.