Association between clinical subtypes and pregnancy outcome of cervical incompetence: a retrospective cohort study

Abstract

Objective

To investigate the association between clinical subtypes and pregnancy outcomes of cervical incompetence.

Methods

The clinical data of emergency cerclage group (96 cases) were analyzed retrospectively. According to the different degree of cervical dilatation and amniotic sac protrusion during operation, the emergence cerclage group was divided into 4 subtypes: Type I(43 cases), Type II(27 cases), Type III(14 cases), and the Type IV(12 cases).

Results

①Patients with type IV in the emergency cervical cerclage group had a higher frequency of late miscarriage and preterm birth when compared to the other three subtypes (type I, type II and type III) (P < 0.05);②Patients with type IV in the emergency cervical cerclage group had a lower gestational age at surgery than type I and II patients, while type III patients had a longer duration of surgery than type I and II patients, and longer length of hospital stay than type I (P < 0.05);③Patients with type IV in the emergency cervical cerclage group had a lower gestational age at termination than type I and type II patients, lower birth weight of newborns than type I and type III patients, lower term delivery rate than type I patients, and higher neonatal admission to NICU rate than type I patients (P < 0.05).

Conclusion

Cervical incompetence can be classified into four subtypes based on the degree of cervical dilation and amniotic sac protrusion; Transvaginal amniotic fluid reduction provides a possible surgical solution for patients with cervical incompetence type IV.

Introduction

Cervical incompetence (CIC) refers to a disease in which a pregnancy cannot be maintained without uterine contractions due to abnormalities in the anatomical structure or function of the cervix, resulting in miscarriage or preterm labor. CIC typically occurs in the second trimester of pregnancy. About 8% of recurrent midpregnancy fetal loss is caused by cervical incompetence [1]. The treatment of cervical imperfection includes non-surgical treatment (conservative treatment) and surgical treatment, and the non-surgical treatment includes bed rest, progesterone and pessary treatment, etc., but the effect is still unclear and there is insufficient confirmatory medical evidence. At present, surgery is the only effective method for the clinical treatment of CIC, which can be divided into preventive cerclage and emergency cerclage according to the different timing of surgery. Preventive cerclage refers to cervical cerclage performed based on medical indications (second trimester abortion or very premature birth) and ultrasound indications (non-accidental cervical length < 25 mm before 24 weeks), and emergency cerclage refers to cervical cerclage performed after cervical dilation during pregnancy [2]. The objective of this study is to investigate the effect of cervical cerclage in patients with different severity of cervical incompetence.

Materials and methods

Subjects

The clinical records of 341 cases of single pregnancies with diagnosed cervical incompetence, who were admitted to the Department of Obstetrics and Gynecology, the First Affiliated Hospital of Chongqing Medical University for inpatient treatment from January 2010 to July 2023, were collected. The data included general information (age, height, weight, gravidity and parity at the time of cervical cerclage, previous obstetric history including number of miscarriages, induced abortions, and preterm births), details of the surgical procedure (gestational week at the time of surgery, duration of surgery, intraoperative blood loss, length of hospital stay, postoperative complications such as postoperative vaginal bleeding, vaginal infection, and rupture of membranes), and maternal and neonatal outcomes (gestational week at termination of pregnancy, prolongation of pregnancy days, gestational week at delivery, mode of delivery, meconium-stained amniotic fluid, newborn weight, newborn Apgar score, and whether the newborn was admitted to the neonatal intensive care unit (NICU)). Prior to the procedure, routine obstetric ultrasound measurements of cervical length and dilatation were performed vaginally. Vaginal examination was conducted to determine the degree of cervical dilation and presence of prolapsed fetal membranes. Preoperative tests including complete blood count, coagulation profile, biochemistry, and cervical secretion examination were conducted to identify any surgical contraindications. Patients and their families were provided detailed information about the condition and surgical risks before the procedure, and they signed informed consent forms after thorough communication with the medical team. This study was approved by the ethical committee of the First Affiliated Hospital of Chongqing Medical University(2020 − 0230)and adhered to the Declaration of Helsinki (https://www.wma.net/policies-post/wma- declaration-of- helsinki/). We received informed consent from all participants involved in the study.

Even there are different boundary for definition of abortion and preterm, we follow the WHO guidelines in this study [3].

• Abortion: baby delivery before 28 weeks of gestation.

• Early spontaneous abortion: abortion beore 12 weeks of gestation.

• Late spontaneous abortion: abortion between 12 and 28 weeks of gestation.

• Premature labor/preterm labor: labor between 28 and 37 weeks of gestation.

• Full-term birth: labor after 37 weeks of gestation.

Enrollment criteria

Inclusion criteria

This study included singleton pregnancies or pregnancies that had undergone selective reduction to a single viable fetus before surgery, and met the diagnostic criteria for cervical incompetence. Currently, widely used diagnostic methods include the following, meeting any one of which can lead to a diagnosis [2]: ① Diagnosis based on the characteristics of medical history. It is currently believed that even in cases of painless cervical dilation in early or mid-pregnancy, followed by absence of uterine contractions, signs of labor, bleeding, infection, or rupture of membranes, and with a clear pathological history of pregnancy tissue expulsion, a diagnosis can be made; ② Diagnosis based on clinical manifestations. In mid to late pregnancy, there are no obvious uterine contractions, and physical examination reveals shortened cervical length, cervical dilation, and protrusion of the amniotic sac beyond the external cervix os or into the vagina; ③ Diagnosis based on ultrasound examination. When the cervical length is < 25 mm before 24 weeks of pregnancy, there is a risk of cervical incompetence. However, it should be noted that mere cervical shortening or morphological abnormalities do not necessarily indicate cervical incompetence, and comprehensive judgment should be made based on medical history, clinical manifestations, etc.; ④ Experimental diagnosis in the non-pregnant period. Cervical dilation can be assessed using a No. 7 cervical dilator during the luteal phase.

Exclusion criteria: (1) Pregnant women with severe internal or surgical diseases; (2) Various severe complications during pregnancy such as placental abruption, pregnancy-induced hypertension, etc.; (3) Premature rupture of membranes or clear intrauterine infection; (4) Fetus with lethal malformations; (5) Pregnant women with a history of specific cervical surgeries (loop electro-surgical excision procedure, cold-knife conization, laser conization, extensive cervical excision, etc.). Among the 341 cases collected, 54 cases were excluded due to choosing conservative treatment instead of cervical cerclage, 20 cases were excluded due to failure to provide detailed pregnancy outcomes, 15 cases were lost to follow-up, 1 case was excluded due to placental abruption in late pregnancy, 1 case was excluded due to diagnosis of severe preeclampsia in late pregnancy, 2 cases were excluded due to fetal growth restriction, and 2 cases were excluded due to pre-rupture of membranes before surgery. Finally, a total of 246 cases were included in this study.

Research groups

This is a retrospective cohort study. A total of 246 cases were included in this study and were divided into two groups based on the timing of the surgery, the elective cervical cerclage group (n = 150) and the emergency cervical cerclage group (n = 96). According to the degree of cervical dilation and amniotic sac protrusion at the time of surgery, the emergency cerclage group was divided into foursubtypes (Fig. 1): Type I (The inner cervix os was dilated on ultrasound and the external os can accommodate a No. 7 Hegar dilator on examination, n = 43), Type II (Both the inner and the external cervix os were dilated on ultrasound, and the amniotic sac was visible, n = 27), Type III (Both the internal and the external cervix os were dilated, the amniotic sac protruded in the upper 1 / 3 part of the vagina, and the cervical margin was visible., n = 14), and Type IV (Both the internal and the external cervix os were dilated, and the amniotic sac protruded in the middle and lower segments of the vagina, with cervical margin invisible., n = 12). The flowchart of case collection and enrollment process is shown in Fig. 2.

Fig. 1

Four subtypes of cervical incompetence

Fig. 2

Flowchart of case collection and enrollment

Surgical methods

The transvaginal McDonald operation was performed in all patients. Transvaginal cervical cerclage mainly includes McDonalds and Sharidkar operations. The literature reports that the clinical outcomes of these two surgical methods are similar [4], but Sharidkar operation is more difficult and prone to complications such as bleeding and injury. Therefore, McDonald’s operation was chosen for all cases in this study. If the gestational age is less than 16 weeks and the cervical length is less than 10 mm, we choose laparoscopic cervical cerclage surgery through the abdomen, but it was not included in the data analysis of this study group.

Before cervical cerclage surgery, each pregnant woman should undergo routine vaginal swab analysis. If vaginal inflammation or subclinical infection is detected, Nitrofurateyr nystatin capsules should be used for vaginal medication at least one week. Cervical cerclage surgery cannot be performed unless the vaginal inflammation or cervical cytology is normal. Vaginal examination and/or insulin-like growth factor test paper was used to exclude premature rupture of membranes.

The anesthesia method was lumbar anesthesia combined with epidural anesthesia, and all operations were performed by the same surgeon. The patient’s bladder was taken to lithotomy position, vulva and vagina were routinely disinfected, a sterile towel was spread, and the vagina was peeped with a vaginal hook. Allis forceps were used to pull the labium anterius and labium posterius, and inserted the cervix with 1 − 0 Johnson suture at the place of 2.5 cm from the external cervix os, without penetrating the cervical mucosa. The specific steps are as follows [5]:① At the internal cervix os near the fornix of the vagina, the first needle was given in at 2 o’clock and out at 1 o’clock of the cervix, and the second needle was given in at 11 o ‘clock and out at 10 o ‘clock. According to this rule, the last needle was given out at 4 o’clock. Each stitch spacing was about 1 cm. Then we tightened the suture in turn, tied the knot, and kept the length of the suture broken end about 6 cm; ② From the last knot point 1 cm upward, we reinforced by sewing again according to step ① For patients with type IV cervical incompetence, transvaginal amniotic fluid reduction was performed: First, the vagina and amniotic sac were cleaned with normal saline, and about 10-20 ml of amniotic fluid was pumped until the cervical margin could be exposed with a disposable skin test needle (disposable intravenous infusion needle, 0.45*13.5RWLB, Shandong Aoset Medical Equipment Co., LTD.). The amniotic sac at the puncture site was smeared with the topical freeze-dried human fibrin adhesive (2 ml/branch of Shanghai Leshi Blood Products Limited) to occlude. Then we returned the sealed amniotic sac into the cervical canal, and rang the cervix according to steps ①②. After surgery, patients were instructed to stay in bed for a week, took cefuroxime sodium for 3 days to prevent infection, and Progesterone muscle injection (if gestational week less than 20 weeks) or ritodrine intravenous injection (if gestational week more than 20 weeks) was used for one week to prevent uterine contraction after operation. No corticosteroids was used in this study because all operations were done between 16–24 gestational weeks.

Statistical methods

Statistical analysis was carried out using SPSS26.0 statistical software. For continuous data meeting normal distribution, parametric tests such as T-test or ANOVA were adopted, and the data description was expressed as mean ± standard deviation. When the quantitative data did not meet the normal distribution, non-parametric tests such as Wilcoxon test or Kruskal-WallisH test were adopted, and the data description was expressed by the median (25% quantile, 75% quantile). When the data are classified data, Chi-square test or Fisher exact probability test is adopted, and the data description ratio (component ratio) is represented. P < 0.05 indicated that the difference was statistically significant.

Results

The comparison of general conditions and high-risk factors between the two groups is shown in Table 1. The BMI of patients in the elective cervical cerclage group was lower than of patients in the emergency cervical cerclage group. The number of pregnancies, the number of abortions and the number of late abortions of patients in the elective cervical cerclage group were all higher than those of the patients in the emergency cervical cerclage group. There was no significant difference in age, the number of deliveries, the number of induced abortions, the number of early spontaneous abortions, the number of induced labors and the number of preterm labors between the two groups (P > 0.05).

Table 1 Comparison of the clinical characteristics of the 2 group of patients

The comparison of surgical conditions and postoperative complications between the two groups is shown in Table 2. The gestational age at operation and the length of hospitalization of patients in the elective cervical cerclage group were less than those of patients in the emergency cervical cerclage group. There were no significant differences in the operation duration, the intraoperative blood loss, the postoperative vaginal infection rate, the postoperative abnormal vaginal bleeding rate and the postoperative premature rupture rate between the two groups (P > 0.05).

Table 2 Comparison of surgery and postoperative complications of the two groups

The comparison of pregnancy outcomes between the two groups is shown in Table 3. The gestational age at termination of pregnancy, the extended gestation days, the rate of full-term birth and the newborn birth weight of patients in the elective cervical cerclage group were more than those of patients in the emergency cervical cerclage group. The rate of neonatal asphyxia and the rate of neonatal NICU admission of patients in the elective cervical cerclage group were lower than those of patients in the emergency cervical cerclage group. There were no significant differences in the rate of live birth (including preterm birth and full-term birth), mode of delivery (vaginal birth or cesarean section), and the rate of fecal amniotic fluid staining between the two groups (P > 0.05).

Table 3 Analysis of pregnancy outcomes of the two groups

The comparison of general conditions and high-risk factors of different types of patients in the emergency cervical cerclage group is shown in Table 4. There were statistically significant differences in the number of late spontaneous abortions, induced labors and preterm labors among the four types of patients (P < 0.05). After multiple comparison, it was found that the number of late spontaneous abortions in type IV was higher than that in the other three types of patients, the number of preterm labors in type IV was higher than that in the other three types, and the number of induced labors in type II was higher than that in type I. There were no significant differences in the age, the BMI, the number of pregnancies, the number of deliveries, the number of abortions, the number of induced abortion times and the number of early spontaneous abortions among the four types (P > 0.05).

Table 4 Comparison of general conditions and high risk factors of patients in the emergency cerclage surgery group

The comparison of surgical conditions and postoperative complications of different types of patients in the emergency ligature surgery group is shown in Table 5. There were statistically significant differences in the gestational age at operation, the operation duration and the length of hospitalization among the four types of patients (P < 0.05). After multiple comparisons, it was found that the gestational age of type IV was lower than that of the other three types, and the operation duration of type III was longer than that of type I and type II. There was no significant difference in the operation duration between type I and type IV. The length of hospitalization in type I was less than that in type III. There were no significant differences in the intraoperative blood loss, the postoperative vaginal infection rate, the postoperative abnormal vaginal bleeding rate and the postoperative premature rupture rate among the 4 types of patients (P > 0.05).

Table 5 Comparison of surgical conditions and postoperative complications of all patients in the emergency cerclage surgery group

The pregnancy outcomes of different types of patients in the emergency ligature surgery group are shown in Table 6. There were statistical differences in the gestational age at termination of pregnancy, the full-term birth rate, the mode of delivery, the newborn birth weight and the neonatal NICU admission rate among the four types of patients (P < 0.05). After multiple comparisons, it was found that the gestational age at termination of pregnancy in type IV was less than that in type I and type II. The neonatal birth weight of type IV was less than that of type I and type III. The neonatal birth weight of type II was less than that of type I. The full-term birth rate of type IV was lower than that of type I. There was a significant difference in the mode of delivery between type I and type II, and the NICU admission rate of neonates in type IV was higher than that in type I. There were no significant differences in the extended gestation days, the live birth rate (including premature birth and full-term birth), the fecal amniotic fluid staining rate and the neonatal asphyxia rate among the 4 types of patients (P > 0.05).

Table 6 Analysis of postoperative pregnancy outcomes of all patients in the emergency cerclage surgery group

The multiple logistic regression analysis of factors affecting pregnancy outcome is shown in Table 7. The dependent variable is the gestational age at termination of pregnancy (< 28 weeks is denoted as 0, ≥ 28 weeks is denoted as 1), and the independent variables are the BMI, the number of pregnancies, the number of abortions, the number of late spontaneous abortions, the number of induced labors and the number of premature labors. The results showed that the history of late spontaneous abortions and previous preterm labors are the factors influencing the gestational week at the time of termination of pregnancy.

Table 7 Logistic regression analysis of factors influencing pregnancy outcomes

Discussion

The typical clinical manifestations of cervical incompetence are painless cervical dilation in the second and third trimester of pregnancy, followed by amniotic sac prolapse protruding from the vagina, rupture of the membranes, and delivery of the fetus. The causes of cervical incompetence mainly include congenital factors such as cervical structural dysplasia, connective tissue disease, maternal diestrostilbestrol exposure during pregnancy [6], and acquired factors such as repeated abortion, mechanical cervical dilation caused by uterine clearance and hysteroscopy, cervical laceration caused by childbirth, cervical resection, infection, etc. Among pregnant women clinically diagnosed with cervical incompetence, only a small number of cases do have anatomical or tissue structure defects, most cases may be related to subclinical infection and local inflammation. And Polycystic ovary syndrome has also been proved to be an independent risk factor [7]. Clinical treatment for cervical incompetence includes non-surgical treatment (conservative treatment) and surgical treatment. Surgical treatment has been clinically proven to be an effective method for the treatment of cervical incompetence, which can be divided into elective and emergency cervical cerlcage according to the operation time, and transvaginal and transabdominal cervical cerlcage according to the operation path. Transvaginal cervical cervix ceration mainly includes McDonald cerclage and Sharidkar cerclage. Sharidkar cerclage is mainly applicable to people with shorter cervicovaginal and smaller parts. Due to the higher position of cervix suture, the surgical difficulty and bleeding risk are greater. Odibo et al. [4] reported that there was no significant difference in efficacy between the two surgical methods. In this paper, all cases of cervical incompetence were treated by McDonald surgical method.

The results of this study showed that among 246 patients undergoing cervical cerclage, the rate of full-term birth was 55.3%, the rate of premature birth was 27.6%, and the rate of abortion and induction of labor was 17.1%. Cervical cerclage could significantly prolong the pregnancy time and improve the survival rate of newborns. The data of this study showed that the gestational age at termination of pregnancy, the extended gestation days and the full-term birth rate of pregnant women in the elective cervical cerclage group were significantly higher than those in the emergency cervical cerclage group, and the neonatal asphyxia rate and the NICU admission rate were significantly lower than those in the emergency cervical cerclage group. Emergency cervical cerclage is a difficulty in the surgical treatment of cervical incompetence.

Emergency cervical cerclage, also known as rescue cervical cerclage, is mainly used in the case of dilation of the internal cervix or even the external dilation of the oral cavity, and amniotic sac protruding into the vagina. In the past, patients have chosen conservative treatment or abandoned this pregnancy. The emergence of emergency cervical cerclage undoubtedly gives such patients another choice, reducing the loss of precious babies and the disability and even death of perinatal infants. The results of this study showed that cervical incompetence in the emergency cervical cerclage group could be divided into four subtypes according to the degree of cervical dilation and amniotic sac protrusion during surgery (Fig. 1): Type I (only the internal cervix os was dilated during B-ultrasonography, the external cervix os was closed without amniotic sac visible during vaginal examination, and the cervical canal could accommodate a No. 7 dilating stick), Type II (B-ultrasonography showed dilation of both the internal and external cervix os, vaginal examination showed dilation of the external cervix os but amniotic sac did not protrude into the vagina), Type III (B-ultrasonography showed dilatation of both the internal and external os of the cervix, vaginal examination showed dilatation of the external os of the cervix, amniotic sac protruded from the external opening of the cervix to the upper 1/3 of the vagina, and the margin of the external opening of the cervix was visible), Type IV (B-ultrasonography showed dilation of both the internal and external cervix os, vaginal examination showed dilation of the external cervix and the amniotic sac protruded from the middle and lower part of the vagina, but the margin of the external cervix was invisible). Among them, type I and type II surgery for cervical incompetence were easier to perform, and the difficulty and pregnancy outcome were similar to those of elective cervical ceration. But type III surgery was difficult due to the amniotic sac protruding from the external opening of the cervix to the upper 1/3 of the vagina, and was prone to surgical complications and infections. The margin of the external opening of the cervix invisible significantly increased the difficulty of surgical operation and the rate of intraoperative rupture of the membranes, causing the cervical surgery unable to be completed.

Several researchers have investigated the feasibility and safety of transabdominal amniotic fluid reduction before emergency cervical cerclage. In a retrospective analysis by Proctor et al. [8], emergency cervical cerclage was performed on 9 pregnant women with painless cervical dilation and gestational age of 24–24 + 6 weeks or uterine orifice dilation ≥ 4 cm. Among them, 7 cases underwent transabdominal amniotic fluid reduction and McDonald cerclage after the amniotic sac in the vagina was completely reduced. Five (56%) pregnant women had good obstetric outcomes (the gestational age at termination of pregnancy was greater than 34 weeks), three pregnant women delivered at term, and only one pregnant woman developed amniotic infection. This study indicated that emergency cervical cerclage had clinical significance in improving pregnancy from 24 to 24 + 6 weeks or uterine orifice dilation ≥ 4 cm. In addition, the reduction of transabdominal amniotic fluid reduction during operation is helpful to the development of emergency cervical cerclage. In the study of Cakiroglu et al. [9], 56 cases underwent emergency cervical cerclage, 26 cases underwent transabdominal amniotic fluid reduction, and the remaining 30 cases did not. The gestational age of cerclage, delivery and the prolonged gestational interval between the two groups were similar, and the live birth rate and perinatal mortality were not significantly different between the two groups. The study also pointed out that the decision to perform amniotic fluid reduction should be based on suspicion of chorioamniotic inflammation and the patient’s motivation to know exactly what the risk of chorioamniotic infection is. A retrospective controlled study by Zhang et al. [10] included 46 pregnant women with cervical dilation of at least 1 cm and accompanied by the amniotic sac protruding during the second trimester, and divided them into the group with amniotic fluid reduction (16 cases) and the group without amniotic fluid reduction (30 cases). The degree of cervical dilation was greater in the group with amniotic fluid reduction than in the group without amniotic fluid reduction. There were no significant differences in gestational age, operation time, pregnancy prolongation, and pregnancy outcome between the two groups. This study suggested that amniotic fluid reduction may be a safe and feasible option to use before emergency ceration, especially for patients with significant cervical dilation and amniocele. At present, no studies have reported transvaginal amniotic fluid reduction. In this study, we reported that 12 patients with cervical incompetence type IV were treated the protrusion of amniotic sac with the transvaginal amniotic fluid reduction before routine McDonald cervical cerclage for the first time. The results showed that the average gestational age could be extended by 76.67 days. Among them, 4 cases were live births at 28–36 weeks. The results of this study indicate that transvaginal amniotic fluid reduction is feasible, especially for pregnant women with a strong desire to preserve the fetus, such as test-tube babies. The transvaginal amniotic fluid reduction can be used as a choice for the treatment of cervical incompetence type IV. However, due to the small number of cases, more clinical cases need to be accumulated to explore its effectiveness and safety.

Through the multivariate logistic regression analysis, this study found that the history of late spontaneous abortion and preterm birth were risk factors for termination of pregnancy < 28 weeks for single pregnancy patients who underwent vaginocervical cerclage. In recent years, a number of studies have proved that patients with multiple history of late abortion or preterm birth were more likely to have adverse outcomes. In order to achieve better pregnancy outcomes, individual treatment plan and rational decision should be made.

Advantages of this study: (1) All cervical cercations in this study were performed by the same surgeon, limiting confounding factors commonly associated with surgical procedures in this type of retrospective study. (2) In this study, cervical incompetence was divided into four types according to the degree of cervical dilation and the degree of amniotic sac protrusion at the time of operation for the first time. (3) This study was the first to investigate the feasibility of transvaginal amniotic fluid reduction, providing an effective surgical solution for patients with cervical incompetence type IV. Limitations of this study: (1) The small sample size of different subtypes of cervical incompetence, especially type IV patients, may lead to the limitations of the study. In the future, it is necessary to increase the sample size to further explore its effectiveness and safety. (2) Transvaginal amniotic fluid reduction is not suitable for patients with cervical incompetence whose fetal body has entered the vagina, because the fetus will be delivered quickly if the amniotic fluid reduction is performed.

Conclusion

This study is the first time to classify cervical incompetence into four subtypes according to the degree of cervical dilation and the degree of amniotic sac protrusion before surgery. For type I and type II, it is easy to make operation (cervical cerclage). For type III, operation should be made very carefully because of a little bit risk of premature rupture of membranes. For type IV, even operation is a forbidden area in most cases, but transvaginal amniotic fluid reduction surgery may provide a possible effective surgical solution for some patients.