Mid-trimester cerclage outcomes in singleton and twin pregnancy: a single tertiary center experience

Objective

The aim of this study was to evaluate the maternal and neonatal outcomes of patients who underwent ultrasonography (USG) and emergency indicated cerclage in the mid-trimester in singleton and twin pregnancies

Methods

A total of 55 patients, 43 with singleton and 12 with twin pregnancies who underwent cerclage for short cervix (<25mm) or cervical dilation between January 2015 and December 2021 were included the study.  The primary outcome was gestational age at birth, and secondary outcomes were neonatal birth weight, admission to neonatal intensive care unit status, neonatal survival, and the neonatal birth rates at <24 weeks, 24-27⁺⁶ weeks, 28-33⁺⁶ weeks, 34-36⁺⁶ weeks and >37 weeks.

Results

In singleton pregnancies, delivery interval was 15.05(±2.9) weeks in the USG indication group and 2.8(±2.5) weeks in the emergency indication group (p<0.001). The rate of pregnant women in the USG indication group who gave birth between 24-27⁺⁶ gestational weeks was 4.9% (n=2), and the rate of pregnant women in the emergency indication group was 55.6% (n=5) (p<0.001). In total, in singleton pregnancies the rate of take-home baby was 85.7%, and neonatal mortality was 14.3%. In twin pregnancies delivery interval was 12±1.41 weeks in the USG indication group, it was 1.8±0.83 weeks in the emergency indication group (p<0.003). In twin pregnancies the take-home baby rate was 94% and neonatal mortality was 6%.

Conclusion

Cervical cerclage reduces the possible risks of preterm delivery by prolonging the interval until delivery, especially in patients with singleton and twin pregnancies for whom USG is indicated, and promising neonatal outcomes are achieved.

Keywords

Preterm birth,, cervical cerclage, twin pregnancy, emergency cerclage, ultrasound indicated cerclage

Introduction

Preterm birth is defined as birth before 37 weeks of gestation and is one of the leading causes of perinatal morbidity and mortality. Morbidity is inversely related to the gestational week at birth, and the most critical adverse outcomes occur in births below 32 weeks [1]. A cervical length screening is a proven method to identify patients at risk of spontaneous preterm delivery. Cervical length values of 25 mm or less measured with transvaginal USG (ultrasonography) in the mid-trimester of pregnancy are considered a short cervix [2-4].

Cerclage procedure is performed in cases with a gynecological or obstetric history of preterm birth risk (history indication), short cervix determined after ultrasonographic evaluation (USG indication), and cases with cervical dilation (rescue indication) after the vaginal examination [5]. History-indicated cerclage is applied prophylactically in the first trimester of pregnancy to patients with a previous history of 3 or more preterm births and/or second-trimester pregnancy loss. Ultrasound-indicated cerclage is recommended for patients with a previous history of one or more preterm births and/or mid-trimester pregnancy loss and a cervical length of <25 mm on USG and is applied up to the 24th gestational week. Emergency or rescue cerclage is recommended for pregnancies below the 24th gestational week in the absence of apparent infection, inflammation, and active labor and in the presence of membrane prolapse from the dilated cervical canal [5]. Although there is not enough evidence to support the use of USG or history-indicated cerclage for multiple pregnancies, it is widely believed that cerclage can be beneficial in cases where the cervical length is <15mm (5).

Although cervical cerclage is mainly performed with the transvaginal approach, it can be applied in the cervicoisthmic region via the transabdominal route in patients who have a previous unsuccessful cervical cerclage history vaginally or who cannot be performed cerclage vaginally due to anatomical limitations (e.g., history of trachelectomy) [6].
The present study aimed to evaluate the maternal and neonatal outcomes of patients who underwent USG- and emergency-indicated cerclage in the mid-trimester in singleton and twin pregnancies.

Methods

Within the scope of this study, the records of a total of 67 singleton and twin pregnancies who underwent cerclage for short cervix (<25mm) or cervical dilation between January 2015 and December 2021 in Necmettin Erbakan University Meram Medical Faculty Hospital Obstetrics and Gynecology Clinic were reviewed retrospectively. Ethics approval was obtained from the hospital ethics committee (2022/3637). Patients with preterm premature rupture of membranes (PPROM), vaginal bleeding, clinical chorioamnionitis, active uterine contraction, fetal anomaly or no fetal heartbeat, and patients with monochorionic monoamniotic twin pregnancy were not included. Twelve patients with ongoing pregnancies or whose neonatal results could not be reached were excluded. A total of 55 patients, 43 with singleton pregnancies and 12 with twin pregnancies, were included in the study. In the second trimester, patients with a history of preterm birth and/or second-trimester pregnancy loss and a cervical length of <25 mm by transvaginal USG were included in the USG-indicated group, and patients with a short cervix with accompanying cervical dilatation and/or membrane prolapse were included in the emergency (rescue) cerclage group.

Demographic (age, gravida, parity, previous abortion, preterm birth, previous cerclage history), obstetric (week of gestation at which cerclage was performed, presence of cervical length or cervical dilatation by transvaginal USG, complications such as chorioamnionitis or premature rupture of membranes occurring within three weeks after cerclage, the gestational week at birth, type of delivery) and neonatal data (newborn birth weight, gender, APGAR score, neonatal intensive care unit (NICU) admission status) of the patients were accessed from the hospital medical computer registry system. Neonatal outcomes were collected from the files registered in the hospital archive system and by contacting the patients by telephone. Gestational age (GA) was determined by first-trimester USG examination and measuring crown-rump length. Placental chorionicity in twin pregnancies was determined according to first-trimester USG records. PPROM was defined as the observation of active amniotic fluid on speculum examination or the positive detection of the AmniSure (QIAGEN Sciences, LLC, Germantown, MD, USA) test. The clinical diagnosis of chorioamnionitis was made based on the presence of at least one of the major criteria or at least two of the minor criteria. Major criteria: 1. Foul-smelling cervical discharge in speculum examination, 2. Uterine tenderness. Minor criteria: 1. The maternal axillary temperature of ≥38ºC, 2. Maternal tachycardia (≥100 bpm), 3. Fetal tachycardia (≥160 bpm) and leukocytosis (≥15,000/mmᵌ).

The primary outcome was gestational age at birth, and secondary outcomes were neonatal birth weight, admission to NICU status, neonatal survival, and the neonatal birth rates at <24 weeks, 24-27⁺⁶ weeks, 28-33⁺⁶ weeks, 34-36⁺⁶ weeks,  and >37 weeks. The cerclage procedure was performed vaginally in the lithotomy position under general anesthesia with the Mc-Donald technique. No:5 Mersilene polyester tape (Ethicon) was used as the suture material. Before the procedure, the vagina was gently cleaned with povidone-iodine, and in the presence of prolapsed membrane, the membrane was pushed upwards from the cervical os with a sterile wet sponge or Foley catheter balloon (15-20cc inflation). The Foley catheter was left in place until the end of the procedure to prevent membrane prolapse. A single dose of intravenous (iv) first-generation cephalosporin or Clindamycin in case of penicillin allergy was administered to the patients before the procedure as a preoperative prophylactic. After the procedure, patients were given a single dose of 100mg rectally and oral indomethacin 25mg every 6 hours for 48 hours, and 200mg/day of micronized progesterone vaginally until the 36th week of gestation. The patients were discharged 24-72 hours after the procedure. The patients were advised to rest and prohibited intercourse in the postoperative period. At the end of the first week and first month postoperatively, a speculum examination was performed to exclude the presence of lower genital tract infection.

Routine transvaginal USG was not performed in the follow-ups. In case of active labor, chorioamnionitis, premature rupture of membranes, active vaginal bleeding, or intrauterine dead fetus, cerclage suture material was removed regardless of the gestational week. In the absence of these conditions, the suture material was removed in the 36th week. In our clinic, dichorionic twin pregnancies are delivered at the 37-38th gestational week and monochorionic twin pregnancies at the 36-37th gestational week or earlier when indicated. All infants weighing over 500mg or 24 weeks of age (considered the limit of viability) were resuscitated by the neonatal team. 2 doses of 12mg betamethasone intramuscularly for fetal lung maturation for all pregnancies considered viable 24 hours apart and for women with imminent preterm birth (≤31⁺⁶ weeks) magnesium sulfate intravenous (iv) for fetal neuroprotection (4gram loading dose over 30 minutes, followed by 1g/h maintenance infusion until birth) was applied.

Data were uploaded to SPSS 22 (Statistical Package for Social Sciences) (IBM, Armonk, NY, USA) and analyzed in the computer environment. The conformity of the variables to the normal distribution was examined using visual (histogram and probability graphs) and analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk Test). Comparison of groups was performed by Student's t-test for normally distributed numerical data and Mann Whitney U test for non-normally distributed numerical data. Pearson Chi-Square test and Fisher's Exact test evaluated the categorical variables. P<0.05 was considered statistically significant.
Ethics approval: For this study, permission was obtained from the ethics committee of Necmettin Erbakan University with the decision number 2022/3637 dated 04/02/2022.
 

Results

Of the 55 patients included in the study, 43 had singleton pregnancies, and 12 had twin pregnancies. Age, parity, gravida, and abortion histories of the patients who underwent cerclage with singleton pregnancies USG indication (n=34) and emergency indication (n=9) were similar, and there was no statistical difference between them (Table 1).
In singleton pregnancies, the gestational week of cerclage was 19.05(±2.9) weeks in the USG indication cerclage group and 21.8(±2.4) weeks in the emergency indication cerclage group (p<0.001). The interval (time from cerclage week to delivery) was 15.05 (±2.9) weeks in the USG indication group and 2.88 (±2.5) weeks in the emergency indication group (p<0.001). The delivery types of the patients and the gender of the babies are summarized in Table 2. Week of birth, birth weight, newborn 1st and 5th minute APGAR scores were statistically significantly higher in the USG indication group, and the findings are presented in Table 3.
Considering the complications after the cerclage of the singleton pregnancies, complications occurred in 8.8% of the patients with the USG indication, while it was 33.3% in the patients with the emergency indication (p<0.001). PPROM developed in 2 (22.2%) patients and spontaneous abortion in 1 (11.1%) patients who underwent cerclage for emergency indication (p<0.001). In the USG indication group, 3 (8.8%) chorioamnionitis were detected.
When the birth week was classified categorically in singleton pregnancies, the rate of delivery below 24 weeks was 5.9% (n=2) in the USG indication group, while it was 33.3% (n=2) in the emergency indication group (p<0.001). Again, the rate of pregnant women in the USG indication group who gave birth between 24-27⁺⁶ gestational weeks was 4.9% (n=2), and the rate of pregnant women in the emergency indication group was 55.6% (n=5) (p<0.001). While the rate of patients who delivered over 37 weeks of gestation was 47.1% (n=16) in the USG indication group, this rate was 0% (n=0) in the emergency indication group (p<0.001). There was no statistically significant difference between the patients who gave birth at 28-33⁺⁶ and 34-36⁺⁶ gestational weeks (Table 4).
Considering their birth weight in singleton pregnancies, all newborns (n=8, 100%) born in the emergency indication group were <1500g, and the rate of newborns (n=6) in this category in the USG indication group was 17.6% (p<0.001). There were 23.5% newborns in the 1500-2500 g category and 58.8% in the >2500 g category in the USG indication group, and the rate of newborns in these categories in the emergency indication group was 0% (p<0.001) (Table 4).
In terms of neonatal outcome in singleton pregnancies, more NICU admission rates (87.5% vs. 26.5%) were detected in the emergency indication group compared to the USG-indication group, and the newborn with no illness ratio was higher in the USG group than in the emergency group (70.6% vs. 0%) (p<0.001).
The neonatal mortality rate in singleton pregnancies was 37.5% in the emergency indication group, which was 8.8% in the USG indication group (p=0.037).  In total, the rate of take-home baby was 85.7%, and neonatal mortality was 14.3% (Table 2).
Considering the subgroup analysis of twin pregnancies, cerclage was performed in 58% (n=7) with USG indication and 42% (n=5) with emergency indication. The rate of spontaneous abortion as a complication was 33% (n=4), and all were in the emergency indication group. There was no difference between the groups in terms of cerclage week, and the week of delivery was higher in the USG indication group (32.5±1.8) than in the emergency indication group (25.0±0) (p<0.012). While the interval was 12±1.41 weeks in the USG indication group, it was 1.8±0.83 weeks in the emergency indication group (p<0.003). When the week of birth was examined categorically, 50% (n=4) of the deliveries were at 28-33⁺⁶ week, 38% (n=3) at 34-36⁺⁶ week, and 12% (n=1) at 24-27⁺ week. As birth weight, 69% (n=11) of newborn twins were 1500-2500g, 18% (n=3) were <1500g, only 13% (n=2) were >2500g (Table 5,6).
In twin pregnancies, there was NICU admission in 81%, and newborn with no illness rate was 19%. We determined the take-home baby rate as 94% and neonatal mortality as 6% (Table 6).

Discussion

The present study revealed that cervical cerclage applied in patients with a history of preterm birth or second-trimester abortion in a previous pregnancy and short cervical length in transvaginal ultrasonography (TvUSG) was more successful in prolonging the gestational period compared to the group in which cervical dilation was detected and then cerclage was applied. Likewise, perinatal and neonatal outcomes in the group with a short cervix in twin pregnancies were more satisfactory than in the emergency cerclage group.
Wang et al., in their study on singleton pregnancies, indicated that the degree of cervical length and perinatal outcomes were inversely related, and especially those with a cervical length of 25-30mm had better results [7]. Many studies have been published in recent years evaluating the efficacy, perinatal outcomes, and complications of cerclage with emergency and USG indications[4, 8-11] However, the number of randomized controlled studies with large samples evaluating the effectiveness of emergency cerclage in singleton and especially twin pregnancies is limited [12-14]. Ciavattini A. et al. reported that emergency cerclage had worse pregnancy outcomes than elective cerclage performed in early pregnancy, but it was superior to the conservative method alone. The results were better, especially in the group with cervical dilatation of less than 5 cm [15]. Emergency cerclage is associated with a poor outcome, especially if cervical dilatation is 4 cm or more and a bulging membrane [16]. In our study, in singleton pregnancies the delivery interval was 15 weeks in the USG-indicated group and 2.8 weeks in the emergency-indicated group, and we found the mean delivery week to be 34 weeks in the USG-indicated group and 24.5 weeks in the emergency-indicated group. Our study determined in singleton pregnancies the take-home baby rate to be 91.2% in the USG-indicated group, 62.5% in the emergency indicated group and 83.7% overall.
A previous report stated that USG-indicated cerclage emerged to avoid unnecessary history-indicated cerclage [17]. The retrospective study of a large sample of Rie Seyama et al. demonstrated that cerclage with history and USG indications did not prevent preterm birth compared to the control group. In contrast, cerclage with physical examination indication significantly reduced the risk of preterm birth in each pregnancy period. They even stated that USG-indicated cerclage might contribute to preterm deliveries under 31 weeks. The reason for the result being this way in the study of Rie Seyama et al. can be explained by both the sample size and the non-cerclage group nature of the control groups [11]. Our study revealed a significant increase in deliveries under 24 and 28 weeks in the emergency indication group in singleton pregnancies compared to the USG indicated group (33.3% vs. 5.9%, 55.6% vs. 4.9%, respectively). The rate of deliveries over 37 weeks was higher in the USG-indicated group than in the emergency-indicated group (47.1% vs. 0%).
Mid-trimester cervical cerclage application remains the subject of discussion in twin pregnancies. Although previous studies could not prove the superiority of cerclage over the conservative method [18], studies performed in recent years have reported successful results in mid-trimester cerclage in twin pregnancies [19]. In a meta-analysis examining mid-trimester cerclage in twin pregnancies with a short cervical length (<25mm), the benefit of cerclage could not be proven [20]. Mian Pan et al. concluded that the gestational week at birth was higher in the cerclage group compared to the control group in their retrospective cohort study in which they applied physical examination-indicated cerclage in twin pregnancies (32.5 vs. 27.5 weeks), and they found a significant decrease in the incidence of spontaneous preterm births <24 weeks, <28weeks, <32weeks and <34weeks in the cerclage group compared to the control group[21]. Our study determined the mean delivery week as 32.5 in the USG indicated group and 25 in the emergency group in twin pregnancies. We observed that 50% of the deliveries were between 28-33⁺⁶ weeks and 38% were between 34-36⁺⁶ weeks.
Cilingir et al. reported that the delivery interval was 6.4 weeks on average, 4.1 weeks in the group with bulging membrane patients, and 10 weeks in the group with a short cervix, in the study where they applied emergency cerclage and included twins with both short cervix and cervical dilation [22]. This result shows that the group with cervical dilation and bulging membranes in twin pregnancies has a poorer prognosis than those with a short cervix, similar to a singleton pregnancy.
In a randomized controlled multicenter study published in 2020, they compared 17 patients who underwent physical examination indicated cerclage in twin pregnancies with 13 patients who did not[14]. The Data and Safety Monitoring Board advised ending the experiment after an interim analysis was conducted due to a significant drop in perinatal mortality in the cerclage group. Comparing the cerclage group to the group that did not have a cerclage, the rate of preterm birth drastically dropped as seen below: birth that occurs <34 weeks of pregnancy 70% vs 100%, <32 weeks 64.7% vs 100%, <28 weeks 41% vs 84%. Mean gestational age at delivery was 29 vs 22.5, mean delivery interval was 8.3 vs 2.9. Perinatal mortality rate decreased from 77% to 17.6% [14].
 
The limitations of our study are the retrospective, single-center design of the study and the absence of a control group. However, we believe that it is unethical to compare the results with the control group, as current studies have proven the superiority of cerclage over the conservative wait-and-see approach. Another issue is the study's small sample size and the lack of a sufficient number of patients to categorize the degree of cervical dilation, especially in the emergency cerclage group.
Conclusion
Our study has concluded that cervical cerclage reduces the possible risks of preterm delivery by prolonging the interval until delivery, especially in patients with singleton and twin pregnancies for whom USG is indicated, and promising neonatal outcomes are achieved.

Conclusion

In conclusion, the cervical cerclage reduces the possible risks of preterm delivery by prolonging the interval until delivery, especially in patients with singleton and twin pregnancies for whom USG is indicated, and promising neonatal outcomes are achieved.

[1] Hickland MM, Story L, Glazewska‐Hallin A, Suff N, Cauldwell M, Watson HA, et al. Efficacy of transvaginal cervical cerclage in women at risk of preterm birth following previous emergency cesarean section. Acta Obstetricia et Gynecologica Scandinavica. 2020;99:1486-91.
[2] Committee on Practice Bulletins—Obstetrics TACoO, Gynecologists. Practice bulletin no. 130: prediction and prevention of preterm birth. Obstet Gynecol. 2012;120:964-73.
[3] Conde-Agudelo A, Romero R. Predictive accuracy of changes in transvaginal sonographic cervical length over time for preterm birth: a systematic review and metaanalysis. American journal of obstetrics gynecology. 2015;213:789-801.
[4] Gulersen M, Bornstein E, Domney A, Blitz MJ, Rafael TJ, Li X, et al. Cerclage in singleton gestations with an extremely short cervix (≤ 10 mm) and no history of spontaneous preterm birth. American Journal of Obstetrics Gynecology MFM. 2021;3:100430.
[5] Shennan A, Story L, Jacobsson B, Grobman WA, Birth FWGfP, Simpson JL, et al. FIGO good practice recommendations on cervical cerclage for prevention of preterm birth. International Journal of Gynecology Obstetrics. 2021;155:19-22.
[6] Obstetricians ACo, Gynecologists. ACOG Practice Bulletin No. 142: Cerclage for the management of cervical insufficiency. Obstet Gynecol. 2014;123:372-9.
[7] Wang S, Feng L. A single‐center retrospective study of pregnancy outcomes after emergency cerclage for cervical insufficiency. International Journal of Gynecology Obstetrics. 2017;139:9-13.
[8] Diamant H, Mastrolia SA, Weintraub AY, Sheizaf B, Zilberstein T, Yohay D. Effectiveness and safety of late midtrimester cervical cerclage. The Journal of Maternal-Fetal Neonatal Medicine. 2019;32:3007-11.
[9] Enakpene CA, DiGiovanni L, Jones TN, Marshalla M, Mastrogiannis D, Della Torre M. Cervical cerclage for singleton pregnant patients on vaginal progesterone with progressive cervical shortening. American Journal of Obstetrics Gynecology. 2018;219:397. e1-. e10.
[10] Gluck O, Mizrachi Y, Ginath S, Bar J, Sagiv R. Obstetrical outcomes of emergency compared with elective cervical cerclage. The Journal of Maternal-Fetal Neonatal Medicine. 2017;30:1650-4.
[11] Seyama R, Makino S, Nojiri S, Takeda J, Suzuki T, Maruyama Y, et al. Retrospective study of the recurrence risk of preterm birth in Japan. The Journal of Maternal-Fetal Neonatal Medicine. 2022;35:515-9.
[12] Israfil-Bayli F, Morton VH, Hewitt CA, Ewer AK, Gray J, Norman J, et al. C-STICH: Cerclage Suture Type for an Insufficient Cervix and its effect on Health outcomes—a multicentre randomised controlled trial. Trials. 2021;22:1-14.
[13] Otsuki K, Nakai A, Matsuda Y, Shinozuka N, Kawabata I, Makino Y, et al. Randomized trial of ultrasound‐indicated cerclage in singleton women without lower genital tract inflammation. Journal of Obstetrics Gynaecology Research. 2016;42:148-57.
[14] Roman A, Zork N, Haeri S, Schoen CN, Saccone G, Colihan S, et al. Physical examination–indicated cerclage in twin pregnancy: a randomized controlled trial. American Journal of Obstetrics Gynecology. 2020;223:902. e1-. e11.
[15] Ciavattini A, Delli Carpini G, Boscarato V, Febi T, Di Giuseppe J, Landi B. Effectiveness of emergency cerclage in cervical insufficiency. The Journal of Maternal-Fetal Neonatal Medicine. 2016;29:2088-92.
[16] Hashim HA, Al-Inany H, Kilani Z. A review of the contemporary evidence on rescue cervical cerclage. International Journal of Gynecology Obstetrics. 2014;124:198-203.
[17] Berghella V, Odibo AO, Tolosa JE. Cerclage for prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination: a randomized trial. American journal of obstetrics gynecology. 2004;191:1311-7.
[18] Roman AS, Rebarber A, Pereira L, Sfakianaki AK, Mulholland J, Berghella V. The efficacy of sonographically indicated cerclage in multiple gestations. Journal of ultrasound in medicine. 2005;24:763-8.
[19] Levin I, Salzer L, Maslovitz S, Avni A, Lessing JB, Groutz A, et al. Outcomes of mid-trimester emergency cerclage in twin pregnancies. Fetal diagnosis
therapy. 2012;32:246-50.
[20] Saccone G, Rust O, Althuisius S, Roman A, Berghella V. Cerclage for short cervix in twin pregnancies: systematic review and meta‐analysis of randomized trials using individual patient‐level data. Acta obstetricia et gynecologica Scandinavica. 2015;94:352-8.
[21] Pan M, Zhang J, Zhan W, Ouyang X, Jiang X, Yang Dy. Physical examination-indicated cerclage in twin pregnancy: a retrospective cohort study. Archives of Gynecology
Obstetrics. 2021;303:665-76.
[22] Cilingir IU, Sayin C, Sutcu H, Inan C, Erzincan S, Yener C, et al. Emergency cerclage in twins during mid gestation may have favorable outcomes: Results of a retrospective cohort. Journal of gynecology obstetrics human reproduction
2018;47:451-3.

	File/Dsecription
	Table-5 Twin pregnancy obstetric outcomes
	Table-6 Twin pregnancy perinatal and neonatal outcomes
	Table-1 Demographics of study population in singleton pregnancies
	Table-3 Comparison of obstetric and neonatal outcomes in two groups in singleton pregnancies
	Table-4 Complications and neonatal outcomes according to the groups in singleton pregnancies
	Table-2 Obstetric and neonatal outcomes in singleton pregnancies