Cerclage for sonographic short cervix in singleton gestations without prior spontaneous preterm birth: systematic review and meta-analysis of randomized controlled trials using individual patient-level data.

OBJECTIVE: The aim of this systematic review and meta-analysis was to quantify the efficacy of cervical cerclage in preventing preterm birth (PTB) in asymptomatic singleton pregnancies with a short mid-trimester cervical length (CL) on transvaginal sonography (TVS) and without prior spontaneous PTB. METHODS: Electronic databases were searched from inception of each database until February 2017. No language restrictions were applied. All randomized controlled trials (RCTs) of asymptomatic singleton pregnancies without prior spontaneous PTB, found to have short CL < 25 mm on mid-trimester TVS and then randomized to management with either cerclage or no cerclage, were included. Corresponding authors of all the included trials were contacted to obtain access to the data and perform a meta-analysis of individual patient-level data. Data provided by the investigators were merged into a master database constructed specifically for the review. Primary outcome was PTB < 35 weeks. Summary measures were reported as relative risk (RR) with 95% CI. The quality of the evidence was assessed using the GRADE approach. RESULTS: Five RCTs, including 419 asymptomatic singleton gestations with TVS-CL < 25 mm and without prior spontaneous PTB, were analyzed. In women who were randomized to the cerclage group compared with those in the control group, no statistically significant differences were found in PTB < 35 (21.9% vs 27.7%; RR, 0.88 (95% CI 0.63-1.23); I2 = 0%; five studies, 419 participants), < 34, < 32, < 28 and < 24 weeks, gestational age at delivery, preterm prelabor rupture of membranes (PPROM) and neonatal outcomes. In women who received cerclage compared with those who did not, planned subgroup analyses revealed a significantly lower rate of PTB < 35 weeks in women with TVS-CL < 10 mm (39.5% vs 58.0%; RR, 0.68 (95% CI, 0.47-0.98); I2 = 0%; five studies; 126 participants) and in women who received tocolytics (17.5% vs 32.7%; RR, 0.54 (95% CI, 0.31-0.93); I2 = 0%; four studies; 169 participants) or antibiotics (18.3% vs 31.5%; RR, 0.58 (95% CI, 0.33-0.98); I2 = 0%; three studies; 163 participants) as additional therapy to cerclage. The quality of evidence was downgraded two levels because of serious imprecision and indirectness, and therefore was judged as low. CONCLUSIONS: In singleton gestations without prior spontaneous PTB but with TVS-CL < 25 mm in the second trimester, cerclage does not seem to prevent preterm delivery or improve neonatal outcome. However, in these pregnancies, cerclage seems to be efficacious at lower CLs, such as < 10 mm, and when tocolytics or antibiotics are used as additional therapy, requiring further studies in these subgroups. Given the low quality of evidence, further well-designed RCTs are needed to confirm the findings of this study. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Effectiveness of cerclage according to severity of cervical length shortening: a meta-analysis.

OBJECTIVES: To estimate the effectiveness of cerclage according to degree of cervical length (CL) shortening. METHODS: A meta-analysis was carried out of trials of women with singleton gestations and second-trimester transvaginal sonographic CL < 25 mm randomized to cerclage or no cerclage. The degree of CL shortening was correlated to the efficacy of cerclage in preventing preterm birth. RESULTS: There was a significant reduction in preterm birth < 35 weeks in the cerclage compared with no cerclage groups in 208 singleton gestations with both a previous preterm birth and CL < 25 mm (relative risk, 0.61; 95% CI, 0.40-0.92). In these women, preterm birth < 37 weeks was significantly reduced with cerclage for CL < or = 5.9 mm, < or = 15.9 mm, 16-24.9 mm and < 25 mm. None of the analyses for 344 women without a previous preterm birth was significant. CONCLUSIONS: Cerclage, when performed in women with a singleton gestation, previous preterm birth and cervical length < 25 mm, seems to have a similar effect regardless of the degree of cervical shortening, including CL 16-24 mm, as well as CL < or = 5.9 mm.

A five century evolution of cervical incompetence as a clinical entity.

Since cervical incompetence was introduced in the English literature in 1678, our understanding and obstetric management of this clinical entity, have changed tremendously over the years. This review shows the historical perspective of the development of cervical incompetence as a distinct clinical entity and an all or nothing phenomenon to cervical incompetence as part of a spectrum leading to preterm delivery, which can express differently in subsequent pregnancies. These changes in our understanding imply consequences for the obstetric management of cervical incompetence. This review focuses on the obstetric management of women considered to be at high risk of preterm delivery due to cervical incompetence, by transvaginal ultrasonographic follow-up of cervical length and transvaginal cervical cerclage.

Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): effect of therapeutic cerclage with bed rest vs. bed rest only on cervical length.

OBJECTIVE: To compare the effects of therapeutic cerclage and bed rest vs. just bed rest on cervical length and to relate these effects to the risk of preterm delivery. DESIGN: Cervical length was measured in patients at high risk of cervical incompetence. When a cervical length < 25 mm was measured before 27 weeks' gestation, randomization for therapeutic cerclage and bed rest vs. just bed rest was performed. After randomization, cervical length was measured weekly. For statistical analysis, t-test and Fisher's exact tests were used and P < 0.05 was considered statistically significant. RESULTS: Nineteen women were randomly allocated to receive a therapeutic cerclage and bed rest and 16 were allocated to receive bed rest only. Mean cervical lengths and mean gestational ages before randomization were comparable between both groups, overall 19.8 mm and 20.7 weeks. Cervical length was measured again at a mean gestation of 22.1 weeks. Mean cervical length (31 mm) was significantly (P < 0.0001) longer after cerclage than after bed rest only (19 mm). A cervical length > or = 25 mm was measured in 22 of the 35 included women, 16 in the cerclage group and six in the bed-rest group (P = 0.006). Of these 22 women, only one delivered before 34 weeks' gestation, which was significantly less frequent than six out of 13 women with a cervical length < 25 mm (P = 0.006). CONCLUSIONS: Therapeutic cerclage with bed rest increases cervical length more often than bed rest alone. A postintervention cervical length > or = 25 mm reduces the risk of preterm delivery in women at high risk of cervical incompetence and a preintervention cervical length < 25 mm.

Final results of the Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): therapeutic cerclage with bed rest versus bed rest alone.

OBJECTIVE: To compare preterm delivery rates (before 34 weeks of gestation) and neonatal morbidity and mortality in patients with risk factors or symptoms of cervical incompetence managed with therapeutic McDonald cerclage and bed rest versus bed rest alone. STUDY DESIGN: Cervical length was measured in patients with risk factors or symptoms of cervical incompetence. Risk factors for cervical incompetence included previous preterm delivery before 34 weeks of gestation that met clinical criteria for the diagnosis of cervical incompetence, previous preterm premature rupture of membranes before 32 weeks of gestation, history of cold knife conization, diethylstilbestrol exposure, and uterine anomaly. When a cervical length of <25 mm was measured before a gestational age of 27 weeks, a randomization for therapeutic cerclage and bed rest (cerclage group) or bed rest alone (bed rest group) was performed. The analysis is based on intention to treat. RESULTS: Of the 35 women who met the inclusion criteria, 19 were allocated randomly to the cerclage group and 16 to the bed rest group. Both groups were comparable for mean cervical length and mean gestational age at time of randomization, mean overall 20 mm and 21 weeks. Preterm delivery before 34 weeks was significantly more frequent in the bed rest group than in the cerclage group (7 of 16 vs none, respectively; P =.002). There was no statistically significant difference in neonatal survival between the groups (13 neonates survived in the bed rest group vs all in the cerclage group). The compound neonatal morbidity, defined as admission to the neonatal intensive care unit or neonatal death, was significantly higher in the bed rest group than in the cerclage group (8 of 16 vs 1 of 19, respectively; P =.005; RR = 9.5, 95% CI, 1.3-68.1). CONCLUSIONS: Therapeutic cerclage with bed rest reduces preterm delivery before 34 weeks of gestation and compound neonatal morbidity in women with risk factors and/or symptoms of cervical incompetence and a cervical length of <25 mm before 27 weeks of gestation.

Loop electrosurgical excision procedure of the cervix and time of delivery in subsequent pregnancy.

OBJECTIVE: To study the effect of the loop electrosurgical excision procedure (LEEP) on gestational age at delivery in the subsequent pregnancy. METHOD: Identification of women with LEEP. Chart analysis and inquiry into gestational age at the subsequent delivery. Exclusion of first trimester abortions, multiple gestations, cold knife conizations and women over 40 years during LEEP. For comparison, 40 weeks was used as the mean date of delivery in a normal population. Wilcoxon signed rank test was used and P<0.05 was considered significant. RESULT: Fifty-six women delivered after LEEP. Seven delivered preterm of whom three were induced and one had a history of preterm delivery. Deliveries prior to 32 weeks of gestation did not occur. Mean gestational age at delivery was 39 2/7 weeks (95%CI: 38 5/7-39 6/7) which is significantly earlier (P=0.03) than the hypothetical 40 weeks. CONCLUSION: After LEEP, deliveries prior to 32 weeks did not occur. Gestational age at delivery was only 5 days earlier than expected. LEEP cannot be considered a risk for early preterm delivery.

Cervical incompetence prevention randomized cerclage trial (CIPRACT): study design and preliminary results.

OBJECTIVE: The objective of this study was to compare different management strategies for women at risk for cervical incompetence. STUDY DESIGN: In an ongoing randomized trial patients with a previous preterm delivery at <34 weeks' gestation who met clinical criteria for the diagnosis of cervical incompetence are allocated to receive a prophylactic cerclage (prophylactic cerclage group) or not (observational group) in a proportion of 1:2. Transvaginal ultrasonographic follow-up examination of the cervix is performed in both groups. When a patient of the latter group has a cervical length <25 mm at <27 weeks' gestation, a further random assignment of therapeutic cerclage or no cerclage is performed. The analysis is by intent to treat. RESULTS: Primary random assignment allocated 23 women to the prophylactic cerclage group and 44 to the observational group. Both groups were comparable with respect to obstetric history. No significant difference was found between the prophylactic cerclage group and the observational group in preterm delivery at <34 weeks' gestation (3/23 vs 6/44, respectively) and neonatal survival (21/23 vs 41/44, respectively). A cervical length <25 mm was found in 18 patients (41%) in the observational group at a mean gestational age of 19.1 +/- 2.9 weeks' gestation. Incidence of preterm delivery at <34 weeks' gestation was significantly higher in the group with short cervical length (6/18 vs 0/26; P =.003). Secondary random assignment of the 18 patients with short cervical length allocated 10 to undergo therapeutic cerclage. Preterm delivery at <34 weeks' gestation was significantly less frequent in the therapeutic cerclage group (1/10 vs 5/8). CONCLUSION: Transvaginal ultrasonographic serial follow-up examinations of the cervix in women at risk for cervical incompetence, with secondary intervention as indicated, appears to be a safe alternative to the traditional prophylactic cerclage. Transvaginal ultrasonographic follow-up examination of the cervix can save the majority of women from unnecessary intervention. Placement of a therapeutic cerclage may reduce the incidence of preterm delivery at <34 weeks' gestation among high-risk patients.

The effect of therapeutic McDonald cerclage on cervical length as assessed by transvaginal ultrasonography.

OBJECTIVE: Our goal was to study the effect of therapeutic McDonald cerclage on cervical length with the use of transvaginal ultrasonography. STUDY DESIGN: Cervical length was measured serially in singleton pregnancies in which there were doubts regarding cervical competence. When shortening of the cervix was substantial before 27 weeks' gestation a McDonald cerclage was applied. Wilcoxon signed rank test was used, and 1-tailed P <.05 was considered significant. RESULTS: In the 34 pregnancies studied, the mean cervical length measured at a mean gestational age of 14 weeks had decreased significantly (P <.0001) from 42 mm (95% confidence interval 38-47) to 21 mm (95% confidence interval 19-23) at a mean gestational age of 20 weeks 5 days, when a cerclage was applied. After the cerclage the mean cervical length increased significantly (P <.0001) to 34 mm (95% confidence interval 30-38) at a mean gestational age of 22 weeks 1 day (95% confidence interval 21 weeks 1 day-23 weeks 2 days). CONCLUSIONS: Therapeutic McDonald cerclage results in a longer cervical length as measured by transvaginal ultrasonography.

Change in paternity: a risk factor for preeclampsia in multiparous women?

BACKGROUND: Preeclampsia is often thought of as being a disease of first pregnancies. The incidence of preeclampsia in subsequent pregnancies, after a previous normal pregnancy is lower. However, it has been reported that this beneficial effect of multiparity is lost with a change in paternity. The aim of this study was to assess the impact of change in paternity on the incidence of preeclampsia in Dutch multiparous pregnant women. METHODS: 364 Multiparous patients with hypertension (diastolic blood pressure > or = 100 mmHg) were identified in the obstetric database of the Academic Hospital Vrije Universiteit Amsterdam for the period 1989-1996. The diagnosis in their obstetrical history (Preeclampsia, HELLP-syndrome, chronic hypertension) was defined in a pragmatic way in view of the retrospective nature of the study. The control group consisted of 281 multiparous women from a midwife clinic, with normotensive pregnancies in the same period. Patients and controls were asked, by telephone, if the index pregnancy was from the same partner as the previous pregnancy and what the sex of the newborns had been in each pregnancy. Fisher's Exact test was used for statistical analysis and P < 0.05 was considered significant. RESULTS: The final study group consisted of 333 multiparous patients with hypertension. The control group consisted of 182 multiparous women without hypertension. The prevalence of new paternity was significantly higher (P < 0.0001) both for preeclamptic and HELLP patients in comparison with the controls, with an odds ratio of 8.6 (95%CI: 3.1-23.5) and 10.9 (95%CI: 3.7-32.3), respectively. CONCLUSION: This study confirms that change of partner raises the risk for preeclampsia in subsequent pregnancies. Immune maladaptation on the fetal maternal interface could be an underlying mechanism. Multiparous women with a new partner should be approached as being primigravid women.