Cervical Insufficiency

Etiology

Cervical insufficiency is thought to be due to congenital or acquired defects in the structure or function of the cervix. The human cervix is a fibromuscular organ that undergoes extensive changes throughout gestation and parturition. During gestation, the maternal cervix undergoes a complex remodeling process involving timed biochemical cascades, interactions between the extracellular and cellular compartments, and cervical stromal infiltration by inflammatory cells. Any disruption in these processes or to the structural integrity of the cervix itself could result in early cervical ripening, cervical insufficiency, and preterm birth or miscarriage. 

Congenital etiologies contributing to cervical insufficiency are relatively uncommon. Frequently, patients with underlying congenital etiologies present with severely shortened cervical lengths.[4] These congenital causes include Müllerian duct anomalies, conditions associated with abnormal or deficient collagen production such as Ehlers-Danlos syndrome, and in utero exposure to diethylstilbestrol.[5][3] 

The most common acquired cause of cervical insufficiency is cervical trauma, which may result from cervical lacerations during childbirth, especially if the birth was precipitous or following a prolonged second stage of labor, cervical conization, loop electrosurgical excision procedures (LEEP), or any other surgical procedure requiring mechanical cervical dilation, including dilation and curettage or hysteroscopy.[3][6] Additionally, inflammation or infection at the placenta-decidua interface may prematurely activate this final pathway of parturition.[7][8] Studies have also demonstrated that dysplasia of cervical connective tissue may play a role.[9] Therefore, patients with a history of cervical trauma or surgery are at risk for cervical insufficiency. Other significant risk factors for cervical insufficiency include a history of miscarriage and a shortened cervix in the current pregnancy.[10]

Epidemiology

Cervical insufficiency complicates up to 1% of pregnancies in the general population.[3] Wide variation in the incidence of cervical insufficiency has been reported, which is likely due to fundamental biological differences among the study populations, the criteria used to establish the diagnosis, and reporting bias between general practitioners and referral centers.[11] In a study of 158 individuals with a history of second-trimester miscarriage, cervical insufficiency was identified as the likely cause of second-trimester loss in 8% of the cohort.[12] 

History and Physical

The diagnosis of cervical insufficiency is typically made in one of the following scenarios:

• Exam-based diagnosis: Painless dilation in the second or early third trimester in the absence of contractions or other clear pathologies such as bleeding, PPROM, infection, or placental abruption.
• History-based diagnosis: Patients with a clinical history consistent with cervical insufficiency, which includes a history of at least 1 to 3 consecutive second-trimester losses or early preterm births related to painless cervical dilation (definitions vary slightly by organization) and patients with a history of a prior exam-indicated cerclage. [2][1][13]
• Ultrasound-based diagnosis: Patients with a history of at least 1 preterm birth or second-trimester loss AND a shortened cervical length before 24 weeks EGA in the current pregnancy.

All pregnant patients should be assessed for risk factors for cervical insufficiency at their initial pregnancy evaluation. Careful attention should be paid to the obstetric history and the details surrounding past preterm births, differentiating medically induced preterm delivery from spontaneous preterm birth. If possible, records from any prior preterm births should be reviewed to clarify the underlying cause. Additionally, any previous cervical procedures (eg, LEEPs or dilation and curettage) that may affect the structural integrity of the cervix should be noted.[2] 

Cervical insufficiency is, by definition, asymptomatic or associated with only mild, nonspecific symptoms, including pelvic pressure, backache, an increase in vaginal discharge, or vaginal spotting.[8] In patients diagnosed with cervical insufficiency for the first time on an examination in the second trimester, the cervix is typically soft, effaced, and dilated. Fetal membranes may also be visible within the cervical canal or vagina.[7][14] 

Evaluation

Ultrasonography

Cervical insufficiency is a well-recognized cause of second-trimester fetal loss and early preterm birth, and the diagnosis is often made retrospectively. Therefore, multiple professional guidelines recommend that individuals with a prior spontaneous preterm birth should be screened with serial cervical lengths in the second trimester.[1][2][13][15] Screening is typically performed via transvaginal sonography every 1 to 2 weeks between 16 and 24 weeks gestation. Some clinicians also assess the cervical length in the first trimester, typically between 11 and 14 weeks gestation. A shortened cervix is typically defined as a cervical length of less than 25 mm in patients undergoing serial screening ultrasounds.[1][2][13][15] Funneling, which refers to a ballooning of the fetal membranes into the cervical canal, and debris within the amniotic fluid may also be seen as the cervix shortens.

In patients at high risk for cervical insufficiency, shear-wave elastography can also be used to assess the softness of the cervix.[16][17] A soft cervix, often defined as a mean elastography below the tenth percentile, is associated with a relative risk of 7.8 for spontaneous preterm delivery before 34 weeks gestation compared to those with normal elastography findings.[16] Conversely, serial cervical length screening is not recommended for patients without a history of a prior spontaneous preterm birth or second-trimester loss. Instead, professional guidelines recommend assessing cervical length during the routine mid-pregnancy ultrasound at 18 to 24 weeks gestation.

Before placing a cerclage, an obstetric ultrasound should be performed to ensure fetal viability, confirm the gestational age and cervical length, and exclude clinically relevant structural anomalies.[2][18] 

Amniocentesis

Cerclage is one of the primary treatment modalities for cervical insufficiency but is contraindicated in patients with intraamniotic infection (IAI) or inflammation. However, the frequency of subclinical IAI in patients with cervical insufficiency and exposed membranes has been reported to be as high as 50%.[19][20] Despite this, whether outcomes are influenced by performing amniocentesis to rule out infection before cerclage placement is unclear; routine use of amniocentesis is not recommended.[21][2] If clinical evidence of potential IAI is noted, an amniocentesis is appropriate to exclude infection before placing a cerclage.

Additional Diagnostic Studies

The Society of Obstetricians and Gynaecologists of Canada (SOGC) recommends obtaining a urine culture and sample of vaginal secretions to rule out bacterial vaginosis at the initial antenatal appointment in all patients with a history of cervical insufficiency. Any abnormal results should be appropriately treated.[2]

Historical Tests

Previously, patients were evaluated in the nonpregnant state to assess their cervical competence. These diagnostic studies included hysterosalpingography, radiographical imaging of balloon traction against the cervix, and assessment of a patulous cervix with cervical dilators. None of these tests have been validated for the evaluation of cervical insufficiency, and these tests are not used in modern clinical practice.

Treatment / Management

The primary treatment options for cervical insufficiency include cerclage placement and vaginal progesterone. 

Cerclage

A cerclage is a nonresorbable suture placed around the cervix to improve mechanical strength and prevent premature dilation. Cerclage indications include varying criteria (see Table. Cervical Insufficiency Recommendations). Contraindications for cerclage include active preterm labor, PPROM, placental abruption, intrauterine infection, fetal demise, and fetal anomalies incompatible with life. Therefore, before placing a cerclage, an obstetric ultrasound should be performed to ensure fetal viability, confirm the gestational age, and exclude clinically relevant structural anomalies.[2][18] Patients are also often observed for a period of time before cerclage placement to rule out active labor and abruption. Additionally, patients should be clinically assessed for signs and symptoms suggesting cervicovaginal and intraamniotic infections.

A cerclage may be placed via the transvaginal or transabdominal route. Transabdominal cerclage (TAC) is associated with higher morbidity, in part because these patients require cesarean delivery. For this reason, the transvaginal approach is preferred during pregnancy in appropriate candidates.

Transvaginal cerclages are typically placed using modifications of the McDonald or Shirodkar techniques. The McDonald technique involves placing a nonresorbable purse-string suture around the cervix, as high on the cervix as technically possible at the cervicovaginal junction; the knot is usually tied anteriorly to facilitate removal.[1][3] The Shirodkar technique involves dissection of the paracervical tissue and cephalad reflection of the bladder and rectum off of the cervix, allowing placement of sutures as close to the internal cervical os as possible; the mucosa is then sutured over the knot.[1][3] Clinicians often prefer the McDonald cerclage as this type of cerclage is easier to place and remove than a Shirodkar cerclage. A transvaginal cerclage is typically removed between 36 and 37 weeks gestation, before the onset of spontaneous labor.[1]

A TAC can be placed via laparotomy or laparoscopy.[2][22][23][24][25] In these procedures, the suture is placed right at the cervicoisthmic junction, theoretically providing the greatest structural support to the cervix. However, due to the increased morbidity associated with a TAC, these procedures are usually reserved for patients with a history of spontaneous preterm birth before 28 weeks gestation despite having a transvaginal cerclage in place.[3] Additionally, a TAC may be appropriate in patients with a history of trachelectomy, multiple LEEPs, or other anatomic reasons why a transvaginal cerclage would be exceedingly difficult to place.[2][3][26][22] Compared to open techniques, laparoscopic TACs, including robotic-assisted procedures, are associated with lower blood loss, fewer wound complications, and quicker recovery. Furthermore, neonatal outcomes are similar or better with laparoscopic TACs than with open procedures.[22]

After any cerclage placement, continuing to monitor the cervical length provides no additional benefit; theoretically, continued surveillance may provide some psychological benefit to the patient.[15]

Supplemental Progesterone

Progesterone is thought to suppress myometrial contractility and proinflammatory pathways and may affect cervical remodeling throughout pregnancy. Although progesterone levels are already relatively high during pregnancy, vaginal progesterone is associated with a decreased risk of preterm birth in select patients, including:

• Patients with an incidentally discovered short cervix with a cervical length of less than 25 mm who lack a history of prior preterm birth
• Patients with a history of prior preterm birth and cervical length less than 25 mm as an alternative or adjunct to an ultrasound-indicated cerclage
• Patients with a history- or exam-indicated cerclage

Importantly, for patients with only a history of preterm birth undergoing cervical length screening, vaginal progesterone does not appear to reduce the risk of recurrent preterm birth in these patients without a shortened cervix.[27] The typical dosing regimen is a single 90 mg daily dose of an 8% intravaginal gel or 200 mg of micronized progesterone vaginal capsules.[28] Additionally, 17-hydroxyprogesterone caproate (17-OHP) is ineffective in reducing the risk of recurrent preterm birth in those with a pertinent history. For this reason, 17-OHP is no longer recommended to prevent recurrent preterm birth.[29]

Management Approach Selection Factors

Management depends on how cervical insufficiency was diagnosed (history, exam, or ultrasound), cervical length, and whether or not the patient has a history of a prior spontaneous second-trimester loss or preterm birth (see Table. Cervical Insufficiency Recommendations). Patients with multiple gestations are usually managed similarly to singleton gestations, though management is often individualized. Specifically, multiple gestation on its own is not an indication for a prophylactic cerclage or vaginal progesterone.

Exam-based diagnosis of cervical insufficiency 

An exam-based cerclage, also known as an emergency or rescue cerclage, should be considered in patients less than 28 weeks gestation presenting with cervical dilation between 1 cm and 4 cm in the absence of labor and other contraindications.[1][2] Although the procedure becomes more technically difficult as the cervix dilates, reports of successful exam-indicated cerclage placements at advanced dilations of 4 cm or greater and effacement have been documented. Amnioreduction before cerclage placement may improve outcomes in these situations; shared decision-making and an individualized approach are recommended.[30]

Vaginal progesterone is also appropriate to consider in patients receiving an exam-based cerclage based on the results of a meta-analysis that found the combination of cerclage plus vaginal progesterone reduced the risk of preterm birth more than either cerclage or progesterone alone in patients with a cervical length less than 10 mm or history- or ultrasound-indicated cerclage.[31](A1)

History-based diagnosis (or suspicion) of cervical insufficiency

The American College of Obstetricians and Gynecologists (ACOG) recommends a history-indicated cerclage in patients who have either a history of an exam-indicated cerclage or at least 1 prior loss or preterm birth at less than 28 weeks gestation related to painless cervical dilation in the second trimester.[1] Other guidelines, including those from the SOGC and the Royal College of Obstetricians and Gynaecologists (RCOG), recommend history-indicated cerclages only after 3 or more second-trimester losses or preterm births.[2][13] A history-indicated cerclage is typically placed between 12 and 14 weeks gestation; they can also be placed before conception, often with a laparoscopic TAC.[1][2][22] Notably, TACs placed before conception may be more effective and are not associated with subfertility.[13]

Vaginal progesterone is also appropriate in patients meeting history-based criteria for cervical insufficiency. It is most effective when given from 16 to 36 6/7 weeks gestation based on the previously mentioned meta-analysis study.[31](A1)

Ultrasound-based diagnosis of cervical insufficiency

Ultrasound-indicated cerclage is recommended in patients with a singleton gestation and a history of a prior spontaneous preterm birth or second-trimester loss who are found to have a cervical length less than 25 mm before 24 weeks gestation but do not meet criteria for a history-indicated cerclage.[1][13][2] Vaginal progesterone can also be considered in these patients.[31](A1)

Patients with an incidentally discovered shortened cervix of less than 25 mm but no current cervical dilation or history of preterm birth should be treated with vaginal progesterone to reduce the risk of preterm birth.[32] If the cervix is between 10 mm and 25 mm, cerclage does not appear to offer any additional benefit in this population and is not recommended by professional societies.[2][13][28] However, in patients without a history of preterm birth or second-trimester loss who have a cervical length of less than 10 mm, vaginal progesterone plus cerclage does appear to increase the latency period compared to progesterone alone.[33] For this reason, ACOG states that cerclage can be considered in patients without a history of preterm birth or second-trimester loss when the cervical length is less than 10 mm; shared decision-making is recommended in these situations.[21](A1)

Table. Cervical Insufficiency Recommendations

*American guidelines: at least 1, British and Canadian guidelines: at least 3

PTB = preterm birth; CL = cervical length

Additional Interventions

Activity restriction and bed rest have not been proven to be effective in the treatment of cervical insufficiency, and they are not recommended as a primary treatment strategy. However, some organizations, such as the SOGC, recommend that clinicians "consider advising the patient to reduce physical activity, especially those with physical employment, prolonged periods of standing, or frequent and repetitive lifting."[2] Patients can also be informed that no good data is available on the safety of intercourse in the setting of cervical insufficiency, and the option of limiting or abstaining from sexual activity can be discussed. 

Cervical pessaries have been studied, but no high-quality data supports their effectiveness.[21] Corticosteroids should be considered to promote fetal maturation after the point of viability.[2]

Differential Diagnosis

When patients present with cervical dilation in the second or early third trimester, the following conditions should be considered:

• Preterm labor
• PPROM
• Intraamniotic infection (IAI)
• Placental abruption
• Fetal loss
• Fetal anomalies incompatible with life

Prognosis

Adverse outcomes associated with cervical insufficiency are primarily related to the effects of preterm birth. With appropriate interventions for cervical insufficiency, the neonatal prognosis improves. Exam-based (ie, emergency) cerclage placement has been shown in observational studies to prolong pregnancy between 6 and 9 weeks compared to pregnancy prolongation of fewer than 4 weeks with expectant management.[2] For individuals receiving a history-indicated cerclage, a Cochrane review found that cerclage significantly reduced the risk of PTB compared to no cerclage (RR 0.77).[13]

A randomized controlled trial found that ultrasound-indicated cerclage placement (ie, cerclage placed in patients with a history of PTB and cervical length <25 mm) reduced the risk of previable birth from 14% to 6.1% and perinatal death from 16% to 8.8%. This same study showed a trend towards reducing PTB at <35 weeks gestation (42% versus 32%), though this finding was not statistically significant (CI 0.42-1.07).[34]

A meta-analysis of 5 random controlled trials found that patients with a short cervix (<25 mm) without additional risk factors for PTB who were treated with vaginal progesterone had decreased rates of PTB before 34 weeks compared to placebo (14.5% versus 24.6%), as well as significantly reduced risks of neonatal respiratory distress and neonatal intensive care unit admission.[35]

Complications

Cervical insufficiency is associated with a significant risk of extremely premature birth. The earlier in gestation a fetus is born, the higher the associated morbidity and mortality rates. Common complications of prematurity include:

• Respiratory distress syndrome
• Bronchopulmonary dysplasia
• Intraventricular hemorrhage
• Necrotizing enterocolitis 
• Sepsis
• Retinopathy of prematurity
• Patent ductus arteriosus
• Hypothermia
• Glucose abnormalities
• Failure to thrive
• Poor feeding
• Neonatal death

A cerclage should be removed with the onset of preterm labor, the development of sepsis, or within 48 hours of PPROM.[2] A cerclage is not strong enough to keep the cervix closed in the setting of preterm labor contractions; if a cerclage is in place during labor, the suture will tear through the cervix as it dilates, resulting in significant cervical trauma. Sepsis significantly increases the risk of maternal and neonatal morbidity and mortality. Due to the high risk of sepsis with PPROM, meta-analysis has shown that delayed removal of a cerclage in the setting of PPROM significantly increases the rate of neonatal mortality. Delivery within 48 hours allows time for corticosteroid administration while reducing the risk of sepsis associated with delayed cerclage removal.[36][37]