Disclosures: Vincenzo Berghella, MD Nothing to disclose. Charles J Lockwood, MD, MHCM Consultant/Advisory Boards: Celula [Aneuploidy screening (Prenatal and cancer DNA screening tests in development)]. Equity Ownership/Stock Options: Celula [Aneuploidy screening (Prenatal and cancer DNA screening tests in development)]. Vanessa A Barss, MD, FACOG Nothing to disclose.
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INTRODUCTION — Classically, the term “cervical insufficiency” was used to describe painless cervical dilation leading to recurrent second-trimester pregnancy losses/births of otherwise normal pregnancies. Structural weakness of cervical tissue was thought to cause or contribute to these adverse outcomes. The term has also been applied to women with one or two such losses/births or at risk for second-trimester pregnancy loss/birth.
Although structural cervical weakness is the source of some second-trimester losses/births, most are caused by other disorders, such as decidual inflammation/infection, hemorrhage, or uterine overdistension. These disorders, which are not typically recurrent, can initiate biochemical changes in the cervix that lead to premature cervical shortening and, often, pregnancy loss. (See "Pathogenesis of spontaneous preterm birth".)
RISK FACTORS — Congenital and acquired cervical abnormalities increase the risk of cervical insufficiency; acquired risk factors are more common. Cervical trauma may occur during labor or delivery (spontaneous, forceps- or vacuum-assisted, cesarean) , rapid mechanical cervical dilation before a gynecologic procedure [2,3], or treatment of cervical intraepithelial neoplasia. Congenital abnormalities include genetic disorders affecting collagen (eg, Ehlers-Danlos syndrome) [4-6], uterine anomalies [7,8], in utero diethylstilbestrol (DES) exposure , and biologic variation.
Past obstetrical history — The past obstetrical history of women with cervical insufficiency is characterized by:
●History of second-trimester pregnancy losses/deliveries, often associated with a short labor
●History of progressively earlier deliveries in successive pregnancies
Symptoms — Women with cervical insufficiency may be asymptomatic or may present with mild symptoms, such as pelvic pressure, premenstrual-like cramping or backache, and/or a change in the volume, color, or consistency of vaginal discharge. Volume may increase; color may change from clear, white, or light yellow to pink, tan, or spotting; and consistency may become thinner. These symptoms may begin between 14 and 20 weeks of gestation and may be present for several days or weeks before diagnosis of cervical insufficiency.
Contractions are absent or mild.
Physical examination — The initial clinical examination may reveal a soft, somewhat effaced cervix, with no or minimal dilation . Provocative maneuvers such as suprapubic or fundal pressure or the Valsalva maneuver may reveal fetal membranes in the endocervical canal or vagina; this is always an abnormal finding. Tocodynamometry shows no or infrequent contractions at irregular intervals.
Late clinical presentation is characterized by advanced dilation and effacement (eg, ≥4 cm dilated and ≥80 percent effaced), spotting, unprovoked grossly prolapsed membranes or ruptured membranes, or contractions that seem inadequate to explain the advanced effacement and dilation.
Imaging — The cervix may be short (below the 10th percentile [25 mm]), the fetal membranes may be separated, and debris (sludge) may be seen in the amniotic fluid. A rapid rate of decrease in cervical length over time  and cervical shortening before 20 weeks [12-14] may be noted. (See "Second trimester evaluation of cervical length for prediction of spontaneous preterm birth", section on 'Procedure'.)
Laboratory — Uncomplicated cervical insufficiency is not associated with laboratory abnormalities.
In some cases, cervical insufficiency is caused by, or leads to, subclinical intraamniotic infection, which is diagnosed by laboratory examination of amniotic fluid. (See "Intraamniotic infection (chorioamnionitis)", section on 'Diagnosis of clinical chorioamnionitis'.)
Cervicovaginal fetal fibronectin (fFN) may be positive. In asymptomatic women, the combination of a short (<25 mm) cervix on ultrasound examination and a positive fFN result is predictive of an increased risk of preterm delivery, especially in women with a previous preterm delivery, while two negative tests are reassuring (less than 1 percent chance of preterm delivery in the next week or two) [15-19]. We do not obtain fFN in asymptomatic pregnant women as no intervention is available that will prevent subsequent prelabor labor in asymptomatic fFN positive women.
DIAGNOSIS — We base the diagnosis of cervical insufficiency on either classic historic factors or, preferably, by a combination of historic factors and transvaginal ultrasound (TVU) measurement of cervical length. Physical examination alone is adequate in women with advanced cervical dilation.
●History-based diagnosis of cervical insufficiency – We make a history-based diagnosis of cervical insufficiency in women with ≥two consecutive prior second-trimester pregnancy losses associated with relatively painless early cervical dilation or ≥three early (<34 weeks) preterm births in which other causes of pregnancy loss or preterm birth (eg, infection, placental bleeding, multiple gestation, preterm labor) have been excluded. Risk factors for cervical insufficiency support the diagnosis. (See 'Risk factors' above.)
●History, ultrasound, and physical examination-based diagnosis of cervical insufficiency – We make a diagnosis of cervical insufficiency in women with one or two prior second-trimester pregnancy losses or preterm births and cervical length <25 mm on TVU examination or advanced cervical changes on physical examination before 24 weeks of gestation. Risk factors for cervical insufficiency support the diagnosis. (See 'Risk factors' above.)
The diagnosis of cervical insufficiency is usually limited to singleton gestations because the pathogenesis of second-trimester pregnancy loss/preterm delivery in multiple gestations is usually unrelated to a weakened cervix. In addition, preterm labor, infection, abruptio placenta, bleeding placenta previa, and abruptio placentae should be excluded, as these disorders could account for biochemically mediated cervical ripening leading to second-trimester pregnancy loss or preterm delivery independent of structural/anatomic cervical weakness .
The American College of Obstetricians and Gynecologists (ACOG) defines cervical insufficiency as the inability of the uterine cervix to retain a pregnancy in the second trimester in the absence of clinical contractions, labor, or both .
Can cervical insufficiency be diagnosed before pregnancy? — The diagnosis of cervical insufficiency cannot be made or excluded in nonpregnant women by any test. Evaluation of cervical function with dilators, balloons, or hysteroscopy is not helpful. Ultrasound, magnetic resonance imaging (MRI), or hysterosalpingography may reveal a uterine anomaly, which is a risk factor for cervical insufficiency, but is not diagnostic.
APPROACH TO MANAGEMENT — The following approach to management applies to women with singleton pregnancies. Cerclage is not indicated in any twin or other multiple pregnancies, given the body of evidence shows no improvement in pregnancy outcome compared with appropriate controls without cerclage. (See "Twin pregnancy: Prenatal issues", section on 'Unproven interventions to prevent or delay preterm labor'.)
Women with prior pregnancy losses or preterm births
Candidates for history-indicated cerclage — We suggest a history-indicated transvaginal cerclage at 12 to 14 weeks for women with a history-based diagnosis of cervical insufficiency (table 1). (See 'Diagnosis' above.)
A minority of recurrent second-trimester losses/preterm births is primarily, and perhaps exclusively, caused by congenital or acquired structural weakness of the cervix, and can be treated effectively with support by a history-indicated cerclage. Anatomical, biochemical, and clinical evidence from observational studies and randomized trials consistently support this approach [22-25].
We also treat these women with hydroxyprogesterone caproate weekly from 16 to 36 weeks of gestation [26-28]. Although randomized trials support the benefit of history-indicated cerclage  and the benefit of progesterone supplementation [26-28] in this population, no trials have evaluated the efficacy of combination therapy (both history-indicated cerclage and hydroxyprogesterone caproate).
Candidates for ultrasound surveillance and possible ultrasound-indicated cerclage — The majority of women with suspected cervical insufficiency do not meet criteria for a history-based diagnosis of cervical insufficiency and, in turn, a history-indicated cerclage (see 'Diagnosis' above). For these women, we administer hydroxyprogesterone caproate prophylaxis against preterm delivery, monitor cervical length with TVU (table 2), and apply a cerclage if cervical length is <25 mm . The following lines of evidence provide the rationale for this approach:
●In randomized trials, progesterone prophylaxis with hydroxyprogesterone caproate starting at 16 to 20 weeks of gestation in women with a history of spontaneous preterm birth and continuing until 36 weeks reduced the risk of recurrent preterm birth. (See "Progesterone supplementation to reduce the risk of spontaneous preterm birth".)
●Women with a short cervix on TVU examination in the second trimester are at increased risk of spontaneous preterm birth. (See "Second trimester evaluation of cervical length for prediction of spontaneous preterm birth".)
●Placement of a cerclage upon identification of a short cervix (ultrasound-indicated cerclage) is effective in reducing preterm birth , results in pregnancy outcomes comparable to those with history-indicated cerclage , and avoids cerclage in about 60 percent of patients with a suggestive history . The benefit of ultrasound-indicated cerclage may derive from bolstering cervical strength , preventing membranes from being exposed, and retention of the mucus plug.
•In a 2011 meta-analysis of randomized trials of women with singleton gestation and prior spontaneous preterm birth and short cervical length <25 mm before 24 weeks, placement of an ultrasound-indicated cerclage significantly reduced total neonatal morbidity and mortality (15.6 versus 24.8 percent without cerclage; RR 0.64, 95% CI 0.45-0.91), presumably because cerclage significantly reduced the frequency of preterm birth (delivery <35 weeks RR 0.70, 95% CI 0.55-0.89; 28.4 percent versus 41.3 percent in women without cerclage) .
•In another 2011 meta-analysis of randomized trials of women with singleton gestations and prior preterm birth managed either by (1) cervical length screening with cerclage for short cervical length or (2) history-indicated cerclage, patients with ultrasound-indicated versus history-indicated cerclage had similar rates of preterm birth before 37 weeks (31 versus 32 percent, RR 0.97, 95% CI 0.73-1.29), preterm birth before 34 weeks (17 versus 23 percent, RR 0.76, 95% CI 0.48-1.20), and perinatal mortality (5 versus 3 percent, RR 1.77, 95% CI 0.58-5.35), and only 42 percent developed a short cervical length and received cerclage .
We usually initiate cervical length screening at 14 weeks, but may screen as early as 12 weeks in women with early second-trimester losses, recurrent second-trimester losses, or a prior large cold-knife conization (table 2) . In women with prior preterm birth at 28 to 36 weeks, we initiate screening at 16 weeks. Ultrasound examination is generally repeated every two weeks until 24 weeks as long as the cervical length is ≥30 mm, and increased to weekly if cervical length is 25 to 29 mm, with the expectation that preterm cervical changes will precede overt preterm labor or membrane rupture symptoms by three to six weeks . TVU screening is usually discontinued at 24 weeks of gestation, as cerclage is rarely performed after this time. (See "Second trimester evaluation of cervical length for prediction of spontaneous preterm birth".)
We continue intramuscular hydroxyprogesterone caproate supplementation until 36 weeks, whether or not a cerclage is placed. Although no studies have reported a statistically significant improvement in pregnancy outcome with combined therapy [32,35,36], these studies are retrospective analyses and underpowered. One post-hoc analysis of data from a randomized trial observed that the rate of early preterm birth trended lower in women who received both hydroxyprogesterone caproate and ultrasound-indicated cerclage than in those who received either therapy alone (preterm birth <28 weeks: both interventions: 9 percent versus cerclage alone: 17 percent and progesterone alone: 15 percent; preterm birth <32 weeks: both interventions: 17 percent versus cerclage alone: 25 and progesterone alone: 21 percent) .
No randomized trial has directly compared vaginal progesterone, intramuscular hydroxyprogesterone caproate, and cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix in the midtrimester, singleton gestation, and previous preterm birth. An indirect comparison meta-analysis concluded vaginal progesterone and cerclage were equally efficacious in the prevention of preterm birth in this population . Based on evidence from the direct comparisons in the randomized trials discussed above, we treat women with prior preterm birth with intramuscular hydroxyprogesterone caproate and then perform cerclage if the cervical length becomes <25 mm. (See 'Women with prior pregnancy losses or preterm births' above.)
Alternative approaches include substituting vaginal progesterone for intramuscular progesterone in women with a history of preterm birth who develop a short cervix and performing amniocentesis to assess for subclinical infection before placing a cerclage in women with a short cervix.
Women with no prior preterm birth, but risk factors for cervical insufficiency — Although these women may develop cervical insufficiency, the pregnancy course and outcome need to be evaluated before making this diagnosis. We perform a single TVU cervical length measurement at 18 to 24 weeks in women with no prior preterm birth but risk factors for cervical insufficiency (table 2), and treat those with a short cervix (≤20 mm) with vaginal progesterone supplementation. Administration of vaginal progesterone to women with a short cervix reduces the rate of spontaneous preterm birth and composite neonatal morbidity and mortality and appears to be cost-effective. The evidence supporting this approach, including the rationale for the 20 mm threshold for defining a short cervix, is reviewed separately. (See "Second trimester evaluation of cervical length for prediction of spontaneous preterm birth", section on 'Cervical length screening' and "Progesterone supplementation to reduce the risk of spontaneous preterm birth", section on 'Short cervix in current pregnancy'.)
If the patient delivers preterm, subsequent pregnancies are managed as described above (see 'Women with prior pregnancy losses or preterm births' above), and may warrant an ultrasound-indicated cerclage if cervical length is <25 mm. If she delivers at term, we again perform a single cervical length measurement at 18 to 24 weeks and give vaginal progesterone if the cervix is short.
Physical examination reveals a dilated cervix and visible membranes before 24 weeks — Rarely, a woman presents before 24 weeks with minimal or no symptoms and physical examination reveals a dilated cervix. Occasionally, such findings follow the identification of a very short cervical length (eg, <5 mm) on TVU examination. The management of these cases is governed primarily by whether the patient has a condition that would likely lead to prompt delivery, such as overt infection, ruptured membranes, or significant hemorrhage. In the absence of indications for delivery, the gestational age and cervical dilation are the next considerations. Prior to viability, the goal is prolonging the pregnancy, although some parents may choose pregnancy termination, especially for preterm premature rupture of membranes (PPROM) or advanced (>4 cm) cervical dilation, given the poor prognosis. After viability, the goal is to both prolong the pregnancy and improve neonatal outcome in the likely event of preterm birth.
Data from several studies suggest that a grossly dilated cervix with visible membranes may be an appropriate criterion for placement of a “physical exam-indicated cerclage” (also called “rescue cerclage” or “emergency cerclage”). Placement of a physical exam-indicated cerclage when a dilated cervix and visible membranes are detected on digital examination at <24 weeks appeared to prolong pregnancy and improve pregnancy outcome compared with expectant management in a small randomized trial, a prospective study, and retrospective cohort studies [39-49]. Due to differences in patient populations, actual outcomes varied among these studies. Physical exam-indicated cerclage in women with visible bulging membranes should only be considered in the absence of infection, labor, and vaginal bleeding (abruption). (See "Transvaginal cervical cerclage".)
In women without clinical signs of infection, we suggest amniocentesis to evaluate for subclinical infection when the cervix is ≥2 cm dilated and on a case-by-case basis when ultrasound findings are consistent with inflammation. These findings include membrane edema, separation of the membranes from the decidua, or debris in the amniotic fluid (“sludge”) (image 1). Some studies have reported an association between intraamniotic debris and intraamniotic inflammation, preterm delivery, and other pregnancy complications [50-53]. (See "Intraamniotic infection (chorioamnionitis)", section on 'Amniocentesis' and "Second trimester evaluation of cervical length for prediction of spontaneous preterm birth".)
Prior successful outcome after cerclage — We suggest TVU cervical length screening in future pregnancies for women who received an ultrasound-indicated cerclage in a prior pregnancy and had a successful outcome. The risk of preterm birth in future pregnancies does not warrant routine placement of a cerclage , but if ultrasound surveillance shows a short cervix in a subsequent pregnancy, we place another cerclage.
Successful pregnancy outcome after ultrasound-indicated cerclage does not establish a diagnosis of cervical insufficiency as a substantial proportion of pregnancies with premature cervical effacement have good outcomes in the index pregnancy and future pregnancies in the absence of surgical intervention. This is particularly true in women who, after removal of the cerclage at 36 to 37 weeks, do not go into labor in the next two weeks.
Prior unsuccessful outcome after cerclage — Transabdominal cerclage may be successful in women who deliver very preterm despite placement of a transvaginal cerclage. (See "Transabdominal cervical cerclage".)
Pessary — Vaginal pessaries are intended to alter the axis of the cervical canal and displace the weight of the uterine contents away from the cervix. By changing the angle of the cervix in relation to the uterus, the pessary also obstructs the internal os and thus may provide protection against ascending infection.
Before 2012, only a few observational studies suggested that pessaries may have efficacy equivalent to cerclage and/or progesterone [55-58]. In 2012, a multicenter trial randomly assigned 385 pregnant women with cervical length ≤25 mm at 20 to 23 weeks to use of a cervical pessary or expectant management (no pessary) [59,60]. The majority of these patients (89 percent) had no history of previous preterm birth and none were treated with progestogens or cerclage. The pessary group had a significant reduction in spontaneous preterm <28 weeks (4/190 [2 percent] versus 16/190 [8 percent] OR 0.23, 95% CI 0.06-0.74) and <34 weeks (12/190 [6 percent] versus 51/190 [27 percent] OR 0.18, 95% CI 0.08-0.37).
No adverse effects were noted, other than vaginal discharge and mild discomfort upon insertion. Use of a pessary to prolong pregnancy in women with a short cervical length may be an effective, inexpensive, and easy to implement intervention. However, given the open-label design of this trial with lack of a placebo control and the relatively small number of preterm births accounting for the dramatic results, we do not recommend implementation of this approach instead of cerclage or progestogens until these findings are confirmed by additional randomized and placebo-controlled trials. A subsequent randomized trial published in 2013 did not confirm efficacy .
A review of the different models of pessary used for prevention of preterm birth, as well as sizing, insertion, changing/removing, follow-up, and patient education, has been published by Arabin and Alfirevic .
Indomethacin — A review of data from three randomized cerclage trials found that indomethacin therapy for asymptomatic women with a short cervix (<25 mm) at 14 to 27 weeks who did not receive a cerclage did not reduce spontaneous preterm births <35 weeks, but appeared to reduce preterm births <24 weeks . Further research including a larger number of pregnancies and a randomized trial design is necessary to further clarify the effectiveness, as well as the risks, of this therapy.
Antibiotics — There is insufficient evidence to recommend antibiotics for women with cervical insufficiency, based on poor obstetrical history, short transvaginal ultrasound (TVU) cervical length, or dilated cervix on physical examination.
Lifestyle interventions — Clinicians should consider the available evidence and the patient's individual circumstances when making lifestyle recommendations as there are social, psychological, financial, and medical side effects associated with these interventions. Lifestyle interventions (cessation of work and exercise, abstinence from coitus, bedrest/limited activity) have not been adequately evaluated by well-designed studies. Although coitus is not a risk factor for onset of labor in women at term who are scheduled for induction , there are inadequate data on the safety of coitus in women at risk for preterm birth because of previous preterm birth or preterm cervical ripening . In our practice, we advise women with both a prior preterm birth and a short cervix to avoid coitus.
SUMMARY AND RECOMMENDATIONS — The following algorithm summarizes the author’s approach (algorithm 1).
●Cervical insufficiency describes a presumed physical weakness of cervical tissue that causes or contributes to the early delivery of an otherwise healthy pregnancy, usually in the second trimester. (See 'Introduction' above.)
●Cervical insufficiency may be congenital or acquired. Women at risk include those with a history of cervical trauma, collagen disorders, or congenital anomalies of the uterus/cervix. (See 'Risk factors' above.)
●The diagnosis of cervical insufficiency is either based on historic factors or on a combination of historic factors and transvaginal ultrasound (TVU) measurement of cervical length. (See 'Diagnosis' above.)
•History-based diagnosis of cervical insufficiency – We make a history-based diagnosis of cervical insufficiency in women with ≥two consecutive prior second-trimester pregnancy losses associated with relatively painless early cervical dilation or ≥three early (<34 weeks) preterm births in which other causes of pregnancy loss or preterm birth (eg, infection, placental bleeding, multiple gestation, preterm labor) have been excluded. Risk factors for cervical insufficiency support the diagnosis. (See 'Risk factors' above.)
•History, ultrasound, and physical examination-based diagnosis of cervical insufficiency – We make a diagnosis of cervical insufficiency in women with one or two prior second-trimester pregnancy losses or preterm births and cervical length <25 mm on TVU examination or advanced cervical changes on physical examination before 24 weeks of gestation. Risk factors for cervical insufficiency support the diagnosis. (See 'Risk factors' above.)
Women with singleton pregnancies
●For women with history-based diagnosis of cervical insufficiency, we recommend history-indicated cerclage rather than ultrasound monitoring of cervical length (Grade 1B). (See 'Candidates for history-indicated cerclage' above.)
●For women with suspected cervical who do not meet criteria for history-indicated cerclage, sonographic surveillance should be started early in pregnancy (eg, 14 to 16 weeks). We suggest cerclage for women who develop a short cervix (<25 mm) before 24 weeks (Grade 2B) (see 'Candidates for ultrasound surveillance and possible ultrasound-indicated cerclage' above). Vaginal progesterone administration and placement of a pessary are alternative approaches. (See "Progesterone supplementation to reduce the risk of spontaneous preterm birth", section on 'Short cervix in current pregnancy' and 'Pessary' above.)
●For women with a grossly dilated cervix and visible membranes on digital examination at <24 weeks and no labor or signs of infection, we suggest a physical exam-indicated cerclage rather than expectant management (Grade 2C). (See 'Physical examination reveals a dilated cervix and visible membranes before 24 weeks' above.)
●We recommend progesterone supplementation for women with a history of spontaneous preterm birth (Grade 1B). (See "Progesterone supplementation to reduce the risk of spontaneous preterm birth".)
Women with multiple gestations
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