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)]. Vanessa A Barss, MD, FACOG Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
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 structural support from 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 (25 percent reduction in deliveries <33 weeks)  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 transvaginal ultrasound (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 reduced total neonatal morbidity and mortality by over one-third (15.6 versus 24.8 percent without cerclage; RR 0.64, 95% CI 0.45-0.91), presumably because cerclage reduced the frequency of preterm birth by 30 percent (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, both groups 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) . Only 42 percent of patients in the ultrasound screening group developed a short cervical length and received cerclage versus 100 percent in the history-indicated group.
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.
We consider physical examination-indicated cerclage a reasonable option for these women, in the absence of overt infection, labor, ruptured membranes, or significant hemorrhage (eg, abruption), since these conditions would likely make delivery within hours or a few days inevitable. Other options include expectant management and, where legal, pregnancy termination. In a systematic review including a small randomized trial, two prospective cohort studies, and seven retrospective cohort studies, placement of a "physical examination-indicated cerclage" (also called "rescue cerclage" or "emergency cerclage") in patients with a dilated cervix and visible membranes on digital examination in the second trimester appeared to improve pregnancy outcome compared with no cerclage (neonatal survival 71 percent with cerclage versus 43 percent with expectant management; RR 1.65, 95% CI 1.19-2.28) . The mean age at diagnosis in the cerclage and expectant management groups was 21.7 and 22.8 weeks of gestation, respectively; the mean time to delivery was 57 and 19 days, respectively; and the mean gestational age at delivery was 30.6 and 25.2 weeks, respectively. Although these largely observational data are low-quality evidence, the analysis is the best available evidence to inform decision-making in this setting.
We perform amniocentesis to look for subclinical infection when the cervix is ≥2 cm dilated and on a case-by-case basis when ultrasound findings are consistent with inflammation (eg, debris in the amniotic fluid ["sludge"] (image 1)). We do not perform cerclage if we find evidence of subclinical infection as these pregnancies are at increased risk of preterm delivery and other pregnancy complications [40-43]. (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. In one study, only 50 percent of women with a history of an ultrasound-indicated cerclage required another ultrasound-indicated cerclage in the subsequent pregnancy, and their outcomes were similar to those who underwent planned cerclage in the subsequent pregnancy .
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 [46-49]. 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) [50,51]. 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
●For women with twin or higher order multiple pregnancies, we suggest avoiding cerclage (Grade 2C). (See "Twin pregnancy: Prenatal issues", section on 'Unproven interventions to prevent or delay preterm labor'.)
- Vyas NA, Vink JS, Ghidini A, et al. Risk factors for cervical insufficiency after term delivery. Am J Obstet Gynecol 2006; 195:787.
- Johnstone FD, Beard RJ, Boyd IE, McCarthy TG. Cervical diameter after suction termination of pregnancy. Br Med J 1976; 1:68.
- Shah PS, Zao J, Knowledge Synthesis Group of Determinants of preterm/LBW births. Induced termination of pregnancy and low birthweight and preterm birth: a systematic review and meta-analyses. BJOG 2009; 116:1425.
- Iwahashi M, Muragaki Y, Ooshima A, Umesaki N. Decreased type I collagen expression in human uterine cervix during pregnancy. J Clin Endocrinol Metab 2003; 88:2231.
- Warren JE, Silver RM, Dalton J, et al. Collagen 1Alpha1 and transforming growth factor-beta polymorphisms in women with cervical insufficiency. Obstet Gynecol 2007; 110:619.
- Leduc L, Wasserstrum N. Successful treatment with the Smith-Hodge pessary of cervical incompetence due to defective connective tissue in Ehlers-Danlos syndrome. Am J Perinatol 1992; 9:25.
- Rackow BW, Arici A. Reproductive performance of women with müllerian anomalies. Curr Opin Obstet Gynecol 2007; 19:229.
- Chan YY, Jayaprakasan K, Tan A, et al. Reproductive outcomes in women with congenital uterine anomalies: a systematic review. Ultrasound Obstet Gynecol 2011; 38:371.
- Kaufman RH, Adam E, Hatch EE, et al. Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring. Obstet Gynecol 2000; 96:483.
- Oláh KS, Gee H. The prevention of preterm delivery--can we afford to continue to ignore the cervix? Br J Obstet Gynaecol 1992; 99:278.
- Guzman ER, Mellon C, Vintzileos AM, et al. Longitudinal assessment of endocervical canal length between 15 and 24 weeks' gestation in women at risk for pregnancy loss or preterm birth. Obstet Gynecol 1998; 92:31.
- Owen J, Yost N, Berghella V, et al. Mid-trimester endovaginal sonography in women at high risk for spontaneous preterm birth. JAMA 2001; 286:1340.
- Macdonald R, Smith P, Vyas S. Cervical incompetence: the use of transvaginal sonography to provide an objective diagnosis. Ultrasound Obstet Gynecol 2001; 18:211.
- Andrews WW, Copper R, Hauth JC, et al. Second-trimester cervical ultrasound: associations with increased risk for recurrent early spontaneous delivery. Obstet Gynecol 2000; 95:222.
- Goldenberg RL, Iams JD, Mercer BM, et al. The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network. Am J Public Health 1998; 88:233.
- Iams JD, Goldenberg RL, Mercer BM, et al. The preterm prediction study: can low-risk women destined for spontaneous preterm birth be identified? Am J Obstet Gynecol 2001; 184:652.
- Mercer BM, Goldenberg RL, Meis PJ, et al. The Preterm Prediction Study: prediction of preterm premature rupture of membranes through clinical findings and ancillary testing. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 2000; 183:738.
- Goldenberg RL, Iams JD, Das A, et al. The Preterm Prediction Study: sequential cervical length and fetal fibronectin testing for the prediction of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 2000; 182:636.
- Iams JD, Goldenberg RL, Mercer BM, et al. The Preterm Prediction Study: recurrence risk of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 1998; 178:1035.
- Romero, R, Lockwood, CJ. Pathogenesis of spontaneous preterm labor. In: Creasy & Resnik's Maternal Fetal Medicine, Creasy, RK, Resnik, R, Iams, JD, Lockwood, CJ, Moore, TR (Eds), Saunders, 2009.
- American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No.142: Cerclage for the management of cervical insufficiency. Obstet Gynecol 2014; 123:372.
- Final report of the Medical Research Council/Royal College of Obstetricians and Gynaecologists multicentre randomised trial of cervical cerclage. MRC/RCOG Working Party on Cervical Cerclage. Br J Obstet Gynaecol 1993; 100:516.
- BUCKINGHAM JC, BUETHE RA Jr, DANFORTH DN. COLLAGEN-MUSCLE RATIO IN CLINICALLY NORMAL AND CLINICALLY INCOMPETENT CERVICES. Am J Obstet Gynecol 1965; 91:232.
- Leppert PC, Yu SY, Keller S, et al. Decreased elastic fibers and desmosine content in incompetent cervix. Am J Obstet Gynecol 1987; 157:1134.
- Rechberger T, Uldbjerg N, Oxlund H. Connective tissue changes in the cervix during normal pregnancy and pregnancy complicated by cervical incompetence. Obstet Gynecol 1988; 71:563.
- da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol 2003; 188:419.
- Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med 2003; 348:2379.
- Daya S. Efficacy of progesterone support for pregnancy in women with recurrent miscarriage. A meta-analysis of controlled trials. Br J Obstet Gynaecol 1989; 96:275.
- Society for Maternal-Fetal Medicine Publications Committee, with assistance of Vincenzo Berghella. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. Am J Obstet Gynecol 2012; 206:376.
- Berghella V, Rafael TJ, Szychowski JM, et al. Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth: a meta-analysis. Obstet Gynecol 2011; 117:663.
- Berghella V, Mackeen AD. Cervical length screening with ultrasound-indicated cerclage compared with history-indicated cerclage for prevention of preterm birth: a meta-analysis. Obstet Gynecol 2011; 118:148.
- Owen J, Hankins G, Iams JD, et al. Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length. Am J Obstet Gynecol 2009; 201:375.e1.
- Berghella V, Talucci M, Desai A. Does transvaginal sonographic measurement of cervical length before 14 weeks predict preterm delivery in high-risk pregnancies? Ultrasound Obstet Gynecol 2003; 21:140.
- Iams JD, Cebrik D, Lynch C, et al. The rate of cervical change and the phenotype of spontaneous preterm birth. Am J Obstet Gynecol 2011; 205:130.e1.
- Rafael TJ, Mackeen AD, Berghella V. The effect of 17α-hydroxyprogesterone caproate on preterm birth in women with an ultrasound-indicated cerclage. Am J Perinatol 2011; 28:389.
- Rebarber A, Cleary-Goldman J, Istwan NB, et al. The use of 17 alpha-hydroxyprogesterone caproate (17p) in women with cervical cerclage. Am J Perinatol 2008; 25:271.
- Berghella V, Figueroa D, Szychowski JM, et al. 17-alpha-hydroxyprogesterone caproate for the prevention of preterm birth in women with prior preterm birth and a short cervical length. Am J Obstet Gynecol 2010; 202:351.e1.
- Conde-Agudelo A, Romero R, Nicolaides K, et al. Vaginal progesterone vs. cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis. Am J Obstet Gynecol 2013; 208:42.e1.
- Ehsanipoor RM, Seligman NS, Saccone G, et al. Physical Examination-Indicated Cerclage: A Systematic Review and Meta-analysis. Obstet Gynecol 2015; 126:125.
- Kusanovic JP, Espinoza J, Romero R, et al. Clinical significance of the presence of amniotic fluid 'sludge' in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol 2007; 30:706.
- Espinoza J, Gonçalves LF, Romero R, et al. The prevalence and clinical significance of amniotic fluid 'sludge' in patients with preterm labor and intact membranes. Ultrasound Obstet Gynecol 2005; 25:346.
- Bujold E, Pasquier JC, Simoneau J, et al. Intra-amniotic sludge, short cervix, and risk of preterm delivery. J Obstet Gynaecol Can 2006; 28:198.
- Gorski LA, Huang WH, Iriye BK, Hancock J. Clinical implication of intra-amniotic sludge on ultrasound in patients with cervical cerclage. Ultrasound Obstet Gynecol 2010; 36:482.
- Vousden N, Hezelgrave N, Carter J, et al. Prior ultrasound-indicated cerclage: how should we manage the next pregnancy? Eur J Obstet Gynecol Reprod Biol 2015; 188:129.
- Suhag A, Reina J, Sanapo L, et al. Prior Ultrasound-Indicated Cerclage: Comparison of Cervical Length Screening or History-Indicated Cerclage in the Next Pregnancy. Obstet Gynecol 2015; 126:962.
- Arabin B, Halbesma JR, Vork F, et al. Is treatment with vaginal pessaries an option in patients with a sonographically detected short cervix? J Perinat Med 2003; 31:122.
- Antczak-Judycka A, Sawicki W, Spiewankiewicz B, et al. [Comparison of cerclage and cerclage pessary in the treatment of pregnant women with incompetent cervix and threatened preterm delivery]. Ginekol Pol 2003; 74:1029.
- Acharya G, Eschler B, Grønberg M, et al. Noninvasive cerclage for the management of cervical incompetence: a prospective study. Arch Gynecol Obstet 2006; 273:283.
- Alfirevic Z, Owen J, Carreras Moratonas E, et al. Vaginal progesterone, cerclage or cervical pessary for preventing preterm birth in asymptomatic singleton pregnant women with a history of preterm birth and a sonographic short cervix. Ultrasound Obstet Gynecol 2013; 41:146.
- Goya M, Pratcorona L, Merced C, et al. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet 2012; 379:1800.
- Abdel-Aleem H, Shaaban OM, Abdel-Aleem MA. Cervical pessary for preventing preterm birth. Cochrane Database Syst Rev 2013; 5:CD007873.
- Hui SY, Chor CM, Lau TK, et al. Cerclage pessary for preventing preterm birth in women with a singleton pregnancy and a short cervix at 20 to 24 weeks: a randomized controlled trial. Am J Perinatol 2013; 30:283.
- Arabin B, Alfirevic Z. Cervical pessaries for prevention of spontaneous preterm birth: past, present and future. Ultrasound Obstet Gynecol 2013; 42:390.
- Berghella V, Rust OA, Althuisius SM. Short cervix on ultrasound: does indomethacin prevent preterm birth? Am J Obstet Gynecol 2006; 195:809.
- Tan PC, Yow CM, Omar SZ. Effect of coital activity on onset of labor in women scheduled for labor induction: a randomized controlled trial. Obstet Gynecol 2007; 110:820.
- Yost NP, Owen J, Berghella V, et al. Effect of coitus on recurrent preterm birth. Obstet Gynecol 2006; 107:793.