1. What every clinician should know
Clinical features and incidence
Cervical insufficiency (CI) refers to a condition in which the uterine cervix is weak, and because of this characteristic a woman can experience a pregnancy loss in the second or early third trimester. It was formerly called cervical incompetence, a term which should no longer be used.
The American Congress of Obstetricians and Gynecologists (ACOG) defines CI as painless cervical dilatation leading to recurrent second trimester losses (STLs). This definition implied that CI cannot be diagnosed until at least 2 births fewer than 28 weeks. Unfortunately, prior to pregnancy, there are no good tests to assess the strength, competence or ability of the cervix to retain the conceptus in uterus until term.
A better definition should be a short cervical length (CL) less than 25 mm measured by transvaginal ultrasound (TVU) before 24 weeks in women with singletons gestations and with a prior preterm birth (PTB) before 37 weeks, or other significant cervical risk factors for CI such as significant cervical surgery (see below). This definition, based on both a prior early birth and a short CL, also allows the use of evidence based interventions, i.e. cerclage and progesterone.
CI refers in general to pregnancies carrying singleton gestations. There are no known diagnostic criteria for CI in multiple gestations or effective interventions for prevention of CI or PTB in multiple gestations.
At times, patients with CI may present before 28 weeks with vaginal discharge, spotting, mild abdominal cramping and other subtle symptoms. Others may have preterm premature rupture of the membranes (PPROM). It is imperative that the records and all details of prior pregnancies and gynecologic history are obtained. The key elements of the patient’s history are listed in Table I.
CI is due to an intrinsic weakness of the cervix. Rarely, this is congenital. Most commonly, it is due to significant prior cervical surgery, which has damaged the features that give strength and consistency to the cervix.
Cervical surgery is often the original cause for later CI. Dilatation and curettage (D&C) procedures, dilatation and evacuation (D&E) procedures, loop electrosurgical excision procedure (LEEP), cone biopsy, hysteroscopies or other procedures involving dilatation, surgery or other possible trauma to the cervix are all risk factors for CI.
DES exposure is not common anymore. Uterine anomalies probably have different pathways to PTB than CI. Other risk factors for PTB such as smoking, low maternal weight, drug abuse, infections, etc, have probably also different pathways to CI. (See Figure 1.)
Once a patient with prior PTB and/or STls, and/or short TVU CL, is identified, all risk factors for PTB should be reviewed.
If painless contractions are identified by tocomonitoring in a woman with prior PTB and short CL before 24 weeks, this does not rule out the possibility of CI since, as noted above, CI, by ACOG definition, is ‘painless’.
Nonetheless, presentation of CI is often not linked to prognosis and outcome. That is why more objective criteria to guide management are: (1) gestational age (GA) of prior PTBs or STLs; (2) number of prior PTBs or STLs; (3) any surgeries involving possible trauma to cervix; and (4) TVU CL at 16-23 weeks.
All issues listed in Table I should be reviewed in detail. Typically, a patient with CI reported presenting with minimal symptoms (e.g., vaginal discharge) or no symptoms at all and being found 2 cm or more by physical exam. With increased use of screening TVU CL, this scenario is less and less frequent. Some reports have linked significant trauma during delivery (e.g., cervical lacerations) to subsequent development of CI.
2. Diagnosis and differential diagnosis
Physical exam is not very helpful for the diagnosis of CI. Often visual appearance of the cervix does not correlate to its function.
TVU CL is the best imaging study to diagnose CI. It is best performed between 16 (earliest 14) and 24 weeks and should be performed about every 2 weeks, as long as CL remains greater than or equal to 30 mm. In cases of CL 25-29 mm, TVU CL should be repeated weekly. If CL less than 25 mm is identified before 24 weeks, the diagnosis of CI should be considered, especially in women with prior PTB.
In some patients with symptoms of PTL, if the TVU CL is borderline (20-29 mm), fetal fibronectin (FFN) can help distinguish between those at high risk and those at lower risk for PTB.
No additional laboratory studies are helpful. In the future, genetic testing and testing cervico-vaginal fluid for other inflammatory markers, infectious agents or genetic mutations, may be helpful in the management of patients with possible CI.
There is no need for MRI or other radiologic tests aside from TVU CL for the diagnosis of CI. Cervical biopsies for the diagnosis of CI are used only in research, not for clinical management.
Unfortunately, tests for CI done outside of pregnancy are not sufficiently reliable and predictive of PTB and therefore should not be used clinically.
Only two therapies have been shown to be helpful in patients with CI.
There are different circumstances in which these therapies, cerclage and progesterone, have been shown to be effective in preventing CI.
Asymptomatic women with 3 PTBs or more and/or STLs : these women benefit from a history-indicated cerclage. It should be placed at 12-14weeks. For cerclage in general, the McDonald cerclage has been the type most commonly proven in randomized trials to be effective. All women with one or more PTBs 16-36 weeks should receive 17-alpha hydroxyprogesterone caproate 250mg weekly beginning between 16-20 weeks and continuing until 36 weeks (See Figure 3).
Asymptomatic women with 1-2 PTBs/STLs : All women with 1 or more prior spontaneous PTBs 16-36 weeks should receive 17-alpha hydroxyprogesterone caproate 250mg weekly from 16 to 36 weeks. These women should be followed with TVU CL starting at 14-16 weeks, at least every 2 weeks, until 23 weeks. If CL is found to be less than 25mm, the diagnosis of CI is made and ultrasound-indicated cerclage is recommended. This should be performed within 24-48 hours of the diagnosis of CL less than 25 mm, as feasible (See Figure 2).
Asymptomatic women without prior PTBs/STLs : these women cannot have CI, by definition. Cerclage has not been shown to prevent PTB in these women, even in women with a short TVU CL.
Asymptomatic women with dilated cervix of 1cm or more on manual physical exam before 24 weeks : These women, especially those with prior PTBs/STLs, have CI. A physical exam-indicated cerclage can be recommended and performed within 24-48 hours. An amniocentesis to rule out infection should be performed before cerclage.
Other therapies such as bed rest, antibiotics, tocolytics and others have not been shown to be effective in prevention of CI, and in fact have at times be shown to be harmful. They should therefore be avoided.
Rarely, women with history-indicated cerclage placed at 12-14 weeks for multiple prior PTBs/STLs deliver spontaneous before 33 weeks. These are the women in which CI may be most severe. In these cases, a transabdominal cerclage can be offered, as it has been associated with an 80% chance of delivering after 35 weeks, compared to an approximate 40% chance of the same outcome occurring with a repeat transvaginal cerclage.
5. Prognosis and outcome
Prognosis depends on history (see Table I) and TVU CL. The more PTBs/STLs, the higher the risk of another PTB. The earlier the prior PTB/STL, the higher the risk of another PTB. The shorter the CL, the higher the risk of PTB. The earlier GA a short CL is detected, the higher the risk of PTB.
The goal of effective therapies is to reduce the risk of PTB.
Progesterone works mostly by decreasing inflammation.
Cerclage probably has two mechanisms: the first is mechanical, to keep the cervix closed and prevent descent of the conceptus; the second is to maintain the mucus plug in place and keep the cervix closed to prevent ascending infection.
Women with 3 or more PTBs and/or STLs : history-indicated cerclage placed at 12-14 weeks is associated with a 30-50% reduction in recurrent PTB compared to no cerclage, with rates of PTB of about 20%. 17-alpha hydroxyprogesterone caproate 250 mg weekly from 16-36 weeks reduces recurrent PTB by about a third, compared to no such therapy.
Women with 1-2 PTBs/STLs : 17-alpha hydroxyprogesterone caproate 250 mg weekly from 16-36 weeks reduces recurrent PTB by about a third, compared to no such therapy. If CL is found to be less than 25 mm before 24 weeks, then ultrasound-indicated cerclage is associated with a 30% decrease in PTB less than 35 weeks and a 36% decrease in cumulative perinatal morbidity and mortality.
6. What is the evidence for specific management and treatment recommendations
Berghella, V. (This is an evidence based medicine book focused on the impact, epidemiology, genetics and prevention of preterm birth.)
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Meis, PJ, Klebanoff, M, Thom, E. “Prevention of recurrent preterm delivery by 17 alphahydroxyprogesterone caproate”. N Engl J Med. vol. 348. 2003. pp. 2379-86. (Randomized controlled trial comparing the use of 17P versus placebo in women with a history of prior preterm birth. The evidence showed that intramuscular administration of 17P can decrease the risk of recurrent preterm birth when started between 16-20 weeks and continued weekly until 36 weeks.)
“Use of progesterone to reduce preterm birth. ACOG Committee Opinion No.419”. Obstet Gynecol. vol. 112. 2008. pp. 963-5. (An ACOG committee opinion regarding the Meis trial above.)
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Rush, RW, Isaacs, S, McPherson, K, Jones, L, Chalmers, I. “A randomized controlled trial of cervical cerclage in women at high risk of preterm delivery”. BJOG. vol. 91. 1984. pp. 724-30.
Lazar, P, Gueguen, S, Dreyfus, J, Renaud, R, Pontonnier, G. “Multicentre controlled trial of cervical cerclage in women at moderate risk of preterm delivery”. BJOG. vol. 91. 1984. pp. 731-5.
“Final report of the Medical Research Council/Royal College of Obstetricians and Gynaecologists multicentre randomized trial of cervical cerclage”. Br J Obstet Gynecol. vol. 100. 1993. pp. 516-23. (A randomized controlled trial that found that history indicated cerclage decreased the risk of subsequent preterm birth and morbidity only when placed after 3 prior second trimester losses or preterm births.)
Davis, G, Berghella, V, Talucci, M, Wapner, RJ. “Patients with a Prior Failed Transvaginal Cerclage: A Comparison of Obstetric Outcomes with Either Transabdominal or Transvaginal Cerclage”. Am J Obstet Gynecol. vol. 183. 2000. pp. 836-9.
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. vol. 118. 2011 Jul. pp. 148-55.
Althuisius, SM, Dekker, GA, van Geijn, HP, bekedam, DJ, Hummel, P. “Cervical incompetence prevention randomized cerclage trial (CIPRACT): study design and preliminary results”. Am J Obstet Gynecol. vol. 183. 2000. pp. 823-9.
Berghella, V, Rafael, TJ, Szychowski, JM, Rust, OA, Owen, J. “Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth: a meta-analysis”. Obstet Gynecol. vol. 117. 2011. pp. 663-71.
Berghella, V, Obido, AO, To, MS, Rust, OA, Althiusius, SM. “Cerclage for short cervix on ultrasound: Meta-analysis of trials using individual patient-level data”. Obstet Gynecol. vol. 106. 2005. pp. 181-9.
Fonseca, EB, Celik, E, Parra, M, Singh, M, Nicolaides, KH. “Progesterone and the risk of preterm birth among women with a short cervix”. N Eng J Med. vol. 357. 2007. pp. 462-469.
Hassan, SS, Romero, R, Vidyadhari, D, Fusey, S, Baxter, J. “For the PREGNANT Trial”. Ultrasound Obstet Gynecol. 2011 Apr 6. (This study focused on cervical length screening in a low risk population and subsequent treatment with vaginal progesterone for women found to have a short CL.)
Iams, JD, Goldenberg, RL, Meis, PJ, Mercer, BM, Moawad, A. “The length of the cervix and the risk of spontaneous premature delivery”. NEJM. vol. 334. 1996. pp. 567-72.
Berghella, V, Keeler, SM, To, MS. “Effectiveness of cerclage according to severity of cervical length shortening: a meta-analysis”. Ultrasound Obstet Gynecol. vol. 35. 2010. pp. 468-73.
Althuisius, SM, Dekker, GA, Hummel, P, van Geijn, HP. “Cervical incompetence prevention randomized cerclage trial: Emergency cerclage with bed rest versus bed rest alone”. Am J Obstet Gynecol. vol. 189. 2003. pp. 907
Pereira, L, Cotter, A, Gomez, R. “Expectant management compared with physical-examination indicated cerclage (EM-PEC) in selected women with a dilated cervix at 14-25 weeks: results from the EM-PEC international cohort study”. Am J Obstet Gynecol. vol. 197. 2007. pp. 483
Crowther, CA. “Hospitalization and bed rest for multiple pregnancies”. Cochrane 1. 2005.
Rouse, DJ, Caritis, SN, Peaceman, AM. “A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins”. N Engl J Med. vol. 357. 2007. pp. 454-61.
Berghella, SMFM. “Progesterone and preterm birth prevention: translating clinical trials data into clinical practice”. Am J Obstet Gynecol. vol. 206. 2012 May. pp. 376-86.
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