The Incompetent Cervix
Table Of Contents
Owen K. Davis, MD
SYNDROME OF SPONTANEOUS PRETERM BIRTH
TESTS FOR CERVICAL INCOMPETENCE
PATIENT SELECTION FOR CERCLAGE
ADJUNCTIVE MANAGEMENT STRATEGIES FOR THE INCOMPETENT CERVIX
The original concepts of cervical incompetence and its management evolved from clinical observations and uncontrolled therapies beginning in the middle of the 20th century. The topic, as originally conceived, seemed relatively straightforward. However, in the past 50 years, this diagnosis has become increasingly vague and confusing. Recent recognition of spontaneous preterm birth as a syndrome, comprising several key components, numerous inciting events, and complex, poorly understood, interactive pathways, has increased the biologic stature of the cervix but also provoked questions and controversy. To a large extent, these issues remain unsolved. Although the use of traditional therapies for women with suspected cervical incompetence has expanded, few evidenced-based management guidelines currently exist.
Reports of clinical observations of midtrimester pregnancy loss attributable to a primary cervical etiology appeared in the 17th, 19th, and early 20th centuries, although the term cervical incompetence was first used in Lancet in 1865. Nevertheless, the contemporary concept of cervical incompetence was not widely accepted until the middle of the 20th century after Palmer in 19481 and Lash in 19502 independently described interval repair of anatomic cervical defects associated with recurrent midtrimester loss. Soon thereafter, Shirodkar in 1955,3 McDonald in 1957,4 and later Benson in 19655 described the midtrimester cerclage procedures now widely used in obstetric practice. Other investigators reported success with alternate surgical procedures including Hefner (1961, Wurm bridging procedure),6 Barnes (1961, cone-electrocautery scarification of the external os),7 and Baden (1960, intentionally scarified, suture-closure of the external os).8 Since then, investigators have focused primarily on reporting pregnancy outcomes in cohorts managed with transvaginal (and less commonly, transabdominal cervicoisthmic) cerclage procedures. These were referenced not to appropriate control groups, but rather compared simply to the cohorts' obstetric histories or data from analogous reports. In short, the literature on cervical incompetence has been largely a chronicle of surgical methods to correct (often posttraumatic) anatomic disruption of the internal os in women who had experienced recurrent painless dilation and midtrimester birth.
|SYNDROME OF SPONTANEOUS PRETERM BIRTH|
Spontaneous preterm birth may be best characterized as a syndrome comprising several anatomic and related functional components.9 These include the uterus and its myometrial contractile function (e.g., preterm labor), decidual activation and loss of chorioamnionic integrity (e.g., preterm rupture of membranes) and, finally, diminished cervical competence, either from a primary anatomic defect or from early pathologic cervical ripening (e.g., cervical incompetence). In a particular pregnancy, a single anatomic feature may appear to predominate, even though it is more likely that most cases of spontaneous preterm birth result from the interaction of multiple stimuli and pathways that culminate in the overt clinical syndrome. Nevertheless, the relative importance of these (and possibly other as yet unidentified) components can vary not only among different women but also in successive pregnancies of an individual patient.
Because the underlying processes (i.e., infection, inflammation, etc.) and their interactions with the anatomic components remain poorly characterized, the specific series of events leading to spontaneous preterm birth cannot be accurately determined, either during pregnancy, when the syndrome is recognized and managed, or by a careful retrospective analysis of the past obstetric events. Thus, finding effective preventive management strategies has been generally unsuccessful and only empirically based.
Cervical Competence as a Biologic Continuum
As early as 1962, Danforth and Buckingham10 suggested that cervical incompetency was not an all-or-none phenomenon. Rather, it comprised degrees of incompetency and combinations of factors could cause cervical failure. This hypothesis never gained wide acceptance, despite the obvious heterogeneity observed in clinical practice. Cervical incompetence was generally viewed as dichotomous, possibly because available treatment strategies were similarly devised. These classic investigations demonstrated that the normal cervix predominantly comprises connective tissue, unlike the uterine corpus. This fibrous band is the chief mechanical barrier against the loss of the enlarging products of conception. The cervix and mucous glands also play an important immunologic role in preventing organisms from ascending into the normally sterile intrauterine environment.
Based on analyses of cervical tissue for collagen-to-muscle ratios and recognizing the contribution of past traumatic disruption of cervical continuity, these investigators proposed a classification scheme to explain the clinical syndrome of cervical incompetence.10 In the proposed classification, one group of patients had ostensibly normal cervical tissue, whose integrity as a fibrous ring had been previously damaged. Such defects were usually the result of antecedent obstetric trauma or complications of dilation and curettage. These might even be concealed by a normal-appearing external os and ectocervix. The second group possessed an abnormally low collagen-to-muscle ratio that would compromise its mechanical function and lead to premature dilation. This so-called muscular cervix was probably a congenital problem and would manifest as a poor reproductive history in women with no previous cervical injury. The third group comprised women who had no history of antecedent trauma and who also had normal collagen-to-muscle ratios, but whose obstetric histories mimicked those of groups 1 and 2, presumably from premature triggering of other factors.
In a subsequent report these investigators analyzed cervical biopsy specimens taken from postpartum women and compared them with hysterectomy specimens from nonpregnant patients.11 Pregnancy was associated with increased water content, a marked decrease in collagen and glycoprotein, and increased glycosaminoglycans. The cellular and biochemical changes suggested that cervical dilation in pregnancy is a dynamic process, and this might explain why a woman could have a pregnancy outcome consistent with cervical incompetence in one pregnancy, but then without treatment, have a subsequent term birth. Presumably, the factor(s) inciting the pathologic cervical changes might vary among pregnancies. Women with a more muscular cervix might have an unusual susceptibility or lower threshold for the effects of the factors that precipitated the clinical syndrome of preterm birth.
These earlier observations were enlarged by Leppert and colleagues,12 who reported an absence of elastic fibers in the cervixes of women with clinically well-characterized cervical incompetence on the basis of their reproductive history. Conversely, cervical biopsy specimens from women with normal pregnancies showed normal amounts and orientations of these elastic fibers. Supporting these microscopic observations was the biochemical finding of lower desmosine levels in the women with cervical incompetence, indicating lower elastin content in the specimens. Rechberger and colleagues13 also compared cervical biopsy specimens among nonpregnant controls, women in the mid trimester with clinically defined cervical incompetence, and normal postpartum gravidas. Compared with normal postpartum patients, they found increased collagen extractability and collagenolytic activity in women with cervical incompetence, suggesting a high collagen turnover characterized by higher proportions of newly synthesized collagen with lower mechanical strength. It is unknown whether these microstructural and biochemical phenomena were congenital, acquired from previous trauma, or the result of other pregnancy-associated processes. Collectively, these biochemical and ultrastructural findings support the variable, and often unpredictable, clinical course of women with a history of cervical incompetence.14
Although the traditional paradigm has depicted the cervix as either competent or incompetent, recent evidence, including clinical data15,16,17,18 and interpretative reviews,19,20,21 suggest that, as with most other biologic processes, cervical competence is rarely an all-or-none phenomenon and more likely functions along a continuum of reproductive performance. Although some women have tangible anatomic evidence of poor cervical integrity, most women with a clinical diagnosis of cervical incompetence have ostensibly normal cervical anatomy. In a proposed model of cervical competence as a continuum, a poor obstetric history results from a process of premature cervical ripening, induced by a myriad of underlying factors, including infection, inflammation, local or systemic hormonal effects, or even genetic predisposition. If and when cervical integrity is compromised, other processes may be stimulated, appearing clinically as other components of the spontaneous preterm birth syndrome (i.e., premature membrane rupture or preterm labor). A decision as to whether diminished cervical competence arises via primary endogenous mechanical deficiencies or exogenous factors might define the optimal therapy. A more cogent approach to the concept of cervical competence is to view the cervix as an interdependent participant in the multifactorial model of the spontaneous preterm birth syndrome. The pragmatic clinical question that emerges from this paradigm is whether an individual patient has a significant (and presumably treatable) component of diminished cervical competence.
The Diagnosis of Cervical Incompetence
The incidence of cervical incompetence in the general obstetric population is reported to vary between approximately 1:100 and 1:2000.22,23,24 This wide disparity is likely caused by differences among study populations, reporting bias, and the diagnostic criteria used to establish the clinical diagnosis. Most of what is known about cervical incompetence and its treatment shows that it is primarily a clinical diagnosis, characterized by recurrent painless dilation and spontaneous midtrimester birth, usually of a living fetus. Associated characteristics, such as uterine contractions, bleeding, overt infection, or premature rupture of membranes, tend to shift the cause of spontaneous preterm birth away from cervical insufficiency and support other components of the preterm birth syndrome. Nevertheless, because of the potential for interactive pathways, it is difficult to completely rule out a significant component of diminished cervical competence in any particular case.
Because cervical incompetence is a clinical diagnosis, the diagnosis is usually retrospective and made only after poor obstetric outcomes have occurred (or rarely, are in evolution). Because there are few proven objective criteria, other than a rare, gross cervical malformation, a careful history and review of the past obstetric records are crucial to making an accurate diagnosis. Unfortunately, in many instances the records are incomplete or unavailable, and many women cannot provide a reliable history. Even with excellent records and history, clinicians might reasonably disagree on the diagnosis in all but the most classic cases. Confounding factors in the history, medical records, or current physical assessment might be used to either support or refute the diagnosis, based on their perceived importance. The physician managing a patient who experiences a spontaneous midtrimester birth is in the optimal position to assess whether the typical clinical criteria for cervical incompetence were present. Possibly a more specific diagnosis of cervical incompetence can be made by witnessing incompetence in evolution, an indication for emergent cerclage that will be covered in a later section. Because cervical incompetence is a retrospective diagnosis and depends on a history of untoward outcomes, clinicians have sought criteria that might lead to a prospective and more objective diagnosis. In women considered to be at risk for cervical incompetence, based on an atypical history or because of other identified risk factors, serial examinations may be performed to detect progressive shortening and dilation, leading to a presumptive diagnosis of incompetence that may be amenable to therapeutic intervention.
Risk Factors for Cervical Incompetence
While the historic concept of the diagnosis and treatment of cervical incompetence often includes women with past cervical trauma from birth-associated lacerations, forced dilation, operative injury, or cervical amputation, the prevalence of these antecedent events appears to be decreasing in contemporary practice. Obstetric care and surgical technique have improved, clinicians recognize the importance of gradual cervical dilation before curettage, and cervical amputation is rarely performed. Cervical damage from trauma may be visible or palpable on a careful examination of the cervix before or during the early part of pregnancy and, if detected, should be managed with surgical repair if associated with a previous poor obstetric history or if the defect is believed to involve the internal cervical os.
More common in contemporary practice are patients who have undergone previous treatment of cervical dysplasia using cold-knife cone, laser cone, or loop electrosurgical excision procedures (LEEP). These cervical procedures are plausibly a risk factor for cervical incompetence. In 1995, Ferenczy and colleagues25 reported 574 women who had undergone LEEP and examined the reproductive performance of 55 women who conceived after the surgery. Their goal had been to obtain a nominal 7-mm-thick specimen and cited a maximum excisional depth of 1.5 centimeters. In this series no spontaneous preterm birth less than 37 weeks was observed. A similar report by Althuisius and colleagues26 of 52 women showed an incidence of spontaneous preterm birth of less than 10% and no midtrimester losses that might suggest a clinical diagnosis of cervical incompetence.
Published data on cone biopsy are similarly reassuring. Weber and colleagues27 reported an incidence of preterm birth of only 7% in 577 pregnancies of women with a previous cone biopsy. Leiman and colleagues28 concluded that the risk of preterm birth was greater only when the maximum cone height was more than 2 centimeters or the volume removed was more than 4 mL. Raio and colleagues29 performed a matched cohort study of 64 women who had undergone previous laser conization and observed no difference in the incidence of preterm birth compared with their controls (9.4% vs 4.7%) and statistically similar gestational ages at delivery and birth weights. However, in a secondary analysis, a laser cone height more than 10 mm was a significant independent risk factor for preterm birth. Other earlier reports also suggested that larger biopsies increased the risk of preterm birth. Nevertheless, the distribution of preterm births in these populations did not confirm a disproportionate incidence of midtrimester loss consistent with cervical incompetence.
Kuoppala and Saarikoski30 retrospectively reviewed 62 women who had undergone cone biopsy and an equal number of matched control patients. The pregnancy outcomes of 22 who underwent elective cerclage were similar to those managed without cerclage, with fetal salvage rates of 97% and 100%, respectively. On the basis of their findings and review of seven other published reports, they concluded that prophylactic cerclage was not routinely indicated. Of note, in the largest published randomized trial of cerclage31 (described later in more detail), women who underwent one or more cone biopsies or cervical amputations had an overall preterm birth rate of 35%. However, in this population, there was no benefit from prophylactic cerclage placement.
In summary, most women who underwent previous LEEP or cone biopsy do not appear to have a clinically significant rate of second trimester loss or preterm birth. However, women in whom a large cone specimen was removed or destroyed (including cervical amputations) or who have undergone multiple previous procedures probably have an increased risk of spontaneous preterm birth. Whether cerclage would be an effective preventative strategy in these at-risk women remains speculative. The available clinical trial data do not suggest a benefit from prophylactic cerclage, and so these women may be followed-up clinically for evidence of premature cervical changes. Women with a previous cervical surgery and spontaneous midtrimester loss, suggesting a clinical diagnosis of incompetence, should be considered for prophylactic cerclage in future pregnancies.
A similar controversy arises over the management of women with in utero diethylstilbestrol (DES) exposure: should the finding of abnormal cervical or should uterine anatomy confirm a diagnosis of cervical incompetence in the absence of a typical history? Case series have documented that these women are at increased risk for various types of poor reproductive outcome, including infertility, ectopic pregnancy, early first trimester spontaneous abortion, and preterm birth. However, these reports likely suffer from selection bias, because women who present with established histories of pregnancy complication are more likely to present for care at an academic center and experience a recurrence.
Kaufman and colleagues32 reviewed the pregnancy outcomes of 327 DES-exposed women and classified them by whether their hysterosalpingogram (HSG) findings were normal or abnormal. Women with abnormal radiographic findings had generally worse reproductive outcomes than those with normal findings. However, the poor reproductive performance spanned a wide clinical scope, and there appeared to be no predilection for obstetric histories suggesting cervical incompetence. They also examined a small subset of women who had undergone cerclage and noted outcomes similar to the cohort who had never received cerclage. They concluded that women with abnormal HSG findings were at higher risk for poor outcomes but that prophylactic cerclage was not routinely indicated. They suggested that these women could be followed-up clinically to determine if cervical changes warranted management with cerclage or other therapy.
Ludmir and colleagues33 managed 63 DES-exposed women using a standarized protocol, and they treated 42% with a prophylactic cerclage for either a clinical history of cervical incompetence or a hypoplastic cervix on examination. The remainder were followed-up with weekly cervical assessments, and 44% (N = 16) received an emergent cerclage. There were no perinatal deaths in the prophylactic or emergent cerclage group versus five of 21 in the group who never received cerclage. However, the five perinatal deaths occurred after preterm membrane rupture and were not attributed to cervical incompetence per se. These authors defended their liberal use of cerclage based on this uncontrolled study and other reports of adverse pregnancy outcome in DES-exposed women, even though the contribution of cervical incompetence and the role of cerclage in these women have never been determined in a well-designed clinical trial.
Levine and Berkowitz34 reported a 10-year retrospective cohort study of 50 DES-exposed women, 34 of whom had gross anatomic changes, and reviewed their outcomes from 120 pregnancies. Only one patient received a prophylactic cerclage for a clinical history of cervical incompetence, while one additional patient underwent an emergent cerclage indicated because of acute cervical changes. Although women with obvious anatomic changes were more likely to experience a first trimester loss, in continuing pregnancies there was only a mean 2-week difference in delivery gestational age (39.8 ± 1.5 ± vs 37.3 ± 3.8 weeks), which favored the normal anatomy group. The second trimester loss rate in women with anatomic changes was 6.8% versus 0% in the normal anatomy group. It appeared from their data and other reports35 that the absolute risk of cervical incompetence is small and that these women can be followed-up clinically without the need for prophylactic cerclage in the absence of a typical history.
Because many women exposed to DES in utero were the products themselves of complicated gestations and were presumably born to women with poor reproductive histories, it is plausible that at least portion of the presumed DES effect may simply be of genetic origin.35 Since the use of DES was effectively curtailed in the early 1970s, this congenital risk factor should comprise a steadily diminishing group of patients and will soon be of no clinical concern.
Other factors for cervical incompetence include previous induced or spontaneous first trimester abortions, uterine anomalies, multiple gestation, or the occurrence of previous spontaneous preterm births that did not meet typical clinical criteria.31 Possibly, these characteristics were observed in women with the more classic presentation, and clinicians considered a possible cause–effect association. That women with certain obstetric histories or physical findings (e.g., DES changes) are at increased risk for spontaneous preterm birth is not disputable. Whether they have an appreciable (and also treatable) component of cervical incompetence is, at best, presumptive.
To date, there have been four randomized clinical trials that included women with various risk factors for spontaneous preterm birth whose managing physicians did not believe they required a prophylactic cerclage for a typical history. In 1984 Lazar and colleagues36 randomized 506 women at moderate risk, based on their scoring system comprising historic and physical examination components. Women deemed to be at high risk, based on their scores, were offered a cerclage for cervical incompetence and were not enrolled. In an intent-to-treat analysis, women assigned to cerclage had a slightly higher, although statistically nonsignificant, rate of spontaneous preterm birth (6.7% vs 5.5%). Women assigned to cerclage were hospitalized more frequently and received more tocolytic agents. Because the overall preterm birth rate in the population was only 6% (less than that observed in the general population), this may have not been a valid study population.
In 1982 Dor and colleagues37 randomized 50 women with a twin gestation to cerclage or a control group, and they observed no difference in pregnancy outcome. Because of this relatively small sample size, beta error was a concern. In 1984, Rush and colleagues38 enrolled 194 women at high-risk for spontaneous preterm birth because of at least two previous spontaneous preterm births, one of which had to have occurred between 14 and 36 weeks' gestation. After random assignment to a cerclage or control group, they observed no benefit from cerclage; preterm birth occurred in 34% of the cerclage group versus 32% of controls. As in the trial by Lazar and associates,36 women in the cerclage group were hospitalized for significantly longer periods and also experienced higher rates of premature membrane rupture and postpartum fever, although these latter two differences were not statistically significant.
The largest randomized trial of cerclage was conducted by the Royal College of Obstetrics and Gynecology between 1981 and 1988.31 A total of 1292 women were enrolled in 12 countries because of uncertainty on the part of their managing physicians as to whether a prophylactic cerclage was indicated. As anticipated, these patients comprised a heterogenous group with at least six distinct risk-factor subgroups identified on the basis of their dominant history or physical examination findings. Although women assigned to cerclage had a statistically significant lower rate of preterm birth less at than 33 weeks (13% vs 17%; p = .03), the investigators estimated that approximately 25 cerclage procedures would be required to prevent one such birth. Moreover, women assigned to cerclage received more tocolytic medications and spent more time in the hospital. Puerperal fever was significantly more common in the cerclage group. Of interest is finding in a secondary analysis that only the subgroup of women with at least three previous spontaneous preterm births (including midtrimester losses) appeared to benefit from cerclage (15% vs, 32%; p = .02).
Both an analysis of the clinical history and consideration of various coexistent risk factors for cervical incompetence require considerable judgment on the part of the managing physician, because highly specific and practical objective tests to confirm the diagnosis have not been developed. Unfortunately, clinical assessments are often subject to highly individualized interpretation and, not surprisingly, different clinicians might reasonably disagree over the diagnosis and management in all but the most classic presentations of cervical incompetence.
|TESTS FOR CERVICAL INCOMPETENCE|
Because the diagnosis of cervical incompetence has been determined primarily from past reproductive performance and physical examination findings, the obvious limitations associated with the clinical diagnosis have prompted the search for sensitive and specific tests that could be applied in a prospective manner to women deemed at risk for cervical incompetence, thus obviating the need for recurrent pregnancy loss. Such a test might provide a timely diagnosis and the potential for optimal therapeutic intervention.
Most of the earlier reported tests for cervical incompetence were based on the functional anatomy of the interval os in the nonpregnant state and are of historical interest. In 1953, Rubowitz and colleagues39 used an intrauterine balloon filled with contrast media and imaged with a radiograph to discriminate the normal from the incompetent lower uterine segment and internal os. Mann in 195940 reported a new method for the diagnosis of cervical incompetence that used an intrauterine balloon with a contrast agent and subjected to filling pressures of 200 to 260 mmHg. This, he believed, overcame the limitations of earlier diagnostic studies that used plain hysterosalpingography by measuring the internal os dimensions under pressure. Because this evaluation yielded an internal os measurement, a continuous variable, he chose what appeared to be an arbitrary cutoff point to define incompetence.
In 1973 Peterson and Keifer41 proposed another improvement after concluding that Mann's technique described would artificially cause cervical and uterine dilation using pressures fraught with danger. Their apparatus was similar to Mann's, but the intrauterine balloon had a second port open to the atmosphere and limited the intrauterine pressure. Studying 55 women with suggestive histories, these investigators excluded the diagnosis of incompetence in 16 women when the maximum diameter of the cervical canal was less than 10 mm. They followed-up these women in successive pregnancies and observed 22 neonatal survivors, whereas their previous neonatal loss rate had been 52%; by inference, the etiology of these previous losses was not cervical incompetence. In the women with cervical canal diameters of 10 mm or more, prophylactic cerclage, either before or after conception, was performed, and these 26 women had 31 successful pregnancies. Because the subsequent loss rates could not be determined (the denominators were not reported), it was difficult to understand the magnitude of the benefit attributable to the test results or the prophylactic cerclage.
Other attempts at objective assessments included passage of a number-8 Hegar dilator into the nonpregnant cervical canal without resistance42 and traction forces required to dislodge a Foley catheter, whose balloon was placed above the internal os and filled with 2 to 3 mm of water.43 Subjectively effortless passage of the dilator or removal of the Foley balloon with less than 600 g of force would confirm an objective diagnosis.
More recently in 1988, Kiwi and colleagues44 estimated the elastic properties of the nonpregnant cervix in two cohorts of women: 247 women with a poor obstetric history (defined as three or more first-trimester abortions, one or more second-trimester losses, one or more previous preterm births, or some combination thereof) and 42 controls who may have had no more than two first-trimester abortions and no previous preterm births. Cervical elastance was derived from the pressure-volume slope of a 4-mm balloon placed in the endocervical canal and inflated to pressures as high as 150 mmHg. Although women in the poor obstetric history group had significantly lower elastance values than the controls, there was significant overlap between the two groups. They reported no subsequent pregnancy outcomes, proposed no clinically useful cutoff for their evaluation, and could only suggest that such objective evaluation might ultimately prove to be clinically useful to accurately select patients for cerclage.
In 1993, Zlatnick and Burmeister45 reported their experience with a cervical compliance score derived from the results of three other tests: hysterosalpingography, passage of a number-8 Hegar dilator, and intrauterine balloon traction performed in 138 nonpregnant women. Their histories included previous delivery at less than 34 weeks after clinically diagnosed preterm labor or preterm membrane rupture, with or without antecedent bleeding. A small portion of their cohort had a questionable history of cervical incompetence. Scores could range from 0 to 5, and women with low scores of 2 or less were more likely to have been delivered at 27 to 34 weeks as compared with women with higher scores who were more likely to have been delivered in the mid trimester at 14 to 26 weeks (p < .01). In subsequent pregnancies, cerclage was recommended in all women with a high score of 2 or more, and most underwent surgery. Surprisingly, more women with high scores delivered at 14 to 29 weeks' gestation (p = .07), casting doubt on its clinical usefulness.
All such attempts at providing an objective diagnosis of cervical incompetence failed for a number of reasons, and none of these tests is in common use today. These reports generally suffered from a failure to evaluate standard test characteristics (i.e., sensitivity, specificity) against some reference standard for the diagnosis or another clinically relevant endpoint. They often used subjective criteria, caused patient discomfort, required ionizing radiation, were cumbersome, and were generally only applicable in the nonpregnant state; most women at risk for cervical incompetence present for care after a subsequent conception. Moreover, none of these tests could reasonably predict pregnancy-associated conditions that would lead to premature ripening and cervical dilation. Finally, because there is no universally applicable standard for the diagnosis of incompetence, and because the results of such tests were never evaluated and linked to a proved effective treatment, their clinical usefulness was, at best, theoretical.
Others evaluated the usefulness of scoring systems to aid in patient selection for cerclage procedures, intending to increase the specificity of the clinical diagnosis. In 1976, Block and Rahal46 reported 31 pregnancies in 25 women who received prophylactic cerclage for a diagnosis of cervical incompetence. The score increased based on a greater number of clinical or historical indications for cerclage and, by inference, a more specific diagnosis of cervical incompetence. Women with high scores had a longer cerclage-to-delivery interval as compared with women with lower scores. Women with higher scores also had higher overall pregnancy success rates with cerclage than did the cohort of women who had fewer indications and lower scores. In 1991, Ger and colleagues47 performed an analogous study of 47 women who received a McDonald cerclage based on their obstetric histories and physical examinations, but not necessarily for a clinical history of cervical incompetence. Based on their obstetric histories and examination findings, scores could range from 1 to 5. Similar to Block and Rahal,46 they observed longer cerclage-to-delivery intervals in women with high scores of more than 3 as compared with women with lower scores. While these observations support the multifactorial model of spontaneous preterm birth described, these investigators could provide no practical recommendations.
To be clinically useful, a scoring system or other test for cervical incompetence should be able to accurately discriminate between women who have a condition amenable to a proven effective form of therapy and women with other causes of poor obstetric outcome. Even in the absence of effective therapies, such an assessment would be useful to target at-risk populations, whose optimal treatments could be determined from randomized intervention trials.
Sonographic Evaluation and the Diagnosis of Cervical Incompetence
Over the past two decades, numerous investigators have asserted that cervical incompetence can be diagnosed by midtrimester sonographic evaluation of the cervix. Various sonographic findings including cervical length, funneling at the internal os, and dynamic response to provocative maneuvers (e.g., fundal pressure) have been used to select women for treatment, generally cerclage. In most of these earlier reports, the sonographic evaluations were not blinded, leading to uncontrolled interventions and difficulty determining their value. In many instances the sonographic criteria for cervical incompetence were only qualitatively described and thus, may not be reproducible. Table 1 depicts published reports linking the findings from cervical sonography to a diagnosis of incompetence. Note that the diagnostic criteria are disparate and, in many cases, not described in a quantitative fashion.
GA, gestational age; N/S, not stated; MT, midtrimester; CL, cervical length; CI, cervical incompetence.
More recently, large blinded observational studies using reproducible methods have been published.16,48,49,50,51,52 These investigators studied the relationship between midtrimester cervical sonographic findings and the risk of preterm birth. Iams and his colleagues in the NICHD Maternal-Fetal Medicine Units Network16 completed a study of 2915 unselected women with a singleton pregnancy who underwent a blinded cervical sonographic evaluation at 24 weeks' gestation. The relative risk of spontaneous preterm birth increased inversely proportionally to cervical length. Despite this highly significant relationship, as a test for predicting spontaneous preterm birth at less than 35 weeks, a cervical length cutoff less than 26 mm (the population's 10th percentile), had low sensitivity (37%), and the positive predictive value was poor (18%). These findings were confirmed by Taipale and colleagues49in an unselected, but generally low-risk, Finnish population. Iams and Taipale16,49 and colleagues concluded that cervical sonography was not a viable screening test for spontaneous preterm birth in a low-risk population.
In a more recent study, Owen and colleagues52 examined the usefulness of cervical ultrasound as a predictor of spontaneous preterm birth at less than 35 weeks in women at high risk. Participants included gravidas with a previous spontaneous preterm birth at less than 32 weeks. Women believed to have cervical incompetence (based on a clinical history) were not eligible. Beginning at 16 to 18 weeks of gestation, 163 gravidas underwent serial biweekly sonographic evaluations until week 23 of gestation. Fundal pressure was also used as a provocative measure to determine if dynamic cervical shortening could be induced. This study design permitted analysis of the shortest observed cervical length over time, which also included any fundal pressure-induced (or spontaneously occurring) cervical length shortening. As in the previous studies by Iams16 and Taipale,49 there was a highly significant inverse relationship between cervical length and spontaneous preterm birth. However, in this high-risk population, the sensitivity increased to 69% and the positive predictive value to 55% at a cervical length cutoff of less than 25 mm.
These reports49,16,52 support the conclusion that cervical length, as a surrogate function for cervical competence, operates along a continuum of reproductive performance and provides prospective confirmation of an earlier published retrospective analysis.15 Nevertheless, despite the consistent relationship between shortened cervical length and spontaneous preterm birth, the actual identification of an appropriate cervical length cutoff and confirmation of the potential contribution of related cervical sonographic findings (e.g., funneling at the internal os) remains problematic. Clearly, cervical sonography performs poorly as a screening test in women at low risk women,16,48,49 but it appears to have significant clinical usefulness in women at high risk, defined as a previous early spontaneous preterm birth.50,51,52 Whether cervical ultrasound has similar predictive values in other populations of at-risk women (e.g., DES, previous cervical surgery, uterine anomalies, multiple induced abortions, etc.) remains speculative, because it has not been well studied. Some investigators have included women with these risk factors in study populations primarily comprising women with previous spontaneous preterm birth, but the results could not be subcategorized because of small sample sizes.50
Use of cervical ultrasound in twin gestations has also been reported;53,54 however, the test characteristics, especially sensitivity and positive predictive value (less than 40%), appear to be generally lower than for women with a previous early spontaneous preterm birth. Other case series have documented a low (less than 10%) incidence of significant midtrimester cervical length shortening in populations of multiple gestations.53,55,56
Cerclage for Cervical Sonographic Indications
Under the presumption that shortened cervical length (with or without funneling at the internal os) is diagnostic of cervical incompetence, several investigators have estimated the effect of cerclage on reproductive performance. Both retrospective uncontrolled case series, using reproducible methodologies and action points, and randomized trials have been published, and these are summarized in Table 2.
GA, gestational age; CL, cervical length; CI, cervical incompetence
Using a cervical length cutoff of 15 mm or less at 23 weeks' gestation, Heath and colleagues57 reviewed cohorts of otherwise unselected women who did (N = 22) versus who did not (N = 21) receive a Shirodkar cerclage by their managing physician. They observed a significant benefit from cerclage in the rates of spontaneous preterm birth at less than 32 weeks (5% vs 50%; p = .001). Berghella and colleagues58 reviewed a series of 63 women at high-risk, 39 of whom received McDonald cerclage as an uncontrolled intervention for a cervical length less than 25 mm or more than 25% funneling at the internal os. They observed no benefit from cerclage placement (odds ratio for preterm birth = 1.1; 95% CI: .3–4.6).
Novy and colleagues59 reported a retrospective case series of 35 women who were found to have a cervical length less than 30 mm and internal os funneling when cervical ultrasound was used, either as a screening test in asymptomatic women or as an adjunct to an evaluation of patients with worrisome symptoms or suggestive physical examination findings (marked softening, less than 60% effacement, and external os dilated less than 2 centimeters). Of these 35, 20 received a cerclage. Women in the cerclage cohort were delivered at a mean 6 weeks later in gestation than the 15 who did not receive cerclage.
Hassan and colleagues60 retrospectively reviewed the records of 70 women at high risk who had been evaluated with cervical ultrasound between 14 and 24 weeks' gestation. Twenty-five received McDonald cerclage. These investigators observed a higher rate of preterm birth at less than 34 weeks in the cerclage as compared with the no-cerclage cohort (68% vs 53%). The difference was not statistically significant. However, premature rupture of membranes was observed more frequently in the cerclage cohort (65% vs 36%; p < .05). In one uncontrolled series of twin and triplet gestations,61 there was no apparent benefit from cerclage placed for shortened cervical length less than 25 mm compared with women managed without cerclage.
As of this writing, only two randomized trials of cerclage for sonographic indications have been published. Althuisius and her colleagues in the Netherlands62,63 performed a two-tiered randomized clinical trial of patients at high risk, most of whom were believed to have cervical incompetence because of their obstetric history. In the first tier, eligible patients were randomly assigned to receive either prophylactic cerclage or to begin sonographic surveillance. Thirty-five of the patients assigned to the cervical ultrasound group were found to have a shortened cervical length less than 25 mm and underwent a second randomization to either cerclage or no cerclage. Both cerclage and no cerclage groups were instructed to use modified home rest. Of the 19 assigned to cerclage, there were no preterm births at less than 34 weeks versus a 44% rate in the home rest only group (p = .002). None of the women who maintained a cervical length of at least 25 mm experienced a preterm birth. Rust and colleagues64 studied 138 women who had various risk factors for preterm birth (including 12% with multiple gestations) and were randomly assigned to receive McDonald cerclage or no cerclage after their cervical length shortened to less than 25 mm or funneling more than 25% at the internal os was recognized. Preterm birth at less than 34 weeks was observed in 35% of the cerclage group versus 36% of the no cerclage group.
Consolidation of the findings of the retrospective cohort series is difficult because of different study methodologies, patient populations, and the bias inherent in these types of reports. In the report of Novy and colleagues59 cervical ultrasound was used in the study cohort to aid in clinical patient assessment. Thus, the independent value of cervical ultrasound as an adjunctive test could not be determined. Of the two published randomized trials, the findings of Rust and colleagues64 seem most applicable to obstetric practice in the United States, and this report did not support the use of cerclage for sonographic findings. The trial by Althuisius and colleagues62,63 focused on women whom they believed had a clinical diagnosis of cervical incompetence and who would have likely been candidates for prophylactic cerclage in the United States.65 Nevertheless, their study does suggest a potential role for cervical ultrasound in women with a clinical diagnosis of cervical incompetence, if the intent is to avoid cerclage when the cervical length is maintained in the normative range, (e.g., more than 25 mm). This has also been the conclusion of other investigators.66
Fejgin and colleagues67 reported a case series of 35 women in whom cerclage had been placed in previous pregnancies for questionable indications. Collectively, these women had been managed through 58 pregnancies with cerclage. These investigators followed-up the cohort through an additional 52 pregnancies managed with clinical examinations and sonography up to 28 weeks' gestation without elective, prophylactic cerclage. Compared with the pregnancies managed with elective cerclage, fewer perinatal losses were observed in the group managed with serial examinations (0% vs 16%; p = .01). Larger, multicenter, randomized trials in women at high risk lacking a clinical history of cervical incompetence are needed to further define the potential usefulness of cervical ultrasound screening to select patients for interventions such as cerclage.
Most of what is known about the management of the incompetent cervix is based on case series that reported surgical correction of the presumed underlying mechanical defect in the cervical stroma. The contemporary mainstay of treatment has been a surgical approach using one of the classic cerclage procedures, although both medical treatments and other mechanical supportive therapies have been used. Like many aspects of clinical medicine, current therapeutic standards are often based more on expert opinion and results of studies using uncontrolled interventions than the findings of randomized clinical trials. This is particularly true for cervical incompetence in which, to date, there have been no published placebo-controlled randomized trials of cerclage in women with a typical clinical history.
Branch 198668 and Cousins 198069 collectively tabulated more than 25 case series of cerclage efficacy published between 1959 and 1981. Branch68 estimated a precerclage survival range of 10% to 32% versus a perinatal survival range of 75% to 83% in the same cohorts of women managed with Shirodkar cerclage. Similarly, case series that used McDonald cerclage reported a cohort perinatal survival range of 7% to 50% before and 63% to 89% after cerclage. Cousins69 estimated a mean survival before Shirodkar of 22% versus 82% posttherapy and 27% and 74%, respectively, for investigators who used the McDonald technique. In total, more than 2000 patients have been reported in these historic cohort comparisons. Interpretation of these series, as noted by Cousins,69 is limited by the fact that: (1) diagnostic criteria were not consistent or always reported; (2) definitions of treatment success were inconsistent (but generally recorded as perinatal survival, as opposed to a gestational age-based end point); (3) treatment approaches were not always detailed and might involve multiple combinations of surgery, medication, bedrest, and other uncontrolled therapies; and (4) cases were not subcategorized according to etiology (i.e., anatomic defects versus a presumed functional cause). Nevertheless, based on compelling but potentially biased efficacy data, the surgical management of women with clinically defined cervical incompetence has become standard practice, and it is unlikely that a well-designed intervention trial for classic cervical incompetence will ever be performed if it includes a placebo or no-treatment group.
The most commonly used surgical procedure for the treatment of the incompetent cervix in pregnancy is cerclage. However, patients with an identifiable cervical defect may undergo an interval repair using a Lash procedure.2 Typically, these rare defects are located anterior and can be repaired by dissecting the bladder off the cervix, exposing the defect and then re-approximating the cervical stroma, with or without the removal of attenuated epithelial tissue bridging the defect. This technique may also be used for similar defects in other quadrants. Although originally thought to be as effective as postconception cerclage procedures in selected patients, there remains concern about the potential for iatrogenic infertility. This procedure is rarely used today because of a decreasing incidence of obstetric and gynecologic cervical trauma.
Cerclage procedures still in common use today include those originally described by Shirodkar,3 McDonald,4 and Benson,5 although various modifications to each have gained wide acceptance. The chief advantage to cerclage is that it can be offered in the early second trimester, after most spontaneous abortions have occurred. It also permits a thorough sonographic evaluation of the fetus to rule out many severe or life-threatening anomalies. In selected cases, prenatal diagnosis using chorionic villus sampling can also be performed before surgery. Cerclage procedures are often further classified by their timing and indication. Prophylactic cerclage is performed in appropriately selected candidates before onset of overt cervical changes. In practice, most clinicians place a prophylactic cerclage between 12 and 16 weeks' gestation, although the exact timing is not critical. Conventional wisdom, however, suggests that prophylactic cerclage is more effective when placed earlier in gestation, before onset of cervical dilation. In contrast, a therapeutic, nonemergent cerclage is offered after discernible changes are detected on clinical ex-amination. The term urgent cerclage has occasionally been used to describe the indication for clinically (or sonographically) recognized asymptomatic cervical changes; however, if overt cervical canal dilation has occurred, often with membrane prolapse at or beyond the external os, the term emergent cerclage is applied and is generally considered in women who present with cervical incompetence in evolution.
Although McDonald4 and Shirodkar3 originally reported their surgical techniques in temporal proximity, most clinicians now favor the McDonald method for several reasons. Because it does not require mucosal dissection and elevation to expose the cervix at the level of the internal os, it is easier to perform and is associated with less blood loss. The circumferential suture is tied on the ectocervix and easily accessible, which facilitates later cerclage removal. Although both methods have their proponents, there are no controlled comparative data on treatment efficacy. The findings of uncontrolled cohort series suggest that success rates (usually defined as perinatal survival) are similar and neither technique has an obvious advantage.70,71
To place a prophylactic McDonald cerclage, the anesthetized patient is placed in dorsal lithotomy position. At least one assistant is required to provide exposure using right angle or medium-size Deaver retractors. While some surgeons prefer the use of a weighted speculum, we have found that individually placed retractors permit better exposure around the entire circumference, and especially for the posterior bites. After an antiseptic vaginal preparation, the anterior ectocervix is grasped with a sponge forceps or similar nontraumatic instrument, such as a Babcock clamp, used to provide counter traction. The urinary bladder is generally emptied before the procedure, although some surgeons recommend leaving some urine in the bladder to better-define the position of the bladder as it reflects onto the ectocervix.
For right-handed surgeons, the first tissue bite is taken at the 11:00 or 12:00 position on the cervix, exiting at approximately the 10:00 position. When placing the anterior stitch, the surgeon must avoid the bladder mucosa that can be identified by moving the cervix in and out and noting where the vaginal mucosa folds in as it reflects off the ectocervix. A uterine sound bent in a 180-degree curve and introduced through the urethra can also be used to identify the most inferior aspect of the bladder reflection. Intraoperative cervical ultrasound may also be used to identify the bladder reflection.
The circumferential suture continues with successive bites placed as close to the vaginal fornix as technically feasible. The posterior stitches are the most technically demanding and require coordinated exposure by the assistant and appropriately directed counter traction by the surgeon. To facilitate suture placement, the forceps used for countertraction should be replaced before each bite, just distal to and centrally located between the planned needle entry and exit sites. Jennings72 proposed a modification whereby each successive tissue bite reenters the cervix through the exit hole left by the preceding stitch. This effectively buries most of the suture beneath the mucosa and has a theoretic advantage of minimizing the exposure of the submucosal stroma to vaginal pathogens.
Because the size of the cervix and needle can vary, there is no predetermined number of tissue bites required to completely encircle the cervix, but four to six are generally necessary; however, the exact number of bites is not important. The last bite should exit in close proximity to the original entry site. Another variation of the original procedure uses two sutures placed several millimeters apart.73 This has the theoretic advantage of spreading the suture tension over a larger area and may help prevent the more cephalic stitch from becoming displaced. We use a second stitch if we believe that the first suture was not optimally placed at the bladder reflection anteriorly or as high as possible in the posterior vaginal fornix. It is necessary to record how many stitches were placed and where the knots were tied to facilitate their later removal.
Choice of suture and needle for the McDonald procedure is somewhat operator-dependent. Most surgeons now use a permanent synthetic material such as number-1 or number-2 nylon, Prolene, or Mersilene. Mersilene 5-mm tape has also been proposed, but compared with suture, it is more difficult to pull the tape through the stroma and requires more tissue traction and manipulation. Monofilament suture has the advantage of offering less tissue resistance, which should facilitate both placement and removal. However, monofilament suture is prone to slippage and may be more difficult to tie down firmly. If the desired suture is not available swaged on the proper size needle, the suture can be threaded into a Mayo needle for the procedure. Because the descending branches of the uterine artery are found at 3:00 and 9:00, this area should be avoided when placing the stitches.
After the cerclage stitch has been placed, it is important to take up any slack introduced with the multiple tissue bites, and we use a laundry bag technique whereby traction is applied to each side of the exiting suture while holding countertraction at the exit site with two fingers of the opposite hand. Once this is accomplished, the suture is tied down firmly but should not cause visible blanching of the surrounding tissue. To facilitate later identification and removal, a long tag should be left above the knot. After placement, a digital examination will confirm a closed endocervical canal that is not overly constricted. However, it should not admit a gloved finger. Cervical ultrasound has also been used to assess suture placement, however, its role as a useful adjunct has not been determined.
Shirodkar3 was the first to report a true cerclage operation, and with some modifications, this procedure is still used in contemporary obstetric practice. Although some surgeons empirically prefer this technique over the McDonald, the choice seems more dependent on training and the importance ascribed to its theoretic benefits, i.e., the ability to place mechanical support close to or at the level of the internal os; this goal is generally not attainable using the McDonald approach.
To perform a Shirodkar cerclage, the patient's positioning and preparation are performed as previously described. With good exposure by assistants, the surgeon places an atraumatic clamp on the ectocervix, first on the posterior side, which is used to displace the cervix anteriorly, exposing the posterior aspect of the cervical mucosa. The mucosa is incised in a transverse direction near the fornix, allowing the posterior vaginal mucosa to be detached and elevated to the level of the internal os. The pouch of Douglas should not be entered in this step. Although a linear incision on the posterior side was originally described, a transverse incision facilitates the lateral exposure required to place the suture correctly in the stroma without entering the endocervical canal.
Once the surgeon is satisfied with the posterior incision and dissection, the anterior aspect of the cervix is exposed by moving the grasping tenaculum or forceps to the anterior cervix. The bladder reflection is identified similar to the initial step in a vaginal hysterectomy. To aid in the identification of the incision site and improve the plane of dissection, 5 to 10 mL of sterile saline can be injected into the submucosal tissue. A 1- to 2-centimeter transverse incision is made, and once the correct tissue plane is reached, the bladder is pushed off the cervix with blunt dissection. The dissection continues until the uterine corpus is felt ballooning outward from the cervix. Once this has been accomplished, a curved Allis clamp is used to simultaneously grasp the lateral edges of the anterior and posterior incisions. With downward traction on the ectocervix, the lateral cervical stroma is exposed as far cephalad as possible. This creates an optimal path for the needle and offers sufficient tissue stability to direct its path through the stroma, avoiding the descending branches of the uterine arteries.
The needle and suture, generally 5-mm Mersilene tape, is passed from anterior to posterior on the patient's right (assuming a right-handed operator). Some surgeons use an aneurysm needle threaded with the Mersilene tape. After the anterior–posterior bite is completed, a similar technique is used to stabilize the left side, where the needle is passed from posterior to anterior. The tape is then securely tied without excessively constricting the cervical tissue. The ends of the knot are left approximately 5-mm-long, so that the mucosa can be closed around them using an absorbable suture, leaving the cut ends exposed to facilitate later identification and removal. The posterior incision is also closed over the tape that should complete hemostasis. Some surgeons have suggested reversing the insertion procedure to place the knot posteriorly. Theoretically, this should reduce the risk of chronic bladder irritation.69 However, the choice appears to be operator preference, because no comparative data have been published confirming the superiority of one versus the alternate method.
Cervicoisthmic cerclage, placed at laparotomy, presents the most surgically challenging and morbid cerclage procedure. The decision to place this cerclage means that a patient must generally undergo two abdominal operations, because a safe vaginal birth is impossible and cesarean is required. Originally described by Benson and Durfee,5 a circumferential ligature of 5-mm Mersilene tape is placed near the insertion of the uterosacral and cardinal ligaments at the bifurcation of the uterine artery, between its ascending and descending branches. To gain exposure and better visualize the vascular supply, the bladder is taken down as during hysterectomy, and the incision is extended laterally on both sides to include a portion of the anterior peritoneal reflection of the broad ligament. While an assistant provides fundal traction, the surgeon grasps the uterine vessels and with gentle lateral traction exposes a triangular avascular space between the bifurcation of the artery and the uterine isthmus. Once identified, a right angle clamp is passed from the anterior to posterior, avoiding the vessels and ultimately tenting the posterior leaf of the broad ligament. The tissue overlying the tips of the clamp is incised, exposing the tips, by which a 15-centimeter length of Mersilene tape is brought back through the newly formed space. An identical procedure is performed on the contralateral side and the tape is then tied and secured anteriorly. The cut ends are sutured down flush with the encircling tape with nonabsorbable suture. The bladder reflection is then reapproximated.
Novy74 reported a modification of the original technique whereby a blunt-tip needle and swaged on Mersilene tape is passed through the avascular space from anterior to posterior on one side and from posterior to anterior on the other, thus obviating the need for any blunt dissection. A similar modification was also reported by Topping.75 Mahran76 reported a different modification: after the bladder is taken down, a Mayo needle threaded with 6-mm nylon tape is passed from anterior to posterior within the cervical isthmic tissue, but near its lateral edge at the level of the aforementioned arterial bifurcation. The opposite end is also passed anterior to posterior in an analogous fashion on the contralateral side, and the ends are tied posteriorly. On each side, the needle passes through the tissue of the uterosacral ligaments. Placing the knot on the posterior aspect may make the cerclage easier to remove. None of these reported modifications appears to offer appreciable advantage over the originally described technique, and so the choice is operator-dependent. Case reports of laparoscopic placement and removal of a cervicoisthmic cerclage have been recently published.77,78
The cervicoisthmic cerclage is generally placed between 10 and 16 weeks' gestation. Placement at the earlier range is technically easier, because the expanding uterine volume impairs exposure and increases the risk of bleeding complications. Coordination among the surgeon and assistants is crucial to maintaining the optimal surgical exposure. As with the transvaginal cerclage, individual hand-held retractors provide superior exposure compared to a self-retaining retractor for the critical steps.
It is unclear whether cervicoisthmic cerclage must be removed after childbearing is completed. The most opportune time to remove the cerclage is at the cesarean birth, generally performed at 36 to 37 weeks' gestation after confirming fetal lung maturity. However, some women will desire more children and, reasonably, would choose to maintain the cerclage, even though they might never conceive again. If conception does recur with the cerclage in place, there is still a risk of spontaneous abortion. In general, a first trimester miscarriage can be managed in the usual manner, because the cerclage should not interfere with the passage of a small 8- to 10-mm curette.
|PATIENT SELECTION FOR CERCLAGE|
Because of its unproven efficacy in randomized clinical trials, and because of the attendant surgical risks, the recommendation for prophylactic cerclage should be limited to women with recurrent spontaneous preterm birth syndrome, when a careful history and physical examination suggest a dominant cervical component. Unless the physical examination confirms a significant cervical anatomical defect, consistent with disruption of its circumferential integrity, the clinician should assess the history for other components of the preterm birth syndrome; cervical incompetence remains a diagnosis of exclusion. Although a history of preterm labor is generally considered to exclude the diagnosis of incompetence, patients may have clinically evident uterine activity once their cervix has spontaneously dilated (Ferguson's reflex).
Women with cervical incompetence often have some premonitory symptoms such as increased pelvic pressure, vaginal discharge, and urinary frequency. These symptoms, although neither specific nor uncommon in a normal pregnancy, should not be ignored, particularly in women with risk factors for spontaneous preterm birth. Thus, the history of rapid, relatively painless labor should perhaps better-characterize the diagnosis of cervical incompetence.
Similarly, a history of midtrimester spontaneous membrane rupture, alone, can neither confirm nor refute the diagnosis of incompetence, because spontaneous membrane rupture may occur after some pathologic cervical ripening and dilation has exposed the membranes to the genital tract flora. After spontaneous membrane rupture occurs, chorioamnionitis, vaginal bleeding (abruption), or labor may ensue, and these events may obscure the underlying etiology. However, if midtrimester membrane rupture occurs in the setting of a closed cervix on physical examination, or if it is followed by a typical course of either spontaneous or induced labor, causes other than cervical incompetence should be acknowledged. Conversely, if physical examination after membrane rupture showing marked cervical softening, effacement, and dilation with no antecedent history of painful contractions, the diagnosis of cervical incompetence is supported, particularly if followed by a rapid and relatively painless labor.
A legitimate clinical question arises over the optimal management of a patient who has experienced one spontaneous midtrimester birth, and causes other than cervical incompetence have been excluded by history and physical examination. The observation of a second similar midtrimester birth increases the specificity of the diagnosis (and also the likelihood that prophylactic cerclage would be an effective treatment in her next pregnancy). Clearly, if the index midtrimester birth was associated with an identifiable anatomic defect, interval repair, or prophylactic cerclage in the next pregnancy should be strongly considered. However, in contemporary obstetric practice, such anatomic defects are increasingly uncommon. Although controlled clinical data are lacking, it seems reasonable to follow-up a patient with this history, using serial clinical evaluations in the second trimester instead of empirically recommending cerclage. Currently, the use of cervical ultrasound to select patients for cerclage is considered investigational,79 although in selected cases with worrisome symptoms or pelvic findings, it may be a useful adjunct.59
Once a patient has been properly evaluated and deemed a suitable candidate for a prophylactic cerclage, the optimal method must be selected. In the presence of normal anatomy and either no previous failed cerclage procedures or a previous successful McDonald cerclage, a McDonald procedure is the technique of choice, because it is technically easier to perform and appears to be as effective as Shirodkar.71 Moreover, it is easier to remove the stitch in preparation for vaginal birth, and it is not associated with complications such as a vesicovaginal fistula.80 Shirodkar cerclage should be reserved for women with appreciable anatomic deformities such as an unrepaired cervical laceration or a hypoplastic cervix whereas a McDonald cerclage is felt to be technically inadvisable. In general, a Shirodkar cerclage should be considered whenever there is less than 1 centimeter of visible cervix below the vaginal fornix. A patient with a previous failed McDonald cerclage occasionally presents for subsequent obstetric care or preconceptual counseling. If the previous failure is believed to be caused primarily by cervical insufficiency (as opposed to other components of the spontaneous preterm birth syndrome), then the patient might be considered a candidate for either a Shirodkar or a cervicoisthmic procedure.
Rarely, a patient presents who is a viable candidate for a cervicoisthmic cerclage. Like the more commonly performed transvaginal procedures, there are no controlled clinical data to aid in patient selection or confirm that this procedure is even effective. It is conceivable that some women who present as potential candidates for cervicoisthmic cerclage, because they have had a previous failed transvaginal cerclage (with or without subsequent cervical damage) did not have cervical incompetence as the cause for their previous reproductive adversity. Because of the associated morbidity, a patient should only be selected for cervicoisthmic cerclage only after a careful review of her history and a thorough clinical assessment indicates that the previous (failed) transvaginal cerclage was clinically indicated and that placement of another transvaginal cerclage is technically not feasible because of the magnitude of the anatomic deficiency. Primary cervicoisthmic cerclage might be considered in a patient with a typical history of incompetence and no previous transvaginal cerclage if the cervix is surgically or congenitally absent.
In 2002 Zaveri and colleagues81 published a systematic review of 14 series published between 1965 and 2000, comprising 157 women who had a previous failed transvaginal cerclage and were managed in a subsequent pregnancy with either another transvaginal procedure (N = 40) or a cervicoisthmic cerclage (N = 117). The likelihood of perinatal death or delivery before 24 weeks was 6% in the cervicoisthmic cohort versus 12.5% in the transvaginal cohort. Because patient selection was not consistent across the series, and because the choice of transvaginal and transabdominal cerclage was uncontrolled, one must interpret the comparative efficacy with caution and avoid transabdominal procedures, except when both historic and anatomic criteria are clearly met. Because few patients are suitable candidates and few physicians have surgical experience with the procedure, it would seem prudent to relegate the decision to place a cervicoisthmic cerclage and the procedure itself to a subspecialty center.
Incompetence in Evolution
Almost by definition, every patient with well-characterized cervical incompetence will have experienced her first spontaneous midtrimester birth at some point in her reproductive history. Thus, on occasion, a primigravida will present with symptoms and physical findings that support an antepartum diagnosis of cervical incompetence. This syndrome, however, comprises a wide spectrum of clinical expression. The associated biologic variation supports both the heterogeneous nature of cervical competence as a continuum and the potential contribution of other components of the broader and more complex syndrome of spontaneous preterm birth. Women being followed-up clinically for suspected incompetence who demonstrate early cervical changes that support a primary cervical component are likely on the same biologic continuum as the women who present with few symptoms, no palpable contractions, and are found to be 4-centimeters dilated with membranes prolapsing into the vaginal canal. While in either case, a presumptive diagnosis of incompetence can be reasonably offered, the prognosis and management are different.
Although the efficacy of cerclage remains unproven in controlled studies, women who present with incompetence in evolution, generally defined as a midtrimester cervical dilation of at least 2 centimeters and no other predisposing cause (labor, infection, bleeding, ruptured membranes), are often considered for an emergent cerclage. Similar to case series describing the presumed benefit of prophylactic cerclage, reports describing the outcome of women who present with incompetence in evolution generally have not included a contemporary control group managed with bed rest or other therapy.
Aarts and colleagues82 reviewed eight series published between 1980 and 1992 comprising 249 patients who received an emergent midtrimester cerclage and estimated a mean neonatal survival rate of 64% (reported range: 22% to 100%). Novy and colleagues59 recently published a series of 35 cases of incompetence in evolution (cervical dilation: 2 to 5 centimeters); 19 women received emergent cerclage and 16 were managed with bed rest. Neonatal survival was 80% in the cerclage cohort versus 75% in the bed rest group. In another report using a similar study design, Olatunbosun and colleagues83 documented a neonatal survival of 23% with cerclage versus 40% with bed rest in women presenting with more advanced cervical dilation more than 4 centimeters. Although these reports are not of sufficient scientific quality on which to base firm management recommendations, collectively they demonstrate several important concepts. The earlier the gestational age at presentation and the more advanced the cervical dilation, the greater the risk of poor neonatal outcome. The finding of membrane prolapse into the vagina is also a significant risk factor for poor outcome.84
Other reports85,86,87 show that women who present with incompetence in evolution have an appreciable (nominal 50%) incidence of bacterial colonization of their amniotic fluid or other markers of subclinical chorioamnionitis. Women with these amniotic fluid markers of subclinical chorioamnionitis have a much shorter presentation-to-delivery interval, regardless of whether they receive cerclage or are managed expectantly with bed rest.
Mays and colleagues86 performed amniocentesis in 18 women who presented with this syndrome and analyzed the amniotic fluid for glucose, lactic dehydrogenase (LDH), Gram stain, and culture. An additional seven women were managed with cerclage after refusing amniocentesis. Clinical decisions made based on amniotic fluid biochemistries and low glucose and elevated LDH, which were immediately available, were sufficient for a diagnosis of subclinical infection. Of 11 women who underwent cerclage with no evidence of subclinical infection, the neonatal survival was 100%, and the mean latent phase duration from presentation to delivery was 93 days. Of the seven women with abnormal biochemistries in whom cerclage was withheld, no neonatal survivors were observed, and the mean latent phase was 4 days. Recognizing that at least a portion of the seven women who refused amniocentesis, but who received emergent cerclage, also had subclinical infection, it was predictable that the mean latent phase in this cohort was intermediate (17 days) as compared with the groups with amniotic fluid analyses. These investigators suggested that amniocentesis could aid in selecting candidates for emergent therapeutic cerclage. Although these findings were provocative, the uncontrolled study design did not substantiate that cerclage is effective in these cases, but it demonstrated that incompetence in evolution is frequently associated with intrauterine infection. Still unknown is whether the subclinical infection was the underlying cause of the premature dilation. This would disparage the presumption of primary cervical insufficiency. Conversely, it could be the result of premature cervical ripening. One could postulate that, as a cervix with diminished competence begins to dilate, vaginal flora ascend into the uterine cavity and incite cellular and biochemical responses that stimulate further cervical dilation and hasten spontaneous preterm birth.88
Prophylactic cerclage in the early second trimester need not be a mandatory inpatient procedure,89 although a period of observation for immediate complications seems advisable. There are a number of empiric recommendations regarding physical activity after discharge. A limited interval (24 to 48 hours) of mandatory bed rest is often advised in the immediate postoperative period. Pelvic rest and sexual abstinence for the remainder of gestation are widely prescribed, but resumption of intercourse may be reasonable in selected cases.90 Breast stimulation is known to cause uterine contractions and should also be avoided. Because the use of bed rest in pregnancy as an effective therapy has been seriously questioned,91 it seems reasonable to individualize this recommendation based on a patient's symptoms and physical findings. However, because women with cervical incompetence and cerclage are still at increased risk for preterm birth, physically demanding occupations, or prolonged standing should be curtailed.
On occasion, a patient who has undergone a cerclage procedure may present later in gestation with suture displacement for no discernible reason. In our experience, this has only occurred after the McDonald procedure, and it may be related to the fact that the McDonald cerclage has some inherent and unavoidable slack. Thus, if the cervix were to soften considerably, but slowly, some of the mechanical support realized at placement would be lost and occult cervical dilation and even membrane prolapse might result. If this is recognized in the midtrimester, an emergent cerclage revision might be considered, and another McDonald or a Shirodkar cerclage might be offered to reestablish the presumed benefits of the mechanical support. However, no published data support the efficacy or defines the risks of this approach.
In the absence of indications for earlier removal, most clinicians electively remove the cerclage at 37 weeks' gestation in anticipation of term labor and a vaginal birth. Often performed in an outpatient setting, elective removal may be complicated by hemorrhage or appreciable difficulty locating the suture, which may have become embedded in the cervical stroma. Because of its higher placement and use of 5-mm nonabsorbable tape, removal of a Shirodkar cerclage may be particularly troublesome. Difficult removal increases patient discomfort and, at times, light conscious sedation may be required. Hemorrhage from the suture track may occur, but it can usually be controlled with direct pressure.
For women with cerclage who are planning to undergo a cesarean birth because of previous uterine surgery, malpresentation, or high-order multiple gestations, no clinical trials or even retrospective studies suggest whether the cerclage should be removed or left in situ. For women who have completed their childbearing, the transvaginal cerclage should be removed at delivery. However, because most clinicians recommend cerclage in future pregnancies after an attributable success, leaving the cerclage in place may allow the patient to avoid another surgical procedure. The perceived difficulty of cerclage removal may influence the decision. A McDonald cerclage can be easily removed and should not be retained. Conversely, a Shirodkar cerclage might be considered for retention between pregnancies, particularly if the mucosa has completely epithelialized and obscured the knot. The special case of a cervicoisthmic cerclage was discussed in an earlier section.
Because many women with clinically defined cervical incompetence and cerclage remain at high risk for other components of the spontaneous preterm birth syndrome; indications for cerclage removal remote from term may develop. The combination of active labor forces and large diameter, permanent suture may easily exceed the strength of the cervical stroma and cause significant lacerations, further complicating future pregnancies. Thus, patients with cerclage should be instructed on the symptoms of preterm labor and be able to present early for evaluation. Women with cerclage and preterm labor can be managed empirically with tocolytic medications and should receive corticosteroids according to published guidelines. Nevertheless, if labor is progressive, the cerclage must be removed. This decision is made by the managing obstetrician based on serial visual and manual examination of the cervix and lower uterine segment. Bleeding may be an ominous sign and, besides abruption, could indicate laceration in progress. These complications are particularly troublesome in the case of a previous cervicoisthmic cerclage, whereas the typical findings associated with labor may be concealed by the high suture placement. Clinicians should be cautious in the setting of previous uterine surgery (including cesarean) or multiple gestations, in which uterine rupture would be catastrophic. A lower threshold for intervention in these cases is prudent.
Preterm premature rupture of membranes (PPROM) complicates 25% to 30% of pregnancies managed with cerclage.24,87 Although commonly associated with cerclage, the incidence of PPROM with cerclage is low, and thus, there are no randomized trials to define the optimal management in this situation. Uncontrolled retrospective series have demonstrated that, when the cerclage is removed on admission, perinatal outcomes are indistinguishable from similar cases of PPROM with no antecedent cerclage.92,93,94
Other series have addressed the question of whether the cerclage should be left in place or removed immediately after spontaneous membrane rupture. In 1994 Ludmir and colleagues95 reported a retrospective cohort study of 30 women with PPROM and cerclage. In 10 cases the cerclage was retained at the discretion of the patient and managing physician. Corticosteroids and prophylactic antibiotics (in common use today) were not administered. Although there was a trend toward a longer latent phase in women with retained cerclage (median: 11 vs 5 days), the difference was not statically significant. However, neonatal mortality was 10% in the removed group versus 70% in the retained cohort (p = .001), and most of the deaths were sepsis-associated. Jenkins and colleagues96 reported a 10-year retrospective review of 52 women with cerclage and PPROM, 25 of whom were managed with retained cerclage. Most patients received prophylactic antibiotics and corticosteroids, but tocolytic agents were prescribed more frequently in the retained cohort. The retained cohort experienced a longer latent phase (244 vs 119 hours), but maternal infection was observed twice as frequently (44% vs 22%), and neonatal sepsis was diagnosed three-times as often (16% vs 5%) if the stitch was left in situ. Overall, neonatal survival was similar: 89% in the removed cohort and 96% in the retained group. Finally, McElrath and colleagues97 reviewed 81 women with cerclage complicated by PPROM managed expectantly; in 51 cases the cerclage was left in situ. These investigators observed no differences in latent phase or neonatal outcomes, including sepsis, but there was a statistical trend toward a higher rate of intrauterine infection in the retained group (25% vs 10%; p = .09).
While these retrospective series cannot define optimal management, in the absence of clinical trial data confirming a benefit from leaving the cerclage in place after PPROM, the current weight of evidence suggests that the cerclage should be removed. This management strategy would also prevent cervical lacerations associated with spontaneous labor. However, when PPROM complicates the pregnancy of a patient with a previous cervicoisthmic cerclage, modified expectant management should proceed as usual, and the standard delivery indications (i.e., labor, infection, nonreassuring fetal status) should prevail.
Complications of Cerclage
Because prevention of preterm birth continues to be one of the most complex and persistent problems in obstetrics, recommendations for unproven, empirically derived treatments have pervaded our clinical practice for many decades.79,98 Thus, the willingness of physicians to prescribe and patients to accept various therapies can, at times, be based as much on emotion as scientific data. The perceived simplicity and safety of transvaginal cerclage makes this treatment subject to empiric use, and the associated complications subordinate.98
The most commonly reported complications associated with cerclage are membrane rupture and intrauterine infection. Bleeding may occur, but serious hemorrhage is generally limited to cervicoisthmic procedures. Essentially all transvaginal cerclage procedures are performed under regional anesthesia, which has a low complication rate. Harger98 recently tabulated cerclage-associated complications reported in the past 40 years. Chorioamnionitis complicated .8% to 8% of elective cerclage procedures and 9% to 37% of urgent or emergent procedures. Membrane rupture attributed to elective cerclage was observed in 1% to 18% and was associated with up to 65% of emergent cases, although the reported range with emergent cerclage is extremely wide. Whether cerclage alone can precipitate overt preterm labor seems doubtful. However, the foreign body might lower the threshold for uterine activity because of local inflammatory effects. Uterine activity often occurs in proximity to cerclage placement and women who have undergone cerclage are more likely to receive tocolytic agents during their gestation.31
Because preterm labor, chorioamnionitis, and PROM can complicate any gestation and have all been associated with preterm birth, the attributable risk of these events from cerclage is difficult to ascertain, particularly in the case of incompetence in evolution in which preexisting infection is commonly seen. PPROM and preterm labor may similarly complicate those pregnancies managed expectantly without cerclage. Nevertheless, iatrogenic membrane rupture does occur during emergent cerclage placement and probably shortens the gestation as a result.
In the largest randomized trial of prophylactic cerclage yet published, MacNaughton and colleagues31 noted a (possibly or probably attributable) adverse event rate of 15% of women who received cerclage. Rust and colleagues99 reported a 16% incidence of postoperative chorioamnionitis in a randomized trial of cerclage for cervical sonographic indications. Because the efficacy and safety of prophylactic cerclage for women with a clinical history of cervical incompetence has yet to be evaluated in randomized trials, the attributable risk of complications can only be inferred from existing case series. Nevertheless, any surgical complication that results from an unproven therapy is difficult to justify.
Some cerclage complications are occult and their effects not realized in the index pregnancy. Whether a cerclage is placed for a carefully scrutinized history or for questionable indications, the observation that it may have been associated with a desirable outcome is generally used to justify future cerclage therapy. Cerclage may lead to an increased cesarean rate, if removal is deemed to be difficult or the decision was made to leave it for successive gestations. Although uncommon, cervical lacerations from active labor and in situ cerclage likely affect the prognosis for future pregnancies. Lastly, the use of cerclage as an empiric treatment of the syndrome of spontaneous preterm birth may obscure the underlying cause(s) and unnecessarily impede future research aimed at improving our understanding of the pathophysiology of preterm birth and optimizing therapeutic approaches.
|ADJUNCTIVE MANAGEMENT STRATEGIES FOR THE INCOMPETENT CERVIX|
Many clinicians recommend obtaining cervicovaginal cultures for common pathogens and treating positive cultures before placing a cerclage. Active cervicitis should be considered a contraindication to prophylactic cerclage placement, and this must be successfully treated before surgery. Other contraindications to cerclage include ruptured membranes, lethal fetal anomaly, suspected chorioamnionitis, vaginal bleeding, and labor.
Most clinicians place a prophylactic cerclage at 12 to 16 weeks' gestation. However, absolute limits on the gestational age range have never been established. Awaiting the second trimester significantly lessens the chance of spontaneous abortion from events not related to cervical incompetence. The reported upper limit for placing a cerclage for any indication varies among different investigators and clinicians alike. Because cervical competence operates along a continuum, there may be no true biologic upper limit. Conversely, the later in gestation it presents, the less likely it is caused by an inherent mechanical defect in the cervix and the more likely the apparent incompetence is the result of exogenous processes, including infection. Although this hypothesis is unproven, various lines of evidence support the concept. Other considerations involve the gestational age of viability and the risk of cerclage-associated complications that might impose a more practical upper limit. Essentially, all cerclages placed after 20 weeks are for emergent or urgent indications. A patient who presents after this time with an historic indication for a prophylactic cerclage and no evidence of cervical changes is unlikely to benefit from the procedure and should be followed-up clinically. Women who present at or beyond 24 weeks' gestation have a potentially viable fetus. Because emergent cerclage is of unproven efficacy and associated with significant risk of complications, it would seem prudent to avoid surgery after this time and consider other therapeutic alternatives.
Other Treatments for Cervical Incompetence
Alternative therapies for cervical incompetence can be broadly classified as either providing mechanical support or administering empiric pharmacologic measures to reduce inflammation and infection to maintain uterine quiescence. A review of older case series of cerclage indicate that progesterone (usually 17 -hydroxyprogesterone caproate) and, more recently, various tocolytic agents (usually indomethacin) and various prophylactic antibiotic regimens are widely prescribed adjuncts to cerclage. Whether these agents alone or in combination offer any therapeutic value is unknown, because none has been proved effective in controlled intervention trials. However, of these, progesterone appears to be the most promising.
As early as 1966, Sherman100 reported an uncontrolled comparison of three regimens for patients with cervical incompetence: cerclage, cerclage plus progesterone, and progesterone alone. Of 19 treated with cerclage, 49% had a successful outcome, as compared with an 82% success rate in 33 women with combination therapy and a 92% rate in 74 women treated only with progesterone. Comparable results were not confirmed in other trials, although a meta-analysis of seven randomized trials of 17 -hydroxyprogesterone caproate published by Keirse101 suggested a typical odds ratio for preterm birth of .5 (95% CI: .3 to .85). Recently, the NICHD Maternal-Fetal Medicine Units Network reported the results of a double-blind trial of Delalutin for the prevention of spontaneous preterm birth in women with a previous spontaneous preterm birth. Compared with placebo, weekly intramuscular 17 -hydroxyprogesterone caproate reduced the rate of preterm birth by approximately one-third.102
Investigators in Europe and the United States have studied vaginal pessaries for the treatment of the incompetent cervix.103 In 1961, Vitsky104 proposed the mechanism whereby a lever pessary (Smith, Hodge, or Risser design) might be an effective treatment for the incompetent cervix. A vaginal pessary would displace the cervix posteriorly and shift the gravitational effects of the expanding uterine contents off the internal os and onto the anterior lower uterine segment. Interpretation of the clinical research in this area has been hampered by the frequent use of historic control study designs, strikingly similar to those used in most series espousing the efficacy of cerclage. Likewise, the reported success rates of vaginal pessaries closely mirror those observed with cerclage and nominal success rates are in the 80% to 90% range.103 Only one randomized trial has been located, and this was a German study published in 1986 by Forster and colleagues.105 In this trial, 250 women were randomized to cerclage or pessary (the type was not stated). The cerclage group and pessary group had term delivery rates of 69% and 62%, respectively. Another recent retrospective analysis of 36 women with midtrimester cervical shortening, managed either expectantly or with a Smith-Hodge pessary, showed a significant decrease in the incidence of preterm birth before 35 weeks (0% vs 40%; p = .03).106 Although further comparative efficacy trials are needed, it would seem reasonable to recommend a trial of vaginal pessary in women with unclear histories or those who demonstrate progressive cervical change on serial midtrimester evaluations.
Contemporary lines of evidence indicate that cervical incompetence is rarely a distinct and well-defined clinical entity, but only one component of a larger and more complex syndrome of spontaneous preterm birth. The original paradigm of obstetric and gynecologic trauma as a common antecedent of cervical incompetence has been replaced by the recognition of functional, as opposed to anatomic, deficits as the more prevalent etiology. Cervical competence functions along a continuum, influenced by both endogenous and exogenous factors that interact through various pathways with other recognized components of the preterm birth syndrome: uterine contractions and decidual/membrane activation. Thus, the convenient term, cervical incompetence, may actually represent an oversimplified incomplete version of the broader pathophysiologic process. Consequently, the empiric use of traditional therapies, unsubstantiated by results of clinical trials, must be questioned. Effective evidenced-based management guidelines will be based on a more complete understanding of the preterm birth syndrome. This will improve patient selection and permit specifically tailored treatment regimens to be devised and confirmed by the results of well-designed intervention trials. It should be recognized that even effective therapies will appear ineffective when applied to an unselected or poorly selected patient population.107
Although it is clear that from a teleological standpoint essentially all pregnant cervixes become incompetent at some point in gestation, cervical incompetence remains a clinical diagnosis, because a clinically useful objective test has not been discovered. At present, cervical ultrasound represents a powerful research instrument that can be used to screen selected high-risk populations and identify patients who may have a treatable component of cervical insufficiency and benefit from interventions such as cerclage. Reasonably, if a cervix shortens from inherent mechanical weakness, local mechanical support might aid in prolonging gestation. Alternatively, if cervical insufficiency has already manifest, such support might arrive too late to be effective. The identification and early detection of cervicovaginal fluid or serologic markers of incompetence in evolution might ultimately prove more advantageous. Furthermore, if incompetence is actually the result of other pathophysiologic factors, such support might be ineffective, or even detrimental, if it has associated risks.
This chapter focused on the cervix and its contribution to the problem of prematurity. The author is confident that continued research into the causes and prevention of spontaneous preterm birth will slowly, but ultimately, identify strategies to effectively address the most important and persistent problem in obstetrics. Meanwhile, our incomplete understanding of this syndrome and the evolving controversies over its optimal management will continue to frustrate both patients and clinicians. Nevertheless, we should remain mindful of the importance of evidenced-based solutions and not let enthusiasm for unproven therapies impede our thoughtful scientific investigation.
1. Palmer R, Lacomme M: La béance de l'orifice interne, cause d'avortements à répétition? Une observation de déchrure cervico-isthmique répareeé chirurgicalement, avec gestation à terme consécutive Gynecol Obstet 47:905-906, 1948
18. Ayers JWR, DeGrood R, Compton A, et al: Sonographic evaluation of cervical length in pregnancy: Diagnosis and management of preterm cervical effacement in patients at risk for premature delivery. Obstet Gynecol 71:939-944, 1988
31. MacNaughton MC, Chalmers I, Dubowitz V, et al: Final report of the Medical Research Council/Royal College of Obstetrics and Gynaecology multicentre randomized trial of cervical cerclage. Br J Obstet Gynaecol 100:516-523, 1993
34. Levine RU, Berkowitz KM: Conservative management and pregnancy outcome in diethylstilbestrol-exposed women with and without gross genital tract abnormalities. Am J Obstet Gynecol 169:1125-1129, 1993
48. Tongsong T, Kamprapanth P, Srisomboon J, et al: Single transvaginal sonographic measurement of cervical length early in the third trimester as a predictor of preterm delivery. Obstet Gynecol 86:184-187, 1955
54. Imseis HM, Albert T, Iams JD: Identifying twin gestations at low risk for preterm birth with a transvaginal ultrasonographic cervical measurement at 24 to 26 weeks' gestation. Am J Obstet Gynecol 177:1149-1155, 1997
58. Berghella V, Daly S, Tolosa J, et al: Prediction of preterm delivery with transvaginal ultrasonography of the cervix in patients with high-risk pregnancies: Does cerclage prevent prematurity. ? Am J Obstet Gynecol 181:809-815, 1999
62. Althuisius SM, Dekker G, Hummel P, et al: Final results of the cervical incompetence prevention randomized cerclage trial (CIPRACT): therapeutic cerclage with bed rest versus bed rest alone. Am J Obstet Gynecol 185:1106-1112, 2001
85. Romero R, Gonzalez R, Sepulveda W, et al: Infection and Labor VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: Prevalence and clinical significance Am J Obstet Gynecol 167:1086-1091, 1992
99. Rust OA, Atlas R, Jones K, et al: A randomized trial of cerclage versus no cerclage among patients with ultrasonographically detected second-trimester preterm dilatation of the internal os. Am J Obstet Gynecol 183:830-835, 2000
119. Guzman ER, Pisatowski D, Vintzileos A, et al: A comparison of ultrasonographically detected cervical changes in response to transfundal pressure, coughing, and standing in predicting cervical incompetence. Am J Obstet Gynecol 177:660-665, 1997