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Clinical Expert Series

Cervical Evaluation
From Ancient Medicine to Precision Medicine
Helen Feltovich, MD, MS

Since ancient times, cervical assessment for predicting timing of delivery has relied primarily on
digital (subjective) assessment of dilatation, softening, and length. To date, transvaginal
ultrasound cervical length is the only one of these parameters that meets criteria for a biomarker;
no objective, quantitative measure of cervical dilatation or softening has gained clinical
acceptance. This review discusses how the cervix has been assessed from ancient times to the
present day and how a precision medicine approach could improve understanding of not only
the cervix, but also parturition in general.
(Obstet Gynecol 2017;130:51–63)
DOI: 10.1097/AOG.0000000000002106

T he desire to predict the future is human nature. In


the case of predicting timing of delivery, however,
this desire is coupled with a desire to avoid morbidity:
For all of these decisions, practitioners rely on
evaluation of the cervix, particularly its length,
dilatation, and softness.
as recognized since ancient times, births that happen
earlier than expected, later than expected, or take A TIMELESS QUESTION: WHEN WILL
longer than expected once labor begins can be
SHE DELIVER?
problematic. Cervical length is the parameter most widely used to
Practitioners therefore try to predict timing of evaluate the cervix for spontaneous preterm birth
delivery. In contemporary practice, decisions about prediction and prevention. This has evolved since
candidacy for elective induction, or about a cervical 1996, when the inverse relationship between trans-
ripening strategy if induction is medically indicated, vaginal ultrasound cervical length and risk of sponta-
depend on predicting success of induction of labor. neous preterm birth was established by the landmark
Decisions about interventions for spontaneous pre- prospective, multicenter Preterm Prediction Study in
term birth prevention often are based on predicting its which approximately 2,900 transvaginal ultrasound
risk. Even intrapartum predictions about delivery cervical lengths were obtained in singleton gestations
timing affect decision-making about interventions at 24 weeks of gestation.1 One example of how trans-
such as oxytocin augmentation or cesarean delivery. vaginal ultrasound cervical length has changed prac-
tice is that cerclage was previously offered only to
women with a history of second-trimester loss (his-
From the Department of Maternal–Fetal Medicine, Intermountain Healthcare, tory-indicated) or dilatation in the current pregnancy
Utah Valley Hospital, Provo, Utah; and the Department of Medical Physics,
University of Wisconsin–Madison, Madison, Wisconsin. (examination-indicated), but now the American Col-
Continuing medical education for this article is available at http://links.lww. lege of Obstetricians and Gynecologists (the College)
com/AOG/A964. and the Society for Maternal-Fetal Medicine (SMFM)
The author has indicated that she has met the journal’s requirements for suggest that, for women with a history of spontaneous
authorship. preterm birth of a singleton, serial transvaginal ultra-
Corresponding author: Helen Feltovich, MD, MS, Maternal–Fetal Medicine, sound cervical length monitoring with cerclage only if
Intermountain Healthcare, Utah Valley Hospital, 1034 N 500 W, Provo, UT the cervix shortens (ultrasound-indicated) is a safe
84604; email: hfeltovich@gmail.com.
alternative.2 Another example is that, because vaginal
Financial Disclosure
The authors did not report any potential conflicts of interest. progesterone in the case of a short transvaginal ultra-
© 2017 by The American College of Obstetricians and Gynecologists. Published
sound cervical length reduces the risk of spontaneous
by Wolters Kluwer Health, Inc. All rights reserved. preterm birth in women carrying singletons regardless
ISSN: 0029-7844/17 of history, both the College and the SMFM support

VOL. 130, NO. 1, JULY 2017 OBSTETRICS & GYNECOLOGY 51

Copyright ª by The American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
the use of second-trimester transvaginal ultrasound the risk of cesarean delivery, and many others, includ-
cervical length to determine candidacy for vaginal ing randomized trials, suggesting that, compared with
progesterone.3 An additional use of transvaginal ultra- expectant management, induction of labor actually
sound cervical length is for the triage of women pre- lowers the cesarean delivery rate. What seems clear,
senting in the second or third trimester with preterm however, is that cervical status matters: in two retro-
labor symptoms.3 spective cohort studies of nulliparous women at
Cervical dilatation is the parameter used intra- term undergoing elective induction (total n5396)
partum to try to determine when delivery will occur. compared with expectant management (n5396), the
In the 1950s, Dr. Emanual Friedman observed the cesarean delivery rate was 20.8% among those with
labors of hundreds of women, graphing contraction a favorable,9 and 43.1% among those with an unfavor-
frequency, cervical dilatation and effacement (length), able,10 cervix.
station of the fetal presenting part, and other param- An important fact is usually overlooked in con-
eters. His research, which suggested that dilatation siderations of cervical favorability for obstetric
was most relevant for determining labor outcome, led decision-making: elective induction of labor was
to labor curves4,5 that were widely used until the Con- uncommon in Dr. Bishop’s time, particularly for nul-
sortium on Safe Labor published updated curves liparous patients. Only approximately 7% of women
based on a retrospective study of more than 228,000 (almost all of them multiparous) were induced in the
deliveries across the United States between 2002 and National Collaborative Perinatal Project, a multicen-
2008.6 These updated curves, which demonstrate ter, prospective, observational trial designed to com-
slower labor progress than those of Friedman, have prehensively study labor in more than 50,000 women
been used to encourage and allow slower progress. from 1959 to 1966.6 Simply, the Bishop score was
Cervical softness (consistency) is another param- designed to predict success of elective induction in
eter, typically in combination with length and dilata- the multiparous patient at term. In contrast, induction
tion, used to try to predict timing of delivery. In the is very common today, especially for nulliparous pa-
1950s, in an attempt to identify women with the tients: in 2015, approximately one in four American
highest chance of successful induction of labor, Dr. pregnant women were induced11,12 and in the Con-
Edward Bishop developed a score based on digital sortium on Safe Labor, 43% of nulliparous patients
evaluation of cervical softness, length, and dilatation underwent induction of labor.6 Furthermore, term
as well as its position and station of the fetal presenting induction in gravid patients with a history of vaginal
part.7 He scored cervices of multiparous women at delivery is so successful that cervical status is almost
term (n5500) and then observed length of time to irrelevant, that is, it is not particularly useful for deter-
spontaneous labor. He found that a higher score, cor- mining candidacy in these women.13 Accordingly, the
responding to a cervix that was softer, shorter, and Bishop score, or a version of it, has been repurposed
more dilated, was associated with a shorter time to to predict success of labor induction in nulliparous
labor onset, and he subsequently observed no failed women or to decide who might benefit from cervical
inductions in multiparous women with a high “Bishop ripening regardless of parity or gestational age.
score.”7
Because cervical assessment offers apparent value A TIMELESS APPROACH: EVALUATE
in terms of predicting delivery timing, many College HER CERVIX
and SMFM recommendations address the cervix. As The female reproductive system was extensively
noted previously, both societies recommend trans- described in Herophilus’ midwifery text (3rd century
vaginal ultrasound cervical length screening for pre- BCE), but pregnancy issues were largely ignored until
diction and prevention of spontaneous preterm birth the time of Soranus in the 1st and 2nd centuries CE.
in high-risk women.3 Another example is a recom- Soranus wrote about preterm birth, postdate birth,
mendation from a Eunice Kennedy Shriver National signs of imminent labor, protracted labor, and induc-
Institute of Child Health and Human Development tion of labor.14 He seemed to understand the cervix
(NICHD), SMFM, and College workshop convened fairly well, reflected in the earliest known diagram of
to discuss avoidance of cesarean delivery: offer elec- the female reproductive structures, which is based on
tive induction of labor only to women with a favorable his studies and shows a relatively correct cervix,
cervix (high Bishop or modified Bishop score).8 Con- unlike the (absent) tubes and ovaries (Fig. 1). Many
troversy exists over the proportion of cesarean deliv- recommendations then, like many today, involved the
eries that can be directly attributed to labor induction cervix. Soranus also dictated that a midwife’s hands be
with some studies suggesting that induction increases soft with long, slim fingers and short nails.

52 Feltovich Cervical Evaluation OBSTETRICS & GYNECOLOGY

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Unauthorized reproduction of this article is prohibited.
in rates of infection,16 and vaginal examination again
became standard in most places.
Irrespective of approach, the reasons to examine
the cervix are obvious. Specifically, it is accessible and
parturition (at least grossly) begins and ends with the
cervix: pregnancy is heralded by early cervical
softening, and delivery is immediately preceded by
complete cervical softening, shortening, and dilata-
tion. These three properties (dilatation, length, and
softness) have been evaluated in multiple ways
throughout history.

Dilatation
Soranus taught that a midwife should do frequent
intrapartum examinations to monitor progress of
labor.14 Similarly, the Friedman labor curves were
based on digital appreciation of dilatation, although
Dr. Friedman himself was keen to find something
Fig. 1. Earliest known diagram of the uterus (9th century more objective and quantitative than the practitioner’s
CE). Based on drawings of Soranus of Ephesus (1st and 2nd finger. Toward this end, he and others developed
centuries CE), the original gynecologist. Reprinted from cervimeters. These were instruments based on electri-
Weindler F. Geschichte der gynäkologisch-anatomischen
abbildung, von dr. Fritz Weindler.Mit 122 in den text cal, mechanical, magnetic, or ultrasonic principles,
gedruckten abbildungen. Dresden, Zahn & Jaensch; 1908. which used calipers, strings, electromagnetic coils, or
Courtesy of the National Library of Medicine, Bethesda, MD. ultrasound transducer crystals affixed to the cervix
Feltovich. Cervical Evaluation. Obstet Gynecol 2017. and coupled to some means, outside the vagina, of
recording dilatation.17 An example is Friedman’s
1956 device: proximally, bulldog clips affixed the cal-
This recommendation, of course, was because she ipers to the cervix while the handles on the distal end
performed vaginal examinations. The vaginal were connected to a centimeter rule that depicted cer-
approach to cervical examination was status quo for vical diameter (Fig. 2). Electromagnetic cervimeters
nearly two millennia, until Semmelweiss’ 1847 discov- used induction coils attached to opposite sides of the
ery of the etiology of puerperal fever, after which cervix to create a magnetic field that allowed calcula-
rectal examination was proposed to avoid infection tion of the distance between them, and an ultrasonic
from direct contact with the cervix.15 The rectal device was based on the same principle but instead
approach gained rapid and wide favor, but most preg- used two tiny ultrasound transducers. The problem
nant women did not approve, and in the 1930s, British with these devices was that they easily fell off the
midwives protested that rectal cervical examination is cervix. Even when they remained affixed, they dem-
undesirable because it is painful, increases infection onstrated no advantage over digital evaluation17 and
risk resulting from proximity of the cervix to the rec- so they disappeared by the 1980s, leaving practi-
tum, and makes accurate assessment of dilatation dif- tioners with nothing but their fingers to measure
ficult in addition to which assessing the laboring dilatation.
cervix at all is unnecessary because it does not change
the outcome or speed delivery (Penny W. Letter to the Length
editor. Br Med J 1930.). An obstetrician of the time Unlike dilatation, cervical length can be objectively
countered that intrapartum examination is absolutely quantified and accurately, reliably, and reproducibly
necessary: “How else can he (the practitioner) judge, measured. This measurement is called transvaginal
with any approach to accuracy, when to go away (and ultrasound cervical length. Furthermore, interventions
for how long) and when to stay” (Penny, Br Med J). that reduce risk of spontaneous preterm birth based
He added that a rectal examination is more efficient on transvaginal ultrasound cervical length are available
than vaginal because it does not require gloves or and effective in appropriately selected patients (cerc-
handwashing. In 1986, a randomized controlled trial lage, vaginal progesterone), which makes transvaginal
(RCT) comparing the typical rectal with alternative ultrasound cervical length an effective screening test.
vaginal examination (n5307) reported no difference For these reasons, the College and the SMFM

VOL. 130, NO. 1, JULY 2017 Feltovich Cervical Evaluation 53

Copyright ª by The American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
Box 1. Society Recommendations Regarding
Transvaginal Ultrasound Cervical Length for
Preterm Birth Prediction and Prevention

Screening
 Recommended: routine transvaginal ultrasound cer-
vical length screening for women with a singleton
pregnancy and history of prior spontaneous preterm
birth (grade 1A)*
 Reasonable but not mandatory: transvaginal ultra-
sound cervical length screening in women without
prior preterm birth (Level B)†
Fig. 2. Friedman’s 1956 cervimeter. Proximally, bulldog
clips affixed the calipers to the cervix while the handles on
Therapeutic Options for a Short Cervix at 16–24 Weeks
the distal end were connected to a centimeter rule that
of Gestation (Level A Evidence)
depicted cervical diameter. Modified from van Dessel T,
Frijns JH, Kok FT, Wallenburg HC. Assessment of cervical  Offer progesterone supplementation at 16–24 weeks
dilatation during labor: a review. Eur J Obstet Gynecol of gestation to a woman with a history of singleton
Reprod Biol 1991;41:165–71, Ó1991, with permission spontaneous preterm birth regardless of transvaginal
from Elsevier. cervical length†
Feltovich. Cervical Evaluation. Obstet Gynecol 2017.  Consider vaginal progesterone if transvaginal cervi-
cal length is 20 mm or less at or before 24 weeks of
recommend screening of all women with singleton ges- gestation in a woman without a history of preterm
birth†
tation and a history of spontaneous preterm birth  Consider cerclage if transvaginal cervical length is
(grade 1A evidence)3 (Box 1). The societies also rec- less than 25 mm before 24 weeks of gestation in
ommend that ultrasonographers and practitioners at a woman with a history of preterm birth before 34
screening facilities undergo specific training in acquisi- weeks of gestation‡
tion and interpretation of transvaginal ultrasound cer- *Data from Society for Maternal-Fetal Medicine (SMFM),
vical length (grade 2B evidence)3 because of the risk of McIntosh J, Feltovich H, Berghella V, Manuck T. The role of
inappropriate treatment decision-making resulting routine cervical length screening in selected high- and
low-risk women for preterm birth prevention. Am J Obstet
from inaccurate measurement (Box 2). Although the Gynecol 2016;215:B2–7.
societies do not recommend screening in low-risk pop- †Prediction and prevention of preterm birth. Practice

ulations, they note that a policy of universal screening Bulletin No. 130. American College of Obstetricians
and Gynecologists. Obstet Gynecol 2012;120:
may be considered because vaginal progesterone re- 964–73.
duces the risk of spontaneous preterm birth in unse- ‡Cerclage for the management of cervical insufficiency.

lected women with a short transvaginal ultrasound Practice Bulletin No. 142. American College of
Obstetricians and Gynecologists. Obstet Gynecol
cervical length.3 For instance, a large retrospective 2014;123:37–9.
cohort study of low-risk (singleton gestation, no previ-
ous preterm birth) nulliparous or multiparous women
who delivered at a single tertiary institution between
2007 and 2014 demonstrated a decreased incidence of
spontaneous preterm birth after the 2011 initiation of
a universal transvaginal ultrasound cervical length Box 2. Training for Transvaginal Ultrasound
screening program (incidence of spontaneous preterm Cervical Length
birth at less than 37 weeks of gestation 6.7% compared
 Cervical Length Education and Review (CLEAR),
with 6.0%, adjusted odds ratio [OR] 0.82, 95% confi- a U.S.-based program sponsored by the Society for
dence interval [CI] 0.76–0.88).18 However, a prospec- Maternal-Fetal Medicine and Perinatal Quality Foun-
tive, observational cohort study of more than 9,000 dation (https://clear.perinatalquality.org)
nulliparous women with singleton gestation recruited  Fetal Medicine Foundation Certificate of Competence
from eight sites across the United States between 2010 in cervical assessment (https://fetalmedicine.org)
and 2014 (the NICHD’s Nulliparous Pregnancy Out- Data from Society for Maternal-Fetal Medicine (SMFM),
comes Study: Monitoring Mothers-to-Be) suggested McIntosh J, Feltovich H, Berghella V, Manuck T. The role of
that transvaginal ultrasound cervical length screening routine cervical length screening in selected high- and low-
risk women for preterm birth prevention. Am J Obstet
cannot be recommended in nulliparous women Gynecol 2016;215:B2–7.
because of its low predictive value for spontaneous

54 Feltovich Cervical Evaluation OBSTETRICS & GYNECOLOGY

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preterm birth: the area under the receiver operating force and the tissue’s resistance.24 However, marked
characteristic curve (AUC) for screening at 22–30 variability and erroneous measurements resulting from
weeks of gestation was 0.67 (95% CI 0.64–0.70).19 On variation in pressure (the applied or contact force) by
labor and delivery units, transvaginal ultrasound cervi- the operator prevented its clinical use.
cal length is useful for the assessment of women with Recently, because elasticity imaging has become
symptoms of acute preterm labor, because the high neg- clinically feasible, there has been renewed interest in
ative predictive value (96–100%) of a transvaginal ultra- objective measurement of cervical softness. The
sound cervical length greater than 30 mm is reassuring basic approach of this type of imaging, which is
enough for discharge, whereas a cervical length less than predicated on the physics principle that soft tissues
20 mm confers a high enough risk to justify continued are more deformable than stiff tissues, is to measure
observation and perhaps intervention, and a transvaginal tissue displacement in response to a stimulation. The
ultrasound cervical length of 20–29 mm requires addi- most common type of elasticity imaging is strain
tional evaluation.3 With respect to term spontaneous elastography. Tissue is deformed extrinsically (by
labor, a recent meta-analysis demonstrates that a woman manual compression with the transducer) or intrin-
with singleton gestation and transvaginal ultrasound sically (by motion of the organ against the transducer
cervical length of greater than 30 mm has a less than from breathing or vascular pulsation). Ultrasound
50% chance of spontaneous labor within 7 days, signals are acquired before and after the deformation,
whereas her chance is greater than 85% if her cervical which allows computation of the rate of change in tissue
length is 10 mm.20 These are only a few of the hundreds displacement (relative strain) in a region of interest. This
of studies of transvaginal ultrasound cervical length for relative strain is typically depicted in a color map called
prediction of delivery timing. Fortunately, for measuring an elastogram. The relationship between the applied
cervical length, contemporary practitioners have more (contact) force and strain value depends on tissue
than their fingers at their fingertips. compliance with greater strain seen in softer tissues.
An important point about this type of technique is that
Softness (Consistency) fundamental physics dictate that strain image interpre-
Accurate and reliable measurement of cervical soft- tation is complicated in all but the most trivial condi-
ness is challenging. This is unfortunate because, of all tions.25 Because the cervix is very complex, it should
the parameters used to evaluate the cervix, softness come as no surprise that most studies have suggested
seems particularly revealing: it occurs early (within that elastography is minimally, if at all, useful for cervi-
a few weeks of conception), progresses with advancing cal evaluation. Thus, today’s practitioners use their fin-
gestation, and must reach full expression (complete gers to assess softness and their face as a reference
softness and compliance) to allow delivery at the end standard (soft feels like a cheek, medium a nose, and
of pregnancy. Until the 1900s when urine and serum firm a forehead).
pregnancy testing became available, practitioners often
relied on appreciation of cervical softening for early A TIMELESS FRUSTRATION: CERVICAL
pregnancy diagnosis (eg, Hegar’s sign21 or Dickinson’s EVALUATION IS IMPRECISE
sign22). On the other end of the parturition spectrum, A precise measurement is one that is exact and accurate.
inadequate softening characterizes the cervix that is not This is particularly relevant to medicine because
ready for labor; Soranus recognized this as a potential appropriate choice of treatment based on a measure-
warning sign of postdate pregnancy,14 and the Bishop ment obviously requires that measurement to be pre-
score awards no points for a firm cervix.7 cise. Objective and reliable biological measurements on
In a recent review of cervical assessment methods which practitioners base decisions are called biomarkers.
for evaluating risk of spontaneous preterm birth, chance The National Institutes of Health Biomarkers Defini-
of success of labor induction, and need for cervical tions Working Group defines a biomarker as “a char-
ripening before induction, the importance the practi- acteristic that is objectively measured and evaluated as
tioner accords the fundamental parameter of cervical an indicator of normal biological processes, pathogenic
softness was highlighted.23 To date, however, attempts processes, or pharmacologic responses to a therapeutic
to objectively quantify this putatively critical parameter intervention.”26 Simple examples of biomarkers are
have been largely unsuccessful. In the 1960s, engineers pulse and blood pressure.
built an electromechanical device that was held against
the distal end of the cervix and consisted of a differential Dilatation
transformer with an axial core driven by a spring into There are no biomarkers for this cervical dilatation
the tissue until an equilibrium was reached between the because measurement is subjective, that is, not

VOL. 130, NO. 1, JULY 2017 Feltovich Cervical Evaluation 55

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reproducible or reliable. In addition, assessment of transducer had highest strain, regardless of region of
dilatation is inaccurate. For instance, a 2004 study interest location, leading to the conclusion that elastog-
comparing accuracy of measuring cervical dilatation raphy measurements “may be merely a reflection of the
in soft (closer to the in vivo situation) compared with force applied by the transducer”31 (this is consistent
hard simulation training models reported that, of 360 with fundamental physics principles regarding strain
measurements by physicians, nurses, and residents, elastography24). Subsequent approaches to standardiza-
only 19% of measurements in the soft models and tion of applied force have involved pressing the trans-
54% in the hard models were correct.27 A subsequent ducer into the tissue until no further compression can
prospective, multinational study of women in active be observed (with B-mode imaging) and expressing this
labor (n5188) further confirmed the imprecision of deformation as Lagrangian strain (deformation of tissue
digital examination; using a position-tracking system from its original to its current length), natural strain (like
to verify the practitioner’s measurement of dilatation, Lagrangian strain, but also accounts for instantaneous
they found a mean error 10.268.4 mm.28 Because tissue deformation), or using a ratio of the anteroposte-
decisions about intrapartum intervention are based rior diameter of the cervix before and after the com-
on specific dilatation thresholds, an average 1- to 2- pression (“cervical consistency index”).32 Maintenance
cm difference between digital assessment and actual of a constant color value on a bar indicator displayed on
dilatation seems concerning. the ultrasound screen was proposed as another means
to standardize applied force,33 but this approach seem-
Length ingly disappeared after a bioengineering group revealed
Transvaginal ultrasound cervical length is a solid bio- that the bar indicates only whether the transducer has
marker because it can be objectively measured, and the adequate contact with the tissue (ie, it does not indicate
measurement is meaningful with respect to a biological applied force).34 Another technique uses a reference cap
process: a normal cervical length is considered indicative on the end of the transducer because interposition of
of normal pregnancy, whereas a short cervical length is a material with known stiffness can facilitate calculation
indicative of pathologic pregnancy. Precision is critical, of tissue softness.35 However, biomechanical modeling
however, and small inaccuracies have large implications. suggested an inhomogeneous deformation in both the
For instance, if using a 25-mm threshold to define a short cap and cervix, which would violate measurement as-
cervix in a woman with a singleton gestation and sumptions and lead to inaccurate values.34
a history of spontaneous preterm birth, incorrectly In other words, regardless of whether tissue
measuring her cervix as 26 mm when it is really deformation is intrinsic or extrinsic, or which equation
24 mm means that she will not be offered cerclage, an is used to calculate a value or ratio, a central issue for
intervention shown to decrease her risk of spontaneous strain elastography is that the applied (contact) force
preterm birth. The reverse is also true; measuring her cannot be known, which means that absolute quanti-
cervix as 24 mm when it is really 26 mm could result in fication of softness (elastic modulus) is impossible.36
an unnecessary surgical procedure. Assuming that it can This is not a problem when knowledge of relative
be precisely measured, however, transvaginal ultrasound stiffness is enough such as when the task is to detect
cervical length is a good biomarker. a tumor within surrounding normal tissue. However,
it becomes a significant issue when the task is to
Softness describe overall softening, because that requires cal-
Clinical assessment of softness is perhaps the best culation of elastic modulus.36 As demonstrated by cer-
example of imprecision with respect to cervical evalu- vical elastography studies, simply measuring the
ation. The first published use of elastography in the contact force, trying to maintain a constant force on
pregnant cervix, in 2007, used manual (extrinsic) the transducer, or deforming the tissue by a certain
compression for tissue deformation.29 Similar to the amount is insufficient to define applied force.
device of the 1960s,25 marked measurement variability One potential solution to this problem is shear
was noted, attributed in large part to an inability to wave elasticity imaging.37 Shear wave elasticity imag-
standardize the force applied by the operator. Subse- ing is much less reliant on applied force than strain
quently, another group, this time using the intrinsic elastography because deformation is done with
technique, also noted an inability to quantify applied remote palpation, a relatively long-duration acoustic
force.30 A study in which the investigators attempted pulse (approximately 100 times longer than B-mode
to standardize tissue deformation by applying a com- imaging pulses) that pushes the tissue a few microns.
pression of exactly 1 cm to various regions of interest This causes the immediately adjacent tissue to move,
consistently demonstrated that tissue closest to the then the tissue next to that, and so on, thus inducing

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Shear wave elasticity imaging packages are
commercially available on most high-end clinical
ultrasound systems but have been optimized only
for specific applications (eg, liver fibrosis assessment
or classification of tumors in the breast, thyroid, and
prostate).37 The cervix, as compared with these tis-
sues, is heterogeneous, and a further complication is
that its viscosity dramatically changes during preg-
nancy, but still the technique appears to be more
reliable than strain elastography if data are carefully
acquired and interpreted.38–40 Two cross-sectional
studies using shear wave elasticity imaging techni-
ques on commercially available systems in pregnant
women showed promise, but logistics limited clini-
cal usefulness in one of them41 and measurement
variability was prohibitively large in the other.42
Another feasibility study in pregnant women at term
demonstrated better reliability, but required a pro-
Video 1. Shear wave in human cervix. To create a shear totype transducer (with a linear array with the ultra-
wave, a high frequency ultrasound pulse (“push pulse”) sound waves parallel to each other instead of the
gently pushes the tissue a tiny amount (microns). The speed traditional curvilinear endocavity array in which
of the shear wave can be tracked for a few microseconds as it the waves are more complicated) for correct data
propagates outward over a small area (mm) from proximal to
interpretation.39,40
distal along the cervix. The video shows the prototype linear
transducer that was used to generate the shear wave taped to Other quantitative ultrasound methods are also
the operator’s finger, then a drawing of the transducer con- under development for cervical assessment. These
tacting the cervix. A linear transducer was used, as wave include estimation of ultrasonic attenuation (loss of
behavior can be complex and unpredictable with curvilinear ultrasonic energy as a function of distance), which
transducers (such as a typical transvaginal transducer). The addresses hydration status and collagen organization
red box demonstrates the area where the shear wave was
tracked in the cervix. Time (microseconds) is shown across in the cervical extracellular matrix,43 and analysis of
the top. The Y axis shows depth (mm) into the cervix. The backscattered ultrasound properties to assess intrica-
colors represent tissue displacement (microns) as shown in cies of extracellular matrix microstructure.44
the bar on the right. Video creator: Lindsey Drehfal. Illus- Although these new methods to assess cervical
tration by Helen Feltovich, MD, MS. Used with permission.
softness and microstructure may someday produce
viable biomarkers, they currently are experimental
a shear wave. Shear waves in soft tissue propagate at and therefore practitioners, again, have only their
approximately 1–10 m/s (100 times more slowly than fingers to assess softness.
ultrasound waves), so B-mode image data can be used
to track the shear wave and estimate its speed.
Other Biomarkers
Because shear wave speed is directly proportional to
tissue softness (shear waves move more slowly in soft Measurement imprecision may explain why many
tissue compared with stiff), shear wave speed estima- studies comparing (the gold standard) Bishop score
tion can objectively quantitate tissue softness (Video 1, with transvaginal ultrasound cervical length, elastog-
available online at http://links.lww.com/AOG/A965, raphy, or both for predicting (term or preterm) labor
shows a shear wave propagating through cervical tissue). or successful induction of labor are negative or
inconclusive. For instance, in a review and meta-
analysis of four studies (total n5323), vaginal delivery
was predicted by cervical elastography (diagnostic
OR 5.24, 95% CI 3.23–8.50) and transvaginal ultra-
sound cervical length (diagnostic OR 4.94, 95% CI
2.72–8.98), but not by Bishop score (diagnostic
OR 4.6, 95% CI 0.69–30.94).45 However, a large
Scan this image to view Video 1 on study (n599) that was excluded from this analysis
your smartphone. showed no benefit of elastography.46 In contrast,

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Unauthorized reproduction of this article is prohibited.
a meta-analysis of studies of prediction of induction a 2017 systematic review using multiplex analysis
success concluded that transvaginal ultrasound cervi- concluded that no one of these, or any combination,
cal length offered no advantage over Bishop score predicts spontaneous preterm birth51 nor does the
(likelihood ratio 1.82, 95% CI 1.51–2.20 for transva- combination of an imaging and a biological bio-
ginal ultrasound cervical length and likelihood ratio marker; the AUC for prediction of spontaneous pre-
2.10, 95% CI 1.67–2.64 for Bishop score)47 and a Co- term birth with transvaginal ultrasound cervical
chrane database review comparing transvaginal ultra- length and fetal fibronectin in the Nulliparous Preg-
sound cervical length with Bishop score to determine nancy Outcomes Study: Monitoring Mothers-to-Be
need for preinduction cervical ripening showed no study was 0.67 (95% CI 0.64–0.70).19
difference in the primary outcome of vaginal delivery
(relative risk 1.07, 95% CI 0.92–1.25).48 A 2015 A TIMELESS DISCUSSION: DOES CERVICAL
review including prospective observational trials, EVALUATION MATTER?
RCTs, and systematic reviews also concluded that The other possible explanation for why many studies
transvaginal ultrasound cervical length confers little of predicting (term or preterm) labor or successful
advantage over Bishop score, modified Bishop score, induction have been negative or inconclusive is that
or dilation alone for predicting success of induction of cervical evaluation does not matter. The fact that the
labor or onset of labor at term.23 On the other hand, clinical gold standard is a poor predictor of delivery
another recent systematic review and meta-analysis timing is disturbing enough, but there are also several
reported a moderate benefit of transvaginal ultra- puzzling inconsistencies when it comes to the cervix.
sound cervical length at 37–41 weeks of gestation For instance, cerclage in a woman with a short cervix
for predicting spontaneous labor: a woman with a cer- reduces risk of spontaneous preterm birth if she has
vical length of 30 mm has less than a 50%, whereas a history of spontaneous preterm birth, but not if she
one with a cervical length less than 10 mm has greater does not.52 Also, intramuscular progesterone reduces
than an 85%, chance of delivering within 7 days.20 risk of spontaneous preterm birth in a woman with
However, the pooled sensitivity in this analysis for a history of spontaneous preterm birth (regardless of
cervical length less than 30 mm was only 64% and cervical length), but not in a nulliparous woman with
pooled specificity only 60%. a short cervix,53 whereas vaginal progesterone re-
Disturbingly, the clinical gold standard (Bishop duces risk in all women with a singleton gestation
score) is itself a poor predictor of labor success.49 Per- and a short cervix.54 Perhaps most puzzling is that
haps that is the reason that imaging biomarkers like a woman with second-trimester pregnancy loss result-
transvaginal ultrasound cervical length are not the ing from “cervical insufficiency” has a better than 60%
only kind of biomarkers that have been explored for chance of subsequent term delivery, even without
predicting timing of delivery. For instance, fetal fibro- intervention.55
nectin, a protein released into cervicovaginal secre- Another important observation is that most
tions when adhesion of the fetal membranes to the women with an unfavorable cervix will deliver
uterus is disrupted, can signify an increased risk for vaginally in time, especially if they are Dutch as
impending delivery. Unfortunately, fetal fibronectin opposed to American. Specifically, a post hoc analysis
does not appear to be especially useful. For instance, designed to investigate whether cervical ripeness
a recent systematic review and meta-analysis of RCTs should play a role in the decision for or against
of women at 23 0/7 to 34 6/7 weeks of gestation with induction of labor in women with gestational hyper-
threatened preterm labor demonstrated that the test is tension or mild preeclampsia at greater than 36 weeks
valuable only if a woman’s transvaginal ultrasound of gestation was performed in a cohort of Dutch
cervical length is 20–29 mm (because above this women (approximately three fourths of them nullip-
range, the risk of preterm birth is low, and below this arous) who had been randomized to induction
range, it is high enough that intervention should be (n5377) or expectant management (n5379).56
initiated).50 Furthermore, the Nulliparous Pregnancy Eighty-five percent of those with an unfavorable cer-
Outcomes Study: Monitoring Mothers-to-Be pro- vix ultimately delivered vaginally. Similarly, in a sec-
spective cohort study showed that in nulliparous ondary analysis of a Maternal-Fetal Medicine Units
women, fetal fibronectin screening at 22–30 weeks of trial (pulse oximetry), 63% of nulliparous patients
gestation has a low predictive value for spontaneous (n51,347) with an unfavorable cervix at greater than
preterm birth (AUC 0.59, CI 0.56–0.62).19 Hundreds 36 weeks of gestation delivered vaginally (including
of other bodily fluid biomarkers have been evaluated 39% [28/71] of those who were allowed to remain in
for prediction of spontaneous preterm birth, but a latent phase for more than 12 hours after membrane

58 Feltovich Cervical Evaluation OBSTETRICS & GYNECOLOGY

Copyright ª by The American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
rupture and oxytocin).57 It would be interesting to wrote that after the eighth month, the midwife should
speculate on why a Dutch woman with an unfavorable “dilate the orifice of the uterus, anointing it with her
cervix has a better chance at vaginal delivery than her finger at frequent intervals.”14 In other words, Soranus
American counterpart, but the point is that most recommended membrane stripping. Interestingly,
women with an unfavorable cervix can deliver vagi- a 2015 RCT of membrane stripping to hasten cervical
nally. This begs the question of the importance of ripening during labor induction in nulliparous patients
cervical evaluation for decision-making about induc- with an unfavorable cervix found that time to delivery
tion of labor. was statistically significantly shorter in women whose
Even the need for intrapartum cervical evaluation membranes were stripped (n5198) compared with
is debatable; a Cochrane review of intrapartum those whose membranes were not (n5202).63
vaginal examination reported that knowing dilatation Remarkably, the only apparent difference between
does not help predict timing of delivery.58 Further- the technique used in the 2015 study and that taught
more, a longitudinal study of laboring women (spon- by Soranus is that today practitioners wear gloves.
taneous n5112, induced n532) suggested that Gloves or no, Soranus’ midwives, like today’s
assessment of dilatation is possible without vaginal practitioners, must have been plagued by uncertainty
examination: a correlation was found between height over delivery timing, likely underscored by the same
(above the anus) of a purple line in the buttocks cleft frustration over determining the favorable compared
(presumably as a result of increasing intrapelvic pres- with the unfavorable cervix. The NICHD, SMFM,
sure as the fetal head descends) and cervical dilation and College workshop on preventing cesarean deliv-
(r5+0.36, P5.0001).59 These authors (midwives) ery, while recommending that elective induction be
argue that cervical examination is uncomfortable, offered only to women with a favorable cervix, also
uninformative, and, ultimately, unnecessary. highlighted the lack of consistent definition, either
This is the exact discussion the midwives and in clinical practice or research, of this entity.8 This
obstetricians were having in the 1930s (Penny, Br should not come as a surprise: assessment of dilatation
Med J), and the midwives are not wrong. In fact, is inaccurate, assessment of softness so subjective that
a February 2017 College Committee Opinion recom- it is often eliminated from modified Bishop scores,
mends minimizing interventions during labor because and, although length can be reliably measured, its
many are not of proven benefit, and patient satisfac- interpretation is variable (a short cervix, whereas most
tion is higher without them.60 often defined as 25 mm or less, is also defined vari-
An unfortunate truth pertinent to this discussion is ously as 10 mm, 20 mm, or 30 mm3). Given such
that currently, the best biomarker for evaluating the imprecision around measuring the parameters that
cervix (transvaginal ultrasound cervical length) is not comprise a scoring system for a favorable cervix,
even that good. In the Preterm Prediction Study, only how could there be a clear definition?
27% of women with a second-trimester short cervix In summary, the inability to meaningfully define
delivered before 37 weeks of gestation and fewer than properties of the pregnant cervix, a supposed
18% before 35 weeks of gestation.1 In a large retrospec- prerequisite to understanding it, may explain why
tive analysis (n56,877 women), even a very short cervix not much progress has been made in terms of
(less than 15 mm) conferred only approximately a 50% predicting timing of delivery. Perhaps, for instance,
chance of delivering at less than 32 weeks of gestation.61 this explains why the Born Too Soon Preterm Pre-
Careful read of the original study examining the rela- vention Analysis Group discovered that even if all
tionship between ultrasonographic cervical length and women were screened, all at-risk pregnancies identi-
spontaneous preterm birth reveals that, although 76% fied, and all available interventions applied appropri-
of preterm births were predicted by a transvaginal ultra- ately, the preterm birth rate would be reduced by
sound cervical length less than 39 mm before 30 weeks a disappointingly tiny 5% of the current rate (an
of gestation in a small cohort (n5178), digital examina- absolute reduction of approximately 0.5%).64
tion alone predicted nearly as many (71%).62

A TIMELESS DILEMMA: WHAT IS A PRECISION MEDICINE FOR PARTURITION: A


“FAVORABLE” CERVIX? CONTEMPORARY ANSWER TO
Soranus may not have had any formal scoring system, TIMELESS ISSUES?
but he clearly had opinions about the implications of In the 1950s and 1960s, while Drs Bishop and
an unfavorable cervix at term, because he gave strong Friedman and others were focused on the cervix,
recommendations about making it more favorable: he Dr. Jean Dausset and his colleagues discovered the

VOL. 130, NO. 1, JULY 2017 Feltovich Cervical Evaluation 59

Copyright ª by The American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
role of the major histocompatibility complex in cancer, but recently this reductionist approach, in
immune function, which spurred understanding of which cancer is considered a singular entity that can
how biological uniqueness shapes disease, and ulti- be treated by addressing single targets or pathways,
mately led to the Human Genome Project.65 This is has been replaced by a systems biology approach.66
the cornerstone of precision medicine. Systems biology combines multiomics profiling
In January 2015, President Obama introduced (genome, transcriptome, proteome, metabolome) with
his Precision Medicine Initiative, a $215 million clinical data and computational and mathematical mod-
endeavor to collect genetic information from a million eling.67 This systematic approach facilitates study of
American volunteers to promote personalized medi- complex interactions, and the effects of those interac-
cine or the tailoring of therapeutic approach to each tions, within specific biological systems. It relies on bio-
individual by accounting for variation in a multitude markers, both imaging (eg, nanotechnology) and
of factors from their genetics to their external envi- biological (eg, DNA, RNA, or proteins in blood), to
ronment. A particularly successful example of this detect molecular processes, which, in turn, can lead to
approach is found in the field of oncology. Cancer, development of targeted therapies. This “predictive, pre-
like all diseases, is the end result of a number of ventive, personalized and participatory (P4)”65 approach
pathways that can be affected in a multitude of ways. has led to the previously unthinkable: certain cancer
Researchers previously dreamed of a single cure for phenotypes have become or are becoming curable.

Fig. 3. A simplified schematic of a systems biology approach to precision medicine for parturition. The left portion of the
figure shows a theoretical framework of parturition. Continual interaction of multiple maternal and fetal factors (intrinsic and
extrinsic) contributes to activation or quiescence of codependent pregnancy tissues to determine the ultimate parturition
phenotype. The middle and right portions of the figure show identification of quantitative biomarkers (using imaging
and minimally invasive acquisition of biospecimens), which leads to identification of molecular processes through bio-
informatics, which in turn leads to mathematical and computational modeling of molecular processes and their bio-
mechanical and microstructural effects, through which the molecular signature of parturition is revealed. This could allow
precise targeting of specific therapies for abnormal parturition. BMI, body mass index. The mathematical and computational
modeling portion of the figure is reprinted with permission from House M, Feltovich H, Hall TJ, Stack T, Patel A, Socrate S.
Three-dimensional, extended field-of-view ultrasound method for estimating large strain mechanical properties of the cervix
during pregnancy. Ultrason Imaging 2012;34:1–14.
Feltovich. Cervical Evaluation. Obstet Gynecol 2017.

60 Feltovich Cervical Evaluation OBSTETRICS & GYNECOLOGY

Copyright ª by The American College of Obstetricians


and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
Although the term “precision medicine” was not length predicted spontaneous preterm birth in the
used before 2015, the concept has been around for much Nulliparous Pregnancy Outcomes Study: Monitoring
longer, including in the field of obstetrics. For instance, Mothers-to-Be study with an AUC of 0.67 (95% CI
this statement is from a 2013 review of strategies for 0.64–0.70).71 Because both tests predict spontaneous
spontaneous preterm birth prediction and prevention: preterm birth only marginally better than a coin flip,
“To refer to preterm birth as a single condition which the suggestion to do transvaginal ultrasound cervical
could be predicted by a single test and prevented by length in women with a positive blood test could be
a single intervention is a flawed concept that has resulted interpreted as chasing one’s tail.
in unrealistic expectations and therapeutic nihilism.”68 Alternatively, it could be interpreted as framing
In other words, like precision medicine for cancer, the quest for a better approach in which multiple
precision medicine for parturition would have to take biomarkers are combined to unveil the molecular
into consideration the amazing complexity of preg- underpinnings of parturition. A simple schematic of
nancy tissues, their molecular interactions, and the a precision medicine approach to parturition through
environments in which they exist. The cervix alone is systems biology is depicted in Figure 3. It suggests how
very complex with an extracellular matrix consisting of a combination of imaging and biological biomarkers
interweaving layers: inner and possibly outer zones of that elucidate behavior of and interactions among the
collagen fibers oriented parallel to the endocervical cervix, uterus, membranes, fetus, placenta, and sur-
canal (hypothesized to prevent the cervix from tearing rounding environment could provide data for bioinfor-
off the uterus during dilatation) and a circumferential matics studies (effectively, investigations of normal and
middle band of collagen (hypothesized to serve as pathologic molecular processes in which computer pro-
a ratchet to control dilation) that seems to undergo the gramming is used to process large amounts of data).
most dramatic change during pregnancy.69 Relation- From there, mathematical and computational modeling
ships of proteins, cells, and other factors within the could be used to profile the molecular signature of
cervical extracellular matrix clearly determine its bio- parturition. Profiling of various scenarios (phenotypes)
mechanical properties such as softening, shortening, of parturition (eg, normal term delivery compared with
and dilation.69 Furthermore, the internal os, as com- spontaneous preterm birth resulting from membrane
pared with the external, has greater collagen crosslink rupture or resulting from hemorrhage) could lead to
heterogeneity and a circumferential ring containing novel approaches to abnormal parturition.
50–60% smooth muscle that can be induced to contract A precision medicine approach could thus help
ex vivo (ie, there appears to be a functioning sphinc- obstetric providers figure out what they need to know.
ter).70 This complexity and heterogeneity has implica- Who is most at risk for spontaneous preterm birth and
tions for determining which areas in the cervix may be which intervention(s) will be best? Who might benefit
most relevant for investigation and perhaps differences from awaiting spontaneous labor instead of induction
in regions studied (ie, distal cervix compared with if delivery is elective? Who might benefit most by
proximal) explain part of why studies conflict. cervical ripening (and what kind) if delivery is
Other pregnancy tissues such as the placenta, medically indicated? Finally, who should consider
myometrium, and membranes are as complex as the cesarean delivery without labor because she is nearly
cervix, and their interactions within the context of the certain to fail induction of labor? In other words, the
environment created by the maternal and fetal com- timeless question of “When will she deliver?” could
partments determine the process of parturition (term finally have an answer.
or preterm).69 Figure 3 shows a theoretical framework
for parturition that can accommodate an infinite num-
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