Qualitative estimates of cervical strength are common in the clinical environment, but a quantitative definition is lacking and, without such a definition, objective assessment is not possible. Subjective terms, such as ‘soft,’ ‘ripe,’ ‘mature,’ or ‘favorable’ are often applied to a weak cervix and ‘firm’ or ‘unfavorable’ to its strong counterpart. Cervical strength depends on several factors, including its anatomic features (length of cervix, width of mucosa, width of stroma) and tissue properties. For example, consider the evolution of cervical tissue strength over time. An individual patient has a baseline tissue strength. As gestational age advances, her cervix becomes progressively weaker (‘softens’)3, 4. Close to labor, her cervix becomes weaker still (‘ripens’). It is known that an active inflammatory process has a role in the ‘ripening’ process5–7. What is not known is to what degree baseline strength, cervical softening and cervical ripening determine tissue properties at a particular moment in time.
One approach to quantifying the strength of the cervical stroma borrows from the engineering technique of characterizing the mechanical properties of materials through the use of constitutive models. A constitutive model is a mathematical model that relates the stress response in a material to its deformation history. In complex, multicomponent materials, the macroscopic response is controlled by the behavior of its constituent parts. During pregnancy, the cervical stroma is assumed to be the load bearing part of the cervix. Its constituent parts are predominantly extracellular matrix components (collagen, proteoglycans, elastin and water)7 and cellular components (fibroblasts, smooth muscle and vessels). The extracellular matrix predominates; the cellular components are not present in large quantities8 and are not thought to significantly contribute to the mechanical response9.
In the case of the cervix, only two notable constitutive models have been developed. The first model attempted to explain the reduction in stiffness of cervical tissue over the course of pregnancy using the theory of fiber-reinforced composites10, 11. It was based on the assumption that the tissue can be considered mechanically equivalent to a fibrous network (corresponding to the collagen fibers), embedded in a ground substance (mainly composed of hydrated glycosaminoglycans). The model achieved its objective in a semi-quantitative way by showing how decreased collagen concentration, decreased collagen alignment, changes in collagen–ground substance reinforcement and increased hydration combined to reduce tissue stiffness by a factor of 12 during pregnancy. However its underlying assumptions of linearity and small deformations make it restricted to simple estimates of the material properties.
More recently, a three-dimensional, constitutive model for the large-strain, time-dependent mechanical behavior of the cervical stroma in pregnancy was proposed by our group12. The model captured the global tissue response, which was controlled by the cooperative contributions of the major constituents. In terms of mechanical behavior, the dominant constituents were the collagen fibers and the hydrated network of glycosaminoglycans. The collagen network provided stiffness in tension. The glycosaminoglycans (proteoglycans and hyaluronic acid), owing to their high negative fixed charge density, drew water into the tissue and created a high osmotic pressure responsible for the compressive stiffness of the tissue. Free interstitial fluid flowed in the tissue according to pressure gradients within the porous network, and was a major contributor to the short-term properties of the tissue.
A constitutive model is evaluated on its ability to predict mechanical behavior under different modes of deformation (e.g. tension, compression). If the model predicts different types of mechanical behavior in vitro, presumably it reflects physical reality in vivo. Progress toward a robust constitutive model of cervical stroma, that allows a more complete understanding of its physical properties, will be an important step in quantifying the factors contributing to cervical function and thus dysfunction.
Loading refers to the forces that act to cause cervical deformation, and occurs in two ways: passive and active. Passive loading, the forces acting to cause cervical deformation in the absence of uterine contractions, arises when the expanding amniotic cavity comes into contact with the cervix, usually in the early second trimester. Contributing loading components include tensile stresses along the uterine wall associated with the growth of the baby and the amniotic membrane, hydrostatic pressure and intrauterine pressure. Superimposed on the passive load is active loading due to uterine contractions. The cervix must resist the total load (active + passive) in order to remain closed.
Significant challenges are inherent in estimating cervical loading. The cervix rests on the posterior wall of the vagina. It is attached circumferentially by the endopelvic fascia and lower uterine segment. The cervix is loaded superiorly by the decidua, which also has an adhesive function as it mediates mechanical contact between the fetal membranes and cervix13. In fact, loss of adhesion is thought to be related to the elevated fetal fibronectin in patients at risk for preterm delivery14. In summary, loading during human pregnancy is unique to the geometry and pelvic forces of the individual patient. Although progress in the study of cervical strength may be aided by animal models15, 16, it is difficult to envision an adequate animal model of human cervical loading.
The underlying assumption of cervical insufficiency is that the cervix is unable to resist a normal passive load. Yet this assumption begs the question: how much is a normal passive load? How is the load distributed? Although the cervix is passively loaded for the vast majority of pregnancy, most clinical studies focus exclusively on active loading. For example, the cause of preterm delivery in multiple gestation or polyhydramnios is suspected to be increased uterine distension leading to increased uterine contractility17. Yet increased uterine distension logically causes increased passive loading as well. Clinical studies of the total (passive + active) load may provide more insight than focusing on active loading alone.
The clinical case of cervical ‘change’, whether it is described as funneling, effacement or dilation, is a special case of a more general problem, namely that of solid body deformation. A more precise term for cervical ‘change’ is deformation. Cervical funneling, effacement and dilation are better described as clinically significant deformation of the cervical stroma, a description that incorporates both clinical significance and solid mechanics. Solid mechanics terminology is a highly technical field18. Investigation of clinically significant deformation requires a partnership between engineers and clinicians—the former because of their understanding of how to investigate soft material deformation and the latter because of their understanding of deformation that is clinically important.