Changes in uterine physiology

The uterus consists of bundles of smooth muscle cells which are spontaneously contractile. During pregnancy, rapid changes are re­quired to prevent contractility, accommodate the growing fetus, and supply sufficient nutrients and oxygen.

The muscle cells are arranged into three discrete layers separated by thin layers of connective tissue composed of collagen, elastic fibres, and fibroblasts. The innermost layer contains longitudinal fibres. The middle layer runs in all directions and contains the vas­cular supply and the outer layer has both circular and longitudinal fibres that are partly in continuation with the ligamentous support of the uterus (13). The prepregnancy uterus weighs 40-100 g. During pregnancy, this increases to 300-400 g at 20 weeks and 800-1000 g at term, a 20-fold increase. This growth is due to hypertrophy and elongation of the smooth muscle cells. Prior to pregnancy the smooth muscle cells are approximately 50 μm in length and this increases to between 200 and 600 μm by term (13). In later preg­nancy, the enlargement is more prominent at the fundus, changing the shape of the uterus from the pear shape seen prior to pregnancy to an ovoid shape in the second and third trimesters. The isthmus is the junctional zone between the cervix and the body of the uterus. Regular contractions after 28 weeks' gestation cause the isthmus to stretch and thin. This is completed during labour to form the lower segment, a relatively avascular, thin part of the uterus. The cavity ex­pands from 4 to 4000 mL by term. These changes are stimulated by the increasing levels of oestrogen and progesterone and the effect of the growing fetus.

The blood supply to the uterus prior to pregnancy is almost exclu­sively via the uterine arteries.

The innervation of the uterus is predominantly via the autonomic nervous system. The sympathetic supply from T12-L1 produces vasoconstriction and uterine contraction. The parasympathetic fibres from S2-S4 stimulate vasodilation and uterine relaxation (42). These effects are modulated by hormonal effects. The uterus also has afferent nerve supplies with the main sensory fibres of the cervix arising from S1-S2, and from the uterus from T11-T12. Ferguson’s reflex describes the afferent pathway from the cervix to the hypothalamus whereby stretching of the cervix simulates release of oxytocin (43).

The pregnant human myometrium has spontaneous electrical ac­tivity which is generated from pacemaker cells then transmitted over the whole of the uterus (13). Gap junctions are low-resistance con­nections between two cells that allow rapid propagation of electrical activity allowing synchronous contraction across the myometrium

(44). The continuation of successful pregnancy is dependent on myometrial quiescence until term. The myometrium in pregnancy has much greater compliance than non-pregnant myometrium.

(45). In addition, a number of hormones such as prostacyclin, calci­tonin gene-related peptide, and progesterone are thought to main­tain quiescence by increasing the resting membrane potential and impairing conduction of electrical activity.

Uterine contractions are measurable as early as 7 weeks of ges­tation; although these are very high frequency (two per minute), they are very low intensity (1-1.5 kPa) (46). These continue until approximately 20 weeks’ gestation before gradually increasing in fre­quency and amplitude until term (46). These are often felt by the mother as Braxton Hicks contractions. The sensitivity of the uterus to oxytocin is dependent on the gestational age (46, 47). Prior to 20 weeks’ gestation the uterus is insensitive to oxytocin and following 30 weeks’ gestation, sensitivity is markedly increased. Considerable individual variability exists and therefore oxytocin infusion rates can only be calculated based on the rates of uterine activity (47). In contrast, prostaglandins can induce contractions at any gestational age, by directly affecting myometrial cyclic adenosine monophos­phate or calcium mobilization.

As uterine activity increases during pregnancy, the cervix softens and the canal dilates. In late gestation, the fetus continues to grow but the uterus stops growing, therefore tension across the uterine wall increases. This stimulates the expression of oxytocin and pros­taglandin receptors, sodium channels, and gap junction proteins in preparation for labour. Downregulation of progesterone and the other factors associated with uterine quiescence also occurs.

Clinical considerations

• Cervical changes can be used to predict gestation of labour in prematurity but great individual variation does occur in low-risk women and therefore cervical changes are poor predictors of the gestation at which labour will start.

• The pain of labour is primarily due to cervical dilatation. While Braxton Hicks contractions can be high pressure and cause dis­comfort they are not normally associated with pain, and changes in the cervix are relied on to indicate possible labour.

• The stretched lower segment of the uterus is relatively avascular and thin which makes it the place of choice for incision at cae­sarean section as it recovers well and is less prone to rupture in future pregnancies. However, the lack of muscle fibres in this seg­ment means that women with placenta praevia are at risk of exces­sive bleeding from the vascular placental bed as the lower segment struggles to contract adequately and constrict the vessels.

• Evidence that progesterone is involved in maintaining uterine quiescence during pregnancy is supported by several large trials and meta-analyses suggesting that progesterone may prevent or delay preterm labour in those at high risk (48, 49). In add­ition, progesterone antagonists such as mifepristone can induce labour.