8 The endocrinology of parturition in the human P H I L I P J. S T E E R
One of the commonest questions that obstetricians are asked in the antenatal clinic is 'can you tell me when my baby will come'. At present, the honest answer is 'no'. Many attempts have been made to devise tests which will allow a more informative response but so far they have simply emphasized the extreme complexity of the control of parturition in the human. Some of the hormones known to be involved in parturition are: oestrogens, progestogens, relaxin, catecholamines, oxytocin, vasopressin and prostaglandins. (Despite their importance in ruminants, the adrenal hormones do not appear to play a significant role in human parturition and will therefore not be considered.) The effects of these various hormones are mediated within the cell by so-called 'second messengers' such as cyclic AMP and phosphoinositides and their associated guanine nucleotide-binding regulatory proteins (G proteins). This chapter reviews current concepts of the onset and maintenance of labour in the human. To set the concepts in context it is necessary first to summarize the physiology of uterine contractility and the process of birth.
P H Y S I O L O G Y OF UTERINE C O N T R A C T I O N S AND BIRTH IN THE H U M A N
During pregnancy the human fetus floats suspended in its cushion of liquor within the retaining bag of uterine muscle, protected from the environment by its mother's homoeostatic mechanisms. The uterine muscle remains relatively quiescent; there are non-propagating highly localized contractions ('A' waves) and propagating but infrequent (every 10 to 15min) contractions ('B' waves or Braxton-Hicks contractions). This is not the default condition of myometrium, as in vitro it contracts spontaneously approximately every 3rain. It is evident therefore that its contractility is being suppressed; at present the strongest candidate for the suppressant is progesterone (the so-called 'progesterone block hypothesis' of Csapo (1970)). However, it is also clear that uterine activity in human labour is not simply the release of inhibition, but also represents a cascade of events which initiate and augment uterine contractility. During pregnancy, the cervix remains firm and closed, as in the nonpregnant state. However, as the onset of labour approaches, it 'ripens' and BailliOre's Clinical Endocrinology and Metabolism-333 Vol. 4, No. 2, June 1990 Copyright © 1990, by Bailli6re Tindall ISBN 0-7020-1463-X All rights of reproduction in any form reserved
becomes soft and stretchy, so that when contractions begin it can dilate and allow the fetus to pass through it. During labour the fetus is propelled through the softened cervix by regular uterine contractions. At a cellular level, contractions result from the phosphorylation of myosin (by myosin light-chain kinase), causing it to interact with actin within the muscle fibrils. The interaction shortens the fibrils and thereby the cell itself. This raises the tension in the uterine wall, and results both in a rise in intrauterine pressure and a direct force acting down the long axis of the fetus. All of these act together to force open the cervix against its natural elastic recoil. The action of myosin light-chain kinase requires the protein calmodulin, which is normally present in a free form in the cell and as such is inactive (Figure 1). However, when an action potential or similar stimulus causes a rise in the intracellular calcium level (both from an influx of calcium into the cell and the release of calcium from the sarcoplasmic reticulum), calcium and calmodulin form a complex which has a much higher affinity for the myosin light-chain kinase. Once the complex binds to the kinase, phosphorylation can proceed. When the calcium level subsequently falls again, the calmodulin-calcium complex dissolves and the free calmodulin dissociates from the kinase which is thereby inactivated.
P°tint'' Extracellu~Sarcopl lar asmic Ca2+~m
membrane Calcium Calmodulin Myosin A T P ~ LCK ~
~ADP "~ Myosin-phosphate
"~ Aetomyosin-P Actin
Figure 1. Physiologyof uterine smoothmusclecontraction. MLCK,myosinlight-chain kinase. It is appropriate here to consider the role of 'second messengers' in uterine contraction. Hormones stimulating (or suppressing) uterine activity bind to specific receptors on the outside of the cell membranes. At one time it was thought that all hormones causing uterine contraction worked through cyclic guanosine monophosphate (cGMP) and all hormones causing uterine relaxation worked through cyclic adenosine monophosphate (cAMP). While cAMP is still thought to play an important part in the mechanism of relaxation, the role of cGMP has been disputed. Instead, the role of phosphoinositides (a component of all cell membranes) as the link between hormone binding and contraction has become apparent (Schrey et al, 1986, 1987, 1988; Liggins and Wilson, 1989). The current suggestion is that the binding of specific ligands to their receptors activates phospholipase C which
ENDOCRINOLOGY OF PARTURITION
hydrolyses phosphatidyl 4,5-bisphosphate to diacylglycerol and inositol trisphosphate. This last acts to mobilize intracellular calcium from the sarcoplasmic reticulum. A secondary pathway (Figure 2) whereby diacylglycerol activates protein kinase C, which in turn promotes the combination of active lipocortin with inactive phospholipase A2 to produce active phospholipase A2 has also been postulated (Liggins and Wilson, 1989). Calcium release also promotes phospholipase A2 activation, which causes the release of arachidonic acid from membrane phospholipids. Arachidonic acid is the substrate required for the production of prostaglandins, amongst the most potent known stimulators of uterine contractility. Surprisingly, despite intensive study of prostaglandins for the last 20 years, the precise mode of action of this class of substances remains obscure; the front runner appears to be modulation of calcium fluxes (Huszar and Walsh, 1988).
\ / "------~'*~----i~Ca2* MLC~//K
Phosphatidyl grvcerof Active j phospholipaseJ
Prostaglandins Figure 2. Possible actions of second messengers in the initiation of uterine contractions. SR, sarcoplasmic reticulum; PIP2, phosphatidyl inositol 4,5-bisphosphate; IP~; inositol 1,4,5trisphosphate; DG, diacylglycerol; MLCK, myosin light-chain kinase.
A second level of control of uterine contractility has been suggested; by means of the guanine nucleotides. A separate set of receptors communicates with a pair of guanine nucleotide-binding regulatory proteins (G proteins) in the cell membranes, one of which enhances the production of cAMP (by stimulating adenylate cyclase) while the other inhibits it. There is some evidence that the G proteins are also involved in the regulation of the inositol trisphosphate system. For an exhaustive account of the biochemistry of uterine muscle contraction, readers are referred to the excellent review by Carsten and Miller (1987).
The role of oestrogens (the most active being oestradiol-17-[3) in parturition is complex and sometimes apparently contradictory. On the one hand oestrogens promote the formation of gap junctions between adjacent myometrial cells which provide low-resistance pathways for the conduction of electrical impulses from one myometrial cell to another, thus allowing synchronized uterine contractions (Fuchs and Fuchs, 1984). They also soften the cervix (Gordon and Calder, 1977), and these two actions combined might seem to promote labour. However, on the other hand, oestrogens raise the myometrial cell membrane potential and so suppress uterine activity (Fuchs and Fuchs, 1984). Thus oestrogens are best seen as 'priming agents' which help to create conditions favourable to labour but do not play an active role in parturition itself.
The major naturally occurring progestogen in the human is progesterone itself. It has a two-fold mechanism by which it suppresses uterine activity; it acts directly via its own receptors, and also acts by inhibiting the formation of oestrogen receptors. The direct mechanisms of action of progesterone remain obscure, but the development of the progesterone antagonist RU486 (mifepristone) which leads to abortion in 60% of first trimester pregnancies has illustrated dramatically just how potent its actions must normally be (Webster et al, 1985; Cameron and Baird, 1988; Huszar and Walsh, 1988). Currently postulated mechanisms include diminished cell wall permeability to calcium, increased intracellular calcium binding, and reduced phosphatidyl inositol and prostaglandin biosynthesis (Huszar and Walsh, 1988). The inhibition of oestrogen receptor function prevents the development of gap junctions, vital to the effective propagation of contractions. Despite all this evidence that progesterone is very important during pregnancy, the evidence that it is involved in parturition is weak. Most studies of progesterone concentrations in pregnancy have shown a continuing rise right up to the onset of labour (Anderson, 1980). Csapo's original progesterone block hypothesis suggested that a local direct action of progesterone from the placenta on the myometrium was the critical factor, but the hypothesis has been impossible to confirm or refute. RELAXIN
Although the existence of relaxin has been known since its discovery by Hisaw in 1926, its function in the human remains speculative. It is produced both by the corpus luteum of pregnancy (Khan-Dawood et al, 1989) and the endometrial decidua (Fuchs and Fuchs, 1984). Its earliest demonstrated action in rodents and cows was to relax the pelvic girdle; hence the name of the hormone. Such an action is difficult to confirm in the human, but an
ENDOCRINOLOGY OF PARTURITION
association between pelvic pain and serum relaxin levels in the human has been shown by MacLennan et al (1986a). They hypothesize that the pain is due to stretching of the pelvic girdle which facilitates passage of the fetus during labour. Further evidence for a physiological role for relaxin is that it is known to soften ('ripen') the human cervix, thus facilitating labour (MacLennan et al, 1980, 1986b). Failure of cervical ripening leads to nonprogressive labour and the need for delivery by caesarean section; one such case has been reported in association with absence of the normal level of intrapartum relaxin (Entenmann et al, 1988). Another demonstrated action of relaxin is to suppress uterine contractions, both directly (Porter et al, 1979) and by inhibition of oxytocin release from the posterior pituitary (Jones and Summerlee, 1986; Dayanithi et al, 1987). This might suggest that a fall in relaxin levels could promote parturition, and indeed relaxin levels in the human (unlike the pig) fall from the first to the third trimester (Eddie et al, 1986; MacLennan et al, 1986c; Bell et al, 1987). However, preterm labour is not associated with abnormally low levels of serum relaxin in the human (Bell et al, 1988). The fallin relaxin levels towards term might seem to conflict with the role of relaxin to relax the pelvic girdle; however, levels rise again during labour (MacLennan et al, 1986c). Such an intrapartum rise might be thought to oppose labour by suppressing uterine contractions, but Porter et al (1979) showed that although relaxin inhibits spontaneous contractions, it has no effect on those stimulated by the action of oxytocin. Although relaxin reduces the release of oxytocin from the posterior pituitary, it is not known to have any effect on the formation of oxytocin receptors in the myometrium; it is the increase in these rather than an increase in circulating oxytocin levels which plays the major role in parturition (Chard, 1989). CATECHOLAMINES The tocolytic (contraction suppressing) effect of adrenaline has been known for over 50 years. Bourne and Burn reported in 1927 that the injection of 5 minims of adrenaline into the median vein of a woman in the active phase of labour 'was followed by a complete cessation of uterine contractions during 12 min, after which the pains began again'. This observation was confirmed by Kaiser and Harris in 1950. The debate as to whether adrenaline has a physiological role in human labour has continued ever since, and is as yet unresolved. Bourne and Burn considered that adrenaline was only important in abnormal labour, when 'there is a state of emotional stress which may well induce excessive secretion of endogenous adrenaline' and thus inhibit uterine activity. They adduced as evidence the observation that 'systemic sedation and nerve-conduction blocks may in some cases shorten the length of labour by allaying apprehension'. Techniques claimed to augment labour by reducing adrenaline secretion include caudal anaesthesia (Arthur and Johnson, 1952), epidural anaesthesia (Moir and Willocks, 1967), spinal anaesthesia (Caldeyro-Barcia et al, 1950), hypnotic sleep (Caldeyro-Barcia and Alvarez, 1952) and intravenous pethidine infusions (Jeffcoate, 1963).
Mitrani et al (1975) pursued the connection of adrenaline with hypotonic labour by infusing propranolol intravenously and demonstrating a resultant marked increase in the level of uterine activity. The action of adrenaline is now known to be mediated via the [32-adrenergic receptors on the myometrial cell, with an increase in cAMP and cell membrane potential, making the myometrial cell more resistant to depolarization (Tepperman et al, 1977). a-Adrenergic receptors are also present on the myometrial cell wall, as evidenced by the stimulatory effect of noradrenaline on uterine activity (Anderson, 1980). Fetal production of catecholamines rises dramatically in response to labour, but because the placenta is extremely efficient at degrading catecholamines, it is unlikely that fetal output has any influence on the onset or progress of labour. The tocolytic effect of adrenaline described above led Bourne and Burn to suggest that 'this inhibitory action of adrenaline may have a therapeutic application in conditions when the uterus is in an irritable condition', i.e. it might have a role in the treatment of premature labour. A whole range of [3-sympathomimetics have been developed in an attempt to maximize the tocolytic effect of [32 stimulation while minimizing the [31 (cardiovascular) effects. The most popular in current use is ritodrine, used in 60% of obstetric units, with fenoterol used in 30% (Keirse, 1984). Orciprenaline, isoxsuprine, isoprenaline, salbutamol and terbutaline have all been used at some time. However, the clinical value of tocolysis remains debatable. A metaanalysis of 16 methodologically acceptable trials has shown that there is a small but significant reduction in the frequency of preterm birth and low birth weight associated with their use, but no apparent effect on perinatal mortality or morbidity such as respiratory distress syndrome of the newborn (King et al, 1988). Maternal complications can, however, be severe and include hypotension, myocardial ischaemia, and pulmonary oedema resulting from sodium retention and intravenous fluid overload (Creasy, 1987). Stimulation of glucose release can lead to ketoacidosis in the gestational or established diabetic. OXYTOCIN Oxytocin is the most potent known endogenous uterotonic agent (Fuchs and Fuchs, 1984). It is capable of eliciting contractions of the human uterus at term in concentrations calculated to be as low as 3-10 mU/ml. However, it should be noted in this context that oxytocin, like all hypothalamic hormones, is released in a pulsatile fashion (Chard, 1989). Release has been shown to increase in response to nipple stimulation (the 'let down' reflex so important in breastfeeding) and in response to stretching of the lower genital tract (Ferguson's reflex). Neither of these mechanisms is thought to have any role in the onset of labour, although the Ferguson reflex may be important in the second stage of labour (Goodfellow et al, 1983). It seems now almost certain that maternal levels of oxytocin change little during the onset and progress of labour (Padayachi et al, 1988). The major factor
ENDOCRINOLOGY OF PARTURITION
influencing the role of oxytocin is an increase in the number of myometrial oxytocin receptors. Caldeyro-Barcia and Sereno (1961) were the first to show, conclusively, the dramatic increase in uterine sensitivity to oxytocin which occurs during pregnancy; an increase which can be as much as 200-fold between early pregnancy and labour. This is paralleled by a rise in high-affinity low-capacity oxytocin receptors. Compared with the nonpregnant uterus, the number of receptors increases six-fold by 16 weeks, 80-fold by term, and 200-fold during labour (Fuchs and Fuchs, 1984; Dawood, 1989). Fetal secretion of oxytocin may also be important in the process of labour. Oxytocin can be found in the human fetal pituitary gland from 14 weeks gestation and the amount increases progressively up to term (Chard, 1989). Study of arteriovenous differences in the umbilical vessels shows a significant excess of oxytocin in the artery, suggesting fetal production (Padayachi et al, 1988). Moreover, the arteriovenous difference is greatest following spontaneous birth and lowest following elective caesarean section (Chard, 1989). However, although it may play a part, fetal oxytocin cannot be an absolute requirement for parturition, because spontaneous deliveries can occur with anencephalic fetuses which lack a posterior pituitary and in whom oxytocin cannot be detected in the umbilical circulation (Chard, 1989). Recently, oxytocin receptor blockers have been developed which show considerable ability to block uterine contractions in vitro, in experimental animals (Demarest et al, 1989) and in humans (Andersen et al, 1989). Such a blocker is the oxytocin analogue 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Ornoxytocin. It shows clinical promise at gestations above 30 weeks, but is ineffective earlier than this, presumably because of the relatively fewer receptors at early gestations and the implication that other pathways promoting labour are important in early pregnancy (Andersen et al, 1989). Therapeutic use of oxytocin in parturition
The discovery of a uterotonic factor in extracts of the posterior pituitary gland was reported by Sir Henry Dale as long ago as 1906. It took only 3 years before the extract was in clinical use for the management of postpartum haemorrhage (Blair-Bell, 1909). Over the next 10 years the use of the extract, given subcutaneously, was extended to include the acceleration of slow labour. Unfortunately its effects were unpredictable and there was a significant incidence of uterine hyperstimulation leading to rupture, often with fatal results for mother and fetus (Bourne and Burn, 1927). Theobald in 1948 reported the use of a very dilute intravenous solution (1 part of extract in 10 000 of solution) which substantially reduced this risk. This is because the half-life of oxytocin in the blood is only about 3.5 min (Fuchs and Fuchs, 1984) and thus if uterine hyperstimulation occurs and oxytocin infusion is discontinued, the effect wears off rapidly. The effects of oxytocin infusion were studied extensively by Caldeyro-Barcia and his colleagues, who established the sensitivities of the uterus to oxytocin at various stages of pregnancy and labour (Caldeyro-Barcia et al, 1957; Caldeyro-Barcia and Sereno, 1961).
The cautious approach advocated by Theobald continued to be the norm in the UK until the 1960s. He advocated the use of infusions of no more than 6 mU/min, but using this rigid limit 16% of women took more than 36 h to deliver (Theobald, 1959). This led to the suggestion that higher infusion rates should be used, and Ryan in 1960 advocated a standard infusion rate of 12 mU/min. The increasing use of transcervical intrauterine catheters to measure intrauterine pressure (first reported by Williams and Stallworthy in 1952) resulted in the introduction by Turnbull and Anderson of the concept of infusion rate titration, with the use of infusion rates up to 32 mU/min or even higher, depending upon the level of uterine activity produced (Turnbull and Anderson, 1968). About the same time, the concept of the 'active management of labour' was introduced by O'Driscoll and his colleagues at the National Maternity Hospital in Dublin (O'Driscoll et al, 1969). They recommended the augmentation of uterine activity with oxytocin in all primigravidae whose cervices failed to dilate at 1 cm/h or faster in the active phase of labour. The objective of this management was to ensure that all women in labour delivered within 24 h and they achieved this in all but 0.1%. Their initial report described the use of oxytocin in 20% of primigravid labours, but in keeping with my own observation that the mean rate of cervical dilatation in unstimutated primigravid labour is only 1.2 cm/h (Steer et al, 1984), their second report described the use of oxytocin in no less than 55% of women (O'Driscoll et al, 1973). Their most recent paper describes a fall in the augmentation rate to 41% but the most notable feature of their results is their maintenance of a remarkably low rate of caesarean section, only 5.5% for primigravidae (O'Driscoll et al, 1984). Attempts to reproduce these results in other settings have met with variable success. Boyle et al (1980) in Belfast and Cardozo et al (1982) in London augmented between 35 and 45% of primigravidae but reported intrapartum caesarean section rates in excess of 8%. Turner et al (1988), in a non-controlled study, reported a reduction in caesarean section rate in nulliparae from 15 to 11% following the introduction of active management; but, confusingly, this was not associated with an increase in the proportion of women receiving oxytocin augmentation. In addition, there was a similar decline in the caesarean section rate in multiparae over the same period, even though active management was not used in this group. Another study using historical controls has been reported by Akoury et al (1988). They increased their augmentation rate from 16 to 41% and reduced their caesarean section rate from 13 to 4.3%. They followed the oxytocin infusion regimen recommended by O'Driscoll and used infusion rates starting at 6-7 mU/min increasing in 6-7 mU/min steps up to 40 mU/min and claimed that 'with this oxytocin augmentation method, uterine hyperstimulation causing fetal distress was not encountered'. This is surprising in the light of many previous reports of adverse effects on the fetus of much lower oxytocin infusion rates. For example, Seitchik and Castillo (1982) reported hyperstimulation and/or threatened fetal distress in more than 40% of cases in which 7 mU/min or more of oxytocin was given (this is the starting dose of the O'Driscoll regimen). Arulkumaran et al (1987) have reported that 30%
ENDOCRINOLOGY OF PARTURITION
of women given 14-20 mU/min developed uterine hypertonus and that in about a third of these, abnormal fetal heart rate patterns were also seen. Bidgood and Steer (1987) reported hyperstimulation in 7 of 19 cases given oxytocin according to the O'Driscoll regimen with one case requiring emergency caesarean section because an abnormal fetal heart rate pattern developed associated with acidosis (fetal blood sample pH 7.15). In view of the finding that, in both induced and augmented labour, normal levels of uterine activity can be achieved successfully with oxytocin infusion rates not exceeding 8mU/min (Steer et al, 1985a; 1985b; Dawood, 1989), oxytocin infusion rates as high as those recommended by O'Driscoll seem to be both unnecessary and unwise. A further reason for minimizing the dose of oxytocin infused is the possibility that oxytocin may produce neonatal jaundice, a phenomenon first reported by Ghosh and Hudson in 1972. A spate of similar reports followed (Davies et al, 1973; Calder et al, 1974; Chalmers et al, 1975; Sims and Neligan, 1975; Chew, 1977). A dose-response relationship was then shown by D'Souza et al (1979), and Buchan (1979) showed that a possible mechanism was the reduction of erythrocyte deformability by oxytocin. This may result in increased capillary trapping of red cells, with a consequent increase in the rate of red cell destruction and bilirubin production rate. A further maternal risk is water intoxication (Schwartz and Jones, 1978). Oxytocin has antidiuretic properties (it is structurally similar to its companion product from the neurohypophesis, antidiuretic hormone (vasopressin)-which also has strong oxytocic actions). At oxytocin infusion rates above 16 mU/min this effect can be marked, and if a careful fluid balance chart is not kept in labour, intravenous infusion of dextrose or dextrose saline (a common practice, particularly in prolonged labour when dehydration can become a problem) can lead to hyponatraemia and hypo-osmolality, resulting in maternal brain swelling, convulsions, and even death. In an attempt to reduce the risk of these complications, pulsatile oxytocin infusion has been recommended in an attempt to mimic the natural pattern of release. An initial report by Pavlou et al (1978) was flawed by the fact that although pulsatile infusion was found to be effective, the control of the pulsed oxytocin infusion rate was not good, resulting in total doses of oxytocin being administered which were no lower than could be obtained by careful feedback control from measurement of uterine activity (Steer et al, 1985). More recently, more dramatic reductions in dose have been shown, but only in rats (Randolph and Fuchs, 1989). This is still an area where more human investigation is needed. VASOPRESSIN
The non-pregnant human uterus is more sensitive to vasopressin than to oxytocin (Fuchs and Fuchs, 1984; Schrey et al, 1986, 1987, 1988). This insensitivity to oxytocin is probably related to the paucity of oxytocin receptors and the consequent inability of the oxytocin to affect phosphoinositide hydrolysis, a necessary precursor to prostaglandin production.
However, unlike oxytocin, there have been no reports of a rise in sensitivity to vasopressin as gestation advances. It is known that there is a large arteriovenous difference in vasopressin concentrations, in cord blood, but while this has led some authors to suggest that vasopressin might play a role in parturition, others conclude that since these differences do not correlate with mode of delivery (i.e. the differences are not higher after spontaneous labour compared with delivery by caesarean section) vasopressin is unlikely to be involved (DeVane, 1985). PROSTAGLANDINS
There can be no doubt of the pivotal position of the prostaglandins in human parturition. There is now overwhelming evidence that administration of prostaglandins not only induces uterine activity but also ripens the cervix. Conversely, administration of cyclo-oxygenase inhibitors such as aspirin or indomethacin, which block the production of prostaglandins, ca n suppress human uterine contractions very effectively. The major question, as yet unanswered, is whether prostaglandins are involved in the initiation and maintenance ~of:Uterine contractions, or whether they are ~eleased as a consequence of the onset of labour, and serve simply as the final common pathway of other humoral factors. The basic synthetic pathway starts with phospholipid from the cell membrane. The action of phospholipase A2 produces arachidonic acid, which is converted by cyclo-oxygenase to the cyclic endoperoxide prostaglandins PGG2 and PGH:. These can be transformed by appropriate enzymes into three important groups of active prostaglandins. The first two, prostacyclin (PGI2, produced by prostacyclin oxycyclase) and thromboxane (TXA2, produced by thromboxane synthetase) are primarily vasoactive, being vasodilatory and vasoconstrictive, respectively. The third group comprises the prostaglandins of the PGE2, PGFa and PGD2 series, of which PGE2 and PGFaa are the major uterotonic compounds. In their mechanism of action, the prostaglandins are undoubtedly hormones in that their receptor binding sites are on the extracellular surface of the cell membrane; however, their effects are predominantly local, and they probably act by regulating both the action and secretion of other hormones. Thus the main sites of production are the decidua and the myometrium of the mother (producing both PGE2 and PGFaa) and the membranes of the fetus (producing mostly PGE2). Since the fetal membranes have no blood supply, it is thought that the amnion receives its supply of arachidonic acid from the fetus via the amniotic fluid, whereas the chorion receives its arachidonic acid from the decidua (Huszar and Walsh, 1988). It seems likely that both PGE2 and PGF2a are necessary for normal progress in labour. However, while a rise in PGE2 levels can be induced by increasing uterine activity alone (for example by infusing oxytocin) the rise in PGF2a seems only to occur in the active phase of labour, that is during progressive dilatation of the cervix (Fuchs et al, 1983). Whether this means that PGF2o~ is an important factor allowing cervical dilatation, or is
ENDOCRINOLOGY OF PARTURITION
produced by some process dependent upon cervical dilatation, is as yet unresolved. The fact that, in general, the use of PGE2 has been more successful than the use of PGF2c~ as a clinical agent for the induction of labour suggests that the latter hypothesis is more likely to be correct.
Therapeutic use of prostaglandins in parturition Following the rise in the popularity of induction of labour in the 1960s there was a search for an agent that would induce uterine contractions and cervical dilatation with the minimum of maternal inconvenience and risk to both mother and fetus. Intravenous oxytocin was known to be effective when the cervix was favourable, but venous cannulation was uncomfortable for the mother. Oral oxytocin is not effective because, following gastric absorption, it is destroyed in the liver. Buccal (sublingual) oxytocin was tried, to bypass the liver, but because the rate of absorption was unpredictable this resulted in a series of reports of uterine hyperstimulation and even uterine rupture (reviewed in Lauersen and Wilson, i974). The simultaneous discovery of the prostaglandins in 1964 by workers in Holland and Sweden soon led obstetricians to investigate its use for the induction of labour. Initial reports of the use of the intravenous route by Karim and coworkers ~in 1968 were encouraging but this route was soon abandoned because of an unacceptable incidence of side-effects such as venous spasm, nausea and vomiting, uterine hypertonus and fetal bradycardia (Lauersen and Wilson, 1974). However, the appearance of an oral preparation stimulated a new wave of enthusiasm that oral therapy with these new agents might be effective. Kelly et al (1973) declared that oral PGE~ was 'a safe and convenient way of inducing l a b o u r . . , and kinder to the uterus and to the fetus than (intravenous) Syntocinon'. Thiery et al (1974) found it 'satisfactory' and Wilkin et al (1974) thought it suitable for low risk, favourable multigravidae, as did Murray and Clinch (1975). However, Friedman and Sachtleben (1974) sounded a note of caution with a report of 13% failed inductions, 6% mild hypertonus and 40% nausea and vomiting. Over the next 3 years further reports put the incidence of maternal vomiting anywhere between 15 and 50% (Elder and Stone, 1975; Morewood and Alaily, 1975; Nelson and Bryans, 1976; Scott and Craft, 1976; Visscher et al, 1977). Scott and Craft went so far as to declare the technique 'unsuitable for routine use'. The oral route having been abandoned, attention turned to intravaginal administration. A variety of gels (Williams, 1979), tablets (Gordon-Wright and Elder, 1979) and wax-based pessaries (Shepherd et al, 1979) soon appeared. Recommended doses ranged from 2.5rag to as high as 10mg (Embrey et al, 1980). At this time the major drawback of the method appeared; failure to induce labour in up to 40% ofprimigravidae (MacKenzie et al, 1981; Shepherd et al, 1981). In addition, there were reports of abnormal uterine action following prostaglandin administration, with adverse effects on the fetus (Sutton and Steer, 1979; Lamb, 1981). These problems have since led to a change in emphasis, so that most reports now concentrate on the value ofprostaglandins as ripening agents for the unfavourable cervix (Ekman et al,
1983; Embrey and MacKenzie, 1985; Bernstein et al, 1987). However, the induction of uterine contractions at an indeterminate time following instillation of the prostaglandin still remains a problem in the high-risk pregnancy with, for example, a uterine scar or growth-retarded fetus. There have also been several reports associating the use of vaginalprostaglandins with uterine hypertonus (with an incidence of about 1 in 300) and placental abruption (Simmons and Savage, 1984; Leung et al, 1987). Thus, attempts to find other agents to ripen the cervix without inducing contractions continue, using agents as varied as oestradiol (Gordon and Calder, 1977), dehydroepiandrosterone sulphate (Sasaki et al, 1982), Lamicel (Johnson et al, 1985) and the Foley catheter (Thomas et al, 1986). The use of vaginal prostaglandin to induce labour following spontaneous rupture of the membranes after 34 weeks of gestation has also been investigated, with equivocal results. Magos et al (1983) found PGE2 to be effective but less reliable than intravenous oxytocin, Chapman et al (1984) found no difference in the value of the two methods, while Day et al (1985) preferred prostaglandins on the grounds that they were easier to use. Termination of pregnancy in the second trimester has been of concern to gynaecologists in the UK since the Abortion Act of 1967. Initial use of hypertonic saline injected into the amniotic sac proved effective but carried a significant maternal mortality due to occasional escape of the hypertonic solution into the maternal circulation. Intra-amniotic prostaglandin and hypertonic urea (the latter to ensure that the fetus is born dead) proved safer but still had rare complications such as maternal collapse, uterine rupture and cervical laceration secondary to tumultuous uterine contractions. Many clinicians in the UK now prefer extra-amniotic administration, 1 mg/h by intermittent or continuous infusion, as a safer alternative. Recently, however, the use of vaginal PGE2 in conjunction with progesterone synthesis inhibitors has shown promise (Webster et al, 1985), as has the use of gemeprost (16,16-dimethyl-trans-82 prostaglandin E~ methyl ester) (Cameron and Baird, 1984). SUMMARY
Current evidence suggests that oestrogens, progesterone, relaxin, the prostaglandins, and oxytocin are all hormones concerned to a major degree with the onset and maintenance of parturition. Oestrogens, relaxin, and the prostaglandins are particularly involved with cervical ripening, while prostaglandins, progesterone and oxytocin are more involved in regulating myometrial contractility. Catecholamines may also have some regulatory function in relation to uterine contractions. Progesterone dominance during pregnancy is associated with a firm closed cervix, few myometrial gap junctions, low calcium levels in the cells, and a quiescent myometrium. At term, a change in the oestrogen/progesterone balance favours cervical ripening and increased uterine activity. Of particular importance at the level of the muscle cell are changes in the number of oxytocin receptors; a complex interaction between cAMP and phosphoinositide metabolism
ENDOCRINOLOGY OF PARTURITION
governs the intracellular level of calcium, thus regulating contractile activity. REFERENCES Akoury HA, Brodie G, Caddick R et al (1988) Active management of labour and operative delivery in nulliparous women. American Journal of Obstetrics and Gynecology 158: 255-258. Anderson A (1980) The genital system. In Hytten F & Chamberlain G (eds) Clinical Physiology in Obstetrics, pp 328-380. Oxford: Blackwell Scientific. Andersen LF, Lyndrup J, Akerlund M & Melin P (1989) Oxytocin receptor blockade: a new principle in the treatment of preterm labor? American Journal of Perinatology 6: 196-199. Arthur H R & Johnson GT (1952) Continuous caudal anaesthesia in the management of cervical dystocia. Journal of Obstetrics and Gynaecology of the British Commonwealth 59" 372-374. Arulkumaran S, Ingemarsson I & Ratnam SS (1987) Oxytocin titration to achieve preset active contraction area values does not improve the outcome of induced labour. British Journal of Obstetrics and Gynaecology 94: 242-258. Bell R J, Eddie LW, Lester A R et al (1987) Relaxin in human pregnancy serum measured with an homologous radioimmunoassay. Obstetrics and Gynecology 69: 585-589. Bell RJ, Eddie LW, Lester A R et al (1988) Antenatal serum levels of relaxin in patients having preterm labour. British Journal of Obstetrics and Gynaecology 95: 1264-1267. Bernstein P, Leyland N, Gurland P & Gate D (1987) Cervical ripening and labor induction with prostaglandin E2 gel: a placebo controlled study. American Journal of Obstetrics and Gynecology 156: 336-340. Bidgood KA & Steer PJ (1987) A randomized control study of oxytocin augmentation of labour. 1. Obstetric outcome. British Journal of Obstetrics and Gynaecology 94: 512-517. Blair-Bell W (1909) The pituitary body and the therapeutic value of the infundibular extract in shock, uterine atony, and intestinal paresis. British Medical Journal 2: 1609-1613. Bourne A & Burn JH (1927) The dosage and action of pituitary extract and the ergot alkaloids on the uterus in labour, with a note on the action of adrenalin. Journal of Obstetrics and Gynaecology of the British Empire 34: 249-272. Boyle DD, White RG & Ritchie JW (1980) An assessment of active management of primigravid labour. Irish Journal of Medical Science 149: 465-468. Buchan PC (1979) Pathogenesis of neonatal hyperbilirubinaemia after induction of labour with oxytocin. British Medical Journal 2: 1255-1257. Calder AA, Moar VA, Ounsted MK & Turnbull AC (1974) Increased bilirubin levels in neonates after induction of labour by intravenous prostaglandin E2 or oxytocin. Lancet ii: 1339-1340. Caldeyro-Barcia R & Alvarez H (1952) Abnormal action during labour. Journal of Obstetrics and Gynaecology of the British Empire 59: 648-654. Caldeyro-Barcia R & Sereno JA (1961) The response of the human uterus to oxytocin throughout pregnancy. In Caldeyro-Barcia R & Heller H (eds) Oxytocin, pp 177-202. Oxford: Pergamon Press. Caldeyro (Barcia) R, Alvarez H & Reynolds SRM (1950) A better understanding of uterine contractility through simultaneous recording with an internal and a seven channel external method. Surgery Gynecology and Obstetrics 91: 641-650. Caldeyro-Barcia R, Sica-Blanco Y, Poseiro JJ et al (1957) A quantitative study of the action of synthetic oxytocin on the pregnant human uterus. Journal of Pharmacology 121: 18-31. Cameron IT & Baird DT (1984) The use of 16,16-dimethyl-trans-delta2 prostaglandin E1 methyl ester (gemeprost) vaginal pessaries for the termination of pregnancy in the early second trimester. A comparison with extra-amniotic prostaglandin E2. British Journal of Obstetrics and Gynaecology 91" 1136-1140. Cameron IT & Baird DT (1988) Early pregnancy termination: a comparison between vacuum aspiration and medical abortion using prostaglandin (16,16 dimethyl-trans-~2-PGE1 methyl ester) or the antiprogestogen R U 486. BritishJournalofObstetrics and Gynaecology 95: 271-276.
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Cardozo L, Gibb DMF, Studd JWW et al (1982) Predictive value of cervimetric labour patterns in primigravidae. British Journal of Obstetrics and Gynaecology 89: 33-38. Carsten ME & Miller JD (1987) A new look at muscle contraction. American Journal of Obstetrics and Gynecology 157: 1303-1315. Chalmers I, Campbell H & Turnbull AC (1975) Use of oxytocin and incidence of neonatal jaundice. British Medical Journal 2: 116-118. Chapman M, Lawrence D, Sims C & Bennett M (1984) Induction of labour with prostaglandin pessaries or oxytocin infusion after spontaneous rupture of membranes. Journal of Obstetrics and Gynaecology 4" 185-187. Chard T (1989) Fetal and maternal oxytocin in human parturition. American Journal of Perinatology 6: 145-152. Chew WC (1977) Neonatal hyperbilirubinaemia--a comparison between prostaglandin E2 and oxytocin inductions. British Medical Journal 3: 679-680. Creasy RK (1987) Inhibition of preterm labour. Prostaglandin Perspectives 3" 38-39. Csapo A (1970) The diagnostic significance of the intrauterine pressure. Obstetrics and Gynecology Survey 25: 403-435. Dale HH (1906) On some physiological actions of ergot. Journal of Physiology 34: 163-206. Davies DP, Gomershall R, Robertson R et al (1973) Neonatal jaundice and maternal oxytocin infusion. British Medical Journal 3: 476-477. Dawood MY (1989) Evolving concepts of oxytocin for induction of labor. American Journal of PerinatoIogy 6: 167-172. Day A, MacLennan A & Green R (1985) A comparison of intravaginal PGF2c~ and intravenous oxytocin to stimulate labour after membrane rupture. Australia and New Zealand Journal of Obstetrics and Gynaecology 25: 252-255. Dayanithi G, Cazalis M & Nordmann JJ (1987) Relaxin affects the release of oxytocin and vasopressin from the neurohypophesis. Nature 325: 813-816. Demarest KT, Hahn DW, Ericson E et al (1989) Profile of an oxytocin antagonist, RWJ 22164 for treatment of preterm labor in laboratory models of uterine contractility. American Journal of Perinatology 6: 200-204. DeVane GW (1985) Vasopressin levels during pregnancy and labor. Journal of Reproductive Medicine 30" 324--327. D'Souza SW, Black P, Macfarlane T & Richards B (1979) The effect of oxytocin in induced labour on neonatal jaundice. British Journal of Obstetrics and Gynaecology 86: 133-138. Eddie LW, Bell R J, Lester A et al (1986) Radioimmunoassay of relaxin in pregnancy with an analogue of human relaxin. Lancet i: 1344-1346. Ekman G, Forman A, Marsal K & Ulmsten U (1983) Intravaginal versus intracervical application of prostaglandin E2 in viscous gel for cervical priming and induction of labor at term in patients with an unfavorable cervical state. American Journal of Obstetrics and Gynecology 147: 65%661. Elder MG & Stone M (1975) Induction of labour using oral prostaglandin E2 tablets. Journal of International Medical Research 3: 300-303. Embrey MP & MacKenzie IZ (1985) Labour induction with a sustained release prostaglandin E2 polymer vaginal pessary. Journal of Obstetrics and Gynaecology 6: 38-41. Embrey MP, Graham NB & McNeill ME (1980) Induction of labour with a sustained release prostaglandin E2 vaginal pessary. British Medical Journal 281: 901-902. Entenmann AH, Seeger H, Voelter W & Lippert TH (i988) Relaxin deficiency in the placenta as a possible cause of cervical dystocia. Clinical Experimental Obstetrics and Gynecology 15: 13-17. Friedman E A & Sachtleben MR (1974) Oral prostaglandin E2 for induction of labour at term. Obstetrics and Gynecology 43: 178-184. Fuchs A R & Fuchs F (1984) Endocrinology of parturition: a review. British Journal of Obstetrics and Gynaecology 91: 948-967. Fuchs AR, Husslein P, Kofler E et al (1983) Effects of cervical application of prostaglandin (PG)E2 on plasma 13,14-dihydro-15-keto-PGF2a and oxytocin in pregnant women at term. British Journal of Obstetrics and Gynaecology 90: 612-617. Ghosh A & Hudson FP (1972) Oxytocic agents and neonatal hyperbilirubinaemia. Lancet ii: 823. Goodfellow CF, Hull MGR, Swaab DF et al (1983) Oxytocin deficiency at delivery with epidural analgesia. British Journal of Obstetrics and Gynaecology 90: 214-219.
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Gordon AJ & Calder AA (1977) Oestradiol applied locally to ripen the unfavourable cervix. Lancet 2: 1319-1321. Gordon-Wright AP & Elder MG (1979) Prostaglandin E2 tablets used intravaginally for the induction of labour. British Journal of Obstetrics and Gynaecology 86: 32-36. Hisaw FL (1926) Experimental relaxation of the pubic ligament of the guinea pig. Proceedings of the Society of Experimental Biology and Medicine 23: 661-663. Huszar G & Walsh MP (1988) A cellular view of uterine function: myometrium and cervix. In Egarter C & Husslein P (eds) Prostaglandins for cervical ripening and~or induction of labour, pp 9-30. Vienna, Austria: Facultas universitatslag. Jeffcoate TNA (1963) Dystocia due to or associated with abnormal uterine action. In Claye A & Bourne A (eds) British Obstetric and Gynaecological Practice, pp 63%669. London: William Heinemann Medical Books Ltd. Johnson IR, Macpherson MBA, Welch CC & Filshie GM (1985) A comparison of lamicel and prostaglandin E2 vaginal gel for cervical ripe.ring before induction of labor. American Journal of Obstetrics and Gynecology 151: 604-607. Jones SA & Summerlee AJS (1986) Relaxin acts centrally to inhibit oxytocin release during parturition: an effect that is reversed by naloxone. Journal of Endocrinology 111: 99-102. Kaiser IH & Harris JS (1950) The effects of adrenalin on the pregnant human uterus. American Journal of Obstetrics and Gynecology 59: 775-784. Keirse MJNC (1984) A survey of tocolytic drug treatment in preterrn labour. British Journal of Obstetrics and Gynaecology 91: 424-430. Kelly J, Flynn AM & Bertrand PV (1973) A comparison of oral prostaglandin E2 and intravenous syntocinon in the induction of labour. Journal of Obstetrics and Gynaecology of the British Commonwealth 80: 923-926. Khan-Dawood FS, Goldsmith LT, Weiss G & Dawood Y (1989) Human corpus luteum secretion of relaxin, oxytocin, and progesterone. Journal of Clinical Endocrinology and Metabolism 68: 627-63l. King JF, Grant A, Keirse MJNC & Chalmers I (1988) Betamimetics in preterm labour: an overview of the randomized controlled trials. BritishJournalofObstetrics and Gynaecology 95:211-222. Lamb MP (1981) Prostaglandins in obstetrics. British Medical Journal 282: 1398. Lauersen NH & Wilson KH (1974) Induction of labour with oral prostaglandin E2. Obstetrics and Gynecology 44: 793-801. Leung A, Kwok P & Chang A (1987) Association between prostaglandin E2 and placental abruption. British Journal of Obstetrics and Gynaecology 94: 1000-1002. Liggins GC & Wilson T (1989) Phospholipases in the control of human parturition. American Journal of Perinatology 6: 153-158. Mackenzie IZ, Bradley S & Embrey MP (1981) A simpler approach to labor induction using lipid based prostaglandin Ea vaginal suppository. American Journal of Obstetrics and Gynecology 141: 158-161. MacLennan AH, Green RC, Bryant-Greenwood GD et al (1980) Ripening of the human cervix and induction of labour with purified porcine relaxin. Lancet i: 220-223. MacLennan AH, Nicolson R, Green RC & Bath M (1986a) Serum relaxin and pelvic pain of pregnancy. Lancet ii: 243-245. MacLennan AH, Green RC, Grant P & Nicolson R (1986b) Ripening of the human cervix and induction of labor with intracervical purified porcine relaxin. Obstetrics and Gynecology 68: 598-601. MacLennan AH, Nicolson R & Green R (1986c) Serum relaxin in pregnancy. Lancet ii: 241-243. Magos AL, Noble MCB, Wong Ten Yuen A & Rodeck CH (1983) Controlled study comparing vaginal prostaglandin E2 pessaries with intravenous oxytocin for the stimulation of labour after spontaneous rupture of the membranes. BritishJournalofObstetrics and Gynaecology 90: 726-731. Mitrani A, Oettinger M, Abinader EG et al (1975) Use of propranolol in dysfunctional labour. British Journal of Obstetrics and Gynaecology 82: 651-655. Moir DD & Willocks J (1967) Management of incoordinate uterine action under continuous epidural anaesthesia. British Medical Journal 3: 396-400. Morewood GA & Alaily A (1975) Fixed dose prostaglandin Ez tablets in the induction of labour in multipara. Current Medical Research and Opinion 3: 232-236.
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Murray CP & Clinch J (1975) Comparative study of labour induced by oral prostaglandin E2 and intravenous syntocinon. 1fish Medical Journal 68: 135-139. Nelson GH & Bryans CI (1976) A comparison of oral prostaglandin E2 and intravenous oxytocin induction of labor in normal and high risk pregnancies. American Journal of Obstetrics and Gynecology 126: 549-554. O'Driscoll K, Jackson RJA & Gallagher JT (1969) Prevention of prolonged labour. British Medical Journal 2: 447-480. O'Driscoll K, Stronge JM & Minogue M (1973) Active management of labour. British Medical Journal 3: 145-137. O'Driscoll K, Foley M & MacDonald D (1984) Active management of labour as an alternative to caesarean section for dystocia. Obstetrics and Gynecology 63: 485-490. Padayachi T, Norman RJ, Dhavaraj K et al (1988) Serial oxytocin levels in amniotic fluid and maternal plasma during normal and induced labour. British Journal of Obstetrics and Gynaecology 95: 888-893. Pavlou C, Barber GH, Roberts A & Chamberlain GVP (1978) Pulsed oxytocin infusion in the induction of labour. British Journal of Obstetrics and Gynaecology 85: 96-100. Porter DG, Downing SJ & Bradshaw JMC (1979) Relaxin inhibits spontaneous and prostaglandin driven myometrial activity in anaesthetised rats. Journal of Endocrinology 83: 183-192. Randolph GW & Fuchs A R (1989) Pulsatile administration enhances the effect and reduces the dose of oxytocin required for induction of labor. American Journal of Perinatal Medicine 6: 159-166. Ryan TJ (1960) Further observations on the safety of the Pitocin drip. Journal of Obstetrics and Gynaecology of the British Empire 67: 962-965. Sasaki K, Nakano R, Kadoya Y e t al (1982) Cervical ripening with dehydroepiandrosterone sulphate. British Journal of Obstetrics and Gynaecology 89: 195-198. Schrey MP, Read AM & Steer PJ (1986) Oxytociu and vasopressin stimulate inositol phosphate production in human gestational myometrium and decidua cells. Bioscience Reports 6: 613-619. Schrey MP, Read AM & Steer PJ (1987) Stimulation of phospholipid hydrolysis and arachidonic acid mobilization in human uterine decidua cells by phorbol ester. Biochemical Journal 246: 705-713. Schrey MP, Cornford PA, Read AM & Steer PJ (1988) A role for phosphoinositide hydrolysis in human smooth muscle during parturition. American Journal of Obstetrics and Gynecology 159: 964-970. Schwartz RH & Jones RWA (1978) Transplacental hyponatraemia due to oxytocin. British Medical Journal h 152-153. Scott JM & Craft I (1976) Buccal prostaglandin E2 for induction of labour. British Journal of Obstetrics and Gynaecology 83: 729-730. Seitchik J & Castillo M (1982) Oxytocin augmentation of dysfunctional labour. American Journal of Obstetrics and Gynecology 144: 899-905. Shepherd JH, Pearce JMF & Sims CD (1979) Induction of labour using prostaglandin E2 pessaries. British Medical Journal 2: 108--110. Shepherd JH, Bennett MJ, Laurence D, Moore F & Sims CD (1981) Prostaglandin vaginal suppositories: a simple and safe approach to the induction of labor. Obstetrics and Gynecology 58: 596-600. Simmons K & Savage W (1984) Neonatal death associated with induction of labour with intravaginal prostaglandin E2. Case report. British Journal of Obstetrics and Gynaecology 91: 598-599. Sims DG & Neligan GA (1975) Factors affecting the increasing incidence of severe nonhaemolytic neonatal jaundice. British Journal of Obstetrics and Gynaecology 82: 863-866. Steer PJ, Carter MC & Beard RW (1984) Normal levels of active contraction area in spontaneous labour. British Journal of Obstetrics and Gynaecology 91: 211-219. Steer P J, Carter MC & Beard RW (1985a) The effect of oxytocin infusion on uterine activity levels in slow labour. British Journal of Obstetrics and Gynaecology 92:1120-1126. Steer P J, Carter MC, Choong K et al (1985b) A multicentre prospective randomized controlled trial of induction of labour with an automatic closed-loop feed-back controlled oxytocin infusion system. British Journal of Obstetrics and Gynaecology 92:1127-1133. Sutton M & Steer PJ (1979) Induction of labour. British Medical Journal 3: 671.
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Tepperman HM, Beydoun SN & Abdul-Karim RW (1977) Drugs affecting myometrial contraction in pregnancy. Clinical Obstetrics and Gynecology, vol. 20, no. 2. New York: Harper & Row. Theobald GW (1959) The choice between death from postmaturity or prolapsed cord, and life from induction of labour. Lancet 1." 59-65. Theobald GW, Graham A, Campbell J e t al (1948) The use of post-pituitary extract in physiological amounts in obstetrics--a preliminary report. British Medical Journal 2" 123-125. Thiery M, Sian YL, Hemptinne DD et al (1974) Induction of labour with prostaglandin E2 tablets. Journal of Obstetrics and Gynaecology of the British Commonwealth 81" 303-306. Thomas IL, Chenoweth JN, Tronc GN & Johnson IR (1986) Preparation for induction of labour of the unfavourable cervix with Foley catheter compared with vaginal prostaglandin. Australia and New Zealand Journal of Obstetrics and Gynaecology 26: 30-35. Turnbull AC & Anderson ABM (1968) Induction of labour. Journal of Obstetrics and GynaecoIogy of the British Commonwealth 75: 24-41. Turner MJ, Brassil M & Gordon H (1988) Active management of labour associated with a decrease in the cesarean section rate in nulliparas. Obstetricsand Gynecology 71: 150-154. Visscher RD, Struyk CD & Visscher HC (1977) Guidelines for the elective induction of labour with oral prostaglandin E2. Obstetrics and Gynecology 49: 15-19. Webster MA, Phipps SL & Gillmer MDG (1985) Interruption of first trimester human pregnancy following Epostane therapy. Effect of prostaglandin E2 pessaries. British Journal of Obstetrics and Gynaecology 92: 963-968. Wilkin D, Graham F, Shields M & Craft I (1974) Selective induction of labour following administration of an oral prostaglandin E2 0.5 mg tablet hourly. Prostaglandins 6: 405411. Williams RM (1979) Induction of labour with intravaginal prostaglandin E2 gel. British Journal of Clinical Practice 34: 131-132. Williams EA & Stallworthy JA (1952) A simple method of internal tocography. Lancet 1: 330-332.
Oxytocin: It helps in the uterine contractions during parturition and the release of milk during breastfeeding.What triggers parturition in a human female during birth? ›
The mechanism by which parturition is initiated in humans is largely unknown. The placenta and fetal membranes appear to play the major role in the initiation of labour, and the fetus may influence the timing of labour.What is the function of parturition? ›
Parturition constitutes transport of the fetus and its associated membranes from the maternal to the external environment, and represents transition of the fetus to a neonate.What causes parturition? ›
Evidence suggests that there are multiple paracrine/autocrine events, fetal hormonal changes, and overlapping maternal/fetal control mechanisms for the triggering of parturition in women. For parturition to occur, two changes must take place in a woman's reproductive tract.What are the different types of parturition? ›
The 3 Stages of Parturition: Dilation, Expulsion, and Placental.What is called parturition? ›
Definition of parturition
: the action or process of giving birth to offspring : childbirth.
Parturition is the process of giving birth to a baby. The physical activities involved in parturition like uterine and abdominal contractions, dilation of the cervix, and passage of baby are collectively called labour. Labour is accompanied by a localised sensation of discomfort or agony called labor pains.What are the three steps of parturition explain them? ›
There are three stages to the birthing process, or parturition: dilation of the cervix, delivery of the calf and delivery of the placenta. Knowing the normal birth process will help you decide whether or not to intervene.Which pituitary hormone helps in parturition? ›
Abstract. Objective: Oxytocin, a nanopeptide secreted by the posterior pituitary gland, has well-established uterotonic activity. Its role in initiating the vigorous and regular contractions of the first stage of labor is still controversial.How is parturition controlled? ›
Many factors influence the contractive activity of the uterus. These factors are discussed and include autonomic motor innervation, estrogens, external environment, fetal stress, ACTH and corticosteroids, mechanical stimulation, oxytocin, progesterone, and prostaglandins.
Parturition means childbirth. It's the mechanism of motioning the onset of labor, or it is a procedure of delivering a toddler after the completion of the pregnancy period. The developed child is born with the discharge of cortisol.What are the 3 stages of delivery? ›
Labour has three stages:
The first stage is when the neck of the womb (cervix) opens to 10cm dilated. The second stage is when the baby moves down through the vagina and is born. The third stage is when the placenta (afterbirth) is delivered.
Your hypothalamus makes oxytocin, but your posterior pituitary gland stores and releases it into your bloodstream. Hormones are chemicals that coordinate different functions in your body by carrying messages through your blood to your organs, muscles and other tissues.What is the role of oxytocin in parturition? ›
Oxytocin stimulates prostaglandin release in many species, mainly in the decidua/uterine epithelium. The effects of oxytocin are mediated by tissue-specific oxytocin receptor expression, which leads directly to contraction in the myometrium and prostaglandin formation in the decidua.What hormones are involved in labor? ›
Hormones and labour
The hormone oxytocin plays a key role in labour. Often called the 'love hormone', oxytocin is associated with feelings of bonding and motherhood. This is also true of another hormone released during labour called prolactin.
- Vaginal Birth.
- Natural Birth.
- Scheduled Cesarean.
- Unplanned Cesarean.
- Vaginal Birth after C-Section (VBAC)
- Scheduled Induction.
Stage 1: The first stage of parturition is dilation of the cervix. The normal cervix is tightly closed right up until the cervical plug is completely dissolved. In stage 1, cervical dilation begins some 2 to 24 hours before the completion of parturition (2 to 6 hours would be most common).Which of the following changes occur during parturition? ›
<br> The stimulatory reflex between the uterine contraction and oxytocin secretion continues resulting in stronger and stronger contractions. <br> This leads to expulsion of the body out of the uterus through the birth canal - parturition.What is parturition in Wikipedia? ›
Birth is the act or process of bearing or bringing forth offspring, also referred to in technical contexts as parturition. In mammals, the process is initiated by hormones which cause the muscular walls of the uterus to contract, expelling the fetus at a developmental stage when it is ready to feed and breathe.What is parturition in topper? ›
Parturition is the expulsion or delivery of the fetus from the mother's body. It occurs at the end of pregnancy. It involves various activities such as contraction of the uterus, dilation of cervix and opening of the vaginal canal. Parturition comes from the Latin word parturire, "to be ready to bear young".
Parturition is the process of delivery of the foetus. It is also called as childbirth. Foetal ejection reflex are the mild uterine contractions generated by placenta when the foetus is fully developed. This reflex is seen during the time of parturition.What is parturition briefly explain the process of parturition Class 12? ›
Parturition is the process of giving birth to a baby. The physical activities involved in parturition like uterine and abdominal contractions, dilation of cervix and passage of baby are collectively called labour. Labour is accompanied by a localised sensation of discomfort or agony called labour pains.What foods contain oxytocin? ›
Oxytocin, also called "love hormone", can be found in a different variety of food, especially the one containing Vitamin D, Vitamin C, magnesium and dietary fats: fatty fish, mushrooms, peppers, tomatoes, spinach, avocados and many more!Which hormone is responsible for lactation? ›
Oxytocin. The oxytocin reflex is also sometimes called the “letdown reflex” or the “milk ejection reflex”. Oxytocin is produced more quickly than prolactin. It makes the milk that is already in the breast flow for the current feed, and helps the baby to get the milk easily.What causes oxytocin deficiency? ›
Genetic factors, hormonal imbalances, and nutritional deficiencies are all potential causes of decreased oxytocin levels.What hormone has the most direct effect on the contraction of the uterus? ›
Oxytocin stimulates the uterine muscles to contract and also increases production of prostaglandins, which increase the contractions further.How many cm is active labour? ›
Active labor. During active labor, your cervix will dilate from 6 centimeters (cm) to 10 cm. Your contractions will become stronger, closer together and regular. Your legs might cramp, and you might feel nauseated.Do I need to shave before giving birth? ›
In previous years, traditional childbirth recommended hair removal on the pubic area before delivery. However, modern childbirth finds that it's not necessary to shave your pubic hair before delivery. Clinical research shows that shaving or not shaving pubic hair doesn't necessarily affect birth.Which injection is given for normal delivery? ›
Oxytocin injection is used to begin or improve contractions during labor. Oxytocin also is used to reduce bleeding after childbirth.What type of protein is oxytocin? ›
Oxytocin is the second cyclic nonapeptide synthesized in the magnocellular nuclei and stored in the posterior pituitary. Oxytocin, like AVP, is synthesized as a single 20-kd peptide molecule, termed prooxyphysin, which contains the 1-kd peptide hormone and its nonglycosylated 10-kd carrier protein, type I neurophysin.
Oxytocin triggers feelings of love and protection, which naturally occurs when parents and children look into one another's eyes or when they embrace. Other relationship-enhancing effects also include empathy, trust, and the processing of bonding cues.Do males have oxytocin? ›
Do both men and women produce oxytocin? Yep, but women typically have higher oxytocin levels than men. (It's a key hormone involved in childbirth and lactation, after all). Biological differences aside, men and women appear to experience oxytocin in many of the same ways.When is oxytocin released in females? ›
Oxytocin has been best known for its roles in female reproduction. It is released in large amounts during labor, and after stimulation of the nipples. It is a facilitator for childbirth and breastfeeding.What increases oxytocin? ›
Hugging, kissing, cuddling, and sexual intimacy can all trigger oxytocin production, which can strengthen bonds between adults, too. These effects have led oxytocin to be grouped with the other happy hormones — hormones known to have a positive impact on mood and emotions.Where is oxytocin stored? ›
Oxytocin in both sexes is produced by the hypothalamus and stored and secreted into the bloodstream from the posterior pituitary gland.Which is commonly known as birth hormone? ›
Progesterone is also known as birth hormone.Which hormone is not produced during pregnancy? ›
So, the correct answer is 'Estrogen'.What endocrine gland is a pregnant woman? ›
The placenta is a temporary endocrine organ formed during pregnancy, which produces hormones important in the maintenance of a healthy pregnancy and in preparation for labour and breastfeeding.What is the role of oxytocin in parturition? ›
Oxytocin stimulates prostaglandin release in many species, mainly in the decidua/uterine epithelium. The effects of oxytocin are mediated by tissue-specific oxytocin receptor expression, which leads directly to contraction in the myometrium and prostaglandin formation in the decidua.Why is oxytocin necessary for parturition? ›
Oxytocin stimulates the uterine muscles to contract and also increases the production of prostaglandins, which increases the contractions further. The release and the binding of the hormone to the muscle receptors lead to contraction of uterine smooth muscle which enables parturition or childbirth.
Relaxin is a hormone produced by the ovary and the placenta with important effects in the female reproductive system and during pregnancy. In preparation for childbirth, it relaxes the ligaments in the pelvis and softens and widens the cervix.What is parturition Class 12? ›
Parturition is the expelling of the fully formed young one from the mother's uterus after the gestation period of 280 days in human females. It is also known as labour. It is the mechanism of signalling the onset of labour (or) a procedure of delivering a child after the completion of pregnancy period.Which gland produces oxytocin? ›
Your hypothalamus makes oxytocin, but your posterior pituitary gland stores and releases it into your bloodstream. Hormones are chemicals that coordinate different functions in your body by carrying messages through your blood to your organs, muscles and other tissues.What type of hormone is oxytocin? ›
Oxytocin (Oxt or OT) is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, reproduction, childbirth, and the period after childbirth.What is the love hormone? ›
Oxytocin is a hormone that's produced in the hypothalamus and released into the bloodstream by the pituitary gland. Its main function is to facilitate childbirth, which is one of the reasons it is called the "love drug" or "love hormone."Which pituitary hormone helps in parturition? ›
Abstract. Objective: Oxytocin, a nanopeptide secreted by the posterior pituitary gland, has well-established uterotonic activity. Its role in initiating the vigorous and regular contractions of the first stage of labor is still controversial.What are the three steps of parturition explain them briefly? ›
The steps involved in parturition are dilation, expulsion, and placental. Dilation is the first step of parturition where the cervix is fully dilated. Expulsion is the stage that includes full dilation and continues until birth. The placental is a stage that includes after birth and ends with delivery.What is parturition and its control mechanism? ›
Parturition means childbirth. It's the mechanism of motioning the onset of labor, or it is a procedure of delivering a toddler after the completion of the pregnancy period. The developed child is born with the discharge of cortisol.What is progesterone pregnancy? ›
Progesterone is a hormone that helps the uterus grow during pregnancy and keeps it from contracting. Treatment with progesterone during pregnancy may help some people reduce their risk for premature birth. If you have a short cervix, treatment with vaginal progesterone gel may help prevent premature birth.What hormone relaxes muscles? ›
The hormones relaxin and progesterone relax muscles and loosen ligaments and joints, especially in the pelvic area.
Progesterone helps to prepare the body for pregnancy by stimulating glandular development and the development of new blood vessels. This provides a good environment for implantation by a fertilized egg. If the egg isn't fertilized, the corpus luteum breaks down, leading to a drop in progesterone levels.