Induction of labour: a comparison of a single prostaglandin E2 vaginal tablet with amniotomy and intravenous oxytocin

Summary. In a randomized controlled study of 100 women of low parity and favourable induction features, induction of labour by means of a single vaginal tablet containing 3 mg of prostaglandin E₂ (PGE₂) was compared with the conventional method of amniotomy and intravenous oxytocin. Four of the patients (8%) who received the prostaglandin tablet required additional intravenous oxytocin to achieve delivery. The prostaglandin group had a longer mean overall induction-delivery interval but a shorter amniotomy-delivery interval than the oxytocin group. One patient in the PGE₂ group and two in the oxytocin group required caesarean section. The PGE₂ treated patients expressed a higher level of satisfaction with their method of induction, they required less analgesia, had less blood loss at delivery and their babies had a lower incidence of neonatal jaundice.     

Comparison of Prostaglandin E2 Vaginal Tablet with Amniotomy and Intravenous Oxytocin for Induction of Labour

Summary: Prostaglandins have been increasingly used in obstetrical practice for cervical ripening and induction of labour. We set out to investigate the effectiveness of prostaglandin E₂ (PGE₂) vaginal pessaries in inducing labour in the Chinese population in Hong Kong. In the period August, 1991 to August, 1992, we recruited 206 pregnant Chinese women who required induction of labour for various obstetrical indications into the trial. The study group had induction of labour by PGE₂ vaginal pessaries and the control group underwent amniotomy plus oxytocin infusion. These patients were alternately assigned either method of induction. They were further divided into primiparous and multiparous (parity 1 and 2 only) groups.
Only 101 primiparas and 99 multiparas were available in the final analysis of the trial. Various aspects of labour, delivery, maternal and fetal outcome were compared. For primiparas, the traditional combined induction was the preferred method. For multiparas, both induction methods were quite satisfactory and there was a trend toward lesser blood loss and pethidine requirement in the PGE₂ users.     

Labour Induction with Intracervical Prostaglandin E2 Gel and Intravenous Oxytocin in Women with a Very Unfavourable Cervix

Summary: Two hundred and sixty-three gravid women having a very unfavourable cervix and requiring labour induction were studied; 80 primigravidas and 56 multigravidas were administered a single dose of intracervical prostaglandin E₂ gel (PGE₂) and 72 primigravidas and 55 multigravidas had labour induced with an escalating oxytocin infusion. After 24 hours 73.8% of the primigravidas induced with PGE₂ had delivered vaginally compared with only 52.8% of those induced with oxytocin. The incidence of Caesarean sections was very high (47.2%) in the primigravidas receiving an oxytocin infusion. In the multigravidas, there was no significant difference in the proportion of women who had delivered vaginally within 24 hours and in the percentage of Caesarean sections in the 2 induction groups. After 12 hours, a significant increase in the cervical score was seen in all women receiving PGE₂ intracervically. The fetal outcome and perinatal mortality were not affected by the mode of induction. Intracervical PGE₂ appears to be more effective than oxytocin in inducing labour in primigravidas having an unfavourable cervix, whereas in multigravidas, both methods appears to be equally effective.     

The influence of spontaneous and induced labour on the rise in prostaglandins at amniotomy

Summary. Maternal peripheral plasma levels of 13, 14-dihydro-15-keto-prostaglandin F (PGFM) were measured immediately before and 5 min after amniotomy. Three groups of women were studied: women in late pregnancy; women in spontaneous labour; and women who had received intravaginal prostaglandin E₂ (PGE₂) pessary. There was no significant difference in the magnitude of the rise in PGFM after amniotomy in late pregnancy or during spontaneous labour suggesting that labour has no influence on the release of prostaglandin F_2α (PGF_2α) induced by artificial rupture of the fetal membranes. However, local administration of PGE₂ before amniotomy caused a greater rise in PGFM suggesting that PGE₂ can influence the release and/or metabolism of PGF_2α.     

Controlled study comparing vaginal prostaglandin E2 pessaries with intravenous oxytocin for the stimulation of labour after spontaneous rupture of the membranes

Summary. In a prospective randomized study, 36 patients with spontaneous rupture of the membranes of ≥4 h duration were stimulated with 3 mg vaginal prostaglandin E₂ pessaries or intravenous oxytocin. Oxytocin stimulation was associated with shorter labours and a lower incidence of abnormal cervimetric progress. Of the patients given prostaglandin pessaries, 40% required a second dose after 4 h for slow progress; 45% of the primigravidae subsequently developed abnormal labour which was corrected by augmentation with oxytocin in all cases. One caesarean section was carried out for disproportion, and the remaining 35 patients were delivered vaginally. Prostaglandin pessaries were not associated with an increased incidence of hyperstimulation or sepsis. In conclusion, although PGE₂ pessaries are safe in spontaneous rupture of the membranes, intravenous oxytocin is more efficient in stimulating labour.     

Concentration of 13,14-dihydro-15-keto-prostaglandin E2 in the maternal peripheral plasma during labour of spontaneous onset

Summary. The concentration of 13, 14-dihydro-15-keto-PGE₂ (PGEM) was measured by radioimmunoassay in pregnant women in the third trimester, in women at term but not in labour and during labour of spontaneous onset. The plasma concentration of PGEM in pregnant women was elevated above that in a non-pregnant control group. Before the onset of labour no increase of PGEM concentration could be identified. Women in labour had higher PGEM plasma concentrations than before the onset of labour, although there was no progressive increase. Immediately after delivery PGEM levels reached a maximum, which decreased significantly to pre-labour values within 30 min. Artificial rupture of the membranes had no influence on plasma PGEM levels. It is concluded that labour is associated with an increased synthesis of PGE₂ and that PGE₂ may be inved in the mechanism of placental separation. The rapid disaearance of high PGEM levels after labour confirms that PGE₂ is probably synthesized mainly in the fetal compartment.     

Effect of cervical application of prostaglandin (PG) E2 on plasma 13,14-dihydro-15-keto-PGF2α and oxytocin in pregnant women at term

Summary. The concentrations of 13,14-dihydro-15-keto-prostaglandin F_2α (PGFM) and oxytocin were measured by radioimmunoassay in the peripheral plasma of 21 women with low Bishop scores in whom cervical ripening and labour were induced with a cervical cap containing 1.5 mg of prostaglandin (PG) E₂, left in place for 6 h. Blood samples were taken before and at 3, 6, 9 and 24 h after the cap was applied. Four women (control group) had a cap without PGE₂. Labour began in 13 women receiving PGE₂, 12 of whom were delivered within 24 h. In these women plasma PGFM rose progressively to levels seen during spontaneous labour, paralleling the changes in cervical dilatation. The increase became significant at 6 h, when cervical dilatation was 4.5 cm (SEM 0.5). Plasma oxytocin also increased significantly while the cap was in place and then decreased. Plasma PGFM and oxytocin did not change in the control subjects, and in the eight women needing further induction of labour the initial rises were transient and not statistically significant.     

Tocolysis during cervical ripening with vaginal PGE2

Summary. Forty-two primigravidae with unripe cervices (modified Bishop score ≤5) were pretreated with 8 mg of oral salbutamol 30 min before vaginal administration of 5 mg of PGE₂. The proportion of patients in established labour after treatment (19%) was markedly less than results reported previously and cervical improvement occurred in 86% of the non-labouring patients. The improved outcome of labour associated with the prior administration of PGE₂ when the cervix is unripe, including reduced induction-to-delivery intervals and higher rates of vaginal delivery was maintained. Apart from some minor side-effects, there were no adverse effects noted as a direct consequence of the tocolytic; blood loss was not increased, although one patient suffered an intrapartum abruption. This approach allows a greater control of induced uterine activity and timing of delivery which may be of particular importance in women with suspected placental insufficiency.     

A randomised controlled trial of early versus delayed use of amniotomy and oxytocin infusion in nulliparous labour

Objective To compare routine amniotomy and early intravenous oxytocin (active management of labour) with a more selective use of amniotomy and oxytocin in women in true labour who received comparable continuous supportive midwifery care.
Design Randomised controlled trial of nulliparous clinic patients in spontaneous labour at term. Setting Labour and delivery ward of a university teaching hospital.
Participants Three hundred and six parturients: 152 received active management of labour; 154 were more selectively managed.
Interventions 1. Active management: early amniotomy, early use of oxytocin. 2. Selective intervention management: no routine amniotomy and more selective use of oxytocin.
Outcome measures Use of oxytocin and amniotomy. Labour duration, mode of delivery.
Results Maternal characteristics were comparable in both groups. Amniotomy was more often performed (91% versus 57%,   P < 0.01  ) and oxytocin more often used (53% versus 27%, P < 001) in the active management group. The first stage of labour, however, was only shortened by half an hour in the active management group (254 min versus 283 min,   P = 0.087  ). Caesarean section rate (3.9% versus 2.6%), spontaneous vaginal delivery rate (78% versus 79%) and neonatal outcome were not significantly different between groups.
Conclusion Within a set-up of strict labour diagnosis and supportive midwifery care, routine amniotomy and early use of oxytocin offered no advantage over a more selective use of amniotomy and oxytocin in terms of mode of delivery and labour duration.     

Cervical Ripening Before Induction of Labour in Patients with an Unfavourable Cervix: A Comparative Randomized Study of the Atad Ripener Device, Prostaglandin E2 Vaginal Pessary, and Prostaglandin E2 Intracervical Gel

Summary: One hundred and nineteen women with singleton pregnancy and cephalic presentation requiring induction of labour in the presence of an unfavourable cervix (Bishop score ≤ 4) were studied. Five patients were excluded because of failure to comply with the protocol. Cervical ripening was carried out using 3 different methods; 36 used the Atad Ripener Device, 39 received 0.5 mg PGE, intracervical gel and 39 received at least one 3 mg PGE₂ intravaginal pessary. There were no differences in the demographic characteristics and the indications for induction. Five patients developed complications during the ripening period necessitating intervention; 3 required emergency Caesarean section and 2 delivered vaginally. Although statistically there were no differences among the 3 methods of cervical ripening, the power of the study is probably not large enough to show the differences. The PGE₂ pessary appears to be more effective with 68% of patients either going into labour during cervical ripening or succeeding in the cervical ripening compared to around 50% in the Atad and PGE, gel groups. The vaginal delivery rate was 87.2% in the pessary group compared to 72.2% in the Atad group and 84.6% in the gel group. The duration of labour was also shorter in the pessary group with 73.5% delivered within 24 hours compared to 57.7% in the Atad group and 57.6% in the gel group. Although the results of the Atad device seem to be inferior, the risk of uterine hyperstimulation from the use of the device is probably lower than that of the PGE₂ and may therefore be preferable in women with fetuses at high risk of fetal hypoxia.     

The Safety of Vaginal Prostaglandin F2α for the Stimulation of Labour

Summary: In an audit of 15,102 consecutive deliveries between 1986 and 1991, 3,168 labours were induced with intravenous oxytocin and 824 with 40 mg prostaglandin F₂a (PGF₂α) vaginal gel. Four hundred and twenty women received PGF₂α alone and 404 received PGF₂α followed by oxytocin. The main aim of the study was to audit the safety of PGF₂01 gel to stimulate labour. There were no maternal or neonatal complications attributable to this therapy. In particular, there were no cases of uterine rupture or hyperstimulation requiring surgical or pharmacological intervention. There was little difference in the evidence for fetal distress between induction methods. Although the prostaglandin and oxytocin groups were not comparable in all respects, the results of this large retrospective study confirmed the results of smaller prospective randomized trials showing a significantly shorter labour and reduced analgesia, surgical delivery and postpartum haemorrhage rates in women treated with PGF₂α alone. This is the largest reported series of PGF₂α induced labours and provides evidence of its safety and is in keeping with physiological data suggesting that PGF₂α is the main prostaglandin and oxytocic associated with normal progressive labour. Its apparent safety and potential to reduce both intervention in labour and postpartum complications merits greater attention.     

Oral Prostaglandins E2 and F2a in the Induction of Labour

Summary: Oral prostaglandins E₂ and F_2a were used to augment amniotomy in the induction of labour in 173 patients. The success rate was significantly higher with prostaglandin E₂ than with prostaglandin F_2a (89% and 75%, respectively). This was achieved despite a significantly lower incidence of gastrointestinal side effects. No serious maternal or fetal complications occurred with either drug. It is concluded that oral prostaglandin E₂ is more efficient than oral prostaglandin F_2a in the induction of labour.     

Maternal plasma prostaglandin E2 metabolite levels during human pregnancy and parturition

Summary. Because of methodological problems associated with the measurement in biological fluids of both prostaglandin E₂ (PGE₂) and its unstable principal circulating metabolite 13,14-dihydro-15-keto-PGE₂ (PGEM), there is little reliable information on these prostaglandins in human pregnancy and parturition. The recent discovery of a stable PGEM degradation product 11-deoxy-13,14-dihydro-15-keto-11β, 16-cyclo-PGE₂ (bicyclo-PGEM) has provided a means of studying endogenous plasma levels of PGEM which circumvents the problems encountered with direct measurements of PGE₂ and PGEM. Using a radioimmunoassay for bicyclo-PGEM we have therefore determined maternal peripheral plasma PGE₂ metabolite levels during human gestation. PGE₂ metabolite levels did not alter significantly during the second or third trimesters nor during labour. This contrasts with maternal peripheral plasma levels of the principal circulating metabolite of PGF_2α 13,14-dihydro-15-keto-PGF_2α (PGFM) which increases several fold during labour. Compared t o PGE₂ therefore. PGF_2α may be quantitatively the more significant prostaglandin associated with human parturition.     

The Effect of Intravaginal Prostaglandin F2α on Labour after Spontaneous and Artificial Rupture of the Membranes

Summary: The effect on labour of 50 mg intravaginal PG F_2α or a standard intravenous oxytocin regimen was compared in 2 randomised trials involving a total of 83 patients, 23 of whom had experienced spontaneous rupture of the membranes (S.R.O.M.) and 60 of whom had artificial rupture of the membranes (A.R.M.) to induce labour. In each trial, labour had not been initiated by membrane rupture alone. In both trials only 20% of the patients receiving PG F_2α required further augmentation of labour with intravenous oxytocin. The mean length of labour in patients receiving PG F_2α was 2.5 hours shorter in the A.R.M. trial and 3.0 hours shorter in the S.R.O.M. trial than the mean length of labour in patients receiving intravenous oxytocin (P < 0.01). In the A.R.M. trial, the PG F_2α-treated group had significantly less analgesic requirements (P < 0.001). Although more normal deliveries occurred in the patients treated with PG F_2α than oxytocin in both trials, die numbers did not reach statistical significance.
No side effects occurred in the PG F_2α-treated patients or their babies and this method was much preferred by patients and nursing staff alike.     

Uterine action after induction of labour with oral prostaglandin E2 tablets compared with intravenous oxytocin.

Uterine action throughout the whole of labour induced by low amniotomy and either oral prostaglandin E2 tablets or intravenous ocytocin was studied in 10 randomly matched pairs of patients. Oral prostaglandin E2 tablets induced fewer contractions per hour, and these contractions were longer and more variable in length than those induced by intravenous oxytocin. There was no difference in basal uterine tone or in the amplitude of contractions. A comparison was made between the outcome of labour induced by low amniotomy and either oral prostaglandin E2 tablets 0-5 mg. hourly in 65 patients, or intravenous ocytocin in 41 patients. This dose of prostaglandin E2 tablets was an inadequate adjunct to low amniotomy in nulliparous patients. Despite this, the induction-delivery interval for the whole prostaglandin group was not significantly greater than that for the oxytocin group. There were no significant differences in fetal heart rate pattern, or in the incidence of gastro-intestinal side-effects between the two groups.     

A Double Blind Dose Trial of Intravaginal Prostaglandin F2α for Cervical Ripening and the Induction of Labour

Summary: A randomised double-blind trial involving 90 patients was set up to compare the efficacy of 25 mg PG F_2α, 50 mg PG F_2α and a placebo on cervical ripening when given in a vaginal tylose gel on the evening before surgical induction of labour. Preliminary stretching of the cervix and sweeping of the fetal membranes was not undertaken. In the 30 control patients, labour was not initiated and the mean improvement in the cervical score before surgical induction the next morning was 0.86. In the group of 30 patients receiving 25 mg PG F_2α, labour commenced during the night in 9 patients and the mean improvement in the cervical score was 3.76 (P < 0.0005); the corresponding figures for the 30 patients receiving 50 mg of PG F_2α were 10 patients coming into labour and cervical score improvement of 4.63 (P < 0.0005). he difference in the mean improvement of the cervical score between the 2 prostaglandin groups was not significant. Significantly fewer prostaglandin-treated patients needed augmentation during labour with intravenous oxytocin (P < 0.025) and there was a significant increase in the spontaneous delivery rate in the combined prostaglandin-treated group (P < 0.025). There was no statistical difference in the outcome of labour between the 2 prostaglandin groups. It was not possible to predict the patients whose cervices would not respond to PG F_2α pretreatment (15%) or those in whom labour would be initiated (30%). No side effects were experienced.     

Randomised trial comparing a policy of early with selective amniotomy in uncomplicated labour at term

Objective To compare two management policies: rupture of the fetal membranes when women are in normal labour or leave them intact as long as feasible.
Setting The labour ward of a city university hospital.
Design Automated randomised clinical trial.
Participants 1540 women in uncomplicated term labour. Data on labour duration, blood loss, oxytocin use and fetal condition were collected from 1132 women. Some data from nulliparous women has been presented earlier by the UK Amniotomy Group.
Main outcome measures Duration of labour, Apgar score, fetal morbidity and maternal morbidity including perineal injury, mode of delivery, epidural rates and the total number of vaginal examinations in the first stage of labour after amniotomy.
Interventions Amniotomy at the next vaginal examination or amniotomy only if indicated. The median cervical dilatation at membrane rupture was 2 cm greater in the first group.
Results A policy of routine amniotomy in labour had no measurable advantage over selective amniotomy for parous women (difference = 4 min) but shortened labour in nulliparous women by 1 h (Mann-Whitney U test:   P < 0.05  ). There was a suggestion of a higher caesarean section rate (OR 1.9; 95% CI 0.9–3.5), and there were more vaginal examinations after membrane rupture in the group allocated routine amniotomy. There were no measurable differences in oxytocin use, fetal condition at birth, retained placenta rates, blood loss, pain or analgesia requirements.
Conclusion Routine amniotomy may shorten the first labour but not subsequent ones. There is a suggestion that routine surgical interference may be harmful by increasing the risk of caesarean section, and this agrees with data from other trials (common odds ratio 1.2; 95% CI 0.92–1.6).     

A randomised controlled trial of amniotomy and immediate oxytocin infusion versus amniotomy and delayed oxytocin infusion for induction of labour at term

Background  There is uncertainty as to the optimal time interval between amniotomy and oxytocin administration when inducing labour. The aim of this study was to compare the efficacy of amniotomy and immediate oxytocin infusion with amniotomy and delayed oxytocin infusion for induction of labour at term. Method  A total of 123 women were randomly chosen to receive either amniotomy and immediate oxytocin infusion (referred to as the ‘immediate group’) or amniotomy and delayed oxytocin infusion (referred to as the ‘delayed group’). The main outcome measure was the proportion of women in established labour at 4 h as well as the proportion that delivered within 12 h of amniotomy. Data were analysed using standard statistical methods. Results  Women in the immediate group were more likely to be in established labour 4 h post-amniotomy [relative risk (RR) 12.8; 95% CI 55.1–111.7], have a shorter amniotomy to delivery interval (P < 0.001) and achieve vaginal delivery within 12 h (RR 1.5; 95% CI 1.2–12.6). There was no difference between the groups with regards to the mode of delivery, incidence of uterine hyperstimulation and abnormal foetal heart rate recording. Compared to the delayed group, women in the immediate group were more likely to be satisfied with the induction process (RR 4.1, 95% CI 1.1–16.1) and the duration of labour (RR 1.8 95% CI 1.0–3.3). Conclusion  In induction of labour at term, amniotomy and immediate oxytocin infusion is associated with the establishment of active labour at 4 h, a shorter amniotomy-delivery interval and greater maternal satisfaction.     

Are leukotrienes involved in human uterine contractility?

Summary. The effects of leukotrienes (LT) on the contractility of human and rat myometrial strips in vitro were compared with the effects of prostaglandins (PGs) and oxytocin. Preparations of human myometrial membranes were investigated for the presence and characteristics of LTC₄ receptors. Neither the peptido-leukotrienes (LTC₄, LTD₄, LTE₄) nor LTB₄ had any consistent effect, stimulatory or inhibitory, on human pregnant or non-pregnant myometrium, at doses up to 1·25 μM; nor did they have any effect in rat non-pregnant myometrium. As expected, PGE₂, PGF_2α (0·3 μM) and oxytocin (5 nM) stimulated human pregnant myometrium. PGF_2α stimulated and PGE₂ inhibited human non-pregnant myometrium but oxytocin had no effect; all three compounds stimulated rat non-pregnant myometrium. The binding of ³H-LTC₄ to human myometrium was specific (LTC₄> LTD₄ >>> LTE₄, LTB₄, PGE₂, PGF_2α, arachidonic acid) but of low affinity compared with the binding of ³H-PGE₂ to the same membrane preparations. These data support the view that leukotrienes have little direct influence on myometrial contractility.     

A comparison of prostaglandin E2 pessaries and laminaria tents for ripening the cervix before termination of pregnancy

Summary. Forty primigravid womcn aged 15–45 years were randomly allocated to receive either an intravaginal pessary of 3 mg prostaglandin E, (PGE₂) or an intracervical 5-mm laminaria tent (LT) 12–16 h before termination of pregnancy at 6–14 weeks gestation. The degree of dilatation of the cervix a t operation and its resistance t o further dilatation during the procedure were assessed by a 'blind' operator. Laminaria tents were more effective in achieving dilatation and softening of the cervix than were PGE₂ pessaries and in 40% of women no further dilatation was necessary. There were no associated side-effects or complications. A cervical tear occurred in two of 20 patients treated with PGE₂ pessaries and all 20 required further dilatation of the cervix. Laminaria tents provide a simple. safe, acceptable and effective means of 'ripening' the cervix prior to termination of early pregnancy.