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.     

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.     

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.     

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.     

Primary dysmenorrhoea: the importance of both prostaglandins E2 and F2α

Summary. Menstrual fluid was collected in a contraceptive diaphragm from 16 women with primary dysmenorrhoea and 12 matched control subjects without dysmenorrhoea. Prostaglandins F_2α (PGF_2α), E₂ (PGE₂) and 6-oxo-prostaglandin F_1α (6-oxo-PGF_lα) were extracted and measured using gas-chromatography: mass spectrometry (GC:MS). The concentrations of both PGF_2α and PGE₂ were higher on days 1 and 2 in the dysmenorrhoea group than in the control group and the concentration of PGF_2α was higher on day 1 than on day 2 in the dysmenorrhoea group. The concentrations of 6-oxo-PGF_1α (the stable metabolite of PGI₂) were low in both groups. These results confirm suggestions that PGF_2α is important in the aetiology of dysmenorrhoea and also indicate that PGE₂ may be involved.     

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.     

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.     

Oral Prostaglandin E2in Induction of Labour

Summary: In a randomised study of 207 patients, labour was induced with oral prostaglandin E₂in 107 and intravenous oxytocin (Syntocinon) in the remainder, half in each group with medication alone, the other half with fore-water amniotomy as well. Prostaglandin and oxytocin were found to be more effective when preceded by amniotomy. Once labour was established, the time taken to achieve vaginal delivery was the same with either drug, as also the number of successful vaginal deliveries. There were 6 failed inductions, but no statistical significance in the percentage differences between PGE₂ and oxytocin could be found. The two perinatal deaths which occurred could not be attributed to either drug. Oral PGE₂is therefore as effective as intravenous oxytocin with no observed hypertonus and little side-effects.     

The Use of Prostaglandin F2α for the Induction of Mid-Trimester Abortion

Summary: Ninety-eight patients were given prostaglandin F_2α for the induction of mid-trimester abortion. In 42 the PGF_2α was administered by the extra-amniotic route and 37 aborted. A further 56 received the PGF_2α intra-amniotically and 55 aborted. Dose regimens are compared.     

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.     

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.     

Quantitative production of prostaglandin E2 and its metabolites by human fetal membranes

Summary. Cultured amnion, choriodecidua and intact fetal membrane produced similar quantities of prostaglandin E₂ (PGE₂) (1–5 ng/ml). Choriodecidua and intact fetal membrane also produced very high levels of PGE₂ metabolites (100–1000 ng/ml). The total production of PGE (PGE₂ metabolites) was similar in intact fetal membrane and in choriodecidua, suggesting that the amnion, although a source of PGE₂ contributes little to the overall PGE production by fetal membranes.     

The use of 16,16-dimethyl-transδ2 prostaglandin E1 methyl ester (gemeprost) vaginal pessaries for the termination of pregnancy in the early second trimester. A comparison with extra-amniotic prostaglandin E2

Summary. The use of gemeprost pessaries has been compared in an open randomized trial with the extra-amniotic infusion of prostaglandin E₂ (PGE₂) for the termination of pregnancy between 12 and 16 weeks gestation. The success rates were 77% and 79% for the pessary and infusion group respectively, and these rates were unaffected by parity. There was no significant difference in the cumulative abortion rate between the two groups, nor were there differences in the induction-abortion interval, nor in the time taken to the onset of pain or bleeding. However, women in the pessary group required significantly less analgesia than those in the infusion group. Side-effects, experienced both during treatment and during the 6 weeks after abortion, were similar in both groups. Gemeprost vaginal pessaries are an effective alternative to the extra-amniotic infusion of PGE, for the termination of pregnancy in the early second trimester.     

Vaginal Prostaglandin F2α Gel Before First Trimester Termination of Pregnancy

Summary: Tylose gel containing either 10 mg prostaglandin F_2α or sterile water was inserted into the posterior vaginal fornix of 130 patients either 12 hours or 4 hours before suction curettage. No benefit in terms of cervical softening or blood loss was noted in patients who received the prostaglandin gel.     

Abnormal concentrations of prostaglandins in amniotic fluid during delayed labour in multigravid patients

Summary. Concentrations of prostaglandins E (PGE), F_2α (PGF), 13,14-dihydro-15-keto prostaglandin F_2α (PGFM), 6-keto F_1α and thromboxane B₂ were measured by specific radioimmunoassay in samples of amniotic fluid from 22 multigravid patients during labour. Normal labour in 10 patients was associated with a significant increase of PGE, PGF and PGFM with close correlation to cervical dilatation ( P < 0.05). In the 12 patients with clinically delayed labour, in the absence of cephalopelvic disproportion, there were significantly lower PGF ( P <0.002) and PGFM ( P < 0.05) concentrations obtained while no differences were observed in the other prostanoids measured. Administration of oxytocin to the latter group to enhance labour did not have any effect on the concentrations of prostaglandins obtained in spite of an improvement in intrauterine pressures and accelerated progress of labour.     

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.     

Cardiorespiratory Collapse and Pulmonary Oedema Due to I niravascular Absorption of Prostaglandin F2aL Administered Extraamniotically for Midtrimester Termination of Pregnancy

Summary: A case of severe reaction to extraamniotically administered prostaglandin F_2aL, with cardiorespiratory collapse and pulmonary oedema necessitating transfer to an intensive care unit, is presented. Attention is drawn to the profound haemodynamic effects of systemically administered prostaglandin, and the need for caution and ready availability of facilities for resuscitation when this potent substance is administered. Treatment for the effects of intravascular absorption of prostaglandin F_2aL is discussed.     

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.