Pre-induction priming of the uterine cervix with oral prostaglandin E2 and a placebo

A double blind study was undertaken to determine the effectiveness or oral prostaglandin E2 as a means of improving the pelvic score prior to induction of labour. 48 patients who were greater than 37 were gestation and who had Bishop scores of less than 6 entered the study. Ten tablets were given on an hourly regime. Of 25 patients in the prostaglandin group, 17 were considered successes (68.0%), whereas of 23 patients who received a placebo, 9 were successes (39.1%). No adverse effects were recorded. Prostaglandin E2 is therefore considered a safe and effective method for priming the unfavourable cervix prior to induction of labour.     

Pre-induction priming of the uterine cervix with oral prostaglandin E2 and a placebo.

A double blind study was undertaken to determine the effectiveness or oral prostaglandin E2 as a means of improving the pelvic score prior to induction of labour. 48 patients who were greater than 37 weeks gestation and who had Bishop scores of less than 6 entered the study. Ten tablets were given on an hourly regime. Of 25 patients in the prostaglandin group, 17 were considered successes (68.0%), whereas of 23 patients who received a placebo, 9 were successes (39.1%). No adverse effects were recorded. Prostaglandin E2 is therefore considered a safe and effective method for priming the unfavourable cervix prior to induction of labour.     

Cervical ripening with intravaginal prostaglandin E2 gel.

We describe a technique of administering prostaglandin E2 (PGE2) in a viscous cellulose gel into the vagina to ripen the unfavourable cervix in patients requiring induction of labour. A total of 168 primigravidae were studied, of whom 102 received 2 mg PGE2 in 2% gel and 66 received 5 mg PGE2 in 4% gel. In the latter group, the state of the cervix was significantly improved in 58 patients (87.9%), while 32 (48.5%) had started labour before planned induction. There were no maternal or fetal side effects or complications.     

Prospective study of different methods and routes of administration of prostaglandin E2 to improve the unripe cervix.

Methods of vaginal and extra-amniotic prostaglandin administration to achieve ripening of the cervix as a preliminary to induction of labour are described. Three groups of twenty patients with unfavourable induction features were studied, each receiving prostaglandin E2 the evening prior to planned induction. One group received PGE2 500 micrograms suspended in a viscous medium extra-amniotically. One group received PGE2 3 mg suspended in a viscous medium into the vaginal vault. A third group received a 3 mg PGE2 vaginal pessary to the posterior fornix. Improvement in cervical status at time of induction occurred in all groups but no single group had a significant advantage when regarding mean improvement, the induction-delivery interval or the number of patients in whom labour began before formal induction. However, with regard to relative cost, ease of preparation and storage, as well as patient and medical staff convenience, Prostaglandin E2 in pessary form is a superior form of administration.     

The concurrent in vitro and in vivo release of PGE2 from a controlled-release hydrogel polymer pessary for cervical ripening

Twenty five patients booked for induction of labour, at 38 weeks or more gestation, were administered a controlled release vaginal polymer pessary containing 10 mg prostaglandin E2 (PGE2), designed to release 0.6 mg per hour in vivo. The release profile from the polymer was linear throughout the eight hour observation period with a correlation coefficient of 0.81, and regression slope of 0.93 mg/hr. with 95% confidence intervals of 0.63 mg/hr. to 1.23 mg/hr. This compared with a concomitant release profile in vitro which was uniform with time for the first five hours, but then continued at a decreasing rate with a correlation coefficient of 0.98. The relationship between PGE2 release and cervical score change was linear, with a correlation coefficient of 0.65. The results show that PGE2 release from the pessary in vivo is predictable, and suggest that the controlled release pessary offers the advantages of greater control of cervical ripening than alternative vehicles currently available.     

Preinduction cervical priming with PGE2 vaginal film in primigravidae--a randomised, double blind, placebo controlled study

Previous reports with an 850 micrograms prostaglandin E2 film for cervical ripening before induction of labour in term pregnancy have been favourable. These studies however had no controls. The present study compares this PGE2 vaginal film with a nonmedicated similar vaginal film (placebo) for preinduction cervical ripening in primigravid women at term. A total of 69 women with modified Bishop's cervical scores 1-5 were assigned randomly to either the PGE2 group (33 women) or placebo group (36 women). Cervical score assessments were made at 12 and 24 hours after which labour was induced by amniotomy and oxytocin infusion. Although the cervical scores between placebo and PGE2 groups at 12 and 24 hours were not significantly different, the scores were marginally better with the prostaglandin film. Pregnancy outcome was satisfactory in both groups with no perinatal or maternal mortality and morbidity. The caesarean rate was 30.6% in the placebo group and 24.2% in the PGE2 group. This study emphasizes the need for a control group when studying the success of agents used for ripening the pregnant cervix at term.     

Increased and intermittent prostaglandin release from amnion detected by a new superfusion technique for full thickness fetal membrane

Prostaglandin E2 (PGE) and F2 alpha (PGF) release by the intact fetal membranes is described using a novel superfusion technique allowing for the independent assessment of prostaglandin release from the amnion and chorio-decidua whilst maintaining the anatomical integrity of the fetal membranes. The effect of labour on prostaglandin release is described. Using this system it was confirmed that the amnion is a major site of prostaglandin release and possibly production. Labour resulted in a significant increase of both PGE and PGF release from the amnion side only (Pre-labour: PGE 918 pg/cm2/3h, PGF 370 pg/cm2/3h; Labour: PGE 2993 pg/cm2/3h, PGF 662 pg/cm2/3h). No change in either PGE or PGF release from the chorio-decidual side was observed in relation to labour. In addition a change in the pattern of prostaglandin release from the amnion was observed in tissues obtained after the onset of labour. In 6 of 8 samples obtained after spontaneous labour an intermittent or pulsatile release of both PGE and PGF was observed from the amnion side as compared to the steady state of prostaglandin release from all 10 samples obtained before labour.     

Kielland's forceps: role of antenatal factors in prediction of use.

The association between certain antenatal factors and the use of Kielland''s forceps was analysed retrospectively in liveborn singleton births that occurred at this hospital between January and December 1976. Factors significantly associated with the use of Kielland''s forceps were primiparity, short maternal stature, induction of labour, late engagement of the fetal head, low ratio of maternal height to fetal occipitofrontal head circumference, slow dilatation of the cervix in labour, and the use of epidural analgesia in labour. The findings support a contribution of cephalopelvic disproportion in the genesis of malposition, and when associated with slow dilatation of the cervix delivery should be expedited. Long-term follow-up studies are needed, however, before the role of caesarean section in reducing morbidity associated with malposition can be properly assessed.     

Prospective study of different methods and routes of administration of prostaglandin E2 to improve the unripe cervix

Methods of vaginal and extra-amniotic prostaglandin administration to achieve ripening of the cervix as a preliminary to induction of labour are described. Three groups of twenty patients with unfavourable induction features were studied, each receiving prostaglandin E₂ the evening prior to planned induction. One group received PGE₂ 500 μg suspended in a viscous medium extra-amniotically. One group received PGE₂ 3 mg suspended in a viscous medium into the vaginal vault. A third group received a 3 mg PGE₂ vaginal pessary to the posterior fornix. Improvement in cervical status at time of induction occurred in all groups but no single group had a significant advantage when regarding mean improvement, the induction-delivery interval or the number of patients in whom labour began before formal induction. However, with regard to relative cost, ease of preparation and storage, as well as patient and medical staff convenience, Prostaglandin E₂ in pessary form is a superior form of administration.     

Prostaglandin metabolite levels during cervical ripening with a controlled-release hydrogel polymer prostaglandin E2 pessary

Prostaglandin E and F metabolite (PGEM and PGFM) concentrations in peripheral plasma were assayed following the vaginal administration of a controlled release hydrogel polymer pessary designed to release 0.6 mg PGE2 per hour in vivo. A linear relationship between calculated PGE2 release from the pessary and PGEM levels was observed with a correlation coefficient of 0.78. A significant rise in PGEM levels occurred two hours following pessary administration, with significantly higher PGEM levels in patients delivering within the eight hour observation period compared with those delivering later. PGFM levels increased more slowly. The results suggest that PGE2 released by the pessary crosses the vaginal epithelium and may stimulate endogenous prostaglandin production. The controlled rise of metabolites in association with the polymer pessary suggest that it should provide greater control in labour induction than other vehicles we have studied, but this should be confirmed by clinical trials.     

Induction of labour using prostaglandin E2 pessaries.

The routine method of induction at Queen Charlotte''s Maternity Hospital is now by the use of prostaglandin E2 pessaries. The first 502 consecutive patients thus induced are presented: the caesarean section rate for a failed induction with an unfavourable cervix has fallen to 2%. The prostaglandin E2 pessary is highly efficient and acceptable for all cases in which a simple amniotomy will not suffice.     

Patients' attitudes to induction and labour.

An attempt was made to ascertain patients'' attitudes towards planned induction and labour. Twenty per cent of patients had not heard of induction before their pregnancy, and those who had had most probably heard about it from relations and friends rather than the media. Most patients had no firm opinions on induction of labour but were usually glad to have their pregnancy ended. Many considered that they had not been given enough information by the medical staff on their induction. The amount of pain experienced by patients at amniotomy was related to the "favourability" of the cervix. Possibly women with a low cervical score should be given more premedication or inhalation analgesia at amniotomy. Most patients found injections of narcotic agents adequate analgesia in labour. Those patients who did not receive adequate analgesia were principally those who had either very short or quite long labours. Patients with long labours may benefit from more liberal use of analgesia, but no satisfactory form of analgesia seems to be available for patients who are likely to deliver within two or three hours of induction.     

Uterine priming with oral prostaglandin E2 prior to elective induction with oxytocin.

Fifty pregnant women at term, with a cervix unfavorable for induction, were electively induced with intravenous oxytocin after priming with either oral prostaglandin E2 or a placebo. Oral PGE2 was effective in increasing the Bishop score and in inducing labor prior to the induction, but did not increase the incidence of successful inductions.     

Facilitation of suction termination using extra-amniotic prostaglandins in gel

Extra-amniotic prostaglandin E2 (PGE2) suspended in a slow release gel (Tylose) was instilled in 35 patients prior to a planned surgical termination in an attempt to dilate the cervix, minimize cervical trauma, and reduce the possible risk of cervical trauma, and reduce the possible risk of cervical incompetence and its sequelae. Dilatation occurred in all patients to a minimum of 8 mm and 74% aborted before surgical evacuation performed 6 to 24 hours after injection. No serious side effects occurred. Extra-amniotic PGE2 in gel should be considered as a primary procedure when the cervix is obviously immature on examination. If the cervix is found to be tight and unyielding at surgical dilatation, the latter procedure should be dicontinued and PGE2 in gel injected.     

Randomised comparison of early versus late induction of labour in post-term pregnancy.

In a prospective randomised study of mothers referred for prolonged pregnancy (around the 42nd week) 214 (group 1) were submitted to attempted induction of labour and 195 (group 2) assigned to continue for a further week without intervention. Strict selection criteria were used for the certainty of term. Mothers in group 2 were given regular non-stress tests to ensure fetal wellbeing, as were those in group 1 in whom induction failed. In group 1, 48 (23%) out of 210 first attempted inductions failed. In group 2, 135 (69%) of the births started spontaneously as compared with 38 (18%) in group 1. The mean duration of labour was 7.5 hours in each group. There was no significant difference in incidence of operative delivery, use of analgesics, or signs of perinatal asphyxia. Significantly more children in group 1 needed phototherapy for hyperbilirubinaemia. There was a clustering of births in the late afternoon and evening, which was most pronounced in group 1. A policy of vigilant non-intervention up to the 44th completed week of pregnancy does not appear to jeopardize mother or fetus.     

The mechanisms of preterm labour; the interaction between amnion cells and leukocytes in the metabolism of arachidonic acid.

Chorioamnionitis is frequently associated with preterm labour. We have used a cell culture model system to examine the effects of leukocytes upon the metabolism of endogenous arachidonic acid from within amnion cells. We have demonstrated that activated leukocytes release substances which increase the overall release and metabolism of endogenous arachidonic acid within amnion cells causing an increase in prostaglandin E2 production as well as a smaller increase in non-cyclo-oxygenase metabolism. When amnion cells and leukocytes are cultured together, in addition to prostaglandin E2 production by amnion cells, arachidonic acid released by the amnion cells appears to be metabolised by leucocytes to prostaglandin F2 alpha, prostacyclin and thromboxane A2. Prostaglandins E2 and F2 alpha are the principal cyclo-oxygenase products of this interaction. We postulate that chorioamnionitis stimulates preterm labour not only by causing an increase in prostaglandin E2 synthesis by amnion cells but by metabolism of amnion derived arachidonic acid to the powerfully oxytocic prostaglandin F2 alpha by leukocytes.     

Comparison of natural and synthetic prostaglandin E2 tablets in labour induction.

A multicentre, randomized, double-blind trial compared the efficacy and safety of and tolerance to natural and synthetically produced prostaglandin E2 tablets in the induction of labour in 202 women. The compounds were similarly effective, inducing labour in approximately 66% of patients. The total dose required and the interval between induction and delivery were similar in the two groups, as were the Apgar scores at 1 and 5 minutes and the incidence of maternal and fetal side effects.     

Use of prostaglandin E2 to ripen the cervix of the mare prior to induction of parturition

Eleven light-breed pregnant mares (335 to 347 d gestaton) were used to evaluate the use of prostaglandin E2 as a cervical ripening agent prior to induction of parturition during the months of April and May. Six hours prior to induction, each mare's cervix was examined per vagina for softness and dilation. Each mare was then assigned to 1 of 2 treatment groups: Group PGE mares (n = 7) received 2.0 to 2.5 mg prostaglandin E2 deposited intracervically; Group SAL mares (n = 4) received 0.5 mL of sterile NaCl deposited intracervically. Six hours later, the mares were readied for parturition by wrapping the tail, scrubbing and rinsing the perineum and udder, and examining the cervix as previously described. Each mare was then administered 15 U, i.v. oxytocin at 15-min intervals until the chorioallantois ruptured. Intervals from initial oxytocin injection until rupture of the chorioallantois, from initial oxytocin injection until delivery of the foal, from delivery of the foal until the foal stood unassisted, and from delivery of the foal until the foal suckled were recorded. Mean cervical dilation immediately prior to induction of parturition tended to be greater in Group PGE mares (3.9 +/- 1.7 cm) than in Group SAL mares (1.9 +/- 1.9 cm; P = 0.10). Mean change in cervical dilation over the 6-h period prior to induction (3.4 +/- 1.9 cm vs 1.5 +/- 2.1 cm), mean number of injections of oxytocin required until the chorioallantois ruptured (1.9 +/- 0.7 vs 2.5 +/- 1.0), and mean intervals from initial injection of oxytocin to rupture of the chorioallantois (20 +/- 10 min vs 28 +/- 19 min) and delivery of the foal (28 +/- 7 min vs 34 +/- 22 min) were not different between Group PGE and SAL mares, respectively (P > 0.10). The proportion of foals that stood within 1 h of birth also did not differ between Group PGE foals (6/7; 86%) and Group SAL foals (3/4; 75%; Chi-square = 0.17; P > 0.10). The proportion of foals that nursed within 2 h of birth was higher in Group PGE foals (6/7; 86%) than in Group SAL foals (1/4; 25%; Chi-square = 4.02; P < 0.05). Premature separation requiring manual rupture of the chorioallantois at the vulvar labia occurred in 1 Group PGE mare (cervical dilation of 1.5 cm at time of induction) and 1 Group SAL mare (cervix closed and firm at time of induction). Foals born from the 2 mares with premature placental separation had the longest intervals from initial oxytocin injection to delivery, delivery to ability to stand unassisted, and delivery to suckling within their respective treatment groups. In summary, it appears that cervical ripening prior to induction of parturition favors shorter deliveries and foal vigor. Intracervical administration of prostaglandin E2 may prove useful for ripening the cervix of the mare prior to induction of parturition. Further studies are indicated to determine optimal dosage and method of administration of prostaglandin E2.     

Effect of dehydroepiandrosterone sulfate on uterine cervical ripening in late pregnancy

In order to elucidate the effects of dehydroepiandrosterone sulfate (DHAS) on softening and dilatation of the uterine cervix, changes of oestriol, 17 beta-oestradiol and progesterone levels in serum and cervix, Bishop score and collagenase activity in the cervical tissue were assessed in pregnant women before and after treatment with DHAS. 17 beta-oestradiol level in the serum and cervical tissue markedly increased after the administration of DHAS, while oestriol level remained unchanged. Serum progesterone level did not change in the majority of cases, while it decreased within several hours in patients in whom delivery was accomplished within 24 hours after the administration of DHAS. Among the factors connected with the Bishop score, effacement and consistency of the cervix were remarkably improved by DHAS administration. Total collagenase activity in the cervical tissue of patients treated with DHAS was elevated by an average of 152%. These results suggest that DHAS is potent in ripening the uterine cervix through an activation of collagenase activity induced by the enhanced conversion to 17 beta-oestradiol. Thus, DHAS administration in the late stage of pregnancy is valuable in prepartal treatment for induction of labour.