M. P. Embrey

RIPENING OF THE CERVIX WITH EXTRA‐AMNIOTIC PROSTAGLANDIN E2 IN VISCOUS GEL BEFORE INDUCTION OF LABOUR

A method of extra‐amniotic prostaglandin administration to achieve ripening of the cervix as a preliminary to induction of labour is described. Compared with a control group the method achieved a 25 per cent reduction in the length of the induced labour, a fall in the incidence of maternal pyrexia and fetal distress, an improvement in neonatal condition of the infants and a reduction in the need to resort to Caesarean section.

CONCENTRATIONS OF PROSTAGLANDIN F2α IN AMNIOTIC FLUID AND PLASMA IN SPONTANEOUS AND INDUCED LABOURS

Concentrations of prostaglandins Fα (PGF2α plus PGF1α) have been measured in terms of PGF2α equivalents by specific radioimmunossay in serial samples of amniotic fluid and peripheral plasma from five patients with spontaneous onset of labour, five induced by amniotomy followed by intravenous oxytocin and six by amniotomy followed by intravenous prostaglandin E2. The mean PGFα concentration in amniotic fluid at amniotomy in patients not in labour was 0.68±0.2 (S.D.) ng./ml. After three to four hours stimulation with oxytocin or PGE2, the concentration was 0.76±0.7 ng./ml. This value is significantly lower (p<0.05) than the concentration in the first amniotic fluid sample taken from patients in spontaneous labour (2.34±l.7) ng./ml., despite uterine activity being tocographically greater in the former patients. In patients labouring spontaneously a transient decline was noted in amniotic fluid PGFα from 2.5±l.6 at amniotomy to 0.79±0.6 ng./ml. in the subsequent sample. A rise in amniotic fluid PGFα concentrations was noted in all patients during the course of labour but the extent of the increase was variable reaching 0.8 to 30 ng./ml.; in four of six patients in whom amniotic fluid sampling was continued during the second stage a further rise in PGFα occurred.

Vaginal prostaglandins and labour induction for patients previously delivered by caesarean section.

Summary. Labour was induced at term with vaginal instillation of prostaglandin E2 in 143 patients who had been delivered by caesarean section in a previous pregnancy. The method was simple, safe and effective with 76% achieving a vaginal delivery, and even when the cervix was very unfavourable at the time of prostaglandin treatment, 68% achieved vaginal delivery. The procedure reduces the need for repeat caesarean section with its potential morbidity, without evidence of undue risk of lower segment scar rupture.

A COMPARISON OF PGE2 AND PGF2α VAGINAL GEL FOR RIPENING THE CERVIX BEFORE INDUCTION OF LABOUR

The efficacy of a vaginal gel containing either 5 mg prostaglandin E2 (PGE2) or 25 mg prostaglandin F2α (PGF2α) to ripen the unfavourable cervix for labour induction was assessed in a double blind trial. PGF2α, compared with PGE2, had little effect upon the clinical state of the cervix, but the resultant duration of labour in each of the two groups was shorter than in a control group. While the numbers of patients requiring oxytocin stimulation of labour and regional anal‐gesia were reduced in both groups compared with the controls, PGF2α was much less effective than PGE2. Uterine hypertonus was observed using both prosta‐glandins during an experimental study and the implications are discussed.

PROSTAGLANDINS AND THE UNFAVOURABLE CERVIX

n The prostaglandins(PGs), unlike oxytocin, are powerful stimulants of uterine contractility in early, middle, and late pregnancy. This characteristic has led to the use of PGs as agents for termination of mid-trimester pregnancy. For this purpose, local routes of administration--extraamniotic or intraamniotic--have proven superior to intravenous administration. PGs have proven particularly useful in inducing labor in cases of fetal death in utero, fetal anomaly such as anencephaly, or in complications of pregnancy. PGE was administered extraamniotically to induce labor in cases of fetal death, anencephaly, and hydatidiform mole. The method was similar to that employed for 2nd trimester abortion, i.e., introduction of a Foley catheter through the cervix and retention of the catheter with a balloon. A similar method, minus the balloon, was used for 40 cases at or near term. These studies led to the conclusion that the Foley catheter might be particularly useful in inductions under unfavorable cervical conditions, i.e., cases where the cervix has not dilatated at all or hardly at all. Infusion of PGE2 in 7 cases with very low Bishop cervical scores proved successful in all cases. The exact infusion procedure is explained. The use of a Foley catheter with a balloon is known to have a ripening effect on the cervix. Combination with local PG administration seems to be particularly effective in causing cervical dilatation.n

EXTRA AMNIOTIC PROSTAGLANDINS IN THE MANAGEMENT OF INTRAUTERINE FETAL DEATH, ANENCEPHALY AND HYDATIDIFORM MOLE

Prostaglandin E2 or prostaglandin F2α was administered extra‐amniotically in the treatment of 22 cases of intrauterine fetal death, two of anencephaly and one of hydatidiform mole. Delivery was achieved in 24 out of the 25 patients. The choice of the extra‐amniotic route of administration appeared to result in fewer side effects than have been encountered during intravenous prostaglandin therapy in the treatment of these conditions.

VERY EARLY ABORTION BY PROSTAGLANDINS

309 women whose menstruation was delayed by 3-35 days were treated with intrauterine or vaginal prostaglandins. Of 275 confirmed pregnancies, 229 were successfully terminated without further abortifacient therapy. A successful outcome was often associated with episodes of vomiting, diarrhoea, and uterine cramps in the 24 hours after prostaglandin administration, but the incidence was related to prostaglandin dosage and gastrointestinal side-effects were more common after vaginal administration. The best results were achieved by the analogue 16:16 dimethyl P.G.E2 as a vaginal pessary. 14 patients (6.1%) required uterine curettage for escessive or prolonged bleeding, while 2 patients required blood transfusion. One patient, who had an intrauterine contraceptive device left in situ during treatment, developed acute pelvic sepsis. No deleterious side-effects occurred in 34 patients who were subsequently proven not to be pregnant at the time of treatment. Treatment by intrauterine or vaginal prostaglandins offers promise as a method of pregnancy termination which avoids much of the physical and emotional trauma associated with surgical termination, and has the advantage of not requiring hospital admission in the majority of cases. The present study shows the safety of the method, and its potential as a self-administration technique.

COMPARISON OF INTRAVENOUS OXYTOCIN AND PROSTAGLANDIN E2FOR INDUCTION OF LABOUR USING AUTOMATIC AND NON‐AUTOMATIC INFUSION TECHNIQUES

A double blind trial of prostaglandin E2and oxytocin given by intravenous infusion after amniotomy for induction of labour in 100 primigravidae with unfavourable induction features is reported. No clear‐cut advantage of either drug emerged although PGE2was perhaps superior when the cervix was highly unfavourable. Prostaglandin E2appeared to produce less deleterious effects on the fetus but was associated with a higher incidence of maternal side effects. The automatic Cardiff Infusion apparatus was found to be a safe means of PGE2infusion and to have advantages over the use of non‐automatic techniques both for PGE2and for oxytocin infusion.

CONVULSIONS AND PROSTAGLANDIN-INDUCED ABORTION

: 615 terminations of pregnancy have been performed in Oxford over a 3-year period with prostaglandins as the prime abortifacient agent; an intravenous infusion of oxytocin was used in 50% of cases. The routes of administration and dose regimen were intraamniotic, extraamniotic, and intravenous. 7 patients had a history of epileptic seizures and were receiving anticonvulsant therapy at the time of admission for termination; this was continued during the abortion procedure. 1 of these patients had fits after admission (but before therapy) and after abortion, but none of the 615 patients had convulsions during the administration of the prostaglandins. 6 of the epileptic group received PGE2 extraamniotically, and the 7th patient PGE2 intraamniotically. Abortion occurred between 7 and 35-1/2 hours. A WHO report quotes trials in 2 university centers of 123 patients treated with intraamniotic PGF2 alpha and 126 patients given intraamniotic hypertonic saline assigned to treatment by random allocation. Convulsions occurred in 1 patient in each group: their previous history is unrecorded. The convulsions reported by Lyneham et al. occurred 7-30 hours after instillation of prostaglandins, which probably precludes the possibility of accidental systemic administration, but which may suggest the involvement of circulating metabolites or endogenous production triggered by abortion processes.

In vitro studies of the characteristics of the release of prostaglandins from viscous solutions.

The diffusion rates of prostaglandin E2 in different viscous solutions used in clinical practice for inducing abortion and term labour have been studied in the laboratory. The results indicate that of those currently in use, solutions of Dextran might be more appropriate for the purposes. By increasing the viscosity of solutions in use at present, clinical results may be further improved by aiding retention in the vagina or uterus while producing a slow sustained linear release of prostaglandin.