Lars Wingerup

Treatment of premature labor with the calcium antagonist nifedipine

SummaryThe effect of the calcium antagonist nifedipine on premature labor was investigated in ten carefully selected patients. The main aim of treatment was to inhibit uterine activity and delivery for 3 days during which time fetal lung maturation was accelerated by glucocorticoid treatment. In all 10 patients, uterine activity was abolished during the 3 days of treatment and delivery was also postponed. No serious maternal side effects were observed. All children were delivered in good condition. All survived and were alive and well at 1 year.

Ripening of the Uterine Cervix and Induction of Labour at Term with Prostaglandin E2 in Viscous Gel

Abstract. In order to achieve ripening of the uterine cervix or induce labour in patients at term with an unfavourable cervical state, 1 mg of prostaglandin E2 (PGE2), suspended in a viscous gel, was instilled into the cervical canal. In a pilot study, 41 patients received the PGE2‐gel. Twentythree of these, (56%), went into labour, and delivery occurred without further stimulation within 15 hours. In the remaining 18 patients, there was a marked improvement of the cervical state, which changed from an average (modified) Bishop score of 2.5 to 6.1 within 24 hours. In a double‐blind study comprising 20 nulliparae, 10 received gel containing PGE2 and 10 gel without prostaglandin. Cervical state did not change significantly (Bishop score 3.6 and 4.0) after 24 hours in patients receiving placebo gel. In those receiving PGE2 gel, 8 went into labour and were delivered without further induction within 13 hours. Two patients showed an increase in Bishop score from 3 to 6 and 7, respectively, after 24 hours. They were then induced by oxytocin and delivery occurred after 8 and 10 hours. The results suggest that administration of PGE2 intracervically can induce ripening of the cervix in patients at term with an unfavourable cervical state, and thus facilitate delivery.

Biochemical Changes in Human Cervical Connective Tissue after Local Application of Prostaglandin E2

Intracervical application of prostaglandin E2 in the late first trimester induces (1) softening of the cervix tissue; (2) increase in sulfated glycosaminoglycans (18 +/- 12%, mean +/- SEM); (3) no change in hyaluronic acid and water; (4) decrease in pepsin-extractable collagen, and (5) apparent decrease in collagenase. A high activity of collagenase in combination with a replacement of collagen with sulfated glycosaminoglycans may be of importance for the ripening process.

Evidence for a local effect of intracervical prostaglandin E2-gel☆

Eight primigravid women with a mean gestational age of 9.4 weeks (9 to 10 weeks) who were admitted for first-trimester abortion by dilatation and evacuation were preoperatively treated for 6 hours with either intravenous infusion of oxytocin or a strictly intracervical application of prostaglandin E2 (PGE2) in viscous gel. Myometrial activity was monitored by intrauterine pressure recording throughout the treatment. Contractile activity was more pronounced in the oxytocin-treated group, whereas cervical priming occurred after the PGE2 treatment only. Intracervical PGE2-gel is suggested to have direct effects on the cervical tissues, independent of uterine contractile activity. Furthermore, myometrial stimulation induced by escape of gel into the extra-amniotic space can be avoided by adjusting the volume of gel and technique of application to the dimensions of the cervix.

Ripening of the cervix by intracervical application of PGE2-gel before termination of pregnancy with dilatation and evacuation.

Abstract. In a randomized double‐blind study a viscous gel, containing 0.25 mg prostaglandin E2 (PGE2‐gel) or without prostaglandin (placebo gel), was applied intracervically in twenty‐two nulliparous patients just before termination of early pregnancy by dilatation and evacuation (D & E). Within twelve hours a marked ripening of the cervix was found in all the eleven patients receiving PGE2‐gel. Thus, a significant change in cervical dilatation from mean 5.4 mm to mean 10.7 mm occurred. Furthermore, a considerable softening of the cervix was registered. In the eleven patients receiving placebo gel, no significant changes in cervical dilatation or consistency were found. The subsequent D & E was easily performed in all patients treated with PGE2‐gel. However, in three of the patients given placebo gel, D & E was difficult to carry out because of an unfavorable cervical state.

A new gel for intracervical application of prostaglandin E2.

Abstract. A new gel‐formulation for intracervical application of prostaglandin E2 (PGE2) has been prepared. As a vehicle for the gel a cross‐link starch polymer is used. PGE2 substance is added to the starch polymer and after homo‐genization and lyophilization a PGE2 powder is obtained. The powder can be stored at room temperature for more than four months without inactivation of the prostaglandin. Before clinical application a few ml of saline is added to the powder giving, within 30 seconds, an easily‐handled ready to use PGE2‐gel. Chemical analysis by spectrophotometric technique reveals that the amount of unchanged PGE2 is the same in the new gel‐formulation as in a conventional cellulose gel.

RIPENING OF THE CERVIX AND INDUCTION OF LABOR IN PATIENTS AT TERM BY SINGLE INTRACERVICAL APPLICATION OF PROSTAGLANDIN E2 IN VISCOUS GEL

Abstract. Prostaglandin E2 (PGE2) suspended in a viscous gel was deposited intracervically to 115 patients at term with an unripe cervix. 45 of these patients were given a single dose of 1.0 mg PGE2, whereas the remaining 70 received only half that dose, i.e. 0.5 mg. Irrespective of dose <60 per cent of the patients were induced into labor and delivered without further stimulation within less than 24 hours. The mean induction delivery time was 10 hours. In the remaining patients a considerable ripening of the cervix was registered. Hypercontractility did occur in one patient given 1.0 mg PGE2, otherwise no maternal side effects were observed. There were no adverse effects on the fetuses. The number of instrumental deliveries was 19 per cent including 9 per cent cesarean sections.

Intracervical application of PGE2-gel combined with early intravenous infusion of oxytocin for induction of term labor in women with unripe cervix.

SummaryFifty-four women with an unripe cervix at term were given 0.5 mg intracervical prostaglandin E2 (PGE2) gel. In 37 of them (70%) the cervix ripened within 5 h and seven of them were in labor at that time. Of the remaining 30 patients, 15 were randomly given an i.v. oxytocin infusion and 13 were delivered within 12 h. In 17 women (30%) the cervix was still unfavorable 5 h after PGE2-gel application but seven of them had a favorable cervix when reassessed 24 h after PGE2-gel instillation. All these patients went into labor with an i.v. infusion of oxytocin. The remaning 10 patients required another dose of PGE2-gel and subsequent i.v. oxytocin. Only in two of these patients did induction fail so that delivery by Caesarean sections was required. All infants were born in good condition.

Human cervical connective tissue and its reaction to prostaglandin E2.

A survey of connective tissue in general and human cervical connective in particular is presented. It is concluded that about 90% of the human cervix consists of fibrous connective tissue which, according to the composition of the collagen and the proteoglycans, is very similar to that in skin and sclera. The high activity of collagenase probably gives the cervical connective tissue from pregnant women its potential to ripen following prostaglandin treatment. Electron microscopical examination has revealed an increased amount of amorphous substance after such treatment. This may be caused partly by degraded collagen fibers and partly by newly synthesized proteoglycans.

The impact on labor induction of intracervically applied PGE2-gel, related to gestational age in patients with an unripe cervix.

In 54 patients with an unripe cervix in late third trimester, in which gestational age had been properly determined by repeated ultrasound scannings, labor was induced by intracervical application of 0.5 mg PGE2 in viscous gel. It was found that the outcome of the induced labor was not related to the gestational duration, but to the pre-inductive cervical score. Thus, the number of successful inductions was smaller and induction-delivery time longer, the lower the cervical score. Moreover, instrumental deliveries occurred most frequently in nulliparous women, with a low pre-inductive cervical score. Taking into consideration the difficulties of labor induction in the present type of patient, the overall proportion of instrumental deliveries (17%, including 7% cesarean sections) was low. No maternal or fetal side effects were observed. It is concluded that intracervical application a small dose of PGE2 in gel can be recommended for cervical priming and labor induction in pre- and post-term pregnancy.