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A new gel for intracervical application of prostaglandin E2 (PGE2) has been elaborated and evaluated. The main component of the gel is a cross-linked starch polymer to which prostaglandins can be added and preserved for long-term storage (> 12 months). In a double blind study, 20 patients requiring legal abortion in late first trimester were given gel containing 0.25 mg PGE2 or gel without PGE2. The gel was applied within the cervical canal. In all patients receiving PGE2-gel, a rapid ripening of the cervix occurred which facilitated the subsequent dilatation and evacuation. In patients receiving gel without PGE2 cervix did not ripen. In a subsequent open study, 30 patients were treated with PGE2-gel before therapeutic abortion. The same degree of cervical ripening was registered as for the patients receiving PGE2-gel in the double blind study. In 50 patients at term, intracervical application of 3 ml gel containing 0.05 mg PGE2 induced labor in 27 cases, i.e. 54 per cent of the patients. In the remaining undelivered women, a prominent cervical ripening occurred within 24 hours. No side effects of the treatment were observed. We conclude the new PGE2-gel to be a promising future alternative in the treatment of patients with an unfavorable cervix, prior to surgical evacuation of the uterus in late first trimester abortion, as well as before induction of labor at term.

One hundred nulliparas at term were randomly given oxytocin intravenously or prostaglandin E2 (PGE2) gel (0.5 mg PGE2) intracervically in order to study the effect on cervical ripening and the frequency of successful inductions. In the presence of a favorable cervix both methods seemed equally efficacious in inducing labor. However, when the cervix was unfavorable, 53% of the patients could be delivered with PGE2 gel, compared with 31% when oxytocin was given. In patients with a highly unfavorable cervix this difference was significant (P less than 0.02). In patients not induced into labor, PGE2 gel caused a considerable ripening of the cervix, with a change in Bishop score from 2.9 to 6.3. In patients undelivered after oxytocin stimulation, no change in Bishop score occurred. This effect of locally applied PGE2 gel on cervical ripening was highly significant (P less than 0.001). No adverse maternal or perinatal effects were observed, irrespective of the mode of treatment.

To induce cervical priming and labor, 20 nulliparous term pregnant women with premature rupture of the membranes and unfavorable cervical states were randomly given either oxytocin intravenously or 4 mg prostaglandin E2 in gel intravaginally. One of ten women receiving oxytocin had a favorable cervical state within five hours and vaginal delivery within 24 hours after the start of the infusion compared with six of ten women after prostaglandin E2 gel application. This difference is statistically significant (P less than .01). The number of instrumental deliveries was nine (four cesarean sections and five vacuum extractions) in the oxytocin-treated patients compared with only two vacuum extractions in women who received prostaglandin E2 gel. This difference is also statistically significant (P less than .01, Fischer exact test). In a subsequent open study, 4 mg prostaglandin E2 gel was applied vaginally to 17 term pregnant women of mixed parity with premature rupture of the membranes and unfavorable cervixes. In 12 women a favorable cervical state was achieved within five hours after gel application, and all these women were delivered within 24 hours. None of the women required cesarean section but two required delivery by vacuum extraction. There were no perinatal losses, but two infants in the oxytocin-treated group had Apgar scores less than 7 at five minutes. At pediatric follow-up after two and six months, all infants were normal. In both obstetric and perinatal outcome prostaglandin E2 gel thus seems to be superior to oxytocin for labor induction in term pregnant patients with premature rupture of the membranes and unfavorable cervixes.

92 preeclamptic women with unfavorable cervical states were treated with intracervical application of prostaglandin E2 (PGE2) in gel for cervical priming and/or labor induction. 55 (60%) were delivered after a single PGE2-gel application. In 27 (29%) the cervical state was improved after 24 h and labor could be induced by oxytocin infusion. Thus, 89% of the women were delivered within 48 h after a single PGE2-gel application. In 10 women (11%) a second PGE2-gel application had to be done before oxytocin infusion. The frequency of cesarean sections was low (5%). No case of uterine hypertonus was seen. No gastrointestinal side effects were observed. All newborn infants had an apgar score at 5 min of more than 7 and were in good condition.

In 7 primigravidae admitted for first trimester abortion by dilatation and evacuation, 0.5 mg PGE2 in viscous gel (5 patients) or placebo gel (2 patients) was applied intracervically 6 hours prior to the operation. Throughout the treatment period intrauterine pressure was recorded. Application of placebo gel induced no cervical ripening or myometrial activation. In all patients receiving active gel, a marked improvement of the cervical state was induced by the treatment. In three cases, this priming occurred in parallel to minimal changes in myometrial activity, without regular uterine contractions. In two patients, marked uterine activation was registered due to partly extraamniotic application. It is suggested, that the PGE2-gel has a direct effect on the cervical tissues. Further, the risk of partially applying the gel in the extraamniotic space, thus stimulating the myometrium, depends on the gel volume relative to the dimensions of the cervical canal and the application technique.

A single dose of 0.5 mg prostaglandin E2 in viscous gel was administered intracervically to induce labor in 150 patients with a favorable cervix. All but 5 patients (97 per cent) were delivered within 12 hours. No adverse maternal or fetal effects were registered. The method, which enables induction without primary amniotomy, was easy to perform and well accepted by the patients.

Sixty term pregnant women with unripe cervix were randomly given either 0.5 mg of prostaglandin E2 (PGE2) in 2 ml of gel intracervically or 4 mg of PGE2 in 3 ml of gel intravaginally to prime the cervix and/or to induce labor. In patients with a highly unfavorable cervix (cervical score less than or equal to 3), the intracervical application was significantly more effective than the intravaginal. In patients with a more favorable cervical state (cervical score 4 or 5), the two routes of application were equipotent. Gastrointestinal side effects were registered after intravaginal but not after intracervical application. Myometrial activity was significantly more increased after intravaginal than after intracervical gel application. All children were born in good condition with an Apgar score greater than 7 within 5 minutes.

We combined real-time B-mode ultrasonography with a 2 MHz pulsed Doppler technique to record blood flow in the fetal descending aorta and in the intra-abdominal part of the umbilical vein in 14 pregnant women at term. The blood flow was studied before and after instillation into the vagina of either 4 mg prostaglandin E2 (PGE2) gel or placebo gel. The PGE2 gel was significantly more effective in cervical priming and labor induction than the placebo gel. After instillation of the gel neither group showed a change in the fetal volume blood flow or in the aortic blood velocity waveform. We conclude that the instillation of 4 mg of PGE2 gel does not affect fetal hemodynamics at term.

A new PGE2-gel, based on a cross-linked starch powder, has been developed. This gel seems to have solved several of the pharmaceutical and practical problems connected with local administration of prostaglandins. In a three-center study 120 nulliparous patients were given 0.5 mg PGE2 in 2.2 ml gel intracervically prior to dilatation of the cervix and evacuation of the uterus in late first trimester. Considerable cervical dilatation was obtained within 15 h. The frequency of side effects, including pain and gastro-intestinal discomfort was low. The technique can be recommended for outpatients.

Fourteen consecutive patients (mean gestational age 18.1 weeks, range 15-23 weeks) referred for therapeutic termination of pregnancy were induced into abortion by intra-amniotic PGF2 alpha 40 mg followed by oxytocin stimulation. 14 other patients (mean gestational age 17.9 weeks, range 15-23 weeks) were pretreated with intracervical PGE2 1.0 mg in gel for 4 h prior to induction of abortion with intra-amniotic PGF2 alpha 40 mg without further stimulation. The induction-abortion interval for patients treated with intra-amniotic PGF2 alpha and oxytocin, was 19.1 +/- 2.94 h (+/- SE, n = 14) with a success rate of 80% after 24 h. After pretreatment with intracervical PGE2 1.0 mg in viscous gel, intra-amniotic PGF2 alpha 40 mg induced abortion after 11.2 +/- 1.12 h (+/- SE, n = 14) with a 100% success rate after 24 h. No systemic side effects of the PGE2 pretreatment were noted. No cervical laceration was observed. The results need further confirmation, but still suggest cervical priming with intracervical PGE2 1.0 mg in gel and subsequent induction of abortion by intra-amniotic PGF2 alpha 40 mg as an attractive principle for 2nd trimester abortion.

In a randomized double-blind study we evaluated the effects on cervical ripening and labor induction of 0.5 mg PGE2 in gel given intracervically and 2.0 mg PGE2 given as a vaginal suppository. All patients were at term with unfavorable cervical scores. The indications for induction were toxemia, diabetes mellitus, Rh-immunization, or intrauterine growth retardation. Significantly better results for both cervical priming and labor induction were obtained after intracervical PGE2-gel application than after treatment with placebo or vaginal suppositories. Eleven out of 19 patients (58%) were delivered within 24 h after intracervical PGE2-gel compared to two out of 19 patients given placebo (p less than 0.01). In patients not delivered 24 h after the start of treatment, the mean cervical score had changed from 3.7 to 6.0 (p less than 0.05) after PGE2-gel application compared to a change from 3.9 to 4.3 after placebo treatment (n.s.). The outcome after treatment with PGE2 suppositories did not differ significantly from that with placebo treatment. In a subsequent study 25 patients were given 0.5 mg PGE2-gel intracervically. The results were consistent with those obtained in patients receiving PGE2-gel intracervically in the double-blind study. Few side effects were noted. No patient complained of gastro-intestinal discomfort but increased myometrial activity was observed in two patients; one after placebo and the other after active intracervical PGE2-gel treatment. The hyperactivity was readily countered with the beta 2-agonist, terbutaline. All infants were born in good condition with Apgar scores of 7 or more within 5 min. At pediatric examinations at 1 week and at 6 months of age all children seemed healthy.

The in vitro release profile of prostaglandin E2 (PGE2) from a starch polymer hydrogel was studied. Using a diffusion cell apparatus the in vitro release was measured in a cumulative manner based on a steady-state diffusion concept. The results showed that PGE2 was slowly released for a total of 18 hours. The rate of release was constant for up to 2 hours before changing to a lower value for the remaining time period. The PGE2-hydrogel showed sustained release characteristics which could be of significance in the clinical situation in providing a delayed release mechanism.

Fifty-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 remaining 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.

Cervical biopsies obtained from 7 patients immediately following parturition induced by intracervical application of 0.5 mg prostaglandin E2 (PGE2) in viscous gel were compared with similar biopsies from 11 spontaneously delivered women. A DNP-peptide hydrolytic activity (collagenase) was significantly increased in cervical tissue from the PGE2-induced patients compared with controls. In patients with prompt clinical response, the increase was nearly twofold. No differences were found in the concentrations of water, sulfated glycosaminoglycans, hyaluronic acid, hydroxyproline or leukocyte elastase. Thus, PGE2-induced cervical priming seems to be associated with an increased collagenolytic activity.

In 21 women undergoing simultaneous urethrocystometry because of dysuria, urge, and difficulties to empty the bladder, the effects of prostaglandin E2 (PGE2) applied locally in the bladder and urethra were investigated. In all 9 patients receiving PGE2 intravesically, the bladder pressure increased. Simultaneously, there was a signficant decrease in maximum urethral pressure (p less than 0.05), and in urethral closure pressure (p less than 0.005). Residual urine decreased in the 4 patients, in whom it exceeded 50 ml before administration. All 12 patients receiving PGE2 intraurethrally showed a decrease in maximum urethral pressure). There was a significant increase in bladder pressure (p less than 0.05); urethral closure pressure decreased in all patients. Bladder capacity decreased significantly (p less than 0.01). Residual urine exceeding 50 ml was found in 6 patients; it decreased in 4 after PGE2 administration. It is concluded that PGE2 applied intraurethrally can decrease the intraurethral pressure and increase the bladder pressure without side effects. By these actions, the drug might be useful for facilitating bladder emptying in patients with acute retention of urine.

To terminate pregnancy 15 women with an established diagnosis of missed abortion or intrauterine dead fetuses were treated with 1.0 mg Prostaglandin E 2 in viscous gel applied as a single intracervical dose. -- Abortion was induced after a mean of 7.0 hours in 8 patients with a mean gestational age of 15.0 weeks, and a subsequent evacuation of the uterine cavity was easily performed. -- Complete abortion/delivery was obtained in 7 patients with a gestational age of 33 weeks. The over-all mean induction/delivery time was 7.5 hours. -- Apart from pain related to uterine contractions no side effects were observed and no complications occurred. It is concluded that the present technique represents a promising alternative in the treatment of patients with missed abortion or intrauterine dead fetuses.

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.

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 greater than 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. It is concluded that locally applied PGE2-gel can be used to produce ripening of the cervix and/or induce labor in patients at term with an unripe cervix. Since there was practically no difference in efficiency between the two doses but one case of hyperstimulation in patients given 1.0 mg PGE2, the smaller dose, i.e. 0.5 mg is recommended.

A new gel delivery system for the local application of prostaglandin E2 consists of drug incorporated in the matrix of a cross-linked starch polymer. The properties of the starch powder provide a stabilizing milieu for the labile prostaglandin E2 and, by addition of saline, a ready-to-use gel for immediate local administration. The gel offers advantages over existing preparations in terms of chemical and microbiological stability, homogeneity, and dosage safety. This report outlines the pharmaceutical aspects involved in the development of the delivery system.

A single intracervical instillation of prostaglandin E2 (1.0 mg or 0.5 mg in viscous gel) was given to dilate the cervix before dilatation and evacuation in patients with missed abortion or intrauterine fetal death in late pregnancy. The 1.0-mg dose of PGE2 gave more prominent cervical dilatation in early pregnancy. In late pregnancy 1.0 mg PGE2 induced labor in the majority of patients and with shorter induction delivery time than in patients given 0.5 mg PGE2. There was no uterine hypertonus and no patients complained of gastrointestinal symptoms. We conclude that intracervical instillation of 1.0 mg of PGE2 in viscous gel is a safe and effective method both for dilating the cervix before dilatation and evacuation and as a method of inducing labor in patients with intrauterine fetal death.

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.

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. Twenty-three 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.

Thirty-eight term pregnant women with a moderately unfavorable cervix (cervical score 4-5 p.) were randomly given intravenous oxytocin (Group A) or 3 mg PGE2 as a vaginal suppository (Group B) for labor induction. Eight out of 19 in Group A and 17 out of 19 in Group B gave birth vaginally within 24 h. The remaining 11 women in Group A had still an unfavorable cervix after 24 h. They were then given 3 mg PGE2 as a vaginal suppository and all but one had given birth vaginally without complications within 24 h. In Group B only 2 were still undelivered after 24 h. Both had a favorable cervix and were delivered vaginally within 12 h after intravenous infusion of oxytocin. The number of instrumental deliveries in Group A was one cesarean section and two vacuum extractions and in Group B three vacuum extractions. One woman in Group B reported nausea and vomiting and in one had strong uterine contractions in the second stage of labor. Otherwise no side effects were registered. All babies were born in good condition with Apgar scores greater than or equal to 7. In conclusion, vaginal application of 3 mg PGE2 as a suppository seems to be more effective than intravenous infusion of oxytocin for labor induction in women with half-ripened cervices, i.e. cervical scores of 4-5 p.

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 homogenization 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. In a randomized double-blind study the new PGE2-gel was intracervically applied to twenty nulliparae before abortion by dilatation and evacuation (D & E). Ten women were given a gel containing 0.25 mg PGE2 (PGE2-gel) and ten a gel without PGE2 (placebo gel). It was found that the PGE2-gel, in contrast to the placebo gel, produced a rapid ripening of the cervix facilitating the subsequent D & E. No adverse systemic or local reactions were found during or after the treatment.

Sixty-one term pregnant women, 29 nulliparous (Group A) and 32 multiparous (Group B) with unfavorable cervix and premature rupture of the membranes (PROM) were given 3 mg PGE2 in suppository form for cervical ripening and labor induction. Five hours after starting the treatment, 12 women of the 29 in Group A and 21 of the 31 in Group B had a favorable cervix and established labor. The remaining 17 nulliparae and 11 multiparae still had an unfavorable cervix and were then given another PGE2 suppository. Until the next morning, i.e. within 24 h, 19 nulliparous and 22 multiparous women gave birth whereas a further 5 nulliparous women who now had favorable cervix but no uterine contractions were delivered after stimulation with intravenous oxytocin. The remaining undelivered women were given another PGE2 suppository. With or without additional oxytocin stimulation, all but 2 multiparous women could be delivered within a further 12 hours. The total number of instrumental deliveries in Group A was 2 caesarean sections due to disproportion (7%) and 5 ventouses. In Group B, 3 caesarean sections (9%) had to be carried out, one due to fetal distress and 2 due to failed induction. From the results of this study we conclude that vaginal application of 3 mg PGE2 in suppository form can be used to induce labor in patients with PROM and unripe cervix. However, when the results are compared with those obtained in previous studies after application of PGE2 in gel, the latter technique seems preferable.

A new gel for local application of prostaglandins has been elaborated. The new gel, based on a lyophilized prostaglandin E2 (PGE2) starch powder, seems to have solved most of the pharmaceutical and clinical problems associated with local administration of prostaglandins. In a randomized double-blind study, 50 nulliparous patients with an unfavorable cervical state at term were given 2 ml gel containing 0.5 mg PGE2 (PGE2 gel) or gel without PGE2 (placebo gel). The gel was deposited into the cervical canal. Among patients given PGE2 gel, 11 of 25 had induced labor, delivering without further stimulation within 24 hours. In patients given placebo gel, 2 of 25 were delivered with 24 hours. This difference is statistically significant (P less than .01). Patients undelivered after treatment with PGE2 gel achieved a considerable and statistically significant improvement of cervical score, whereas in patients in whom labor was not induced successfully by placebo gel treatment no significant changes in cervical score were registered. In a subsequent open study another 70 term patients of varied parity were given 0.5 mg PGE2 gel. Thirty-eight patients (54%) had successfully induced labor. Among the remaining undelivered patients, considerable ripening of the cervix occurred. Thus, the cervical score changed from a mean of 3.2 prior to treatment to a mean of 6.5 by 24 hours after treatment. Gastrointestinal discomforts were not observed. Signs of uterine hyperstimulation were registered in 1 patient.

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. To eliminate or decrease myometrial activity the calcium antagonist nifedipine was given orally to eight patients at application and five hours after application of 0.25 mg PGE2-gel. None of the patients recognized uterine contractions. However, also in these patients significant changes in cervical consistency and dilatation occurred within twelve hours. No side effects of the treatment were observed. It is concluded, that a preoperative, intracervical single application of 0.25 mg PGE2 seems to be useful to ripen the unfavorable cervix before subsequent termination of early pregnancy by D & E.

In this survey the effect of intracervically applied prostaglandin E2 (PGE2) on the pregnant uterus is outlined. It is concluded that PGE2 decreases cervical resistance and stimulates the myometrium to contract. In small doses (0.25 mg and 0.5 mg) PGE2 produces a rapid and prominent ripening of the cervix without systemic side effects and indepedent of prominent uterine contractions. Prostaglandin E2 applied intracervically in viscous gel seems to be superior to previously used methods for treatment of patients with an unfavorable cervical state.

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.

The methods used to date to ripen the unfavorable cervix during pregnancy have considerable disadvantages, chiefly from the practical point of view. Intracervical application of a small dose (0.5 mg) of prostaglandin E2 (PGE2) in viscous gel is a safe, easily performed and effective method to ripen the cervix in both early and late pregnancy. A new starch-based gel seems to have solved the pharmaceutical problems associated with gel preparations used hitherto. The histological and biochemical changes induced by local application of PGE2 are similar to those occurring spontaneously during late pregnancy.