Interruption of first trimester human pregnancy following Epostane therapy. Effect of prostaglandin E2 pessaries

The effect of Epostane, a competitive inhibitor of the 3 beta hydroxy steroid dehydrogenase enzyme system in combination with prostaglandin E2 (PGE2) for induction of abortion in early first trimester pregnancy has been studied in a group of 20 women awaiting termination of pregnancy. The women were consecutively assigned to four treatment groups. The first group was treated with PGE2 alone, administered vaginally as a lipid based (Witepsol) pessary. The remaining three groups received Epostane at differing doses for 5 days, and were treated with PGE2 on the fourth day. Significant falls in serum progesterone and oestradiol occurred in the Epostane-treated patients. Abortion was induced in one of the five control patients and in three of 10 patients treated with low doses (300-400 mg) of Epostane. Intrauterine pressure monitoring showed an increased reactivity to PGE2 in the treated groups. At the highest dose (600 mg) of Epostane, serum progesterone and oestradiol showed the greatest decline to 8% and 21% of the pretreatment values, a prompt and sustained pressure response occurred to PGE2 and abortion was induced in all five patients. A critical degree of progesterone suppression appears to sensitize the myometrium to exogenous prostaglandin. This combined treatment is an effective method of early pregnancy termination and may have a role in the management of mid-trimester abortion.     

Myometrial activity in first trimester human pregnancy after Epostane therapy. Effect of intravenous oxytocin

The effect on myometrial activity of Epostane, a competitive inhibitor of the 3 beta-hydroxy steroid dehydrogenase enzyme system (3 beta-HSD) has been studied in 20 women awaiting termination of pregnancy. The women were randomly allocated by a double-blind procedure into two groups. In the Epostane-treated group there were significant falls in serum progesterone and oestradiol concentrations after 3 days of treatment. The placebo-treated group showed a small but significant decline in serum progesterone concentration. Insertion of an intrauterine balloon catheter for pressure measurements produced significantly greater uterine activity in the Epostane-treated group. The oxytocin response was variable and there was no significant difference between the two groups. A small rise in the peripheral plasma concentration of a prostaglandin F2 alpha metabolite (PGFM) was observed in the placebo group following oxytocin injection. There was a significant inverse correlation between post treatment progesterone values and uterine activity. Epostane appears to sensitize the myometrium to endogenous oxytocics and this probably results from progesterone 'withdrawal'. This effect may prove useful in potentiating the action of exogenous myometrial stimulants, such as prostaglandins, and may have a role in the termination of early pregnancy.     

Myometrial activity in first trimester human pregnancy after Epostane therapy. Effect of intravenous oxytocin

Summary. The effect on myometrial activity of Epostane, a competitive inhibitor of the 3β-hydroxy steroid dehydrogenase enzyme system (3β-HSD) has been studied in 20 women awaiting termination of pregnancy. The women were randomly allocated by a double-blind procedure into two groups. In the Epostane-treated group there were significant falls in serum progesterone and oestradiol concentrations after 3 days of treatment. The placcbo-treated group showed a small but significant decline in serum progesterone concentration. Insertion of an intrauterine balloon catheter for pressure measurements produced significantly greater uterine activity in the Epostane-treated group. The oxytocin response was variable and there was no significant difference between the two groups. A small rise in the peripheral plasma concentration of a prostaglandin F20r metabolite (PGFM) was observed in the placebo group following oxytocin injection. There was a significant inverse correlation between post treatment progesterone values and uterine activity. Epostane appears to sensitize the myometrium to endogenous oxytocics and this probably results from progresterone 'withdrawal'. This effect may prove useful in potentiating the action of exogenous myometrial stimulant5, such as prostaglandins, and may have a role in the termination of early pregnancy.     

Controlled study of 16,16-dimethyl-trans-delta 2 prostaglandin E1 methyl ester vaginal pessaries prior to suction termination of first trimester pregnancies

A pessary containing the prostaglandin analogue, 16,16-dimethyl-trans-delta 2 prostaglandin E1 methyl ester (Cervagem) was inserted into the vagina of primigravid women 2 h before suction termination of pregnancy. The cervix was softer, easier to dilate and more widely dilated at the start of the procedure than in a control group of women who received placebo pessaries containing the vehicle alone. Intra-operative blood loss was diminished. The incidence of pre- and post-operative abdominal cramps was increased in the Cervagem-treated group. No gastrointestinal side-effects were noted.     

Collagenase activity in the human cervix uteri after prostaglandin E2 application during the first trimester.

Cervix biopsies were obtained during the first trimester from plurigravidae and primigravidae at various times after intracervical application of prostaglandin E2. The tissues were extracted with Ca(2+)-containing buffer, and collagenase activity was determined in these extracts using a solid phase assay in which triple helical 125I-labelled collagen was cleaved. Collagenase was detected in all samples but elevated activity was present only during a short temporal window after prostaglandin application. Maximal activity was observed 1 and 2 h after application of prostaglandin in multigravidae and 4 h in primigravidae. These data can explain why collagenase activity in cervical tissues after prostaglandin application had previously not been found. They indicate somewhat different mechanisms of cervical ripening in primigravide compared to multigravidae.     

Induction of labor with vaginal prostaglandin E2 pessaries

Prostaglandin E2 vaginal pessaries (3 mg) were compared with conventional amniotomy and oxytocin infusion as a method of induction of labor in 160 patients in the study group compared with 160 in the control group. Each group consisted of 100 primigravidae and 60 multigravidae. When the features of labor, delivery and fetal status were analyzed for the study and the control groups, the patients who received PGE2 pessaries had a better outcome. The difference was more significant for those patients with a low Bishop score. Compared with controls, the PGE2-treated patients had fewer cesarean sections either for failed induction or fetal distress (P less than 0.01); the incidence of infants with low Apgar score was significantly less (P less than 0.05) and there were fewer postpartum haemorrhages (P less than 0.01).     

Interruption of pregnancy by prostaglandin 15-methyl F2alpha.

The current study was formulated to investigate the abortifacient activity of prostaglandin 15-methyl F2alpha (15-methyl PGF2alpha) administered intramuscularly to 80 healthy women with gestations between 8 and 22 weeks. Goals were the establishment of an effective dosage schedule and assessment of the incidence and severity of side effects. All 80 gravidas were aborted, with a mean time to abortion of 15.70 hours (SD, 6.52). Gastrointestinal side effects occurred in 89% of the patients; temperature elevations greater than or equal to 100.6 degrees F were noted in 14 cases. No other significant complications were encountered. Transabdominal intra-amniotic pressure monitoring indicated the need to administer the drug at 2-hour intervals. The 15-methyl PGF2alpha patients were matched for parity and gestational length with 80 gravidas aborted with PGE2 20-mg vaginal suppositories. The difference in interval to abortion in the two groups was not statistically significant. While gastrointestinal side effects were more common with 15-methyl PGF2alpha, the frequency of drug-induced temperature elevations was reduced.     

Reduced dose of Rh immunoglobulin following first trimester pregnancy termination.

The efficacy and safety of a 50-microgram dose of Rh immune globulin for prevention of Rh isosensitization following first trimester vacuum abortion are evaluated in this study. A total of 1027 women undergoing abortion at three outpatient facilities participated in the study; 755 (73.5%) completed follow-up serologic screening 6 months after termination of pregnancy. None showed serologic evidence of Rh sensitization at the time of followup. No serious adverse reactions to the drug were observed.     

A comparison of single prostaglandin E2 vaginal tablet with prostaglandin E2 vaginal pessaries for induction of labor at term.

This study represents the first of its kind in Kuwait. Two preparations of prostaglandin E2 (PGE2) have been compared as agents for induction of labor. In a randomized controlled study of 200 women of low parity and unfavorable cervical induction features induction of labor by means of a single vaginal tablets of PGE2 was compared with locally prepared PGE2 vaginal pessaries. The gradual increase of uterine contractions and the establishment of labor in a similar way to that observed during spontaneous labor was more apparent after PGE2 tablets. Labor induction was successful in 80% of patients in PGE2 tablet group compared with 59% in PGE2 pessaries group. The incidence of cesarean section was equal in both groups (4%), but none was performed due to uterine hyperactivity. The data presented indicate that the PGE2 vaginal tablet is safe and effective in induction of labor in healthy women at term.     

The effect of vaginal prostaglandin E2 pessaries on induction of labor

In a prospective randomized study, patients with a valid obstetric indication for induction of labor received either 3 mg prostaglandin E₂ vaginal pessaries immediately prior to oxytocin (prostaglandin group, n = 99), or oxytocin alone (oxytocin group, n = 103). At the conclusion of the second day of induction, a significant reduction was noted in the incidence of failed induction in the prostaglandin group (4%) as compared to the oxytocin group (13%) (p < 0.05). Twenty percent of patients in the prostaglandin group experienced successful induction with prostaglandin pessaries only. When oxytocin was required in the prostaglandin group, the maximal concentration of oxytocin infused and the duration at this concentration were significantly less than in the oxytocin group. No perinatal complications were attributed to the use of prostaglandin. Three minor maternal complications that were attributed to vaginal prostaglandin E₂ did not require treatment. Our conclusion is that patients who require an induction of labor, when artificial rupture of the membranes is not feasible, benefit from the use of prostaglandin pessaries before the administration of oxytocin.     

A comparison of prostaglandin E2 pessaries and laminaria tents for ripening the cervix before termination of pregnancy

Forty primigravid women aged 15-45 years were randomly allocated to receive either an intravaginal pessary of 3 mg prostaglandin E2 (PGE2) or an intracervical 5-mm laminaria tent (LT) 12-16 h before termination of pregnancy at 6-14 weeks gestation. The degree of dilatation of the cervix at operation and its resistance to further dilatation during the procedure were assessed by a 'blind' operator. Laminaria tents were more effective in achieving dilatation and softening of the cervix than were PGE2 pessaries and in 40% of women no further dilatation was necessary. There were no associated side-effects or complications. A cervical tear occurred in two of 20 patients treated with PGE2 pessaries and all 20 required further dilatation of the cervix. Laminaria tents provide a simple, safe, acceptable and effective means of 'ripening' the cervix prior to termination of early pregnancy.     

Successful pregnancy outcome following first trimester pelvic inflammatory disease

Pelvic inflammatory disease rarely complicates pregnancy. Although few in number, most of the previously reported cases have resulted in spontaneous abortion or intrauterine fetal demise. At 5 weeks gestation, a 20 year old gravida 2 para 1 underwent uterine curettage and diagnostic laparoscopy for a suspected ectopic gestation. Seventeen days later, she presented with severe bilateral lower abdominal pain, cervical motion tenderness, uterine tenderness, and bilateral adnexal tenderness. After 84 hours of intravenous cefazolin, gentamycin, and clindamycin, the patient had resolution of all symptoms. She then completed 14 days of outpatient antibiotic therapy with oral cephalexin. At 39 weeks gestation, she delivered a 3611 g male fetus via spontaneous vaginal delivery. Successful pregnancy outcome can occur after first trimester pelvic inflammatory disease.     

Changes in circulating alphafetoprotein following administration of mifepristone in first trimester pregnancy.

The occurrence of fetomaternal haemorrhage was investigated in 30 women by measuring maternal serum alphafetoprotein (AFP) levels before and after the administration of mifepristone (RU 486) for termination of first trimester pregnancy. A significant rise in AFP levels was seen in 21 women (70%), the increase ranging from 6 to 660% of baseline levels. The apparent frequency of fetomaternal haemorrhage was similar to that reported previously for surgical termination of first trimester pregnancies.     

Mid-trimester termination of pregnancy with 16,16-dimethyl-trans-delta 2 PGE1 vaginal pessaries: a comparison with intra- and extra-amniotic prostaglandin E2 administration.

PGE1 analogue (gemeprost) vaginal pessaries administered three hourly for three doses has been compared with a single extra- or intra-amniotic injection of PGE2 for mid-trimester termination of pregnancy in 450 women between 13 and 20 weeks gestation. The mean (SD) induction-abortion interval (IAI) in the vaginal pessary group of 19.5 (8.4) h was significantly longer than the respective intervals of 14.4 (9.3) and 16.1 (6.8) h in the patients treated extra- or intra-amniotically (P less than 0.001). Seventy-three percent treated with gemeprost aborted within 24 h of initial treatment compared with 84% and 87%, respectively in the extra- and intra-amniotic groups (P less than 0.05). Patients treated with gemeprost were more likely to need further prostaglandin treatment and had an increased incidence of gastrointestinal side effects. Despite these differences vaginal gemeprost pessaries provide a safe, effective, easy to administer method for midtrimester termination of pregnancy.     

Termination of second trimester pregnancy with gemeprost vaginal pessaries and intra-amniotic PGF2 alpha. A comparative study

152 women admitted for legal abortion in the second trimester of pregnancy were included in an open, randomized, controlled six-centre study. 75 patients received gemeprost 1 mg vaginal pessaries at 3 hours intervals up to a maximum of 5 mg and 66 patients were treated with a single 40 mg intra-amniotic dose of PGF2 alpha. The 24-hour success rate was 81% (n = 61/75) in the gemeprost and 64% (n = 42/66) in the PGF2 alpha group (p less than 0.02). The mean abortion times were 14.3 and 14.8 hours in the gemeprost and the PGF2 alpha groups, respectively. The mean time to onset of pain was shorter and more patients experienced blood loss over 100 ml during the induction in the PGF2 alpha group than in the gemeprost group (p less than 0.02). Apart from that, the nature and severity of side effects were comparable between the two groups. Besides significantly better efficacy, the non-invasive gemeprost treatment was found to be easier and safer as compared to the PGF2 alpha treatment.