Termination of early gestation with a vaginal polysiloxane device impregnated with (15S) -15 methyl prostaglandin F2a methylester

An investigation of the abortifacient activity of (15S) -15 methyl prostaglandin F2_a methyl ester released from a vaginal polysiloxane device was performed in eleven pregnant women of 49 days gestation or less. Bleeding and contractions were induced in all women, but only seven aborted their pregnancies. Five subjects received a vaginal device impregnated with 3 mg of drug and two aborted fetal tissue. Six women were given a vaginal device containing 5 mg of drug and five aborted fetal tissue. Ten of the patients had significant side effects, nausea, emesis, diarrhea and chills. Six women expelled the device prior to the termination of therapy. This prostaglandin analogue, when administered from a vaginal polysiloxane device in early gestation was an effective abortifacient but was accompanied by systemic side effects and a high incidence of expulsion of the evidence prior to its scheduled removal.     

Post-conceptional induction of menses with a single vaginal suppository of (15S)-15-methyl prostaglandin F2 alpha methyl ester

The induction of post-conceptional menses needs a technically simple method which would avoid instrumentation of the uterus. One possible method investigated in this study is the abortifacient effect of a single dose long-acting vaginal suppository containing 3.0 mg of (15S)-15-methyl prostaglandin F2 alpha methyl ester. Pregnancy was terminated successfully in 13 of the 14 subjects. Two successful patients required curettage for prolonged bleeding and retained products of conception. Prolonged vaginal bleeding and the uncertainty of endpoints with particular reference to human chorionic gonadotropin (HCG) constitute the major problem with this non-invasive method, and are discussed in the light of the data obtained.     

Mid-trimester abortion with 15 (S) methyl prostaglandin F 2 alpha

The efficacy of intramuscular administration of 15 methyl (15S) prostaglandin F2alpha (PGF2a) in midtrimester pregnancy termination was evaluated in 16 healthy patients (mean age, 23.3; mean parity, 1.4; mean number of menstrual weeks, 16.1) by measuring dose response; oxytocin conversion; abortion time; side effects; intrauterine dynamics and progesterone withdrawal. Labor was monitored using extraovular balloon placed transvaginally; transcervically; and connected to a Physiograph machine. Patients not aborting within 48 hours after the first dose were considered failures. Blood samples were collected at 0, 3, and 6 hours and at abortion time for plasma progesterone measurement. Average dose given was 789 +or- 60 micrograms. Only 9 of 10 patients aborted within the prescribed 48 hours: 7 were complete abortions, and 2 were incomplete and required suction curettage. Mean induction to abortion time was 20.2 +or- 2.7 hours. Nausea, vomiting and diarrhea were the main side effects. The findings suggest that 15 methyl PGF2a in the dosages and routes prescribed is not as efficient as PGF2a. It is also suggested that prostaglandin affects the myometrium at 2 levels: 1) a membrane effect, and 2) a more fundamental intracellular regulatory effect which is necessary to initiate labor.     

Termination of second trimester pregnancy with intra-amniotic 15 (S) 15 methyl prostaglandin F-2alpha - a two dose schedule study.

Termination of second trimester pregnancy with intra-amniotic administration of 15 (S) 15 methyl prostaglandin F-alpha (15 me F-alpha) was attempted in fifty patients. One group (26 patients) was given 1 mg of the analogue and the other group received 2.5 mg. The abortifacient efficacy of 15 me F-2alpha was similar in both groups; over 90% of the patients aborted with a single dose. There was a higher incidence of vomiting, diarrhoea and incomplete abortions in the group treated with 2.5 mg 15 me F-2alpha. Although the mean injection-abortion interval in the 2.5 mg group was shorter, it is concluded that intra-amniotic administration of 1 mg 15 me F-2alpha provides a better regime, giving high efficacy with a single dose, a low incidence of side effects and greater safety in case of inadvertent entry of the intra-amniotic dose into systemic circulation.     

Hormone changes occurring during second trimester abortion induced with 15 (S)-15-methyl prostaglandin F2alpha.

Changes in progesterone, human placental lactogen (HPL), cortisol and estradiol-17B were measured during second trimester abortion induced by I.M. 15-methyl PGF2alpha. A rapid decline in progesterone and HPL was found, indicating perhaps an initial effect on the placenta. A rapid rise in cortisol was found, but it is not clear if this is due to stress or part of the termination mechanism. The changes of estradiol were not as distinct and may reflect opposite effects of the prostaglandin on the placenta and adrenals. Similar hormonal changes were observed regardless of the duration of gestation.     

15(S)15-methyl prostaglandin F2alpha for termination of very early human pregnancy. A comparative study of a single intramuscular injection and vaginal suppositories.

The results of a comparative study of the efficacy and acceptability of 15(S)15-methyl prostaglandin F2alpha (15-Me-PGF2alpha) administered as a single i.m. injection or vaginal suppositories (15-Me-PGF2alpha methyl ester) every 3rd hr for termination of very early human pregnancy is reported. The amenorrhoic period varied from 37 to 60 days. Group I (30 cases) received 0.6 mg as a single i.m. injection without any pretreatment. Retrospectively 24 of the 30 women were in fact pregnant and 22 of them aborted. Group II received suppositories (1.0 or 1.5 mg per suppository). In this group all women were pregnant and they all aborted. Symptoms such as pain, bleeding, vomiting and diarrhea started in general earlier in the i.m. group and they were more marked. In the present series the efficacy and acceptability were highest for the vaginal route of administration.     

Post-conceptional induction of menses with a single vaginal suppository of (15S)-15-methyl prostaglandin F2α methyl ester

The induction of post-conceptional menses needs a technically simple method which would avoid avoid instrumentation of the uterus. One possible method investigated in this study is the abortifacient effect of a single dose long-acting vaginal suppository containing 3.0 mg of (15S)-15-methyl prostaglandin F₂α methyl ester. Pregnancy was terminated successfully in 13 of the 14 subjects. Two successful patients required curettage for prolonged bleeding and retained products of conception. Prolonged vaginal bleeding and the uncertainty of endpoints with particular reference to human chorionic gonadotropin (HCG) constitute the major problem with this non-invasive method, and are discussed in the light of the data obtained.     

Intrauterine injection of 15(S)-15-methyl-prostaglandin F2alpha for termination of early pregnancy in out-patient.

15-me-PGF2alpha was administered as single intrauterine injection for interruption of very early pregnancy in 30 out-patients. After 2 weeks, abortion was complete in 60% induced with 125 or 200 mug and 80% induced with 300 mug. After 3 weeks, abortion was complete in 90% induced with 125 mug, in 70% induced with 200 mug and in 100% induced with 300 mug. One failure occurred in patients treated with 200 mug and 2 curettages were performed because of incompleteness of abortion. No serious complications occurred. Compared with our previous results it appears that 15-me-PGF2alpha is as effective as natural PGF2alpha in inducing abortions during very early pregnancy but causes somewhat fewer side-effects.     

Mid-trimester abortion with 15 (S) methyl prostaglandin F2α

A Prostaglandin analog 15 Methyl PG F_2α administered intra-muscularly was used to induce mid-trimester abortion in 16 patients. The average dose given was 789 ± 60 ugm, and this resulted in only 9 successful abortions. The incidence of side effects was thought to be prohibitive. PG appears to produce two types of action on the myometrium, a membrane effect, and a more fundamental intracellular regulatory effect.     

Farrowing induction with a combination of prostaglandin F(2alpha) and a peripherally acting alpha(2)--adrenergic agonist AGN 190851 and a combination of prostaglandin F(2alpha) and oxytocin

We studied the effect of prostaglandin (PG) F(2alpha)-AGN 190851 on farrowing induction and compared it with that of PGF(2alpha)-oxytocin. Eighty crossbred, multiparous sows were randomly assigned to the following 4 treatment groups of 20 sows each: 1) control, saline-saline; 2) PGF(2alpha) (10 mg/sow)-oxytocin (30 IU/sow); 3) PGF(2alpha) (10 mg/sow)-AGN 190851 (0.06 mg/kg); and 4) PGF(2alpha) (10 mg/sow)-AGN 190851 (0.1 mg/kg). Either PGF(2alpha) or saline was administered intramuscularly on Day 111 of gestation at 11:30 h; AGN 190851, oxytocin or saline was administered intramuscularly 20 h after the first injection. The PGF(2alpha)-AGN 190851 (0.1 mg/kg) treated sows had the shortest mean farrowing interval (2.1 +/- 1.6 h, mean +/- SD) compared with the remaining treatment groups (control: 67.1 +/- 26.2 h; PGF(2alpha)-oxytocin: 5.6 +/- 6.7 h; PGF(2alpha)-AGN 190851 [0.06 mg/kg]: 3.0 +/- 2.8 h). Duration of farrowing, litter size, litter weight and interval from weaning to first estrus in sows were not significantly changed by these treatments. The PGF(2alpha)-oxytocin group had a significantly higher stillbirth rate than the control group, whereas the PGF(2alpha)-AGN 190851 (0.1 mg/kg) group had the lowest number of pigs born dead and stillbirth rate among the 4 treatment groups. These results suggested that the PGF(2alpha)-AGN 190851 combination can be used as an alternative method to PGF(2alpha)-oxytocin for synchronizing farrowing.     

Response of the midpregnant human uterus to systemic administration of 15(S)-15-methyl-prostaglandin F2alpha

The contractile response of the midpregnant human uterus to a new (PG) prostaglandin analogue, 15(S)-methyl-PGF2alpha (15-me-PGF2alpha), was investigated and compared to the effect of natural PGF2alpha. It was found that the threshold dose of 15-me-PGF2alpha was around 10 mcg when given as a single intravenous injection, which is approximately 1/10 of the corresponding dose of PGF2alpha. It was also found that higher intravenous doses of 15-me-PGFalpha resulted in a uterine response of longer duration than that following PGF2alpha. Intramuscular injection of the analogue at doses of 1.0-1.5 mg induced a marked uterine stimulation sustained for 5-7 hours without causing local reaction. Intravenous infusion of 5 mcg/min of 15-me-PGF2alpha stimulated a level of uterine activity equivalent to that of 75 mcg/min of PGF1alpha. The incidence of gastrointestinal side effects was the same in the 2 treatment groups. However, there seemed to be a tendency toward a significantly higher abortion rate with the analogue.     

Serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha in the induction of abortion.

Abortion was successfully induced in 62 of 68 patients in the 9th to the 26th week of pregnancy be serial intramuscular administration of 15(S)-15-methyl-prostaglandin F2alpha (15-ME-PGF2alpha). In 6 patients who failed to abort after 24 hours of prostaglandin administration, a concomitant infusion of oxytocin was initiated; 5 of these patients aborted within 12 hours of the combined therapy. A single patient failed to abort, even with the combined therapy, and underwent surgical evacuation. The mean abortion time in the 67 successful inductions was 14.56 hours. Parous patients aborted somewhat fasteter, mean 13.98 hours, as compared to nulliparous patients, mean 15.02 hours, but this difference was not statistically significant. In this study initial intramuscular injection of 100 mug 15-ME-PGF2alpha was followed in 1 hour by 250 mug and then 250 mug every 2 hours with concomitant oxytocin therapy initiated after 24 hours. The results with this dose schedule were compared to the results obtained in a previous study with a higher dose schedule, an initial dose of 100 mug 15-ME-PGF2alpha, followed in 1 hour by 250 mug then 500 mug every 2 hours. There was significant difference in the mean abortion time and the incidence of side effects between the 2 dose schedules. The mean abortion time for patients with gestational ages 16 weeks and less was the same with both dose schedules, however patients with gestational ages of 17 weeks and higher aborted somewhat faster with the higher dose schedule. It might therefore be advisable for patients with gestations of 17 weeks and higher to be treated with the higher dose schedule. In earlier gestations patients could be started on the lower schedule, and if abortion had not occurred within 15 hours the dose of 15-ME-PGF2alpha could then be increased to 500 mug every 2 hours.     

Effect of PGF2 alpha and 15(S)-15-methyl PGE2 methyl ester on feline generalized penicillin epilepsy.

The effect of PGF2alpha and 15(S)-15-methyl PGE2 methyl ester on transient generalized epilepsy in the cat induced by penicillin was examined. Epileptic activity before and after administration of the prostaglandins by several routes was determined from continuous EEG recordings and expressed in epileptic bursts per min. The PGE2 analogue given in single non-toxic doses (1.6-3 mug/kg) by intramuscular or intravenous routes at the peak of epileptic activity significantly reduced epileptic activity for up to four hours. Subcutaneous administration was less effective. PG2alpha given by the intramuscular route (0.3 mg/kg) also markedly reduced the number of epileptic bursts. Increasing the dosage 4-fold almost completely suppressed epileptic activity. Intracarotid infusion of PGF2alpha for one hour (10 mug/min) almost abolished all epileptic activity. Neither prostaglandin given in non-toxic doses induced EEG abnormalities in non-epileptic cats. Toxic doses of the E2 analogue (greater than 16 mug/kg) caused bilaterally synchronous high voltage slow wave activity. It is concluded that these prostaglandins reduce penicillin epilepsy in the cat. The findings are consistent with either a direct excitatory action on neurones of the medial reticular formation or anatagonism of the depressant action of norepinephrine on Purkinje cells.