Induction of abortion by intra- and extra-amniotic prostaglandin F2α administration

Legal abortion was induced by intrauterine administration of prostaglandin F_2α in 115 patients during the 11th – 20th week of pregnancy. An intra-amniotic method was used in 61 of the cases, an extra-amniotic one in 54 cases. The average total dose administered was 35.1 mg (range 5 – 65 mg) in the intra-amniotic group, and 6358 μg (range 1500 – 14000 μg) in the extra-amniotic group. Abortion rate was 92 % in the intra-amniotic material and 72 % in the extra-amniotic material, and side-effects, mainly gastrointestinal irritation, were noted in 74 % of the intra-amniotic cases and 54 % of the extra-amniotic ones. If total doses of 4750 μg or more were administered in the extra-amniotic cases, abortion rate went up to 80 %, but the frequency of side-effects simultaneously increased to 64 %. No serious complications occurred. Intrauterine prostaglandin induction is well suited therapeutic abortions in the second trimester, and the intra-amniotic technique is more practicable than the extra-amniotic one. The latter is applicable in cases where the puncture of the amniotic cavity is difficult to achieve, e.g. in cases of fetus mortuus and hydatiform mole.     

Blood Coagulation Changes during Mid-trimester Abortion Induced by Prostaglandin F2α

Serial studies on the coagulation system were made during second-trimester abortion induced by extra-amniotic, intra-amniotic, vaginal, and intravenous prostaglandin F₂α. No significant changes were found in the prothrombin time, partial thromboplastin time, or levels of fibrin-fibrinogen degradation products. An increase in the activity of factor X occurred with all routes of administration; the activity of factor VIII increased during extra-amniotic, vaginal, and intravenous administration; factor V activity increased during extra-amniotic and vaginal administration; and the activity of factor VII-X complex increased slightly at the time of abortion with all methods.The findings suggest that though prostaglandin induction of second-trimester abortion produces changes in the coagulation system the effects are much less than those which accompany induction of abortion by hypertonic saline or abdominal delivery in late pregnancy.     

Hormone changes in relation to the time of fetal death after prostaglandin-induced abortion

The changes in unconjugated estradiol-17β and estriol, progesterone and chorionic somatomammotropin (HCS) in peripheral plasma have been studied in 18 women at 30-minute intervals following intra-uterine prostaglandin E₂ administration for therapeutic termination of second trimester pregnancy. The hormonal changes were related to the time of fetal death detected by the disappearance of fetal heart pulsations. Prostaglandin E₂ was given by the intra-amniotic route with urea (5 patients) or with intravenous oxytocin (5 patients), or by the extra-amniotic route with intravenous oxytocin (8 patients). Fetal death occurred rapidly with intra-amniotic PGE₂, but usually at a late stage with extra-amniotic PGE₂. Three fetuses in the extra-amniotic group died at or just before abortion. A variety of fetal heart changes were noted and the time of fetal death did not appear to influence the time of abortion within each treatment subgroup.Estradiol and estriol showed a slight but persistent fall over 24 hours prior to induction of abortion. A more rapid fall usually occurred after induction, with a consistent fall around the time of fetal death. Progesterone and HCS usually fell much less before and immediately after fetal death. A marked rise in estradiol sometimes occurred before fetal death, particularly in the intra-amniotic PGE₂ and urea subgroup. Estriol levels declined more rapidly before than after fetal death, whereas fetal death had less consistent effects on the other hormones. All hormones had usually fallen considerably at the time of abortion, and in some individuals marked fluctuations in hormone levels were seen.     

Intrauterine administration of prostaglandin by the extra-amniotic route

The present study was undertaken to explore whether abortion in the 13th-16th week of gestation could be induced by a single extra-amniotic injection of prostaglandin. A long acting prostaglandin analogue 15(S)-15-Methyl-PGF2alpha was utilized and different vehicles and injection techniques tried. The clinical results of the single injection method were compared with those using multiple injections of PGF2alpha as has been described earlier. It was found that approximately 80% of the patients aborted following a single injection of 750 mc 15-me-PGF2alpha and that the side effect rate was acceptable from a clinical point of view. The method seems to be an attractive alternative usable during the "difficult" period for induction of abortion, i.e., when the uterus is too large for vacuum aspiration but too small for abdominal puncture of the amniotic sac.     

Midtrimester abortion induced by single intra-amniotic instillation of two dose schedules of 15(S)-15-methyl-prostaglandin F2alpha.

Midtrimester abortion was successfully induced in a series of 20 patient by intraamniotic instillation of 15(S)-15-methyl-prostaglandin F2alpha with a mean abortion time of 17.78 hours. The patients in this study was divided into two groups, Groups 1 received an initial dose of 2.5 mg 15-ME-PGF2alpha and aborted in a mean time of 16.26 hours. The patients in Group II received 3.0 mg 15-ME-PGF2alpha and aborted in a mean time of 18.94 hours. There was no significant difference in the abortion time, occurrence of side effects or the initiation of uterine activity between Group I and Group II. Parous patients aborted somewhat faster than nulliparous patients but this difference was not significant. In this study 80% of the patients aborted in 24 hours or less, and the intra-amniotic instillation of 15-ME-PGF2alpha was an effective abortifacient technique from the 15th to the 23rd week of gestation. The uterine response to intra-amniotic instillation of 15-ME-PGF2alpha was characterized by the gradual appearance of low amplitude, high frequency contractions accompanied by a rise in baseline intrauterine tonus. Uterine activity developed gradually and peaked at 1:50 hours after intraamniotic instillation of 15-ME-PGF2alpha. In this small series 15-ME-PGF2alpha administered via intra-amniotic instillation did not appear to have a distinct advantage over the naturally occuring PGF2alpha administered by the same method for the induction of midtrimester abortion; a large series in indicated to define the advantage of either technique.     

Midtrimester abortion induced by a single intra-amniotic instillation of two dose schedules of 15(S)-15-methyl-prostaglandin F2α

Midtrimester abortion was successfully induced in a series of 20 patient by intra-amniotic instillation of 15(S)-15-methyl-prostaglandin F_2α with a mean abortion time of 17.78 hours. The patients in this study were divided into two groups, Groups I received on initial dose of 2.5 mg 15-ME-PGF_2α and aborted in a mean time of 16.26 hours. The patients in Group II received 3.0 mg 15-ME-PGF_2α and aborted in a mean time of 18.94 hours. There was no significant difference in the abortion time, occurrence of side effects or the initiation of uterine activity between Group I and Group II. Parous patients aborted somewhat faster than nulliparous patients but this difference was not significant. In this study 80% of the patients aborted in 24 hours or less, and the intra-amniotic instillation of 15-ME-PGF_2α was an effective abortifacient technique from the 15th to the 23rd week of gestation. The uterine response to intra-amniotic instillation of 15-ME-PGF_2α was characterized by the gradual appearance of low amplitude, high frequency contractions accompanied by a rise in baseline intrauterine tonus. Uterine activity developed gradually and peaked at 1:50 hours after intra-amniotic instillation of 15-ME-PGF_2α. In this small series 15-ME-PGF_2α administered via intra-amniotic instillation did not appear to have a distinct advantage over the naturally occurring PGF_2α administered by the same method for the induction of midtrimester abortion; a larger series is indicated to define the advantages of either technique.     

Serum hormone levels in women undergoing abortion with intra-amniotic,extra-amniotic or intra-muscular administration of 15(S)15-methyl-prostaglandin F2α

The serum levels of estradiol-17β, progesterone and HPL have been estimated by specific radioimmunoassay in thirty women undergoing abortion with 15-methyl-PGF_2α given by intra-amniotic, extra-amniotic or intra-muscular route. A significant decline in the levels of these hormones was observed in 27 cases in which the pregnancy was terminated. However, in the remaining three cases, 15-methyl-PGF_2α was found to be unsuccesful, and no significant change in the hormone levels was evident. The decline in these hormones was more marked by intra-muscular route, than that observed by the other routes. The pattern of estradiol-17β decline was more consistent when compared with progesterone and HPL. The levels of progesterone and HPL, in a few cases, rather showed an increase in the initial hours of 15-methyl-PGF_2α administration before the decline began and this pattern was more prominent on extra-amniotic administration. In general, the decline in the hormone levels was slower in cases which took longer time for abortion than cases with shorter induction-abortion time (IAT).The decline in estradiol-17β levels was about 65 percent at six hour of intra-muscular administration of 15-methyl-PGF_2α, whereas the corresponding fall with intra-amniotic and extra-amniotic routes was 29 and 22 percent, respectively. However, the net drop in its levels during IAT was not significantly different (range 70 to 80 percent) by the three routes. About 38 percent fall in progesterone levels was observed at six hour of intra-muscular administration whereas, by intra-amniotic the fall was 19 percent. The net decline in progesterone levels, during IAT, was in the range of 46 to 60 percent by the three routes. Similarly, intra-muscular 15-methyl-PGF_2α evoked a sharper decline in HPL levels as compared with other routes. The total decline during IAT was 58 to 66 percent. The results, thus indicated that the abortion with 15-methyl-PGF_2α was associated with a fall in the serum hormone levels, which could be resultant effect of alterations in the hormone production by the foeto-placental unit. This along with the uterine contractions may play a significant role in the abortifacient action of 15-methyl-PGF_2α.     

Midtrimester abortion induced by serial intravaginal administration of prostaglandin E2 suppositories in conjunction with a contraceptive diaphragm

Midtrimester abortion was successfully induced in a series of 20 patient by intra-amniotic instillation of 15(S)-15-methyl-prostaglandin F_2α with a mean abortion time of 17.78 hours. The patients in this study were divided into two groups, Groups I received on initial dose of 2.5 mg 15-ME-PGF_2α and aborted in a mean time of 16.26 hours. The patients in Group II received 3.0 mg 15-ME-PGF_2α and aborted in a mean time of 18.94 hours. There was no significant difference in the abortion time, occurrence of side effects or the initiation of uterine activity between Group I and Group II. Parous patients aborted somewhat faster than nulliparous patients but this difference was not significant. In this study 80% of the patients aborted in 24 hours or less, and the intra-amniotic instillation of 15-ME-PGF_2α was an effective abortifacient technique from the 15th to the 23rd week of gestation. The uterine response to intra-amniotic instillation of 15-ME-PGF_2α was characterized by the gradual appearance of low amplitude, high frequency contractions accompanied by a rise in baseline intrauterine tonus. Uterine activity developed gradually and peaked at 1:50 hours after intra-amniotic instillation of 15-ME-PGF_2α. In this small series 15-ME-PGF_2α administered via intra-amniotic instillation did not appear to have a distinct advantage over the naturally occurring PGF_2α administered by the same method for the induction of midtrimester abortion; a larger series is indicated to define the advantages of either technique.     

Induction of Abortion by Extra-amniotic Administration of Prostaglandins E2 and F2 α

The use of prostaglandins E₂ and F₂α, administered by extra-amniotic instillation, for the induction of abortion was studied in 94 patients in the first and second trimesters of pregnancy. Abortion was successfully induced in 87% of patients within 36 hours and in 94% within 48 hours. The mean abortion time was 22·4 hours. In 60% of patients abortion was complete.Though the differences were not statistically significant, on average multigravid patients aborted more quickly than primigravidae, while the mean abortion time in PGE₂-treated patients was less than in those receiving PGF₂α.No serious complications occurred. Some side effects were observed. Occasional vomiting was the commonest symptom but the incidence of side effects was lower than with alternative routes of administration. A leucocytosis was often noted but there were no significant instances of infection.The method has proved a safe and effective means of terminating pregnancies in the second trimester.     

Termination of pregnancy with prostaglandin E2 methyl ester

Prostaglandin E₂ methyl ester was several times more potent than PGE₂ (free acid) in stimulating the human uterus at mid-pregnancy, when administered by the intra-amniotic, extra-amniotic and intravaginal routes. At effective abortifacient dosage, however, the frequency and intensity of gastrointestinal, central nervous and cardiovascular side effects were high. This precluded further clinical trials with the compound. It is suggested that rapid entry of the drug into the systemic circulation takes place.     

Induction of abortion with intra-amniotic or intra-muscular 15(S)-15-methyl-prostaglandin F2α

In order to evaluate the efficacy and acceptability of 15(S)-15-methyl-prostaglandin F_2α (15-me-PGF_2α) for pregnancy termination, we induced 30 abortions with single intra-amniotic injections of 2,5 mg of 15-me-PGF_2α and 25 abortions with intra-muscular 15-me-PGF_2α administered 200 g initially and 300 g every third hour until 30 hrs or abortion. Abortion occurred within 30 hrs in 97 % of cases in the intra-amniotic group, with a mean abortion time of 17,6 hrs and in 80 % in the intramuscular group, with a mean abortion time of 15.0 hrs. Neither parity nor gestational age was significantly related to the abortifacient efficacy of 15-me-PGF_2α. No serious complications occurred. Vomiting (83–84 %) and diarrhoea (23–92 %) were the most common complaints. Uterine contractions were more painful if induction was effected with intra-amniotic rather than intramuscular injections. 15-me-PGF_2α appears to be an effective and practicable abortifacient which can be used intra-amniotically or intramuscularly according to the ease of amniocentesis.     

Induction of abortion with intra-amniotic or intra-muscular 15(S)-15-methyl-prostaglandin F2α

In order to evaluate the efficacy and acceptability of 15(S)-15-methyl-prostaglandin F_2α (15-me-PGF_2α) for pregnancy termination, we induced 30 abortions with single intra-amniotic injections of 2,5 mg of 15-me-PGF_2α and 25 abortions with intra-muscular 15-me-PGF_2α administered 200 μg initially and 300 μg every third hour until 30 hrs or abortion. Abortion occurred within 30 hrs in 97 % of cases in the intra-amniotic group, with a mean abortion time of 17,6 hrs and in 80 % in the intramuscular group, with a mean abortion time of 15.0 hrs. Neither parity nor gestational age was significantly related to the abortifacient efficacy of 15-me-PGF_2α. No serious complications occurred. Vomiting (83–84 %) and diarrhoea (23–92 %) were the most common complaints. Uterine contractions were more painful if induction was effected with intra-amniotic rather than intramuscular injections. 15-me-PGF_2α appears to be an effective and practicable abortifacient which can be used intra-amniotically or intramuscularly according to the ease of amniocentesis.     

Laminaria augmentation of intra-amniotic prostaglandin F2α for the induction of mid-trimester abortion

From interpretation of 24-hour dose-response curves, it is improbable that mid-trimester abortion rates greater than about 80% can be accomplished with any one dose schedule of Prostaglandin F2α (PGF2α). To determine whether augmentation of intra-amniotic PGF2α with laminaria would improve the abortion rate, the results of a group of 22 gravidas treated with intra-amniotic PGF2α were compared to those of a group of 21 subjects treated with laminaria and an identical dose schedule of PGF2α. Patients with laminaria not only had a shorter mean abortion time (14.6 hours), but 95% aborted within 24 hours and all patients aborted within 24.5 hours of the initial PGF2α injection. Patients without laminaria had a longer mean abortion time (18.9 hours); only 68% aborted within 24 hours and one failed to abort within the 48-hour trial period. No significant differences in the frequency or severity of complications between the two groups were observed. Uterine contractility over the initial 6 hours of the induction was similar in the two groups. Therefore, augmenting the intra-amniotic PGF2α method with laminaria appears practicable.     

Prostaglandin E2 induced abortion with vaginal suppositories in a contraceptive diaphragm

Prostaglandin E₂, 20 mgm vaginal suppositories were administered to two groups of women seeking termination of pregnancy. One group had the suppository inserted inside a contraceptive diaphragm. Statistical comparisons were carried out for instillation to abortion time, side effects, and intra-uterine pressure parameters. The usage of the diaphragm significantly reduced side effects, and resulted in an instillation to abortion time of 12.8 ± 2.3 hours with no failures. The quantitative analysis of the uterine pressure recordings revealed activity significantly different than that seen with intra-amniotic or extra-ovular PG F_2α. The development of uterine activity simulates that of normal labor in that elevation of resting pressure does not occur and maximum active pressure evolves slowly.     

Vaginally administered 16,16-dimethyl-PGE2 for the induction of midtrimester abortion

Thirty patients in the 13th–20th week of gestation underwent therapeutic abortion utilizing vaginally administered 16,16-dimethyl-PGE₂ (free acid) suppositories. The first 15 patients obtained individual doses in the range of 400–1200 μg given every three hours (mean total dose 4.2 mg). In the following 15 patients a fixed dose schedule was used (800 μg followed by 1000 μg every three hours; mean total dose 5.3 mg). All but one of the 30 patients aborted. The mean induction-abortion interval for all patients was 16.8±6.9 hours (mean ± S.D.) With the fixed dose regime the success rate was 100% and the induction-abortion interval 16.0±5.9 hours. Because gastro-intestinal side effects were minimal, neither anti-emetic nor anti-diarrheic medication was required. A slight elevation of temperature was noted in five patients. The uterine response to the vaginal administration of this compound was characterized by a gradual increase in uterine tonus followed by sustained stimulation. The results are interpreted to suggest that the vaginal administration of 16,16-dimethyl-PGE₂ is a useful alternate method for the induction of second trimester abortion. Moreover, this compound seems to cause fewer gastro-intestinal side effects than other prostaglandins administered by the vaginal route at our department.     

Administration of prostaglandins by various routes for induction of abortion merits and demerits

Prostaglandin F_2α and its methyl analogues were used for induction of abortion in 598 patients with gestational age from 9 to 20 weeks. Different routes of administration were studied and varous dosages given. The incidence of gastrointestinal side effects were within acceptable range for all methods. Both intra-amniotic injections of 50 mg PGF_2α and 2.5 mg 15-methyl PGF_2α as well as intramuscular and vaginal administration of 15-methyl PGF_2α or its methyl ester, respectively, were highly effective in termination of pregnancy. The intramuscular route was, however, associated with the highest frequency of gastrointestinal side effects. If both efficacy and side effects were taken into consideration, the intra-amniotic and vaginal routes were superior. The ease of administration as well as the applicability over a wider range of gestation in termination of pregnancy may, however, in many situations speak in favour of the repeated vaginal administration of 15-methyl PGF_2α methyl ester.     

Extra-amniotic 15(S)-15 methyl PGF2α to induce abortion: A study of three administration schedules

Abortion was induced in 60 patients between 8 and 18 weeks gestation using 15(S)-15 methyl PGF₂α in one of three extra-amniotic administration schedules: 1.0 mg in viscous medium (Tylose), 1 mg in viscous medium (Hyskon) or 0.5 mg in non-viscous medium repeated at 12 hours. Eighty per cent of patients aborted within 24 hours in each group. The overall mean induction-abortion interval (± S.E.) was 17.6 ± 2.0: there was no significant difference between the three groups. Twenty patients treated with 1.0 mg in viscous medium had the catheter removed immediately following the prostaglandin injection and the success rate was not significantly altered.Gastro-intestinal side effects (vomiting in 50%, diarrhoea in 32.5%) were more frequent in the patients treated with the larger dose though the difference was not statistically significant. No significant haematological or biochemical changes were detected during the 24 hours following the start of treatment in 24 patients investigated. Thirty seven of the 60 patients (61.5%) aborted completely and did not require surgical evacuation, and none lost more than 500 ml of blood, nor required transfusion.It is concluded that abortion can be induced with a single extra-amniotic injection of 1 mg of 15(S)-15 methyl PGF₂α in viscous medium in a large percentage of patients but that the incidence of side effects is high.     

Essential fatty acid deficiency and platelet fatty acids of normotensive and genetically hypertensive rats

Termination of pregnancy in missed abortion and intra-uterine fetal death was accomplished using vaginal suppositories of 20 mg PGE₂ in 31 cases and the results were compared with oxytocin induction (with or without estrogen pre-treatment) in 17 cases at the doses routinely used in our hospital. The PG suppositories proved much more superior (96.7%) than oxytocin (47.7%), but induced a higher rate of side effects. The latter were not serious and were generally tolerated by the patients. There was a positive correlation between duration of fetal retention in utero and the induction expulsion time. The over all patient acceptance of the method was quite favourable and the approach appears to be a definite advance towards management of these cases.     

Management of missed abortion and fetal death in utero

Termination of pregnancy in missed abortion and intra-uterine fetal death was accomplished using vaginal suppositories of 20 mg PGE₂ in 31 cases and the results were compared with oxytocin induction (with or without estrogen pre-treatment) in 17 cases at the doses routinely used in our hospital. The PG suppositories proved much more superior (96.7%) than oxytocin (47.7%), but induced a higher rate of side effects. The latter were not serious and were generally tolerated by the patients. There was a positive correlation between duration of fetal retention in utero and the induction expulsion time. The over all patient acceptance of the method was quite favourable and the approach appears to be a definite advance towards management of these cases.     

Uterine rupture as a complication of second trimester abortion using intraamniotic prostaglandin E2 and augmentation with other oxytocic agents

Two cases of ruptured uterus are presented following attempted induction of midtrimester abortion using intra-amniotic prostaglandin E₂ and augmentation with other oxytocic agents. With continued uterine stimulation the diagnosis of rupture may not be obvious and the diagnostic features are discussed. Patients of high parity appear to be particularly susceptible to uterine rupture during induced midtrimester abortion.