Intra-amniotic prostaglandin F2α and urea for abortion

Prostaglandin F_2α (PGF_2α) 20 mg combined with urea 80 g was injected intra-amniotically in 20 patients to induce mid-trimester abortion. Abortion resulted in all subjects within 24 hours in a mean time of 12 hours 38 minutes (range 5 hours 50 minutes to 20 hours 45 minutes).Plasma sex steroids were evaluated before and hourly for 5 hours after the injection. A progressive decline in levels occurred with time. Decreases in plasma progesterone, estrone, estradiol and estriol were significant as soon as one hour after injection.Gastrointestinal side effects occurred with a greater frequency than when a comparable dose of PGF_2α is given alone and 2 patients had small cervical lacerations requiring suture. Further studies are indicated to establish whether a lower dose of PGF_2α will be associated with fewer side effects and be as effective.     

Intra-amniotic urea and prostaglandin E2 for abortion. A clinical study to determine the efficacy of using a variable prostaglandin dosage

Intra-amniotic urea 80 g combined with either prostaglandin E₂ 5 mg or 10 mg was injected in two groups of patients to induce mid-trimester abortion. Abortion invariably resulted within 24 hours with both schedules used. The mean injection-abortion interval was not significantly shorter in those receiving the higher dose of prostaglandins. There were fewer gastrointestinal side effects in those receiving the lower dosage. This combined technique has some advantages over other methods used for a single initiating procedure only is required and nursing involvement is minimal.     

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.     

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.     

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.     

Induction of midtrimester abortion by serial intravaginal administration of 15(S)-15-methyl-prostaglandin F2alpha (THAM) suppositories.

Midtrimester abortion was successfully induced in 13 of 22 patients by serial intravaginal administration of 15(S)-15-methyl-prostaglandin F2alpha (THAM) suppositories. Nine patients, 4 nulliparas and 5 multiparas, failed to abort after 24 hours of prostaglandin administration and a concomitant infusion of oxytocin was initiated. Seven of the nine patients aborted within 7 hours of the combined therapy and one patient on methadone maintainence aborted after 17.5 hours of combined therapy, 41.5 hours after the first dose of prostaglandin. A single patient failed to abort, despite the concomitant prostaglandin-oxytocin administration and underwent surgical evacuation. The mean abortion time for the 21 successful abortions was 22.56 hours. Nulliparous patients aborted somewhat faster, mean 21.79 hours, than multiparous patients, mean 23.80 hours, but this difference was not statistically significant. In this study, one patient aborted in less than 12 hours, and 62% of the successful cases aborted within 24 hours. The plasma levels of 15-ME-PGF2alpha were analyzed by radioimmunoassay in 10 patients. Plasma prostaglandin levels rose significantly 30 minutes after the insertion of the first suppository, but there was a wide variation in levels from patient to patient. It was observed that the 2 patients with the highest levels had the fastest abortion times and episodes of gastro-intestinal side effects appeared related to a rise in prostaglandin levels. Sixty-four percent of the patients in this study had no gastro-intestinal side effect related to prostaglandin administration.     

Massive initial prostaglandin impact in postconceptional therapy

The abortifacient effect of an initial PGF2alpha impact was examined in 10 obstetrically normal first trimester pregnant patients. Sedated patients were given extraamniotically an average initial dose of 8.1 + or - 0.8 mg PGF2alpha during a 10 minute instillation. Side effects occurred occasionally but were minimal. Uterine contracture developed rapidly reaching an average pressure of 83.2 + or - 11.3mm Hg in about 20 minutes and then slightly declined in time. Superimposed on the contracture response were gradually increasing cyclic changes in intrauterine pressure which reached a magnitude of 129.8 + or - 12.2mm Hg by 10 hours after initial treatment. Initial therapy was augmented in some cases by an average of 4mg PGF2alpha; only 4 patients required oxytocin supportive therapy. The patients aborted in an average of 10.9 + or - 2.0 hours. 7 aborted completely, 2 left behind small placental residues, and 1 retained the placenta during a period of 11.5 hours. An (AbS) abortion score of 92 was obtained in the study which is the highest in 6 consecutive studies using various methods of PGF2alpha administration. Plasma estradiol-17beta and progesterone levels decreased continuously during the instillation abortion time in the complete aborters, while the incomplete aborters showed lesser changes. It is concluded that massive intrauterine PGF2alpha injection is a more efficacious and acceptable form of postconceptional therapy than protracted treatment. Such therapy appears to convert the refractory uterus into a spontaneously active and pharmacologiclly reactive organ by inducing vasoconstriction, myometrial stretch, and fetoplacental insufficiency.     

Determination of selected coagulation parameters in induced abortion by means of 15-methyl-PGF2 alpha]

There were accomplished investigations about changes of bleeding and recalcification time, platelet count, levels of heat-fibrin, prothrombin, partial thromboplastin time, platelet adhesiveness and heparinocytes at 10 women during induction of therapeutic abortion by use of intramuscular injections of 15-methyl-PGF2 alpha in the first and second trimester of pregnancy. The studies were performed before treatment, 30 minutes, 4 and 8 hours after beginning 15-methyl-PGF2 alpha-administration, 2 hours after expulsion of product of conception and 24 hours after first injection. The following investigations showed statistical significant changes: Prothrombin decreased during treatment with 15-methyl-PGF2 alpha and did not obtain the starting value 24 hours after first injection. Platelet count showed an equal attitude. The heparinocytes showed a continuous falling off up to 2 hours after termination the pregnancy. A significant ascent was noticed 24 hours after first investigation. The results of studies did not indicate a strong injury of coagulation system. They support the positive estimate for induction of therapeutic abortion with 15-methyl-PGF2 alpha in the first and second trimester of pregnancy.     

Single intraamniotic injections of prostaglandin F-2-alpha as an abortifacient agent: size of effective dose and effect of parity

This report discusses the authors' experience with intraamniotic administration of single doses of the prostaglandin PGF2alpha as an abortifacient agent. 98 healthy women between the 12th and 26th week of pregnancy admitted to the Clinical Research Unit of the North Carolina Memorial Hospital were given a single intraamniotic dose of PGF2a administered through an indwelling polyethelene catheter inserted either transabdominally or transvaginally. The drug was given as Tham salt with the first 5 mg of any dose being given at the rate of 1 mg/minute for 5 minutes, followed by more rapid administration of the balance of the dose. Abortion which did not occur within 48 hours was considered a failure. Each patient received 1 of the following dosages: 25, 40, 50, and 75. 9 (64%) of 14 patients given 25 mg PGF2a aborted within the 48-hour period. The percentages of abortion in the doses 40, 50, and 75 mg were 88.9% (9 patients), 96.7% (60 patients) and 93.3% (15 patients) respectively. As these figures were almost similar, the 84 patients were combined as a single group (84 patients) relative to the injection-abortion time, effect of parity, and stage of gestation at which the abortion was carried out. Half of the patients in this combined group aborted in approximately 21 hours; more than 90% at the end of 32 hours; and 95% at the end of the 48 hours post-injection. For comparison, the cumulative abortion curve of 552 patients who had intraamniotic saline for abortion showed that 50% of the women aborted within 31 hours, 84% within 48 hours, and 97% within 72 hours. Prostaglandin induced abortions thus are shown to reach the 50% level 10 hours before the saline patients, and the 90% level about 21 hours before the saline patients. Significant side effects (presented elsewhere) were observed in all groups, with the incidence increasing at higher dosages. Mean induction-abortion time for nulliparas at all dosages was 17.4 hours; for multiparas, 20.4 hours. There was no clear relationship between gestational age and parity. The study shows that the effective dose for inducing abortion with PGF2a lies within the 40 to 50 mg dose range.     

Coagulation Changes during Termination of Pregnancy by Prostaglandins and by Vacuum Aspiration

Serial studies on coagulation factors were performed on 12 patients having termination of mid-trimester pregnancy by extra-amniotic prostaglandin F₂α and 11 patients terminated by vacuum aspiration during the first trimester. A significant change in the activity of factors V, VII and X, VIII, and X, and a decrease of the prothrombin time and platelet count were found with prostaglandin termination but no such changes occurred during vacuum aspiration. These findings suggest that the coagulation system is activated during induction of mid-trimester abortion with extra-amniotic prostaglandin F₂α. This is probably related to the physiological changes in the coagulation mechanism which occur by the second trimester of pregnancy. Termination of pregnancy in the mid-trimester may, however, be expected to give rise to defective blood coagulation and thromboembolic complications.     

Aspirin and indomethacin: Effect on instillation/abortion time of mid-trimester hypertonic saline induced abortion

Two acidic non steroid anti-inflammatory drugs, aspirin (acetylsalicyclic acid) and indomethacin were administered to patients undergoing mid-trimester saline induced abortion, to test their analgesic properties and to observe their effect on the instillation/abortion time interval. Both drugs when administered to patients undergoing mid-trimester saline abortion prolong significantly the instillation/abortion interval. These observations on human mid-trimester saline induced abortion treated with aspirin and indomethacin correspond with experimental data recently published relative to the antiprostaglandin activity of acidic non steroid drugs. The analgesic properties of both aspirin and indomethacin are difficult to assess accurately because of the highly emotional state of the patients studied; indomethacin, however, appears to be more effective for the prodromal abortion type of pain experienced by the patient but is still inadequate for sedation for the pain resulting from strong uterine contractions.     

Induction of therapeutic abortion using either extra-amniotic prostaglandin F-2-alpha or hypertonic saline followed by oxytocin

160 women with uteri at 10-20 weeks gestation were treated with either PG(prostaglandin)F2alpha or saline solution followed by oxytocin to effect an abortion. 80 women were in each treatment group. The distribution of the patients according to age, parity, and gestation duration is tabulated. PGF2alpha was administered extraovularly in a concentration of .1 mg/ml with .7 mg being injected in the operating theater and nurses administering the rest based on response to previous injections. Administration continued for up to 30 hours. Saline was given in a volume in ml dependent on the duration of pregnancy multiplied by a factor of 10. Subcutaneous injections of oxytocin were given on subsequent days to speed the abortion. 85% of the PG patients successfully aborted without surgical dilatation of the cervix. The average dosage of PG required was 7.5 mg in 11 instillations. Side effects and complications in the PG group were minimal. 1 instillation of saline followed by 2 days of oxytocin were required to effect a 79% abortion rate in the saline group. Although the number of patients requiring surgical dilatation was the same for both groups, the procedure was much less time-consuming for the PG group. The complication rate was 26% for the saline group as compared to 14% for the PG group. The PG group required a shorter hospital stay.     

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.     

The effect of a 10 cm2, 0.5% 15-ME-PGF2α methyl ester intravaginal silastic device on abortion and plasma prostaglandin concentration

Intravaginal insetion of a 10 cm² silastic device with an 0.5% concentration of 15(S)-15-methyl-prostaglandin F_2α methyl ester alone successfully induced abortion in 27 of 48 patients in the midtrimester and in an additional 11 patients with a concomitant infusion of oxytocin. The mean abortion time for the 38 successful induction was 15.35 hours. In 8 of the 10 patients who failed to abort even with concomitant oxytocin therapy, abortion was induced by serial intramuscular injections of 15-ME-PGF_α; the remaining 2 failures underwent surgical evaccution. The plasma levels of 15-ME-PGF_2α methyl ester in the 11 patients studied varied widely over the first 2 hours after insertion of the device. The maximum mean level was achieved at 2 hours, maintained at 4 hours and then dropped sharply at 8 hours and declined over the abortion period in undelivered patients. Vomiting and diarrhea were the most common side effects and in general well tolerated by the patients. However, there was an adverse reaction in a single patient who experienced almost constant nausea, vomiting and diarrhea. The device was removed 1 hour 50 minutes after insertion and the patient aborted spontaneously 7 hours later. Intravaginal insertion of a silastic device is an effective means of prostaglandin abortion, but their investigation is required to determine the most effective device which would provide a slow, continuous release of the prostaglandin.     

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.     

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

Midtrimester abortion was successfully induced in 68 of 69 patients with serial intravaginal administration of prostaglandin E2 suppositories behind a contraceptive diaphragm. The mean abortion time for the successful inductions was 13.07 hours; multiparous patients aborted somewhat faster, mean 12.72 hours, as compared to nulliparous patients, mean 14.22 hours. In 36 patients the PGE2 suppositories were placed behind an intact diaphragm and the mean abortion time was 14.89 hours. In 33 patients the PGE2 suppositories were placed behind a diaphragm modified by having an opening incised in the center, the mean time in these patients was 11.96 hours. Of the 68 successful abortions 59% of the patients aborted in 12 hours or less and 88% aborted within 24 hours. The most frequently encountered side effect was temperature elevation of 2 degrees F or higher which occurred in 68% of the patients. Temperatures returned to normal levels within 4 to 6 hours after the last adminstration of PGE2. Gastrointestinal side effects occurred in 45% of patients, but these side effects were well tolerated and did not require termination of drug administration in any of the patients. Intravaginal administration of PGE2 suppositories is a very effective abortifacient technque during the midtrimester, however the use of PGE2 in conjunction with a diaphragm did not appreciabley improve the technique although the amount of drug administered and the incidence of side effects was somewhat lower than when the PGE2 suppositories are used alone. If a diaphragm is to be used, a modified diaphragm is indicated since it simplifies the clinical management of the abortion, eases administration of the suppositories and permits a more accurate estimation of cervical changes, vaginal bleeding and abortion.     

Induction of midtrimester abortion by serial intravaginal administration of 15(S)-15-methyl-prostaglandin F2α (THAM) suppositories

Midtrimester abortion was successfully induced in 13 of 22 patients by serial intravaginal administration of 15(S)-15-methyl-prostaglandin F_2α (THAM) suppositories. Nine patients, 4 nulliparas and 5 multiparas, failed to abort after 24 hours of prostaglandin administration and a concomitant infusion of oxytocin was initiated. Seven of the nine patients aborted within 7 hours of the combined therapy and one patient on methadone maintainence aborted after 17.5 hours of combined therapy, 41.5 hours after the first dose of prostaglandin. A single patient failed to abort, despite the concomitant prostaglandin-oxytocin administration and underwent surgical evacuation. The mean abortion time for the 21 successful abortions was 22.56 hours. Nulliparous patients aborted somewhat faster, mean 21.79 hours, than multiparous patients, mean 23.80 hours, but this difference was not statistically significant. In this study, one patient aborted in less than 12 hours, and 62% of the successful cases aborted within 24 hours. The plasma levels of 15-ME-PGF_2α were analyzed by radioimmunoassay in 10 patients. Plasma prostaglandin levels rose significantly 30 minutes after the insertion of the first suppository, but there was a wide variation in levels from patient to patient. It was observed that the 2 patients with the highest levels had the fastest abortion times and episodes of gastro-intestinal side effects appeared related to a rise in prostaglandin levels. Sixty-four percent of the patients in this study had no gastro-intestinal side effect related to prostaglandin administration.     

Induction of Therapeutic Abortion by Intra-amniotic Injection of Urea

A new method of mid-trimester termination of pregnancy is described in which intra-amniotic urea was used. The mean interval between intra-amniotic injection and abortion was 59 hours and the mean length of hospital stay six days; the feto-maternal haemorrhage incidence was one out of 10 cases, which compares favourably with other methods. No complications have yet been encountered.     

Changes in estrogen levels in maternal venous plasma after intra-amniotic infusion of prostaglandin F2 for therapeutic abortion

Peripheral plasma levels of estrone, estradiol-17beta and estriol were measured by the method of Shutt and Cox in 10 women following intra-amniotic infusion of prostaglandin F2alpha (PGF2a) for therapeutic abortion. Initial dose was 30 mg, followed if necessary, by doses of 15 mg at 24 hours and 42 hours. Gestational age of pregnancies ranged from 14 to 19 weeks, with a mean of 16 weeks. All 10 women completely aborted. Mean induction-abortion interval was 24 + or - 12 hours. The mean estrone, estradiol 17beta and estriol levels declined to about half of the pre-infusion levels after 80% of the induction-abortion interval had elapsed. The main decline in estrogen levels occurred in individual women either during the 1st quarter or during the last quarter of the induction-abortion interval. There were no significant relationships between changes in estrogen levels and the interval from 1st administration of PGF2a to subsequent abortion.     

Reassessment of systemic administration of prostaglandins for induction of midtrimester abortion

This investigation was conducted to evaluate the abortifacient efficacy of vaginal and intramuscular administration of different dose schedules of the 15-methyl analogues of prostaglandin F2 alpha. Both 15-methyl PGF2 alpha and 15-methyl PGF methyl ester can be absorbed from the vagina in sufficient amounts to induce abortion. The potency of the methyl ester was approximately twice that of the free acid. The most successful treatment schedule consisted of an initial dose of 0.5 mg of the methyl ester followed by 1.0 or 2.0 mg every third hour. On this treatment all patients aborted within 24 hours. Initially 200 ug of 15-methyl-PGF2 alpha was given. The dose was increased to 400 ug or occassionally to 500 ug depending on the effect and tolerance of the patient and repeated every third hour. The treatment schedule resulted in a 100% abortion rate and the mean induction-abortion interval was 16.1 hours. Both routes were associated with a higher frequency of side effects than that reported for intraamniotic administration of 15-methyl-PGF2 alpha. It seems justified to conclude that the intraamniotic route is preferable after the 14th week when the uterine cavity is easy to puncture, but that vaginal or intramuscular injections of the compounds could be an alternative in late first trimester and early second trimester cases.