Linda G. Staurovsky

Reduction of cervical resistance by prostaglandin suppositories prior to dilatation for induced abortion

Several recent reports citing increased rates of prematurity among women who have had induced first-trimester abortion suggest that forceful cervical dilatation may result in cervical incompetence in future pregnancy. There appear to be conflicting clinical impressions regarding the effectiveness on cervical softening and the reduction of cervical resistance produced by various prostaglandins. The development of the Electronic Force Monitor which is capable of precise measurement of the forces encountered in overcoming resistance during dilatation provided objective evidence with which to evaluate the effects of vaginally administered prostaglandin E2 and F2alpha suppositories. Suppositories were administered 3 hours prior to cervical dilatation, after which suction curettage was performed. Compared to the nonmedicated control group, patients receiving PGF2alpha suppositories exhibited greatly reduced cervical resistance, in some cases permitting direct introduction of the suction curette without need for any preliminary dilatation. Those patients receiving PGE2 suppositories showed an intermediate degree of cervical softening.

Vaginally administered PGF2α for cervical dilatation in nulliparas prior to suction curettage

Because of the need for an atraumatic method to dilate the cervix when performing artificial abortion by suction curettage, cervical dilatation following vaginally administered PGF2alpha was studied. A 50 mg PGF2alpha vaginal suppository was administered to 40 (treated group) first trimester nulliparas 3 hours prior to progressive cervical dilatation from a 19 (circumference in mm) Pratt dilator to a 35 Pratt dialator. The smallest-sized dilator that met resistance was interpreted as being the amount of clinically significant cervical dilatation. The results were compared to 20 (control group) first trimester nulliparas who received no PGF2alpha studied in an identical manner. Independent of gestational age, treated patients were dilated significantly more than the control patients. When subjects of similar gestational age were compared, PGF2alpha treated subjects were more often dilated sufficiently to perform abortion (55%) by suction curettage than control group subjects (5%). Those PGF2alpha subjects needing further dilatation to accept an appropriate sized cannula for their gestational age needed less dilatation than did those subjects of similar gestational age in the control group. No serious complications of PGF2alpha per se were observed and the most frequent side effects, vomiting and diarrhea, did not appear severe enough to limit the clinical practicability of the method.

Intramuscular administration of 15(S)-15-methyl-prostaglandin E2-methyl ester for induction of abortion

An intramuscular dose schedule of 15(S)-15-methyl-prostaglandin E2-methyl ester (15-(S)-ME PGE2) was evaluated for its application as a midtrimester abortifacient route. 20 healthy gravidas aged 18-42 years and 8-22 menstrual weeks of gestation were aborted in the Clinical Research Unit of the University of North Carolina Memorial Hospital. The subjects were given 5 mcg of the PGE2 methyl ester every 4 hours. 85% (17/20) aborted within 48 hours, 65% (13/20) of these within 24 hours. Mean induction-abortion interval was 21 hours. Trials were defined as complete in 55%, incomplete in 30%, and failure in 15%. Shivering, fever, pain, vomiting, and diarrhea were the most common side effects. The transient shivering occurred in 13 (65%) of the subjects within 20 minutes of the first dose. Fever usually started after shivering, and both resolved spontaneously. 2 patients had estimated blood loss exceeding 500 ml, but they were not given transfusions. No clinically significant changes occurred in mean hemotocrit, platelet count, serum creatinine, bilirubin, alkaline phosphatase, electrolytes, serum glutamic oxalacetic transaminase, and serum glutamic pyruvic transaminase. Mean blood cell and neutrophil counts increased, but neither increase was statistically significant.

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

Abstract 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.

Induction of therapeutic abortion with a single dose of intra-amniotically administered prostaglandin F2α*

Abstract To determine the abortifacient effectiveness and complications of a single intra-amniotic injection of 50 mg of Prostaglandin F2α (PGF2α), 40 gravidas were studied. While all subjects received a 50 mg dose of PGF2α at the initiation of the trial with no additional oxytocics or surgical intervention until they had aborted or until the end of the 48-hour trial period, they received intramuscularly administered prochlorperazine by one of two dose schedules. Twenty-five Group I subjects received 10 mg of prochlorperazine whenever they requested medication for alleviation of nausea or vomiting, while 15 Group II subjects received 10 mg one-half hour prior to the administration of PGF2α and at 6-hour intervals until they had aborted. Within the initial 24 hours, 77% of the subjects aborted while within the 48-hour trial period, 95% of the subjects aborted with a mean induction-to-abortion time of 19.1 hours for those aborting. Sixty-eight percent aborted completely, 28 percent aborted incompletely, and 5 percent failed to abort within the trial period. No serious complications were observed. The proportion of patients having no vomiting and the mean number of episodes of vomiting were significantly less in the Group II subjects than in the Group I subjects. No significant differences in the mean abortion times, cumulative abortion rates, or intra-amniotic pressures were noted between the two groups of subjects. It appears that the single intra-amniotic administration of 50 mg of PGF2α results in practicable rates of abortion and the associated vomiting can be significantly attenuated with prochlorperazine without significantly altering the abortifacient or oxytocic effect of PGF2α.

Vaginal administration of prostaglandin F2α for inducing therapeutic abortion

Abstract Because of the need for a safe, rapid, effective self-administered abortifacient, the vaginal administration of prostaglandin F 2α (PGF 2α ) was investigated. Thirty-six physically healthy women between eight and 17 weeks gestation received 50 mg. PGF 2α , on either an every hour or every two hour dosage schedule, for a total period of 24 hours. The effectiveness and tolerance of PGF 2α as the Tham salt was evaluated for two concentrations of solutions, tablets and suppositories. The incidences of vomiting, diarrhea, fever and pain were high, independent of the form or concentration administered, whenever a dosage schedule resulted in adequate rates of abortion within the 24-hour period.

Intra-amniotic administration of 15(S)-15-methyl-prostaglandin F2α for the induction of midtrimester abortion

To determine the practicability of administering 15(S)-15-methyl-prostaglandin F2alpha-tromethamine (15(S)-15-Me-PGF2alpha) intra-amniotically for the induction of midtrimester abortion, initially 2.5 mg. of 15(S)-15-Me-PGF2alpha was administered to 20 physically healthy gravid women, and was repeated after 24 hours in those patients who had not aborted. Within 24 hours, 65% aborted, and within 36 hours, 95% aborted. Although 67% experienced emesis, no serious complications occurred. This abortion rate is similar to that obtained with the recommended dose schedule of the dosage of prostaglandin F2alpha approved by the Food and Drug Administration and those reported with intra-amniotic administration of either hypertonic saline or urea when augmented with high, continuous, intravenous infusions of oxytocin. While the study intra-amniotic dose schedule appeared to be practicable, large, comparative studies will be necessary to determine the most satisfactory dose schedule and whether this method is more acceptable than other available methods.

Changes in human plasma catecholamines and dopamine-beta-hydroxylase produced by prostaglandin F2α

Clinical research was conducted into the possible interrelationships between prostaglandin (PG) F2alpha and the human sympathetic nervous system. The study also permitted comparison of the relative sensitivity of 2 indicators of sympatho-adrenal activity: 1) the determination of circulating catecholamines, epinephrine and norepinephrine; and 2) analysis of plasma dopamine-8-hydroxylase activity. Intravenous PGF2alpha infusion was administered to college students 12-18 weeks pregnant to produce abortion; the results were compared to results from nonpregnant controls. Circulating norepinephrine but not plasma epinephrine or dopamine-8-hydroxylase levels were increased in response to the PG. There was no correlation between plasma epinephrine and plasma norepinephrine levels. Plasma dopamine-8-hydroxylase activity was found not to be significantly changed by pregnancy, administration of the analgesic and antiemetic, or the PG infusion. In fact, central venous dopamine-8-hydroxylase activity did not differ significantly from that of arterial blood. The PG did not affect cardiac output or maximal expiratory flow rate. It is suggested that the nausea and diarrhea accompanying PGF2alpha infusion may put stress on the sympathetic nervous activity causing the observed increase in plasma norepinephrine concentration. Since no changes in blood pressure, heart rate, central venous pressure, or cardiac output were observed, it is unlikely that PGF2alpha causes even slight impairment of sympathetic nervous system activity.

The effect of meperidine analgesia on midtrimester abortions induced with intra-amniotic prostaglandin F2α

To determine whether increased amounts of meperidine significantly affect the induction of abortion with intra-amniotic prostaglandin F2alpha, 42 midtrimester subjects were treated with an identical dose schedule of PFG2alpha and one of two dose schedules of meperidine. Although the group that received more mepridine reported severe pain less frequently, their mean and median induction-to-abortion times, cumulative abortion rate, uterine contractility, and complications were not significantly different from those of the group that received less meperidine.

Practicability of ultrasonography for assessing fetal age and weight in early pregnancy.

Mercer, J. P., Brenner, W. E., Bolan, J. C., Dingfelder, J. R., Edelman, D. A. and Staurovsky, L. G. (Dept. of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC 27514, and International Fertility Research Program, Research Triangle Park, NC 27709, USA). Practicability of ultrasonography for assessing fetal age and weight in early pregnancy.