Menstrual induction by the vaginal application of ICI 81008 gel.

After approximately 2 weeks menstrual delay (positive Pregnosticon Tests) "menstrual induction" was attempted in 75 gravidas by repeated vaginal application of a gel, containing 200 or 400 mug/ml ICI 81008. After approximately 10 minutes, following the 1st vaginal delivery of 400 mug ICI 81008, the uterus responded to this PGF2alpha analogue with sustained contracture. The highest success rate in induced bleeding (93%) and pregnancy termination (79%), without supportive therapy, was achieved when 400 mug ICI 81008 was administered 2 to 5 times at 4 hour intervals. Those gravidas (21%), who failed in induced menstruation, or stopped bleeding within 24 hour- after treatment, had positive Pregnosticon Tests on day 14 and were curetted. The side effects, mostly vomiting and increased blood pressure, were transient and subjectively and medically acceptable. While the vaginal application of the drug is apparently less effective than the intrauterine (1), it has the advantage of simple delivery and the potential of self-administration.

Termination of pregnancy with double prostaglandin impact.

With the "double PG impact" (DPGI) technique in 100 sedated first- and second-trimester volunteers, pregnancy was terminated successfully in 99 with a total extraovular PGF2alpha dose of 19.0 +/- 1.5 mg. in 16.9 +/- 0.9 hours. Two thirds of the patients received only the initial dose of 11.6 +/- 0.5 mg. of PG and aborted in 12.9 +/- 0.7 hours without requiring supplemental treatment. Only mild and transient side effects and 14 indicated curettages were recorded. Excepting one gravida (who failed to abort), plasma progesterone in 99 patients decreased at 3 hours after DPGI from 32.5 +/- 1.7 to 22.7 +/- 1.2 ng. per milliliter (P less than 0.001). The rate of progesterone withdrawal and IAT showed a close relationship and the first-trimester patients aborted at a lower progesterone level than the second-trimester patients (P less than 0.001).

Menstrual induction with the PGF2alpha-analogue ICI 81008.

"Menstrual Induction" (MI) has been studied in 79 volunteers, using the therapeutic principle of "PG-Impact". The PGF2alpha analogue: ICI 81008 was administered under strictly aseptic precautions into the uterine cavity during the 4th week of pregnancy. The treatment catheter (inserted through the cervical canal) delivered a single dose of only 100-200 mug ICI 81008 during the pilot study with this new drug. When it was established that the side effects were acceptable, this moderately effective dose was increased at first to 200-300 mug and eventually to 400 mug. At the 400 mug dose level, 29 (76%) of the 38 study patients had complete and 8 (21%) incomplete abortions, while 1 (3%) failed to bleed. Those 9 women who had incomplete abortions or failed to abort were curetted. In comparison with PGF2alpha (428 cases) and PGE2 (114 cases), ICI 81008 (38 cases at the 400 mug level) provoked lesser side effects, excepting the transient increase in blood pressure. All patients (whose intrauterine pressure was measured) responded to the ICI 81008-impact with rapidly developing high level uterine contracture. Plasma progesterone decreased significantly if treatment was successful and insignificantly in cases of treatment failure. In current studies, the efficacy of the vaginal delivery system of ICI 81008 is examined.

Menstrual induction with PGF2 alpha and PGE2.

PIP: The "prostaglandin impact" (PGI), a massive intrauterine dose of PG, converts the refractory pregnant uterus into a reactive organ by provoking a regulatory imbalance. This regulatory conversion releases the endogenous mechanism of menstruation or abortion. During initial studies, PGI successfully provoked menstrual induction (MI) in 22 and subsequently in 65 volunteers. These results were confirmed and complemented by 2 independent trials in 14 and 36 gravidas respectively. The best clinical outcome was obtained in 20 volunteers, when a "PG-Pellet" (a mini-suppositorium) was inserted in utero, containing only 2.5 mg PGF2alpha. These 157 trials in sedated volunteers had the common features of over 90% efficiency, transient and medically acceptable side effects and infrequent complications. The present study of 542 volunteers focused upon the collection of clinical data regarding efficacy, side effects and complications of MI. All patients had committee approval for legal abortion, during the 2nd week of their missed menstrual period. They volunteered to participate because of their preference for pharmacological rather than surgical pregnancy termination. The clinical outcome of the 542 MI with 5 mg PGF2alpha (428 cases) and 1.5 mg PGE2 (114 cases) was identical. On the average, 95% of the gravidas had complete evacuation of the uterus with the clinical symptoms of delayed menstruation rather than abortion; they experienced spontaneous menstruation in 34 days after having received a single dose of PG.^ieng

The efficacy and acceptability of the "prostaglandin impact" in inducing complete abortion during the second week after the missed menstrual period.

PIP: Clinical research was undertaken using PGF2a (prostaglandin) to induce abortion in 22 pregnant women at 12 +/- 1 days following their missed menstrual period. The PG was administered in a 5 mg single intrauterine dose through the cervix for a 10-minute period. The PG administration caused increased uterine contraction within 20 minutes and raised intrauterine pressure which was sustained for 2 hours. During the initiation of the intrauterine pressure, bleeding started and progesterone and estradiol levels decreased and continued to do so. In those patients who had been sedated, side effects were minimal. At 24 hours following the PG administration, progesterone had been withdrawn at a rate of 44%, bleeding was continuing, and cervical dilatation was at approximately 1 cm. Complete abortion was achieved in 20 out of the 22 women. It is believed that the abortion was effected through the action of endogenous PG, due to the withdrawal effect on progesterone of the exogenously-administered PG.^ieng