EARLY MID TRIMESTER ABORTION - BY INTRAMUSCULAR

15 METHYL PROSTAGLANDIN E 2

BY

S. D. Sharma, M.D.

R. W. Hale, M.D.

Department of Obstetrics and Gynecology

University of Hawaii School of Medicine

Honolulu, Hawaii 96814

ABSTRACT

Intramuscular administration of IS(s) 15 Methyl Prostaglandin E 2 was successful in terminating twelve of thirteen second trimester pregnancies. Two patients had an incomplete abortion and one case was classif ied a fa i lure. Side effects were limited to nausea and vomiting in seven cases, diarrhea in eight cases, ch i l l s in twelve cases and and elevated temperatures in eight cases. The intramuscular route does offer an advantage in early second trimester abortions and in patients where the intra-amniotic route is not available.

ACKNOWLEDGEMENTS

We are grateful to the Upjohn Company for supplying the 15(s) 15 Methyl Prostaglandin E 2.

Accepted September 30, 1974.

PROSTAGLANDINS

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EARLY MID TRIMESTER ABORTION - BY INTRAMUSCULAR

15 METHYL PROSTAGLANDIN E 2

The 15 Methyl analogues of Prostaglandin E and Prostaglandin Fp Alpha are resistant to degradation by the enzyme 15 hydroRydehydrogenase (1) and they display increased potency and prolonged duration of actions. (2) Depending upon the route of administration 15(s) 15 Methyl Prostaglandin E~ is 80-400 times more potent than the parent compound~Prostaglandin E 2 and the duration of actions is prolonged three times. (3)

The purpose of this study was to evaluate the efficacy of intramuscular 15(s) 15 Methyl Prostaglandins E~ in a di f ferent dosage schedule than previously reported (2) for induction of abortion.

Materials and Methods:

This study was carried out on 13 healthy subjects be- tween 18 and 25 years of age ~dmitted for legal terminations of pregnancy) at Kapiolani Hospital. Eleven patients were between 13 and 16 weeks of gestation and two patients were between 18 and 20 weeks. The period of gestation was determined to the nearest whole week based on the f i r s t day of the last menstrual period. An overview of these patients is shown in Table I.

Each patient had a complete physical including vaginal examination on admission and the status of the cervix was evaluated and scored regarding i ts consistency, d i latat ion and position (Table I I ) . A maximum of 5 and minimum of l was scored by these patients.

15(s) 15 Methyl Prostaglandins E~ was injected deep in the gluteal muscle in the dosage schedule in Table I.

The blood pressure, temperature, pulse rate and respiratory rate were recorded before the i n i t i a l dose, every 15 minutes during the f i r s t hour after the drug administration and then hourly unti l 12 hours after abortion or the end of the t r i a l . Chemical tests for hemo- poetic, hepatic and renal tox i ty were monitored in all the patients before start ing therapy and repeated 8 hours and 24 hours after the i n i t i a l dose.

172 OCTOBER 25, 1974 VOL. 8 NO. 2

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O C T O B E R 25, 1974 VOL. 8 NO. 2 173

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Vaginal examination was carried out at three hourly intervals during the treatment to assess the extent of cervical d i la ta t ion and after the abortion to exclude any cervical in jury. The frequency of episodes of diarrhea, vomiting and any other side effects were recorded.

Meperidine (50 mg) and Promethazine hydrochloride (25 mg) were given intramuscularly whenever the patient requested pain re l i e f . Four patients were given 5 mg diphenoxylate hydrochloride with atropine sulphate 30 minutes prior to the in ject ion of 15(S) 15 Methyl Prosta- glandin E9 and repeated after 6 hours, as a prophylactic to controT diarrhea.

Each patient was examined one week after the abortion.

RESULTS

Five patients aborted within 24 hours, 5 patients aborted between 24 to 48 hours, two patients aborted after 48 hours and one patient fai led to abort. Ten patients had a complete abortion and two patients required suction curettage for incomplete abortion.

The induction-abortion interval appears to be related to the cervical status as the i n i t i a t i o n of therapy. Patients with firm, t i gh t l y closed and posterior cervices took much longer to abort than those patients with a soft and pa r t i a l l y dilated cervical canal (Table I)

All the patients had lower abdominal pain and low backache within lO minutes of the in ject ion of lO of 1 5 ~ 15 Methyl PGE~. In one case, when 5 of 1 5 ~ 15 Methyl PGE~ was ~sed on the second day, the patient did not show any El in ical response to i t . One patient ( fai led case) was given 15 of 15(s) 15 Methyl PGE at four hourly intervals on the th i rd day, at this do~age level there was no change in the d i la ta t ion of the cervix but she experienced more side effects than on the previous days when she was given I0 of 15(s~ 15 Methyl PGE 2.

None of the patients complained of any after pains or discomfort at the in ject ion si tes.

174 OCTOBER 25, 1974 VOL. 8 NO. 2

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Side Effects

The only side effects observed (Table I) during the therapy were vomiting, diarrhea, fever and chi l ls . None were fe l t to be severe enough to discontinue the treatment. Twelve patients complained of being cold and began to shake 15 to 30 minutes after each injection. This response lasted for 15 to 45 minutes.

The only c l in ica l ly obvious difference in the case who did not experience this side effect was obesity; this patient weighed 238 pounds. The diarrhea was controlled in all four cases by giving Lomotil. In nine cases, the oral temperature was increased by 2 F above pretreatment levels. This returned to normal level within 2-3 hours after discontinuing the treatment.

Blood and serum levels of creatinine, BUN, SGPT, SGOT, Sodium, Potassium, Chloride, Alkaline Phosphatase, platelet count, hemoglobin, hematocrit and white cell count did not change signif icantly.

Failed Case ~]0)

This 24 year old, Gravida I l l , Para O, had had two previous abortions in the f i r s t trimester, terminated by suction curettage. She had a total dose of 230 15 ~) 15 Methyl PGE~, over 60 hour period. She also failed to abort later wTth lamanaria insertions, intravenous infusion of Pitocin, and intra-amniotic Prostaglandin F~ Alpha. Ultimately on the 6th day when the cervix was T-2 cms dilated, the uterus was evacuated vaginally under general anesthesia.

DISCUSSION

Abortions performed during 12 to 16 weeks gestation pose a technical problem. Suction or dilatation and curettage are ass'ociated with an increased incidence of uterine perforations, hemorrhage and incomplete procedures, while amniocentesis for inst i l la t ions of medications may be d i f f i cu l t and hazardous. The avai labi l i ty of intra- muscular administration of an abortifacient drug during this period of gestation would be deemed. There is also a need in cases after 16 weeks where the fetal membranes have ruptured, or the intra-amniotic route is not available or the sk i l ls needed for intra-amniotic administration are lacking.

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PROSTAGLANDINS

As an abortifacient, Prostaglandins 151s~ 15 Methyl E has been shown to be superior to i ts parent compound P~ostaglandin E (2) Our results using this analogue compare favorably with other reported studies (2,3). In our study the effective dose appears to be lO of 15 (s) 15 Methyl PGE 2, given every three hours. The status of the cervix is to be related to the induction-abortion interval. Though the number of the patients in this study is small, we have found the cervical scoring system to be a helpful parameter. Future studies using large numbers of cases wil l be needed to evaluate its significance. The induction abortion interval was much shorter in patients with a cervical factor of 4 and 5, than in those with a factor of l or 2. This cervical factor may also be influenced by the parity of the patient. Thus a scoring system somewhat similar to Bishop's score for induction of labor(~) should be useful in comparing the abortion results from different centers.

The incidence of side effects especially ch i l ls , the mechanisms of which is not yet known, probably wil l l imit the use of this analogue in the future. However, i t has been reported that this side effect was not seen when this analogue was used intra-amniotically. (5) Because of i ts increased potency and prolonged duration of actions, the 15 Methyl analogue of PGE~ intramuscularly may offer some advantages in selected ca~es.

OCTOBER 25, 1974 VOL. 8 NO. 2 177

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REFERENCES

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.

.

Yankee, E.W., and Bundy, G.: 15 Methyl Prostaglandins. Journal of American Chemical Society, 94, 3651. (1972)

Karim, S.M.M., and Sharma, S.D.: Termination of Second Trimester Pregnancy with 15 Methyl Analogues of Prostaglandins E and F~ Alpha. Journal of Obstetrics and Gynecology oI the B)i t ish Commonwealth, 79, 737.

~1972)

Karim, S.M.M., Sharma, S.D., Filshie, G.M., Salmon, J.A., and Adaikan Ganesan, P.: Termination of Pregnancy with Prostaglandin Analogues. Advances in the BioSciences, g-lnternational Conference on Prostaglandins. Edited by S. Bergstrom and S. Bernhard. Pergamon Press Vie e.g., Oxford, p. 811, 1973.

Bishop, E.G.: Elective Induction of Labor. Obstetrics and Gynecology. 5:51g, 1955.

Amy, J.J. , Karim, S.M.M., and Sivasamboo, R.: Intra- amniotic Administration of Prostaglandin 15 (s) 15- Methyl E~. Methyl Ester for Termination of Pregnancy. Journal Bf Obstetrics and Gynecology of the Bri t ish Commonwealth. 8:1017, 1973.

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