CERVICAL

DILATATION

VAGINAL TERMINATION

WITH PROSTAGLANDIN ANALOGUES PRIOR TO OF FIRST TRIMESTER

PREGNANCY IN NULLI-

PAROUS PATIENTS.

BY

S. M. M. Karim, Department of Obstetrics and Gynaecology, University of Singapore, Kandang Kerbau Hospital, Singapore 8. And H. T. Choo, Peggy Cheng, Department of Obstetrics and Gynaecology, Alexandra Hospital, Singapore 3.

SUMMARY Dilatation of the cervix with prostaglandin analogues prior to vaginal termination of pregnancy was attempted in 125 nulliparous women in the first trimester of pregnancy. The patients were divided into five groups (25 in each group) and given a single extra-amniotic dose of one of the following prostaglandin analogues 14-16 hours prior to the evacuation of the uterus by vacuum (Group B) 15 (S) 15 aspiration. (Group A) 15 (S) 15 methyl PGE (free acid); methyl PGE methyl ester; (Group C) 15 (& 15 methyl PGF20 (free acid); (Group D) 15 (S) 15 methyl PGF 2o methyl ester and(Group E) a mixture of 15 (S) Eva15 methyl PGE2 methyl ester and 15 (S) 15 methyl PGF2o methyl ester. cuation of the uterus without mechanical dilatation of the cervix was possible in 111(90%) of the patients. In an additional 10 patients (8%) there was some degree of cervical dilatation and further mechanical dilatation could be performed easily. With the combination of 15 (S) 15 methyl PGE2 methyl ester and 15 (S) 15 methyl PGF2o methyl ester the incidence of gastrointestinal side effects and pyrexia were considerably reduced. Accepted

April

8, 1975

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1975

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PROSTAGLANDINS

INTRODUCTION Although the vacuum aspiration method of termination of first trimester pregnancy is relatively simple and safe, there is often need for mechanical dilatation of the cervix. Difficulty is sometimes encountered in dilating a nulliparous cervix due to a tightly closed OS and presence of ridges in the cervical canal. Forceful dilatation of the cervix may result in laceration, creation of false passages and perforation of the uterus. In the absence of adequate dilatation of the cervix, there may be incomplete evacuation of the uterus. Cervical incompetence resulting in spontaneous abortion or premature labour during subsequent pregnancies is thought to be a long term complication associated with forceful dilatation of the cervix (1,2,3,4). Attempts to gradually dilate the cervix by repeated extra-amniotic or vaginal administration of prostaglandins E2 and F2ol have been partially successful (5,6,7). More promising results have been obtained with the use of synthetic analogues of prostaglandins E2 and Fa (8,9). The present investigation was undertaken to evaluate the efficacy and safety of four synthetic analogues of prostaglandins for cervical dilatation in nulliparous patients in the first trimester of pregnancy prior to evacuation of the uterus. In order to reduce the incidence of side effects a combination of two analogs has also been tried.

PATIENTS AND METHODS The study was carried out in 125 nulliparous women (62.4% teenagers) admitted to the hospital and approved for legal termination of pregnancy by vacuum aspiration. They were randomly divided into five treatment groups.

Group A Group Group Group Group

B C D E

: 25 ug 15 (S) 15 methyl PGE2 (free acid) : 25 ug 15 (S) 15 methyl PGE2 methyl ester : 250 lug 15 (S) 15 methyl PGF2o (free acid) : 250 ;lg 15 (S) 15 methyl PGF2, methyl ester : A mixture of 125 ug 15 (S) 15 methyl PGF2o methyl ester + 12.5 ug 15 (S) 15 methyl PGE2 methyl ester

The dose of prostaglandin contained in 5 ml physiological saline was instilled into the extra-amniotic space using a Nelaton Catheter (6FG) introduced into the cervix approximately 3 cm beyond the internal OS. The catheter was withdrawn after prostaglandin administration. Blood pressure, pulse, temperature, vaginal bleeding and incidence of side effects were recorded. Fourteen to sixteen hours later dilatation of the cervix was assessed in terms of the size of largest Hegar dilator that could be passed through the internal Vacuum aspiration or curettage was then carried out OS without resistance. under caudal anaesthes ia. In cases where the cervix did not adequately dilate, mechanical dilatation was performed prior to evacuation of the uterus.

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The amount of bleeding at evacuation charged four hours after evacuation two weeks later.

was recorded. The patients were disand returned for a follow-up examination

RESULTS

groups

The distribution of patients is shown in Table I.

in terms

Table

Sroup

Prostaglandin and dose

l-s

Gestation

-

of gestation

and age in the five

I

T T 12 .3

(weeks)

Number of patients

Age (years)

ldand below

19 10and lbove

- -

15(S)15 me PGE2(acid) 25 ug

7

7

2

25

3

10

15(S)15 me PGE2 me ester 25 pg

4

7

3

25

7

8

15(S)15 me PGF20(acid)

8

5

2

25

5

10

5

3

4

25

5

11

6

2

3

25

4

8

15 !4 -

.4 -

125

24 -

47

250 pg 15(S)15 me ZYtPo. me 250 pg Mixture of 12.5 pg 15(S) me PGE2 me ester and 125 ug 15(S)me PGF me este?” Total

APRIL

30 -

1975

!3 -

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17

1

PROSTAGLANDINS

The results in terms of efficacy of the various prostaglandin analogues in dilating the cervix was similar in the five groups and is shown in Table II.

Table II

Group

Fetus expelled before he schedule time of :vacuation

Total

l-

dilatation - C ervical lil

4-6

-

-

5+-t-s 3+-1c

- mm

T

nore thanl(

7 cases

1

I

20

4 cases

0

1

18

12 cases

1

9 cases

1

2 cases

0 -

-

34 cases

3 -

-

Number of patients requiring addie t ional mechanical dilatation

18 1

19

0

22

2

10 -

13

14

97

Adequate cervical dilatation to perform vacuum aspiration or curettage was achieved in 111patients (90%). In further ten patients there was some degree of cervical dilatation and further mechanical dilatation could be achieved with relative ease. A higher proportion (42%) of patients treated with 15 me Fa analogues (groups C and D) expelled the fetus before the schedule time of evacuation compared with those treated with 15 me E2 analogs (22%) (groups A and B). In the group receiving a mixture of 15 (S) 15 me E2 me ester and 15 (S) 15 me F& methyl ester (group E) only 2 patients (8%) aborted. Side effects Side effects encountered were vomiting, diarrhoea,cold and shivering and pyrexia. The incidence varied with the analogue used. There was no significant difference between the free acid and methyl ester of E2 and F2o analogues. Seven patients out of 50 (14%) treated with 15 me E2 analogues (groups A and B) had one episode of vomiting compared with 21 patients (42%) The treated with 15 me F2o analogs who had 1 to 5 episodes of vomiting, incidence of diarrhoea was higher in the E2 analogues group (25% of patients) compared with the F2o analogues groups (10% of patients). Pyrexia (100-102°F) was recorded in 11 patients receiving the E2 analogues and in only 2 patients (4%) given F2a analogues. The temperature elevation occurred approximately

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2 hours after prostaglandin administration and lasted for 3-4 hours. No E ight patients (16%) receiving PGE 2 analogs treatment was given for pyrexia. experienced shivering approximately f hour after prostaglandin administration The incidence of vomiting, diarrhoea and and lasting for 15-20 minutes. pyrexia were considerably less in the group treated with a mixture of 15 (S) 15 me PGE2 me ester and 15 (S) 15 me PGF2@ me ester (See Fig. 1).

DIARRHOEA

VOMITING

Group A : 25yg IS&) 15 me PGE, (acid) Group B 25yg 156) 15 me PGE, me ester Group C : 250~ lS(S115 me PGF, (acid) Group

D:

250~~15&)15 me PGF,, me ester

Group E: 12.5~

lS(S115 me PGE,

me ester

+125~~g lS(S115 me PGFb me ester

( 25 Patients

26 i=a

A

B

C

D

A

E

EFFECTS IN

OF

SINGLE

FIRST

group 1

each

C

D

E

Groups

Groups SIDE

B

In

EXTRA-AMNKJK

TRIMESTER

DOSE

NULLIPAROUS

OF

PROSTAGLANDINS

PATIENTS

Uterine Pain and Analges ia The patients strong. Although all receiving E2 analogs found pain unbearable groups E one patient

APRIL

1975

were asked to request analgesia if uterine cramps were reported some degree of uterine pain only two (4%) (Groups A and B) and 22 (44%) receiving F2a! analogs In and were given pethidine 50-100 mg intramuscularly. was given 50 mg pethidine for strong uterine cramps.

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Blood Loss Most patients had small amount of uterine bleeding during the interval between prostaglandin administration and evacuation of the uterus. In two patients bleeding was heavy (100-150 cc). On examination the fetus was found to be lying in the vagina in both patients. Curettage was performed and the bleeding stopped. The amount of bleeding at evacuation was less than 50 ml in all except three patients who had an estimated blood loss of loo-150 cc. Cervix The cervix was examined in all patients prior to and before evacuation of the uterus and there were no instances of injuries to the cervix or the uterus. Post-operative

Complications

The post operative course was smooth in all except two patients who required repeat curettage three weeks after prostaglandins for continued uterine bleeding. One patient was re-admitted to the hospital one week after prostaglandin administration with a fever of 1010 F. The patient was kept under observations, no treatment was given and the fever subsided within 24 hours and the patient was discharged.

DISCUSSION A Single extra-amniotic dose of 15 methyl analogues of prostaglandins E2 or F20_ is an effective method for gradual dilatation of the cervix in first trimester nulliparous patients prior to the evacuation of the uterus. The efficacy in terms of cervical dilatation has been similar in the five groups but the incidence and frequency of side effects is related to the particular analogue used. With E2 analogues the side effects of pyrexia and diarrhoea are more common whereas with F 2o analogues there is a higher incidence and frequency of vomiting. With a combined regime of E2 and F2, analogues side effects are Blood loss has reduced to an acceptable level without affecting the efficacy. been minimal in most cases and there have not been any serious complications. In the absence of any evidence indicating a direct relaxant effect of prostaglandins on the cervix it is appropriate to conclude that cervical dilataHowever the intensity of contractions tion is the result of uterine contractions. (particularly with E2 analogues) appears to be moderate since only a few patients required analgesia. From previous studies it is known that a single dose of 15 methyl analogues given by various routes has a stimulant effect on the pregnant uterus lasting for up to 10 hours (10). If cervical dilatation with prostaglandins is due to moderate stimulation of the uterus it seems reasonable

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to assume that dilatation occurs gradually and without trauma. However a long term follow-up of patients would be necessary to establish that prostaglandin induced dilatation is atraumatic and does not result in cervical incompetence . The use of prostaglandins for cervical dilatation prior to vaginal termination would be more attractive if efficacy by a non invasive (intramuscular or oral) routes can be established. With 15 methyl FGF2o and 15 methyl PGE2 given intramuscularly the efficacy in terms of cervical dilatation has been low and the incidence of side effects high. Perhaps a combination of analogues or some newer analogs may prove useful.

ACKNOWLEDGEMENTS Part of the work was carried out under USAID Grant No. AID CM pha-c-73 36. Prostaglandins were supplied by the Upjohn Co. of Canada. Financial support from The Upjohn Co. U. S.A. is acknowledged. We are grateful to the Medical and Nursing Staff of the Hospitals for assistance in the study.

REFERENCES 1. Beric, B., Kupresanin, M. and Kapor-Stanulovic, N. (1973): American Journal of Obstetrics and Gynaecology -116 813 2.

Klinger, A. (1970): International Journal of Gynaecology

and Obstetrics

8

680

3.

Pantelakis, S.N., Papadimitriou, G.C. and Doxiadis, S.A. American Journal of Obstetrics and Gynaecology -116 799

4.

Campbell, Wright, C., Lancet 1 1278

5.

Brenner, W.E., C. H. (1974): Prostaglandins

6.

S.

and Beazley,

Dingfelder, 4

819

Craft, I. (1973): Prostaglandins 3

377

M.D.,

7.

Hasp&, A.A. and Neth, F. (1973): Advances in the Biosciences 9 515

8.

Choo, H. T. , Karim, S.M.M. Journal of the Asian Federation

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(1973):

J. (1972):

Staurovsky,

L.G.

and Hendricks,

and Cheng, P. (1973): of Obstetrics and Gynaecology

2

71

637

PROSTAGLANDINS

9.

10.

638

Toppozada, M., Bygdeman, Prostaglandins 4 371

M.,

Papeorgiou,

I&rim ,S.M.M. and Sharma, S.D. Journal of Obstetrics and Gynaecology -79 737

C.

(1972): of the British

AYKlL

and

Wiqvist,

N. (1973):

Commonwealth

1975

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