Prostaglandin F2α for the induction of labor in pregnancies complicated by intra-uterine death, anencephaly and chromosomal anomaly

PROSTAGLANDIN

F2a FOR THE INDUCTION

PREGNANCIES

COMPLICATED

ANENCEPHALY

A.M.

Queen

Elizabeth

Department University

AND

Frumar,

BY INTRA-UTERINE

CHROMOSOMAL

I. D. Smith and A.R.

II Research

of Obstetrics

OF LABOR

Institute

IN

DEATH,

ANOMALY.

Korda

for Mothers

and Infants,

and Gynaecology

of Sydney

N.S.W.

2006

Accepted

March

Australia

15

PROSTAGLANDINS APHIL

25, 1974

VOL.

6 NO. 2

125

ABSTRACT

A group of I0 patients, with pregnancies of varying gestational aget complicated by missed abortion t inlTa-uterine death t anencephaly and chromosomal anomaly~ underwent induction of labor by intra-amniotic prostaglandin F2a fnfusion. Induction of labor was successful in all cases and the l=ide-effects were mild. The induction-dellvery interval did not differ significantly from that recorded when labor in such cases has been induced by intravenous PGF2a. The induction-dellvery interval showed no apparent relation to the state of the fetus (Irving or dead) suggesting that no significantly active role is mediated by the fetus in PGF2a-induced labor.

ACKNOWLEDGEMENT

The PGF2a used in this study was generously supplied by the Upjohn Company.

PROSTAGLANDINS 126

A P R I L 25, 1974

VOL. 6 NO. 2

PROSTAGLANDINS

INTRODUCTION

Intravenous successfully death,

infusions

of prostaglandins

for the induction

anencephaly

intro-amniotic termination

of second trimester

justified

of labor is obviously in situations

complicated

by intro-uterine

This paper reports administration

of PGF

2a

precluded

death,

whilst

the

used for the routine

of labor in pregnancies administration

of PGF2a

with for the it is

is not of concern - such as in pregnancies

death and anencephaly. the results

of an investigation

for the induction

were studied

AND

of labor in such complicated

cases of intra-uterine

two cases of anencephaly the second trimester.

death prior to the 20th week of gestation

Details

of these patients

in Table

VOL. 6 NO. 2

pregnancies.

METHODS

uterine

are given

of the use of intro-amniotic

and these consisted of five

two cases of missed abortion,

25, 1974

However,

in the case of normal pregnancies,

welfare

chromosomal anomaly diagnosed during

APRIL

by intra-uterine

there appear to be no reports of the

the intro-amniotic

PATIENTS

Ten patients

3, 4).

for the induction

where fetal

complicated

has been widely

pregnancies,

use of this route of administration

induction

mole (1, 2,

route of administration

Although

E2 and F2a have been used

of labor in pregnancies

and hydatidiform

such complications.

(PGs)

1.

was classified

and one case of In this study,

intra-

as missed abortion.

At the time of induction

none of the

127

PROSTAGLANDINS

patients

showed any clinical

evidence

Patients were premeditated 10 mg.

intramuscularly

an amniocentesis polythene sac.

catheter

fluid

if required,

an initial

diameter

followed

of PGF2a

patients

having

(5),

needle

inserted

( > 30 weeks gestation),

dose of 30 mg. of PGF2a

of PGF2a. followed

this was subsequently

conditions and a

into the amniotic

100-200

ml.

of

Two dosage regimes by 15 mg. at 24 hours, increased

to an initial

by 25 mg. at 6 and 18 hours if required.

In view of the chronoperiadicity istration

Under sterile

1.02 mm.)

prior to the infusion

was used at first; however,

dose of 45 mg.,

100 mg. and metoclopramide

using a 17 gauge Tuohy epidural

pregnancies

were aspirated

were followed:

with meperidine

(external

In the more advanced

amniotic

labor.

30 minutes prior to amniocentesis.

was performed

epidural

of incipient

the initial

been admitted

PGFZa

to hospital

of the response to the intro-amniotic infusions were carried

admin-

out at 6 p.m.,

the

on the same day.

RESULTS

The results of treatment Intro-uterine

death:

intro-amniotically

Two patients and delivered

The other three patients amniotically, patients

128

are recorded received

at 5.5 received

in Table an initial

dose of 30 mg. of PGF2a

hours and 6 hours respectively. an initial

and a second dose of 25 mg. PGF2a

received

I.

dose of 45 mg. of PGF2a at 6 hours.

a third dose of 25 mg. at 18 hours.

APRIL

intra-

One of these three

These patients

25, 1974

delivered

at

VOL. 6 NO. 2

PROSTAGLANDINS

TABLE I

Details of patients receiving

intm-amniotic

PGF2

for the induction of labor

Weeks Gestation case No.

Diagnosis

Age

Parity

At Diognosis

At Termination

Dose of PGF Initial* To%1

InductionDelivery lnterwl WHoun)

1.

Missed Abortion

22

Missed Abortion

3.

15

16

3omg.

@Jmg.

31

18

20

30 mg.

30 mg.

6.25

D.I.U.

34

22

24

30 mg.

30 mg.

6

4.

D.I.U.

32

20

23

30 mg.

3omg.

5.5

5.

D.I.U.

39

32

34

45 mg.

70 mg.

10

6.

D.I.U.

29

31

33

45 mg.

70 mg.

17.25

7.

D.I.U.

25

31

32

45 mg.

95 mg.

21.5

a.

Anencepholy

28

30

31

45 mg.

70 mg.

13

9.

Anencephaly

29

29

30

#mg.

45 XY Monosomy

23

20

22

2.

10.

0

1

205 mg.

75 mg.

30

53.67

10

* administered at 6 p.m.

APRIL 25,1974 VOL. 6 NO. 2

129

PROSTAGLANDINS

10 hours,

17.4

hours, and 21.5

Four of the five placenta,

which

Four patients

experienced

delivered delivered

by intravenous

syntocinon

were 6.25

received

an initial

requiring

experienced

of mild generalised

Anencephaly:

Induction-

one abortion

nausea and occasional

vomiting

and one patient

pruritis.

Both patients

received

an initial

dose of 45 mg. of PGF2a

One patient

doses at 18, 24 and 30 hours, and a final

dose of 60 mg. at 42 hours.

time was 13 hours and 53.67

nausea and vomiting Chromosomal

(45 XY,

Of ten patients in less than twelve

130

monosomy):

included

receiving

25 mg.

Inductionexperienced

This patient

received

associated

dose of PGF

2a’

an initial

Complete

delivery

dose occurred

nausea and vomiting.

PGF2a

hours and eight

with gross hydramnios the initial

received

Both patients

hours respectively.

and a second dose of 25 mg. at 6 hours.

at 10 hours, and side-effects

after

subsequently

ond one had diarrhoea.

Anomaly

of 45 mg. PGF2a

being

curettage.

and a second dose of 25 mg. at 6 hours.

delivery

and

dose of 30 mg. of PGF2a

hours and 30 hours respectively,

and the other incomplete, Both patienk

infusion.

three had diarrhaea,

and one a second dose of 15 mg. at 24 hours.

intervals

complained

and one had a retained

nausea and three vomiting,

Both patienk

intro-amniotically,

completely,

at all.

Missed abortion:

complete

patienk

was subsequently

one had no side-effeck

abortion

hours respectively.

by the intra-amniotic

had delivered

by twenty

with onencephaly The mean ( f

route, four hours.

delivered

S.E.)

interval

APRIL

25,

five delivered One

approximately to delivery

1974

patient 54 hours

in four

VOL. 6 NO. 2

PROSTAGLANDINS

patients

receiving

in six patients Although

receiving

an initial

receiving

dosage level,

the initial five

30 mg. of PGF2a was 11 .9 *

dose of

there was an obvious,

to the initial

whereas

an initial

dose of 45 mg. of PGF2a

but not statistically

5.2

hours whilst

it was 20.9

significant,

f

6.2

difference

hours.

related

the results were biased by the fact that the four patients

dose of 30 mg. were all

of the six patients

receiving

in the middle

trimester

the 45 mg. initial

of pregnancy

dose were 30 or more

week.5 pregnant. Death of the fetus prior to PGF2a 45 mg.) 7) with 2.7

appeared

not to influence

intro-uterine

hours whilst

to delivery

f

11.5

interval

The administration

of an initial

abortion

trimester

resulted

does not differ

death

cases where preceded

In this study,

interval

to delivery

(5,

6,

of 16.2

f

I iving fetuses had a mean interval

One of the latter

patients

had a prolonged

to be associated

dose of 30 mg. of PGF2a

trimester

dose of

three patients

complicated interval

pregnancies

with gross hydramnios.

to four patients

by intra-uterine of 11.9

from the mean induction-abortion

the fetus was alive

terminated

f

5.2

(1,

2,

3,

death or missed hours which

interval

(10.4

by the identical

f

1 .O

pro-

25, 1974

at the time of PGF2a

infusion

(8,

9,

delivery.

the only patient

30 hours was the one previously

APRIL

10) with

in an induction-delivery

significantly

to delivery:

S.E.)

that was believed

(using an initial

(5). In all

10) fetal

9,

pregnancies

hours) in 14 normal middle cedure

(8,

hours.

induction-delivery

4) with middle

the interval

deaths had a mean ( *

three patients

of 25.6

administration

with an interval

referred

VOL. 6 NO. 2

to delivery

of more than

to as having gross hydramnios.

We believe

131

PROSTAGLANDINS

that the excessive a situation

where

distension

of the uterus associated

the myometrium

was unable

with

to contract

this condition normally

produced

in response to

the PGF2a.

DISCUSSION

In the past,

controversy

existed

of patients

with a known intro-uterine

advocated

the policy

deaths deliver considered,

spontaneously

quite

considerable

of watchful

rightly,

degree

strain

The recent

abortion,

132

practitioners

that most intro-uterine

two or three weeks of fetal

unwise to expose a patient

However,

of active

associated clinical

labor in such pregnancies

replaced

within

conservative

believing

this policy

unsatisfactory intervention

death (6).

Whilst

introduction (1,

2,

spontaneously

when available

methods

hazardous. load and

a dead or an abnormal

baby in utero,

disorders.

of prostaglandins

administration

and extra-amniotic

only the intravenous

or potentially

3, 4) h as provided

intro-amniotic

the intravenous

was advised

risk of coagulation

It was

to what may have been some

stressed the emotional

imposed on a woman with either

and the additional

and reliable.

More

expectancy,

of labor were either

The advocates psychic

death.

in management

of risk when it was possible that she may deliver

over the next few weeks. of induction

as to the method of choice

for the induction

of

a method that is acceptable of prostaglandins

routes for the induction

has largely of middle

trimester

route appears thus far to have been used for the

APRIL

25,

1974

VOL. 6 NO. 2

PROSTAGLANDINS

induction

of labor in complicated

the intro-amniotic

administration

in such pregnancies,

and that

The disadvantages known,

pregnancies. of PGF2

by a low incidence

methods of induction

and have been discussed (2).

provides a method without

can be used for the induction

it is attended

of alternate

The present results indicate

Intra-clmniotic

of labor

of side-effects.

of labor are well

PGF2

most of these disadwntages,

that

, on the other hand,

and the results have been

encouraging. In this study, the pregnancies correlate delivery

due to the bias introduced

treated

with the two dosage regimes,

the induction-delivery interval

mean time to delivery

that no significantly

active

by prostaglandin

.

One of the patients

initial

dose of PGF2

monitor with

and required

uterine

pattern

usually

the presence

APRIL

Although

myometrial

of gross hydmmnios

uterine

inertia.

death was no

These results suggest

prolonged

tocogmph activity

(205 mg). was applied

Following

uterine

by the PGF2

deteriomted

distension,

the

in order to

was stimulated

it subsequently

of labor

induction-delivery

This response was considered

with marked

2

as the

by the fetus in the induction

contmctions,

VOL. 6 NO.

fetuses.

dose of PGF2

(45 mg), an external

seen in uterine

25, 1974

living

ages of

The induction-

by intm-uterine

had a markedly total

dosage.

to the state of the fetus,

role is mediated

studied

gestational

it was not possible to

initial

complicated

involving

an excessive

activity.

low amplitude

with

relation

in pregnancies

longer than in those pregnancies

interval

interval

showed no apparent

F2

by different

into a

to be due to

thus preventing

133

PROSTAGLANDINS

effective

uterine

of a considerable

volume

effective

contractions.

uterine

By comparison administration

of amniotic

with

of PGF

2a

and other side-effects delivery

It wwld

contractions.

seem that such cases require

fluid

prior to PGF2a

the intravenous

involves

(7,

8,

9,

infusion

or other systemic

a lowered

incidence

10) without

in order to allow

routes,

the intro-amniotic

and severity

significant

the aspiration

change

of gastro-intestinal

in the induction-

interval.

REFERENCES

1.

Karim,

S.M.M.

missed labour, British Medical 2.

Filshie,

death,

Use of prostaglandin

and hydatidiform Journal, G.M.

3:196

and hydatidiform

of the British Commonwealth,

73:87

3.

J.F.

Pedersen,

2:2

F

P.H.,

Larsen,

in missed abortion,

E2

mole.

Hickl,

F

und paracervicalblock

K?%ische

E. J.,

Mickan,

Wochenschrift,

Smith,

I. D.,

to the intra-amniotic

Tricomi,

V.,

and Gynaecology, 7. F2a*

134

of intra-uterine

of Obstetrics

and Gynoecology

(1971). and Sorensen,

fetus mortuus,

B.

Induction

of labor with

and anencephalia.

H. and Walther,

D.

bei missed abortion 51:140

prosta-

Prostaglandins,

Shearman,

R. P. and Korda,

injection

Karim, Lancet,

S.M.M.

and Kohl, 74:1092

Kombination

von prostaglandin

und intrauterinem

fruchttod.

(1973).

of prcstaglandin

(1973). 6.

in the management Journal

(19723P

4.

5.

of missed abortion,

(1970).

The use of prcstaglandin

missed abortion

glandin

E2 in the management

mole.

S.G.

Fetal

death

A.R. F

2a

Chronoperiodicity in the human.

in utero.

American

in the response

Nature,

241:279

Journal

of Obstetrics

(1957).

and Filshie,

G.M.,

Therapeutic

abation

using prostaglandin

1 :157 (1970).

APRIL

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Toppozada, M., Bydgeman, M., and Wiqvist, 8. intro-amniotic administration of prostaglandin F *a. Haspels, 9. intra-uterine

A.A.

the Biosciences, 10.

Nyberg,

prostaglandin

and Neth,

administration 9515

R. F2a.

Therapeutic Advances

Inductian

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by

(1971).

Induction of abortion by intravenous and by (extra-and intro-amniotic). Advances in

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135