PROSTAGLANDINS
INTRAUTERINE INJECTION OF 15(S)-l+METHYL-PROSTAGLANDIN
F21
FOR TERMINATION OF EARLY PREGNANCY IN OUT-PATIENT
Ylikorkala,
O., Kirkinen, P., Jouppila, P. and JPrvinen, P.A.
From the Department of Obstetrics and Gynaecology, University of Oulu, Oulu, Finland
ABSTRACT
IS-me-PGF
was administered as single intrauterine injection 2& for interruption of very early pregnancy in 30 out-patients. After 2 weeks, abortion was complete in 60 4% induced with 125 After 3 weeks, abortion
or 200 pg and 80 % induced with 300 ug.
was complete in 90 % induced with 125 ug, in 70 % induced with 200 ug and in 100 % induced with 300 pg.
One failure occurred
in patients treated with 200 ug and 2 curettages were performed because of incompleteness of abortion. occurred.
No serious complications
Compared with our previous results it appears that
15-me-PGF24 is as effective as natural PGF
in inducing abortions 24 during very early pregnancy but causes somewhat fewer side-effects.
We wish to thank the WHO PROSTAGLANDIN TASK FORCE for the supply of 1S-me-PGF2A used in this study.
AUGUST
1975
VOL. 10 NO. 2
333
PROSTAGLANDINS
INTRODUCTION
The ls-methyl analog of the natural prostaglandin F 15(S)-15-methyl-PGF2,, (Is-me-PGF2
24' ) has a greater and longer
acting potency than the parent compound (1) because it is resistant
to the degrading enzyme of 15 hydroxydehydrogenase.
Its efficacy in inducing midtrimester
abortion has been shown
when administered intra-amniotically
(2,3) or intramusctilarly
(3).
Previously we reported 32 interruptions of very early pregnancy with a single intrauterine injection of natural PGF2,( in outpatient (4).
We now publish our results when the same procedure
but 15-me-PGF24 were applied for termination of 30 early pregnancies.
PATIENTS AND METHODS
The series consists of a total of 30 out-patients who undarwent legal abortions (Table I).
The mean delay in menstruation
was 16.7 days.
The same procedure, as reported in detail (41, was applied. The very early viable pregnancy was confirmed by the positive pregnancy test (PregnosticonR, Organon, Holland), by the ultrasonic B-scan and by the findings on pelvic examination. 15-me-PGF2q from 125 to 300 ug was administered as a single
334
AUGUST
1975
VOL. 10 NO. 2
PROSTAGLANDINS
intrauterine injection through the undilated uterine cervix. As a premeditation
50 mg of pethidin was given intramuscularly
lo-15 min before the injection of Is-me-PGF2*.
The patients
were subsequently examined 2 weeks later, and if abortion was incomplete also 3 weeks after induction.
The criteria for
complete abortion were the commencement and disappearence of uterine bleeding, negative Pregnosticon
R
and emptiness of the
uterine cavity determined by ultrasonic B-scan.
Abortion was
incomplete if uterine bleeding was found at follow-up examinations, if the pregnancy test was positive and if the uterine cavity was not empty in the ultrasonic B-scan.
An induction was re-
garded as a failure if bleeding did not start, if the pregnancy test remained positive and if an intact amniotic sac was found on B-scan.
RESULTS
The results are given in Table II.
Uterine bleeding started
within 1-22 hrs after induction and lasted 6-22 regarded heavier than normal menstruation At the first follow-up,abortion
in 7 I.
days.
It was
in 43 % and scantier was complete in 60 %
in the groups of 125 and 200 pg but 80 % in the group of 300 pg. The abortion rate increased somewhat with advancing observation time.
Spontaneous menstruation
occurred within 25-75 days
after induction.
AUGUST
1975
VOL. 10 NO. 2
335
PROSTAGLANDINS
One failure occurred in the group of 200 pg.
Her pregnancy
wa8 terminated with vacuum aspiration 3 week8 after induction. In addition, 2 curettages were performed because of incompleteness of abortion.
These patients were also treated with 200 pg of
15-me-PGF26 .
The side-effects following the induction8 are shown in Table III. Uterine pains started within l-15 min after injection of Is-mePGF2d
and lasted 2-3 hrs.
analgetic.
Three cases required additional
Three patients vomited once, two twice and 3 ca8es
3-6 times.
No serious complications occurred.
One woman induced with
125 ug of 15-me-PGF24 experienced very painful contraction8 and a transient hypotension,
and she was taken into ward over night.
She recovered uneventfully without any additional treatment, and abortion was complete within 3 weeks.
Haemoglobin and
haemotocrit values in the whole series did not decrease during the bleeding-period.
Six women (20 $) were absent l-2 days
from their employment because of heavy bleeding.
DISCUSSION
In our previous study (4) we administered natural PGF2d, l-4 mg as a single intrauterine injection for termination of very early pregnancy.
336
After 2 weeks, abortion was complete
AUGUST
1975
VOL. 10 NO. 2
PROSTAGLANDINS
in 55 % induced with 1.0 mg, in 77 $ induced with 2.0 mg and in all patients induced with 4.0 mg.
After 3 weeks, abortion
was complete in 82 % induced with 1.0 mg and in 100 $ induced Our recent results show that 15-me-PGF
with 2.0 mg.
effective as natural PGF
is as 24 as an abortifacient during very
2G4 early pregnancy but with doses which are only about 10 % of the respective dose of primary PGF
The rates of side-effects 28 and complications were somewhat lower in association with the use than natural PGF2d except for diarrhea.
of 15-me-PGF a(
Vacuum aspiration has been applied for pregnancy interruption
up to the 12th week of pregnancy also as an out-patient procedure when pericervical block or general anaesthesia has been used
(5,6).
The complications occurred in 5.2 W (5)
or in 8.2 X (6)
but one must remember the increased incidence of premature delivery after instrumental dilatation of the uterine cervix
(7).
or preferably its methyl derivate even oi in out-patient base avoids the necessarity of having any anaesthesia
Intrauterine use of PGF2
and may cause fewer cervical complications.
The efficacy and
acceptability of 15-me-PGF2ti could be improved with bigger but divided doses of 15-me-PGF2k and perhaps with more effective premeditation.
AUGUST
1975 VOL. 10 NO. 2
337
PROSTAGLANDINS
%-NC0 . . FLnrc
338
c
. %-
AUGUST
1975
VOL. 10 NO. 2
Nl
G
4
300
200
125
(yg)
15-me-PGF2d
Dose of
4.6
7.1
9.8
2-5
I-14
11.7
l-22
6.0
3.3
Mean
Range
TD uration
4.0
1.3
4-14 4-14
2.8
ean
of
60 80
8-22
60
2 weeks
(I)
100
70
90
3 weeks
after
Complete abortion rate
6-14
6-20
Range
(days)
b leeding
4-28
(days 1 1 Range
Negative PregnosticonR
Mean
(h
bleeding
Onset of
Outcome of induction with 15-me-PGF2d in 30 ou.t-patients
c
Table II
38.4
40.0
37.5
Mean
31-45
25-75
31-42
(d a3 ‘5) Range
after 15-me-PGF2,
r
Next menstruation
PROSTAGLANDINS Occurrence
Table III
Dose
of
pains
,A (pg)
T
125
Uterine
Is-me-PGF2_
of side-effects
1
N
x
9
90
100
4
40
30
2
20
30
4
40
20
1
10
0
N
%
tl AUGUST
1975
VOL. 10 NO. 2
PROSTAGLANDINS
REFERENCES 1.
Toppozada, M., F. Beguin, M. Bygdemsn, and N. Wiqvist. Response of the midpregnant human uterus to systemic administration of 15(S)-15-methyl-prostaglandinFzA, Prostaglandins 2:239, 1972
2.
Bygdeman, M., F. Beguin, M. Toppozada, N. Wiqvist, and S. Bergstram. Intrauterine administration of 15(S)-15-methylprostaglandin FzA for induction of abortion, Lancet 1:1336, 1972
3.
Bygdeman, M., J.N. Martin, N. Wiqviat, K. Green, and S. Bergstram. Reassessment of systemic administration of prostaglandins for induction of midtrimester abortion, Prostaglandins 8:157, 1974
4.
Ylikorkala, O., P. Jouppila, P. Ylbstalo, and P.A. Jlrvinen. Intrauterine injection of prostaglandin F for termination %4 of early pregnancy in out-patient, Prostaglandins 7:57, 1974
5.
Beric, B., and M. Kupresanin. Vacumaspiration using pericervical block for legal abortion as an out-patient procedure up to the 12th week of pregnancy, Lancet 11:619, 1971
6.
Fahraeus, R.
Polikliniska vakuumaspirationer,LLikartidningen
69:4665, 1972 7.
Pantelakis, S.N., G.C. Padadimitriou, and S.A. Doxiadis. Influence of induced and spontaneous abortions on the outcome of subsequent pregnancies, Am J Obstet Gynecol 116:799, 1973
AUGUST
1975
VOL. 10 NO. 2
341
INTRAUTERINE INJECTION OF 15(S)-l+METHYL-PROSTAGLANDIN
F21
FOR TERMINATION OF EARLY PREGNANCY IN OUT-PATIENT
Ylikorkala,
O., Kirkinen, P., Jouppila, P. and JPrvinen, P.A.
From the Department of Obstetrics and Gynaecology, University of Oulu, Oulu, Finland
ABSTRACT
IS-me-PGF
was administered as single intrauterine injection 2& for interruption of very early pregnancy in 30 out-patients. After 2 weeks, abortion was complete in 60 4% induced with 125 After 3 weeks, abortion
or 200 pg and 80 % induced with 300 ug.
was complete in 90 % induced with 125 ug, in 70 % induced with 200 ug and in 100 % induced with 300 pg.
One failure occurred
in patients treated with 200 ug and 2 curettages were performed because of incompleteness of abortion. occurred.
No serious complications
Compared with our previous results it appears that
15-me-PGF24 is as effective as natural PGF
in inducing abortions 24 during very early pregnancy but causes somewhat fewer side-effects.
We wish to thank the WHO PROSTAGLANDIN TASK FORCE for the supply of 1S-me-PGF2A used in this study.
AUGUST
1975
VOL. 10 NO. 2
333
PROSTAGLANDINS
INTRODUCTION
The ls-methyl analog of the natural prostaglandin F 15(S)-15-methyl-PGF2,, (Is-me-PGF2
24' ) has a greater and longer
acting potency than the parent compound (1) because it is resistant
to the degrading enzyme of 15 hydroxydehydrogenase.
Its efficacy in inducing midtrimester
abortion has been shown
when administered intra-amniotically
(2,3) or intramusctilarly
(3).
Previously we reported 32 interruptions of very early pregnancy with a single intrauterine injection of natural PGF2,( in outpatient (4).
We now publish our results when the same procedure
but 15-me-PGF24 were applied for termination of 30 early pregnancies.
PATIENTS AND METHODS
The series consists of a total of 30 out-patients who undarwent legal abortions (Table I).
The mean delay in menstruation
was 16.7 days.
The same procedure, as reported in detail (41, was applied. The very early viable pregnancy was confirmed by the positive pregnancy test (PregnosticonR, Organon, Holland), by the ultrasonic B-scan and by the findings on pelvic examination. 15-me-PGF2q from 125 to 300 ug was administered as a single
334
AUGUST
1975
VOL. 10 NO. 2
PROSTAGLANDINS
intrauterine injection through the undilated uterine cervix. As a premeditation
50 mg of pethidin was given intramuscularly
lo-15 min before the injection of Is-me-PGF2*.
The patients
were subsequently examined 2 weeks later, and if abortion was incomplete also 3 weeks after induction.
The criteria for
complete abortion were the commencement and disappearence of uterine bleeding, negative Pregnosticon
R
and emptiness of the
uterine cavity determined by ultrasonic B-scan.
Abortion was
incomplete if uterine bleeding was found at follow-up examinations, if the pregnancy test was positive and if the uterine cavity was not empty in the ultrasonic B-scan.
An induction was re-
garded as a failure if bleeding did not start, if the pregnancy test remained positive and if an intact amniotic sac was found on B-scan.
RESULTS
The results are given in Table II.
Uterine bleeding started
within 1-22 hrs after induction and lasted 6-22 regarded heavier than normal menstruation At the first follow-up,abortion
in 7 I.
days.
It was
in 43 % and scantier was complete in 60 %
in the groups of 125 and 200 pg but 80 % in the group of 300 pg. The abortion rate increased somewhat with advancing observation time.
Spontaneous menstruation
occurred within 25-75 days
after induction.
AUGUST
1975
VOL. 10 NO. 2
335
PROSTAGLANDINS
One failure occurred in the group of 200 pg.
Her pregnancy
wa8 terminated with vacuum aspiration 3 week8 after induction. In addition, 2 curettages were performed because of incompleteness of abortion.
These patients were also treated with 200 pg of
15-me-PGF26 .
The side-effects following the induction8 are shown in Table III. Uterine pains started within l-15 min after injection of Is-mePGF2d
and lasted 2-3 hrs.
analgetic.
Three cases required additional
Three patients vomited once, two twice and 3 ca8es
3-6 times.
No serious complications occurred.
One woman induced with
125 ug of 15-me-PGF24 experienced very painful contraction8 and a transient hypotension,
and she was taken into ward over night.
She recovered uneventfully without any additional treatment, and abortion was complete within 3 weeks.
Haemoglobin and
haemotocrit values in the whole series did not decrease during the bleeding-period.
Six women (20 $) were absent l-2 days
from their employment because of heavy bleeding.
DISCUSSION
In our previous study (4) we administered natural PGF2d, l-4 mg as a single intrauterine injection for termination of very early pregnancy.
336
After 2 weeks, abortion was complete
AUGUST
1975
VOL. 10 NO. 2
PROSTAGLANDINS
in 55 % induced with 1.0 mg, in 77 $ induced with 2.0 mg and in all patients induced with 4.0 mg.
After 3 weeks, abortion
was complete in 82 % induced with 1.0 mg and in 100 $ induced Our recent results show that 15-me-PGF
with 2.0 mg.
effective as natural PGF
is as 24 as an abortifacient during very
2G4 early pregnancy but with doses which are only about 10 % of the respective dose of primary PGF
The rates of side-effects 28 and complications were somewhat lower in association with the use than natural PGF2d except for diarrhea.
of 15-me-PGF a(
Vacuum aspiration has been applied for pregnancy interruption
up to the 12th week of pregnancy also as an out-patient procedure when pericervical block or general anaesthesia has been used
(5,6).
The complications occurred in 5.2 W (5)
or in 8.2 X (6)
but one must remember the increased incidence of premature delivery after instrumental dilatation of the uterine cervix
(7).
or preferably its methyl derivate even oi in out-patient base avoids the necessarity of having any anaesthesia
Intrauterine use of PGF2
and may cause fewer cervical complications.
The efficacy and
acceptability of 15-me-PGF2ti could be improved with bigger but divided doses of 15-me-PGF2k and perhaps with more effective premeditation.
AUGUST
1975 VOL. 10 NO. 2
337
PROSTAGLANDINS
%-NC0 . . FLnrc
338
c
. %-
AUGUST
1975
VOL. 10 NO. 2
Nl
G
4
300
200
125
(yg)
15-me-PGF2d
Dose of
4.6
7.1
9.8
2-5
I-14
11.7
l-22
6.0
3.3
Mean
Range
TD uration
4.0
1.3
4-14 4-14
2.8
ean
of
60 80
8-22
60
2 weeks
(I)
100
70
90
3 weeks
after
Complete abortion rate
6-14
6-20
Range
(days)
b leeding
4-28
(days 1 1 Range
Negative PregnosticonR
Mean
(h
bleeding
Onset of
Outcome of induction with 15-me-PGF2d in 30 ou.t-patients
c
Table II
38.4
40.0
37.5
Mean
31-45
25-75
31-42
(d a3 ‘5) Range
after 15-me-PGF2,
r
Next menstruation
PROSTAGLANDINS Occurrence
Table III
Dose
of
pains
,A (pg)
T
125
Uterine
Is-me-PGF2_
of side-effects
1
N
x
9
90
100
4
40
30
2
20
30
4
40
20
1
10
0
N
%
tl AUGUST
1975
VOL. 10 NO. 2
PROSTAGLANDINS
REFERENCES 1.
Toppozada, M., F. Beguin, M. Bygdemsn, and N. Wiqvist. Response of the midpregnant human uterus to systemic administration of 15(S)-15-methyl-prostaglandinFzA, Prostaglandins 2:239, 1972
2.
Bygdeman, M., F. Beguin, M. Toppozada, N. Wiqvist, and S. Bergstram. Intrauterine administration of 15(S)-15-methylprostaglandin FzA for induction of abortion, Lancet 1:1336, 1972
3.
Bygdeman, M., J.N. Martin, N. Wiqviat, K. Green, and S. Bergstram. Reassessment of systemic administration of prostaglandins for induction of midtrimester abortion, Prostaglandins 8:157, 1974
4.
Ylikorkala, O., P. Jouppila, P. Ylbstalo, and P.A. Jlrvinen. Intrauterine injection of prostaglandin F for termination %4 of early pregnancy in out-patient, Prostaglandins 7:57, 1974
5.
Beric, B., and M. Kupresanin. Vacumaspiration using pericervical block for legal abortion as an out-patient procedure up to the 12th week of pregnancy, Lancet 11:619, 1971
6.
Fahraeus, R.
Polikliniska vakuumaspirationer,LLikartidningen
69:4665, 1972 7.
Pantelakis, S.N., G.C. Padadimitriou, and S.A. Doxiadis. Influence of induced and spontaneous abortions on the outcome of subsequent pregnancies, Am J Obstet Gynecol 116:799, 1973
AUGUST
1975
VOL. 10 NO. 2
341
