International Journal of Gynecology and Obstetrics (2007) 97, 35–39

a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m

w w w. e l s e v i e r. c o m / l o c a t e / i j g o

CLINICAL ARTICLE

Intravaginal gemeprost and second-trimester

pregnancy termination in the scarred uterus
E. Marinoni a,⁎, M. Santoro a , M.P. Vitagliano a , A. Patella b ,
E.V. Cosmi a , R. Di Iorio a
a
Laboratory of Perinatal Medicine and Molecular Biology, Department of Gynecology, Perinatology and Child Health,
University “La Sapienza,” Rome, Italy
b
Department of Obstetrics and Gynecology, University of Ferrara, Italy

Received 7 November 2006; received in revised form 19 December 2006; accepted 20 December 2006

KEYWORDS Abstract
Abortion;
Cesarean section; Objective: To investigate the effectiveness and complication rate of intravaginal gemeprost, a
Gemeprost; prostaglandin E1 analogue, for second-trimester pregnancy termination in women with a scarred
Prostaglandin analogue; uterus. Methods: Of 439 women undergoing induced abortion between the 13th and the
Uterine scar 23rd week of pregnancy, 67 had a scarred uterus because of 1 or more cesarean sections or
myomectomy. All women received a 1 mg dose of gemeprost intravaginally every 3 h, up to 5
times over 24 h. Those who did not respond received further cycles of gemeprost treatment.
Results: The rate of successful abortions among women with uterine scars was not different from
that observed in the nulliparous controls, but previously vaginal delivery was associated with a
shorter induction to abortion interval. The rate of severe complications did not differ between
the groups, and was about 1%. Conclusion: The rate of complications following intravaginal
administration of a PGE1 analogue for second-trimester pregnancy termination was similar in
women with a scarred or unscarred uterus.
© 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.
All rights reserved.

1. Introduction severe complications is associated with induced abortion after

Abortion-related morbidity and mortality increase signifi-
cantly as pregnancy advances, and a sharp rise in the rate of
⁎ Corresponding author. Department of Gynecology, Perinatology
and Child Health, University “La Sapienza”, Viale Regina Elena, 324,
I-00161 Rome, Italy. Tel.: +39 6 49 13 06; fax: +39 6 44 63 502.
E-mail address: emanuelamarinoni@hotmail.com (E. Marinoni).
14 weeks of pregnancy. A potentially life-threatening compli-
cation in second-trimester termination of pregnancy is uterine
rupture, which has been reported to be more frequent in
multiparous women and in women with uterine scars. The risk
of scar rupture at the time of medical termination of
pregnancy varies depending on the drugs and regimens used
[1–3]. Second-trimester abortion is frequently performed by
administration of prostaglandins analogues. In Italy, as in
several other countries, gemeprost (16,16-dimethyl-trans-Δ2-

0020-7292/$ - see front matter © 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.
All rights reserved.
doi:10.1016/j.ijgo.2006.12.013
36 E. Marinoni et al.

PGE1 methyl ester) is the only prostaglandin licensed for

induction of abortion. Three to 5 doses are administered
as vaginal pessaries, usually at 3- to 6-h intervals [4–7], over
24 h [3,7,8]. Although this method is effective for second-
trimester abortion, with a success rate higher than 95% [3,7,9–
11], terminating a pregnancy in a woman with a uterine scar
is always challenging and it has been suggested that the
standard drug regimen ought to be modified in such cases
[3]. However, there are few data on the effectiveness and
safety of the use of intravaginal prostaglandin analogues in
women with a history of 1 or more cesarean sections (CSs) or
myomectomy.
In this study the effectiveness of a standard gemeprost
regimen in inducing second-trimester abortion and the com-
plications rate associated with a uterine scar have been
investigated. Figure 1 Graphic representation of rates of successful induced
abortion at different time-points in nulliparas and multiparas
with a scarred or unscarred uterus who received gemeprost
2. Materials and methods treatment for second-trimester pregnancy termination.

A retrospective study was carried out between 1998 and 2005

with 429 women undergoing induced abortion for fetal
anomalies between the 13th and 23rd week of a singleton
pregnancy. Pregnancy duration was calculated from the first day
of the last period and confirmed by ultrasonography before the
12th week. All pregnancy terminations were recorded prospec-
tively and the data were collected retrospectively from the
patients' records. Sixty-seven women had a uterine scar, 65 from
lower-segment transverse CS and 5 from transmural myomect-
omy. Of the 62 women with a history of CS, 52 had undergone
1 CS (83.9%), 8 had undergone 2 CSs (12.9%), and 2 had
undergone 3 CSs (3.2%). Although prior spontaneous delivery in
women with a scarred uterus was not an exclusion criterion,
none of the 67 women with a scarred uterus had been delivered
vaginally. Of the 362 women who represented the control group,
222 were nulliparas and 140 had been delivered vaginally at
least once.
Following appropriate counseling, the women received
pessaries containing 1 mg of gemeprost (Cervidil; Serono,
Roma, Italy) in the posterior fornix of the vagina. This treatment
was repeated every 3 h until either the products of conception
were expelled, or any adverse effects had become too severe to
continue drug administration, for a maximum of 5 pessaries over
24 h. If abortion did not occur within 24 h, a new treatment cycle
was administered after an interval of 24 h, for a maximum of 3
complete 24-h cycles.
Successful abortion was defined as delivery of the fetus and
placenta. Failed abortion was defined no delivery after 3
complete 24-h treatment cycles (120 h), after which hyster-
otomy was carried out. Oxytocin (Syntocinon; Novartis Farma,
Origgio, Italy) was prescribed after the application of a minimum
of 5 pessaries in patients who showed progression of labor.
Antiemetic and antidiarrheal agents were administered as
required. Following fetal and placental expulsion, routine uterine
curettage was performed. The women were usually discharged 12
to 24 h after the pregnancy termination, depending on their
clinical condition.
The primary outcomes were incidence of major complica-
tions (such as uterine rupture and/or severe blood loss requiring
blood transfusion); minor complications (such as postabortal

Table 1 Clinical and demographic characteristics of women with and without uterine scars (controls) who received
gemeprost vaginally for second-trimester induced abortion(a)
Characteristic Uterine scar Control P value
Nulliparas Multiparas
(n = 67) (n = 222) (n = 140)
Age, years 36.1 ± 4.35 31.5 ± 5.5 35.2 ± 4.8 NS
Pregnancy duration, weeks 19.3 ± 2.6 19.4 ± 2.9 19.6 ± 2.7 NS
Fetal weight, g 386 ± 330 308 ± 204 337 ± 209 NS
Indication for termination,
no. of anomalies detected by ultrasonography 34 (51) 138 (62) 67 (48) NS
Aneuploidy 29 (43) 80 (36) 65 (47) NS
Maternal disease 0 1 (0.5) 5 (3.5) NS
Previous abortion 31 (46) 65 (29) 50 (36) P < 0.05
1 20 (30) 50 (22) 35 (25) NS
2 8 (12) 14 (6.3) 9 (6.4) NS
≥3 3 (4) 1 (0.7) 6 (4.6) NS
Abbreviation: NS, not significant.
(a)
Values are given as mean ± SD or number (percentage) unless otherwise indicated.
Intravaginal gemeprost and second-trimester pregnancy termination in the scarred uterus
infection, severe bleeding, and need for vaginal and/or uterine
packing); rate of failed abortion; and rate of successful abortion
within 24 h. Severe bleeding was defined as an estimated blood
loss of 500 ml or greater. Secondary outcomes were induction to
abortion interval; number of pessaries needed; number of
treatment cycles; and mild adverse effects (such as nausea,
vomiting, diarrhea, and body temperature > 38 °C).
The means of continuous variables were compared with the
unpaired t test and categorical variables were compared using
the χ2 test or the Fisher Exact test, as appropriate. Linear
regression was performed to evaluate the relationship between
clinical outcome measures and obstetric variables. P < 0.05 was
considered significant.
3. Results
Clinical and demographic characteristics were similar in the
scarred uterus group (study group) and unscarred uterus
group (control group) (Table 1). All but 1 patient experienced
uterine contractions and cervical dilatation following vaginal
administration of gemeprost. Not being delivered after 3
complete 24-h treatment cycles (120 h), this nullipara in the
21st week of pregnancy was given an infusion of oxytocin for
6 h, followed by hysterotomy.
The abortion rate and number of pessaries needed in the 2
groups are reported in Fig. 1 and Table 2. The overall
effectiveness of gemeprost in inducing abortion was almost
similar in the 2 groups (98.4% in the uterine scar group and
98.6% in the control group). The correlations between the
number of gemeprost pessaries needed and pregnancy
duration, fetal weight, and induction to abortion interval
are shown in Fig. 2. A relationship between previous spon-
taneous delivery and induction to abortion interval was
found for multiparas (r = 0.156, P < 0.05). A correlation was
also found between number of previous abortions and
induction to abortion interval for nulliparas in the control
group but not in the study group (data not shown). Five
Table 2 Clinical response to vaginal administration of gemeprost in women undergoing second-trimester induced
abortion(a)
Response Uterine scar
group
(n = 67)
Pessaries needed 4.9 ± 2.3
Treatment cycles 1.3 ± 0.5
Induction to abortion interval, h 24.5 ± 20.1
Time to fetal expulsion
<24 h 49 (73.0)
24–48 h 2 (2.9)
>48 h 15 (22.4)
Treatment cycles to fetal expulsion
1 51 (76.1)
2 13 (19.4)
3 2 (3.0 )
Failed abortion 0 1 (0.5)
Discontinued treatment 1 (1.5)
(a)
Values are given as mean ± SD or number (percentage).
(b)
P < 0.05 vs. nulliparas.
37
women in the study group and 11 in the control group (7%
and 3%, respectively) needed additional treatment following
the full course of gemeprost treatment cycles. Oxytocin
was used in most of them, alone or in combination with
amniotomy.
The rates of complications and adverse effects are shown
in Table 3. Complications were reported for 12% of the
women with in the study group and 19% of the controls.
Severe complications occurred in about 1.0% of all partici-
pants, as hemorrhage in 2 women in the control group and 1
woman in the study group necessitated emergency surgical
uterine evacuation and blood transfusion. None of the 3,
however, had uterine rupture. The woman with a scarred
uterus who required hysterotomy underwent hysterectomy
during the procedure because of uncontrolled uterine
bleeding. She was 38 years old and 20 weeks pregnant, and
had previously undergone 2 lower-segment transverse
cesarean sections. Heavy uterine bleeding occurred shortly
after the second gemeprost application of the second cycle,
given 24 h after the end of the first 5-pessary cycle in the
absence of significant cervical dilatation. Laparotomy was
immediately performed for uterine evacuation, but uterine
atony unresponsive to oxytocin and sulprostone occurred
after fetal delivery and placenta removal. Histologic
examination ruled out placenta accreta. One patient in the
control group, 21 weeks pregnant, had placenta previa.
Severe bleeding started immediately before fetal expulsion,
and worsening after delivery necessitated surgical removal
of the placenta. The other women with severe hemorrhage in
the control group underwent surgical removal of the
placenta by the vaginal route because of failure of placental
expulsion.
Gemeprost administration was discontinued in 4 women.
Two had an allergic reaction and 2 undelivered women
refused to continue treatment after the first cycle (Table 3).
The rate of successful abortion was 80% within 24 h in the
subgroup of 10 women with a history of more than 1 CS. This
rate was even better than the rates for the entire study
Control group
Nulliparas Multiparas
(n = 222) (n = 140)
5.4 ± 2.3 4.8 ± 1.9
1.3 ± 0.5 1.2 ± 0.4
29.5 ± 23.5 24.2 ± 20.2(b)
129 (58.1) 97 (69.3)
34 (15.4) 19 (13.6)
56 (25.2) 22 (15.7)
163 (73.4) 116 (82.8)
50 (22.5) 20 (14.3)
6 (2.7) 2 (1.4)
0
2 (0.9) 2 (1.4)
38 E. Marinoni et al.

this setting, second-trimester pregnancy termination in

women with a scarred uterus has become an increasingly
common circumstance facing obstetricians. Different rates
for ruptured uterus following prostaglandin use have been
reported [1,2]. Although second-trimester pregnancy termi-
nation by dilatation and evacuation has been shown to be
associated with a lower risk of complications than labor
induction, cesarean scar dehiscence causing hemorrhage has
been reported following the procedure [12]. More recently, a
modification of the standard protocol for gemeprost use has
been proposed for second-trimester termination in women
with a scarred uterus, with the administration of gemeprost
pessaries given every 3 h up to 3 times daily [3]. The present
study investigated the safety and effectiveness of a standard
regimen for gemeprost use in a large series of women with a
scarred uterus. The 98.4% vaginal delivery rate achieved in
these women, which was similar to the rate for the control
group (98.6%), is in agreement with other reports on the use
of gemeprost [7,11], or other drugs [13], in women with a
scarred uterus. In this study the standard regimen for
gemeprost treatment was used, 1 dose every 3 h up to 5
doses over 24 h. After the first complete cycle, a 24-h interval
was observed before initiating a second cycle of gemeprost
treatment, at the same dosage. This 24-h interval allowed a
further increase in the rate of successful first-cycle abortion,
with about 3% of the women with a scarred uterus and 14% of
the women with an unscarred uterus delivered between the
end of the first and the start of the second cycle of
gemeprost, thus minimizing the dose-related risk of myome-
trial overstimulation.
Another important finding of this study was that prior
uterine surgery does not appear to increase the incidence of
complications in women who undergo clinically induced
abortion in the second trimester.
Overall, the incidence of severe complications was low, as
major hemorrhage and the need for blood transfusion were
uncommon events. Only 1 of 62 women with uterine scars
underwent hysterectomy for severe hemorrhage, and 2
women in the control group required blood transfusion

Table 3 Complications and adverse effects of vaginal

administration of gemeprost in women undergoing
second-trimester induced abortion(a)
Figure 2 Correlation between pregnancy duration and induc-
tion to abortion interval in women who received gemeprost Uterine Control group
treatment for second-trimester pregnancy termination. Upper scar Nulliparas Multiparas
panel: women with an unscarred uterus (controls); middle group
panel: controls grouped according to parity; lower panel: (n = 67) (n = 222) (n = 140)
women with a scarred uterus (study group).
Hyperthermia (< 38 °C) 3 (4.5) 39 (17.5) 3 (2.1)(b)
Diarrhea 4 (5.9) 9 (4) 5 (3.6)
group or the control group, but the difference was not Vomiting 1 (1.5) 2 (0.9) 3 (2.1)
statistically significant. Fetal expulsion occurred at the end Utero/vaginal packing 2 (3) 8 (3.6) 6 (4.2)
of the first gemeprost cycle in all but 1 woman who, as Hemorrhage (≥500 ml) 1 (1.5) 1 (0.5) 1 (0.7)
reported above, underwent abdominal hysterectomy after 2 Blood transfusion 1 (1.5) 0 1 (0.7)
more pessaries. Hysterotomy/ 1 (1.5) 1 (0.5) 0
hysterectomy
Vaginal placental 0 1 (0.5) 2 (1.4)
4. Discussion removal
(a)
Values are given as number (percentage).
The frequency of cesarean births has been increasing with (b)
P < 0.05 vs. nulliparas.
the incidence of women who undergo prenatal diagnosis. In
Intravaginal gemeprost and second-trimester pregnancy termination in the scarred uterus
following pregnancy termination. The uterine atony requir-
ing hysterectomy in a patient with a scarred uterus did not
appear to be related to the scars. No case of uterine rupture
occurred in this series. All findings are in agreement with
those reported by Dickinson [13] on the use of misoprostol for
second-trimester pregnancy termination in women with a
scarred uterus. The risk of rupture has been reported to be
higher in women undergoing second-trimester termination
with an oxytocin infusion [2,14]. In the present study, this
agent was used in less than 7% of the women with a scarred
uterus, most deliveries occurring with gemeprost treatment
alone. Using 1 uterotonic agent at a time should help reduce
the chance of uterine rupture, particularly in women with a
history of uterine surgery. Since incomplete placental
expulsion is a common complication in second-trimester
pregnancy termination, routine curettage under sedation
was performed in all women. For this reason, the curettage
rate was not included among complications; however, it has
been reported that previous uterine surgery does not affect
its rate [13].
Regarding the secondary outcomes, no differences were
found between the study and control groups in the number of
pessaries needed, induction to abortion interval, abortion
rate within 24 h and 48 h, or number of treatment cycles. The
clinical response to gemeprost was found to be correlated
with pregnancy duration in nulliparas with a scarred or
unscarred uterus, but this correlation was not found in
controls with a history of vaginal delivery. It should be
stressed that, in the present series, all women with a history
of uterine surgery were nulliparas, although this was not an
inclusion criterion. In multiparas the number of previous
vaginal deliveries was the main variable responsible for the
clinical response to gemeprost, as was observed in previous
studies [7,15]. The number of previous induced abortions
correlated with the number of pessaries needed, and the
induction to abortion interval correlated only in nulliparas
with an unscarred uterus, not in women with previous vaginal
deliveries or in women with a scarred uterus. Since in these
women it was not possible to differentiate according to
indication for previous CSs, labor in previous pregnancies
might be a confounding variable.
In conclusion, vaginal administration of gemeprost every
3 h over up to 24 h is an effective regimen for medical
termination of second-trimester pregnancy in women with a
history of 1 or more CSs or other surgical uterine interven-
tions. Although uncommon, uterine rupture, hemorrhage,
and hysterectomy remain complications of second-trimester
pregnancy termination, women with a scarred uterus do
not seem to be at higher risk if an appropriate drug regimen
is used.
39
References
[1] Le Roux PA, Pahal GS, Hoffman L, Nooh R, El-Rafaey H, Rodeck
CH. Second trimester termination of pregnancy for fetal
anomaly or death: comparing mifepristone/misoprostol to
gemeprost. Eur J Obstet Gynecol Reprod Biol 2001;95:52–4.
[2] Chapman SJ, Crispens M, Owen J, Savage K. Complications of
midtrimester pregnancy termination: the effect of prior
cesarean delivery. Am J Obstet Gynecol 1996;41:186–90.
[3] Scioscia M, Pontrelli G, Vimercati A, Santamato S, Selvaggi L. A
short-scheme protocol of gemeprost for midtrimester termina-
tion of pregnancy with uterine scar. Contraception 2005;71:
193–6.
[4] Thong KJ, Robertson AJ, Baird DT. A retrospective study of
932 second trimester termination using gemeprost (16,16
deimethyl-trans delta 2 PGE1 methyl ester). Prostaglandins
1992;44:65–74.
[5] Lim BH, Mahmood TA, Lees DA. The experience of termination
of second trimester pregnancies using gemeprost vaginal
pessaries in a district general hospital. Asia Oceania J Obstet
Gynaecol 1990;16:21–5.
[6] Querido L, Haspels AA. Late second trimester abortion with
16,16 deimethyl-trans delta 2 PGE1 methyl ester (gemeprost).
Contraception 1990;42:43–9.
[7] Kaasen A, Naes T, Haugen G. Which factors influence the number
of gemeprost pessaries used in inducing second-trimester
abortions? Acta Obstet Gynecol Scand 2005;84:371–5.
[8] Ngai SW, Tang OS, Ho OC. Prostaglandins for induction of second
trimester termination and intrauterine death. Best Pract Res
Clin Obstet Gynaecol 2003;17:765–75.
[9] Thong KJ, Baird DT. A study of gemeprost alone, dilapan or
mefipristone in combination with gemeprost for the termina-
tion of second trimester pregnancy. Contraception 1992;46:
11–7.
[10] Cameron IT, Michie AF, Baird DT. Prostaglandin-induced preg-
nancy termination: further studies using gemeprost (16,16
deimethyl-trans-delta 2-PGE1 methyl ester) vaginal pessaries in
the early second trimester. Prostaglandins 1987;34: 111–7.
[11] Thong KJ, Baird DT. An open study comparing two regimens of
gemeprost for the termination of pregnancy in the second
trimester. Acta Obstet Gynecol Scand 1992;71:191–6.
[12] Lichtenberg ES, Frederikson MC. Cesarean scar dehiscence as a
cause of hemorrhage after second-trimester abortion by
dilatation and evacuation. Contraception 2004;70:61–4.
[13] Dickinson JE. Misoprostol for second-trimester pregnancy
termination in women with a prior cesarean delivery. Obstet
Gynecol 2005;105:352–6.
[14] Wiener JJ, Evans AS. Uterine rupture in mid trimester abortion.
A complication of gemeprost pessaries and oxytocin: case
report. Br J Obstet Gynaecol 1990;97:1061–2.
[15] Armatage RJ, Luckas MJ. A randomized trial of 2 regimens for
the administration of vaginal prostaglandins (gemeprost) for
the induction of midtrimester abortion. Aust N Z J Obstet
Gynaecol 1996;36:296–9.