Contraception 67 (2003) 267–269

Original research article

Ectopic pregnancies following emergency levonorgestrel contraception

Galit Sheffer-Mimouni*, David Pauzner, Sharon Maslovitch, Joseph B. Lessing,
Ronni Gamzu
Department of Obstetrics and Gynecology, The Lis Maternity Hospital, Sackler School of Medicine, Tel-Aviv University, 6 Weizman Street,
Tel Aviv 6427, Israel

Received 18 September 2002; received in revised form 15 December 2002; accepted 15 December 2002

Abstract
There are little or no data on the risk of ectopic pregnancy following levonorgestrel treatment as an emergency contraception. We
encountered three cases of ectopic pregnancy following the use of levonorgestrel administered peri- or postovulation. Here we report these
cases and discuss the clinical and epidemiologic implications of this association. Health providers should be alert to the possibility of an
ectopic pregnancy in women who become pregnant or complain of lower abdominal pain after taking levonorgestrel. © 2003 Elsevier
Science Inc. All rights reserved.

Keywords: Emergency contraception; Extrauterine pregnancy; Levonorgestrel

1. Introduction hind-the-counter drugs [3]. They may be overused as a

Unintended pregnancy is a major public health problem
worldwide. According to recent data from the US, in 1994,
approximately 50% of 15– 44-year-old women had at least
one unplanned pregnancy at some time in their lives [1]. In
the last 3 decades, emergency contraception has been sug-
gested and advocated in developing countries as a means to
prevent such unwanted pregnancies, in order to protect
thousands of women against unsafe abortions.
In the past 4 years, contraceptive experts, sociologists
and pharmaceutical companies have campaigned to allow
for a more liberal use of emergency contraception. This
campaign was launched because of health, social and eco-
nomic motives [2]. Consequently, behind-the-counter use of
levonorgestrel (Norlevo™, Levonelle™, Postinor-2™) had
been approved initially in Norway (October 2000) and
thereafter in Sweden (November 2001) and in Israel. In
Belgium, South Africa, UK, France, New Zealand and in
California and Washington State of the US, levonorgestrel-
only emergency contraception pills (ECP) are available P-
status (available from a pharmacist). The use of these drugs
has increased dramatically both as prescription and as be-
* Corresponding author. Tel.: !011-972-3-6447030; fax: !011-972-
3-6447060.
E-mail address: smgalit@hotmail.com (G. Sheffer-Mimouni).
regular contraception method. Therefore, their side effects
or possible hazards should be addressed appropriately.
A MEDLINE search from 1982 to 2002 using the terms
“ectopic pregnancy,” “extrauterine pregnancy,” “emergency
contraception,” “progestin-only contraception,” “postcoital
contraception,” and “levonorgestrel” as well as referenced
articles, failed to reveal any reported case of ectopic preg-
nancy after usage of levonorgestrel as an emergency con-
traception. We hereby present three cases of ectopic preg-
nancy following the use of levonorgestrel (Postinor-2;
Gedeon Richter Ltd, Budapest, Hungary), that occurred in
our institution over a 20-month period, in women without
apparent risk factors for ectopic pregnancy.
2. Case presentations
2.1. Case 1
A 19-year-old, gravida 1, para 0, Caucasian Ashkenazi
Jewish female presented to our emergency room within 24 h
after unprotected intercourse. Her past obstetric history re-
vealed an induced abortion at age 17. Her last normal
menstrual period occurred 2 weeks before the unprotected
intercourse, and she had stopped using oral contraceptive
pills 2 months before. She was not using any medications at

0010-7824/03/$ – see front matter © 2003 Elsevier Science Inc. All rights reserved.
doi:10.1016/S0010-7824(02)00539-5
268 G. Sheffer-Mimouni et al. / Contraception 67 (2003) 267–269
the time of presentation. A pregnancy test was negative, and
she was given two tablets of 750 mcg levonorgestrel (Posti-
nor 2) to take at a 12-h interval. She started oral contracep-
tives immediately after vaginal bleeding, which occurred 2
weeks later, and that was interpreted by her as a period.
After using two cycles of oral contraception, she presented
at the emergency room for vaginal bleeding and abdominal
pain. Her physical examination revealed a small uterus with
left adnexal tenderness. A transvaginal ultrasound docu-
mented an empty uterine cavity, a left normal-appearing
ovary, a complex tubal mass of 2.5 cm diameter and the
presence of pelvic fluid suspected to be blood. A pregnancy
test was positive. The patient underwent laparoscopy, which
confirmed the presence of a ruptured tubal pregnancy, with
bleeding estimated to amount to 400 cc. The right adnexa
and the left ovary appeared normal. A laparoscopic left
salpingectomy was performed. Histologic examination of
the specimen confirmed the left tubal pregnancy.
2.2. Case 2
A 20-year-old, gravida 0, para 0, female presented with
mild abdominal pain to the emergency room. A pregnancy
test was positive. She had regular menstruations every 4
weeks, and her regular last menstruation period had oc-
curred 5 1/2 weeks before. She had had unprotected inter-
course exactly 2 weeks after the menstruation and received
two tablets of 750 mcg levonorgestrel (Postinor 2) at a 12-h
interval. She reported no vomiting after ingestion the med-
ication. One week later, she experienced a mild vaginal
bleeding that was interpreted by her as a period and con-
tinued 2 weeks. At that time, her physical examination
revealed a small uterus with right adnexal tenderness. A
transvaginal ultrasound documented an empty uterine cav-
ity, a left normal-appearing ovary and a round tubal mass of
1.5 cm diameter, as well as the presence of pelvic fluid
suspected to be blood.
The patient was admitted to the gynecological depart-
ment. At that time, her serum hCG was 1,400 IU/L. Twenty-
four hours later, she complained of severe abdominal pain.
She underwent laparoscopy, during which a right ruptured
tubal pregnancy was diagnosed, with the presence of a small
amount of pelvic hemorrhage. A right laparoscopic tubec-
tomy was performed.
2.3. Case 3
A 34-year-old, gravida 1, para 0, female presented with
lower abdominal pain to the emergency room. A pregnancy
test was positive. Her menstruations were regular, occurring
every 30 days. Two months earlier, she had undergone a
first-trimester termination of pregnancy by curettage. She
had had unprotected intercourse exactly 2–3 weeks after the
procedure and received two tablets of 750 mcg levonor-
gestrel (Postinor 2) at a 12-h interval. A pregnancy test at
that time was negative. She reported no vomiting after
ingesting the medication. Five weeks later she experienced
an acute lower abdominal pain with nausea. At admission,
her physical examination revealed a small uterus with right
adnexal tenderness. A transvaginal ultrasound documented
an empty uterine cavity, normal-appearing ovaries and a
round hyperechogenic mass of 1.4 cm diameter, as well as
the presence of pelvic fluid and clots suspected to be blood.
Serial CBC tests did not document any change in the he-
moglobin count. The patient was admitted to the gyneco-
logical department. At that time, her serum !hCG was 625
IU/L. During the following days, her pain regressed and
serial !hCG tests from day 2–5 of her stay revealed a very
mild elevation–plateau: 682, 889, 980, 1029. She was given
IM MTX 85 mg according to her calculated surface area.
During the following weeks, there was a regression of her
!hCG blood concentrations.
3. Discussion
There are little or no data on the risk of ectopic preg-
nancy following levonorgestrel treatment as an emergency
contraception. Previous reports have documented five cases
of ectopic gestation following the use of the Yuzpe regimen
[4 – 6]. and three cases after diethylstilbestrol or stilbestrol
use [7–9]. Nielsen et al. [4] reported one case and reviewed
the other four published cases of ectopic pregnancy follow-
ing the Yuzpe regimen. They concluded that, “in order to
prevent a delay in the diagnosis of ectopic pregnancy, pro-
viders and the package insert should advise women that
ectopic gestation can occur with emergency contraceptive
pill failure.” Yet, none of the previous reports has demon-
strated that emergency contraception (Yuzpe or levonorg-
estrel) may increase the risk of ectopic pregnancy upon
contraception failure.
The large multicenter emergency contraceptive pill
study[10] comparing the Yuzpe regimen with the levonor-
gestrel method, reported the occurrence of 42 pregnancies.
Eleven occurred in the levonorgestrel group versus 31 in the
Yuzpe group. None of these pregnancies were ectopic.
However, the number of pregnant patients in this study may
have been insufficient to display an increase of ectopic
pregnancy rate from the expected baseline rate of approxi-
mately 2% of pregnancies in the general population.
The main mechanism whereby levonorgestrel-based
emergency contraception acts is by interference with lutein-
izing hormone preovulatory surge produced through disrup-
tion of the normal development and/or the hormonal activity
of the growing follicle [11]. These events occur only when
levonorgestrel is given preovulatory.
The effects of peri- and postovulatory effects of
levonorgestrel are still a matter of debate [11]. The peri- and
postovulatory administration of levonorgestrel does not
seem to impair corpus luteum function or endometrial mor-
phology [11]. It is possible that progestin affects the tubal
function. Indeed, high levels of progesterone may cause
 G. Sheffer-Mimouni et al. / Contraception 67 (2003) 267–269
ciliary dysfunction and subsequently may be a possible
cause of ectopic pregnancy [12]. Progestin-only pills ad-
ministered continuously lower the absolute rate of ectopic
pregnancy; however, if pregnancy does occur, the chance
that it will be ectopic is threefold higher than for pregnan-
cies occurring while using no method [13]. Serum levels of
levonorgestrel following the administration of two doses of
0.75 mg are relatively high (30 – 40 nmol/L) [14] compared
to serum levels in Norplant users (3 nmol/L) [15]. In theory,
this relatively high level of levonorgestrel may adversely
affect tubal motility.
Accordingly, some authors [14] have suggested the use
of a single dose of 750 mcg as a potentially equally effective
alternative to the standard current regimen. In theory, lower
doses of levonorgestrel may lessen an adverse effect on
tubal transport.
The question of whether or not the risk of ectopic ges-
tation is increased after failure of levonorgestrel emergency
contraception cannot be answered by our observation. In
particular, we do not have precise information on how many
women took the levonorgestrel-only pill because it is an
over-the-counter drug in our country. However, the three
cases that we report here illustrate the fact that ectopic
pregnancies are possible after levonorgestrel emergency
contraception. In both of our cases, levonorgestrel was ad-
ministered in the peri- or postovulation period. Thus, we
speculate that if levonorgestrel increases the risk of ectopic
pregnancy upon failure, it is more likely to do so when it is
given in peri- or postovulation.
We commend the caution exerted by the manufacturers
of the drug, who carefully specify in the insert leaflet that
“health providers should be alert to the possibility of an
ectopic pregnancy in women who become pregnant or com-
plain of lower abdominal pain after taking Postinor-2™.” In
addition, we believe that routine reporting of such an ad-
verse event by physicians may possibly help determine
whether there is an increase risk of ectopic pregnancy fol-
lowing levonorgestrel-based emergency contraception.
269
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