Open Journal of Obstetrics and Gynecology, 2011, 1, 6-11
doi:10.4236/ojog.2011.11002 Published Online March 2011 (
Published Online March 2011 in SciRes.
Conservative treatment of unruptured ectopic pregnancy in
H. Fletcher, K. Buchanan, L. Jacob
Department of Obstetrics and Gynaecology, University of the West Indies, Mona, Kingston, Jamaica.
Received 15 February 2011; revised 18 March 2011; accepted 25 March 2011.
Medical treatment with methotrexate is now suc-
cessfully replacing conservative surgical treatment in
selected patients. We reviewed patients treated with
methotrexate, compared to salpingectomy and sal-
pingostomy between 1990 to 1995 and 2000 to 2003.
For 1990 - 1995 there were 21 conservative surgical
treatments (5.3% ectopic pregnancies). The ratio of
ectopic to normal deliveries was 1:24. Medical treat-
ment was done for 19 pregnancies (3.4% of ectopic
pregnancies) for 2000 to 2003. During the period
there was an ectopic rate of 1:16.8 births. Patients
treated medically were similar to those treated sur-
gically except that none reportedly having rebound
tenderness and only 1/18 having an ultrasound scan
showing a foetal heart and none with a gestational
sac > 4 cm. In the medically treated group the success
rate was 68% while in the surgically treated groups
success was 100%. There was no significant differ-
ence in the parameters in the conservative surgical
and medically treated groups.
Keywords: Conservative Treatment; Ectopic Pregnancy;
Methotrexate; Linear Salpingostomy
An ectopic pregnancy is the implantation of an embryo
outside of the uterine cavity [1]. In the fallopian tube it
will either be spontaneously reabsorbed, abort from the
tube, or it may grow and rupture [2]. It is this latter type
of ectopic pregnancy that is associated with maternal
morbidity and mortality [3].
The maternal mortality rate in the United States has
decreased to 3.4 per 10,000 cases of ectopic pregnancy
with improvements in diagnosis and management [3]. In
Jamaica during 3 years (1981 to 1983), ten percent of
maternal deaths were from ectopic pregnancy [4].
Ectopic pregnancy may be treated medically or surgi-
cally. In the United States the method of treatment has
changed from the primary surgical to medical treatment
which now commonly predominates [5]. In Jamaica the
primary mode of treatment still remains surgical as the
patients tend to present later when signs and symptoms
of rupture are more commonly present. At The Univer-
sity Hospital of The West Indies 96.8% and 92% of
cases of ectopic pregnancies were treated surgically in
2002 and 2003 respectively. This hospital is also well
known for an extremely high ectopic to delivery rate
first reported by Douglas in 1963 of 1 ectopic in 29
pregnancies [6]. Surgical treatment is associated with the
associated morbidity from both surgical and anaesthetic
complications [7] and often results in the loss a fallopian
tube which may have a bearing on the patient’s fertility.
Surgery may also be done conservatively with linear
salpingostomy salvaging the fallopian tube in cases
where the ectopic is unruptured and the patient is stable.
This method of treatment was more popular at UHWI in
the 1990’s before the advent of medical treatment of
similar patients.
Medical management of ectopic pregnancy is done
with the use of methotrexate. This is a folic acid antago-
nist that interferes with DNA synthesis and is effective
against trophoblastic tissue. It was first used successfully
in the treatment of ectopic pregnancy in Japan in 1982
[8]. The use of methotrexate decreases the need for sur-
gical intervention and the associated morbidity. Meth-
otrexate was also effective for ectopic pregnancies lo-
cated in the cervix, ovary or cornua where surgical in-
tervention carries significant risk [9]. However there is
the associated risk of side effects due to the medication,
the commonest of which are stomatitis and conjunctivitis
but these side effects are usually mild and self-limiting.
Thirty percent of patients who receive single dose man-
agement and 40% of those who receive multi-dose
management experience side effects [10]. Also there is
an associated failure rate 10% to 20% for the single dose
therapy and 6% to 30% for the multidose therapy and
this group of patients requires surgical intervention [1].
The success Medical management is dependent on the
H. Fletcher et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 6-11 7
adherence to strict criteria. The success rate for single
dose therapy has been reported to be 80% to 90% and
70% - 94% for multi-dose therapy [1]. To employ medi-
cal treatment the patient must be:
1) Haemodynamically stable, reliable and compliant.
2) Ultrasonography should fail to show an intrauter-
ine gestation and uterine curettage should fail to
obtain villi
3) There should be no evidence of rupture of the ec-
topic pregnancy
4) The ectopic pregnancy should measure 4cm or less
in diameter
5) βhCG titers should be 10 000 IU/L or less
6) Relative contraindications include the presence of
fetal cardiac activity on ultrasound.
The aim of this study was to look at conservative
treatment of ectopic pregnancy assessing conservative
surgery (linear salpingostomies) done 1990 - 1993 and
also assessing the use of methotrexate management of
ectopic pregnancy at this institution over the period 2000
to 2003 compared with standard surgery during the same
period. The aim was to examine factors associated with
failed versus successful treatment an also to see how
strictly the above criteria was adhered to in patient selec-
tion for medical treatment treatment. We also examined
the reproductive outcome of patients who received me-
dical versus surgical treatment for the ectopic pregnancy
and patient satisfaction of treatment.
This was a retrospective observational study in which we
compared medical therapy with methotrexate with radi-
cal surgical treatment (salpingectomy) during the period
January 2000 to December 2003. The dockets of all the
patients who presented with ectopic pregnancies from
January 2000 to December 2003 were identified from
the hospital database and we were able to find all the
patients who had medical management of the ectopic
pregnancy and these dockets were assessed for the study.
We then randomly selected 19 dockets of patients from
to use as controls using a system of random numbers
given to the dockets of all patients who had surgical
management of the ectopic pregnancy during the period
January 2000 to December 2003.
We also reviewed the operations register in Main op-
erating theatre for all cases of ectopic during the period
June 1990 to July 1993 to identify all cases of conserva-
tive surgery (linear salpingostomy) for unruptured ec-
topic. We used this era, as this was a time when this op-
eration was more popular. During this period we identi-
fied 21 patients who had this surgery but we were only
able to locate 19 dockets (90.5% case identification).
These patients were also compared to the patients with
methotrexate treatment.
In assessing reproductive outcome and patient satis-
faction post treatment all patients in the medically
treated and all patients in the surgically treated arm who
were contactable by phone were given telephone inter-
views. They were asked if they had become pregnant
since they received treatment and if that pregnancy was
a repeat ectopic, or an intrauterine pregnancy and also if
there was any history of secondary infertility after re-
ceiving treatment for their ectopic pregnancy. Also they
were asked if they were satisfied with their treatment
and outcome.
The odds ratio, P-values and confidence intervals (C.I)
were calculated for each arm of the study for the pres-
ence of abdominal pain, per vaginal bleeding, both per
vaginal bleeding and abdominal pain, nulliparity, ab-
dominal tenderness, rebound tenderness, adnexal ten-
derness, gestational age less than 7 weeks, gestational
age less than 10 weeks, the presence of shock, the pres-
ence of free fluid on ultrasound, gestational sac size
greater than 4 cm, the presence of cardiac activity on
ultrasound, patient satisfaction, need for surgery, future
pregnancy and repeat ectopic pregnancy after treatment.
Methotrexate treatment for ectopic pregnancy was done
for 19 pregnancies in total for 2000 to 2003. All 19 pa-
tients received a single dose regime. During the period
there were 563 ectopic pregnancies and 9470 births (ec-
topic rate 1:16.8). Medical treatment was therefore done
in 3.4% of ectopic pregnancies.
In all patients who were considered for methotrexate
therapy a baseline quantitative serum βhCG was done.
Thirteen of these had abdominal pain and ten had ab-
dominal tenderness but none had rebound tenderness. All
of these patients had ultrasonography or diagnostic
laparoscopy or a combination of both procedures prior
medical therapy. Seventeen of these patients had ultra-
sonography, 5 had diagnostic laparoscopy and ultra-
sonography and one had diagnostic laparoscopy only.
Seventeen patients had ultrasonography to rule out the
presence of an intrauterine pregnancy. Of the 17 patients
who had ultrasonography 12 had the gestational sac size
commented on and all sac sizes that were less than 4cm.
Those with failed therapy were more likely to have a sac
size of > 3.5 cm (3/4 or 75% cases with 2 no size re-
corded). While of those with successful treatment only
2/8 or 25% had a sac size > 3.5 cm. One patient had the
presence of cardiac activity noted on ultrasound and she
had failed medical treatment. The one patient who did
not have ultrasonography, had her ectopic diagnosed at
laparoscopy and the size was noted to be less than 4 cm.
Of the five patients who had diagnostic laparoscopy none
opyright © 2011 SciRes. OJOG
H. Fletcher et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 6-11
had evidence of rupture of the ectopic gestation prior to
commencing methotrexate.
Seventeen patients had at least one other quantitative
serum βhCG done after the baseline βhCG was done, the
eighteenth patient had only a baseline βhCG done but
subsequently absconded from the ward. Six of the eight-
een patients did not have follow up of the βhCG as they
had surgery due to failed medical management. Of the
others only one patient had her βhCG followed up until
it was undetectable as outlined by the protocol. The
pre-treatment range of βhCG for the medically treated
group was 130 to 31 860 mIU/ml. Five of 19 patients
and 10 of 19 patients in the medically treated group had
βhCG greater than 5000 mIU/ml and 3000 mIU/ml on
day 1 respectively. Of the six patients who had failed
therapy four (66.7%) had βhCG > 5000 mIU/ml. While
of the 13 who had successful medical therapy only 4
(30.7%) had had βhCG > 5000 mIU/ml. However the
patient with the highest level βhCG (31 860) and longest
gestational age 9 weeks had successful multiple dose
The duration of hospital stay commencing on the day
that the Methotrexate therapy was started varied from 2
to 11 days. All patients had baseline complete blood
counts done prior to Methotrexate therapy. Fourteen of
the 18 patients had renal and liver function tests done
and these were normal prior to starting Methotrexate.
One patient had renal blood test done but no liver func-
tion test prior to commencing treatment (these results
were normal) and 3 patients had no renal or liver func-
tion test done prior to the onset of Methotrexate treat-
ment. Only 2 patients had a repeat of the renal and liver
function tests having received the treatment and this was
done appropriately on day 7 of Methotrexate treatment
and these results were normal.
The dose of the methotrexate given could be verified
as accurate in 10 of the eighteen patients as their weight
and height were documented in their notes and hence the
body surface area could be calculated. Three patients had
only their weight documented and 5 patients had only
their height documented. Of the ten patients who had
their weight and height documented, 7 received an ac-
curate Methotrexate dose, two received a dose that was
higher than the correct recommended dose based on their
body surface area (BSA) and one had a dose that was too
low based on their BSA i.e. 50 mg instead of 80 mg,
however the medical treatment was still successful. Two
patients received doses that were higher than that based
on their BSA 100 mg as against 71.5 mg for one patient
(however that patient’s medical treatment was not suc-
cessful and hence she needed surgery) and 100 mg as
against 75 mg for the other patient (this patients medical
therapy which was successful).
Five patients (26%) had to have surgery (salpingec-
tomy) because of failed treatment. Four patients, because
of a rising βhCG for persistent ectopic on ultrasonogra-
phy and one patient who went into shock after failed
medical treatment.
Sixteen of the eighteen controls had salpingectomy at
laparotomy. One patient had salpingostomy at laparo-
tomy and one patient had laparoscopic salpingostomy.
The median age of patients treated medically was 28
(range 21 - 36). The median age of patients treated sur-
gically was 31 (range 22 - 42 years).
The overall success rate for methotrexate treated ec-
topic pregnancies was 68%. The success rate for the sur-
gically treated (salpingectomy) controls was 100%.
The presence of adnexal tenderness and rebound ten-
derness were more common in the salpingectomy group.
However there was no statistical significance difference
noted between each group for abdominal pain, vaginal
bleeding, nulliparity, abdominal tenderness, shock, ges-
tational age below 7 weeks or above 10 weeks, ultra-
sound presence of cardiac activity, free fluid or gesta-
tional sac size more than 4 cm. There was also no statis-
tical significance noted between the two groups in terms
of patient satisfaction, future pregnancy and future ec-
topic pregnancy (Table 1).
In the patients who had conservative surgery (salpin-
gostomy) the clinical presentation findings were similar
to those who had methotrexate treatment (Table 2).
There were 9571 deliveries and 390 ectopic pregnancies
during the era with 21 (5.4%) conservative surgical
treatment. The ratio of ectopic to normal deliveries was
1:24. The age range in this group was 20 - 38 median
value of 28 years old. A past history of ectopic was pre-
sent in 5/19 patients and all had had a previous salpingec-
Fourteen patients had a positive pregnancy test how-
ever no quantitative βhCG was offered during that pe-
riod. Three patients had a culdo-centesis positive for non
clotting blood. In fourteen cases an ultrasound scan was
done showing and adnexal mass (size not recorded) and
an empty uterus in 13 cases suggestive of ectopic preg-
nancy. Laparoscopy was done in six cases and in all
cases the unruptured ectopic pregnancy was seen.
At surgery all patients had an unruptured ectopic preg-
nancy and linear salpingostomy was performed in all.
Vasopressin was used for haemostasis in 7/19 cases and
diathermy was used in 6/19. The incision was closed in
10/19 patients and was left open in 9/19. None of these
patients had a failed procedure with repeat operation.
Hospital stay ranged from 3 - 5 days with a median of 4
days. A summary of the comparison with the medically
treated patients revealed no significant differences (Ta-
le 2). b
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H. Fletcher et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 6-11
Copyright © 2011 SciRes.
Table 1. A comparison of the clinical and laboratory findings in patients receiving medical (Methotrexate) vs surgical (salpingectomy)
management of ectopic pregnancy.
Variable Medical Surgical Odd ratios (CI) P-values
Nulliparous 12/19 (63.1%) 5/18 (27.8%) 4.45 (1.11 - 17.899) 0.067
Abd pain 13/19 (68.4%) 17/1 (94.4%) 0.127 (0.014 - 1.193) 0.11
Bleeding 17/19 (89.4%) 13/18 (72.2%) 3.269 (0.545 - 19.61) 0.358
Abd pain bleeding 13/19 (68.4%) 13/18 (72.2%) 0.833 (0.203 - 3.427) 0.915
Abdominal tenderness 10/19 (52.6%) 15/18 (83.3%) 0.22 (0.05 - 1.02) 0.1
Rebound tenderness 0/10 (0%) 11/18 (61.1%) 0.017 (0.001 - 0.321) 0.0001
Adnexal tenderness 8/19 (42.1%) 16/18 (88.9%) 0.1 (0.018 - 0.52) 0.013
Free peritoneal fluid 6/12 (50%) 10/14 (71.4%) 0.4 (0.08 - 2.02) 0.474
Shock 1/19 (5.2%) 5/18 (27.8%) 0.063 (0.003 - 1.24) 0.065
Gest sac size > 4cm 2/12 (16.7%) 4/12 (33.3%) 0.25 (0.034 - 1.863) 0.365
Cardiac activity 1/9 (11.1%) 4/8 (50%) 0.125 (0.01 - 1.521) 0.221
Surgery 5/19 (26.3%) 18/18 (100%) 0.01 (0.0010 - 0.201) 0.0001
Gest age < 7 weeks 5/17 (29.4%) 4/17 (23.5%) 1.34 (0.293 - 6.261) 1.0
Gest age > 10 weeks 3/17 (17.6%) 0/17 (0%) 8.448 (0.403 - 177.3) 0.289
Repeat pregnancy 2/7 (28.5%) 2/4 (50%) 0.4 (0.031 - 5.151) 0.953
Repeat ectopic pregnancy 0/7 (0%) 1/4 (25%) 0.156 (0.005 - 4.866) 0.715
Satisfaction 4/7 (57.1%) 4/4 (100%) 0.143 (0.006 - 3.64) 0.506
Table 2. A comparison of the clinical and laboratory findings in patients receiving conservative medical (Methotrexate) vs conserva-
tive surgical (salpingostomy) management of ectopic pregnancy.
Variable Medical Surgical Odd ratios (CI) P-values
Nulliparous 12/19 (63.1%) 11/19 (58.0%) 1.25 (0.339 - 4.6) 1.0
Abd pain 13/19 (68.4%) 15/19 (79%) 0.58 (0.133 - 2.5) 0.713
Bleeding 17/19 (89.4%) 15/19 (79%) 2.27 (0.36 - 14.2) 0.656
Abd pain bleeding 13/19 (68.4%) 9/19 (47.4%) 2.41 (0.64 - 9.03) 0.324
Abdominal tenderness 10/19 (52.6%) 13/16 (68.4%) 0.256 (0.06 - 1.2) 0.156
Rebound tenderness 0/10 (0%) 0/19 (0%)
Adnexal tenderness 8/19 (42.1%) 2/7 (28%) 1.82 (0.28 - 11.9) 0.861
Free peritoneal fluid 6/12 (50%) 2/3 (66.6%) 0.5 (0.035 - 7.10) 0.897
Shock 1/19 (5.2%) 0/19 (0%) 3.2 (0.12 - 82.6) 1.0
Gest sac size > 4cm 2/12 (16.7%) Not available
Cardiac activity 1/9 (11.1%) Not available
Surgery 5/19 (26.3%) 19/19 (100%) 0.36 (0.11 - 1.19) 0.155
Gest age < 7 weeks 5/17 (29.4%) 6/19 (31.6%) 0.909 (0.22 - 3.7) 0.825
Gest age > 10 weeks 3/17 (17.6%) 2/19 (10.5%) 1.82 (0.27 - 12.5) 0.893
Repeat pregnancy 2/7 (28.5%) 4/5 (80%) 0.1 (0.006 - 1.54) 0.242
Repeat ectopic pregnancy 0/7 (0%) 0/5
Satisfaction 4/7 (57.1%) Not available
H. Fletcher et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 6-11
The rate of ectopic pregnancies at the University of the
West Indies Hospital, in this study is very high at 1:17 to
1:24 deliveries even higher than that reported in 1963 [6].
It is believed that this high rate is due to the fact that the
hospital is a referral teaching hospital, with a low deliv-
ery rate for its size. The findings of this study revealed a
lower success rate for single dose therapy than reported
in the literature. The success rate for single dose meth-
otrexate was 68% as against 80% - 90% as quoted by
Thoen et al [11]. The higher failure rate seen for medi-
cally managed patient in this study may have been that
the criteria for medical management were not strictly
adhered to as 13 of 19 patients and 10 of 19 patients
medically treated had abdominal pain and abdominal
tenderness (respectively) which may have been inherent
signs of rupture. In one series the presence of the symp-
tom of abdominal pain in the absence of abdominal ten-
derness resulted in a treatment failure 56% of the times
as compared to 17% of the times when there was no ab-
dominal pain or tenderness and the presence of vaginal
bleeding was associated with a treatment failure 53% of
the times compared with 16% when vaginal bleeding
was present [12]. However Dilbaz et al [13] did not find
that the presence of clinical signs and symptoms on ad-
mission predicted treatment failure.
Stika et al [14] found day 1 βhCG levels > 5000
mIU/ml had a greater probability of requiring either sur-
gical intervention or multidose methotrexate. Dilbaz et
al [13] also found that a βhCG level above 3000mIU/ml
was predictive of treatment failure. It is essential to fol-
low up the βhCG levels until it is undetectable however
only in one case in this series was the βhCG followed up
until it was undetectable. Lui et al [3] found that the
initial βhCG level and the trend of the serial βhCG re-
sults were the most important factors that predicted the
success of medical management. The risk of tubal rup-
ture is 10% when the serum βhCG is less than 1000
mIU/ml and rupture has been known to occur when the
serum βhCG is less than 100 MIU/ml in isthmic preg-
Cardiac activity has been associated with an increased
risk of single dose methotrexate management failure [15]
and the one patient medically treated who had presence
of cardiac activity had failed management requiring sur-
The presence of free fluid is not a contraindication for
medical therapy with methotrexate [3]. The finding of
free fluid on ultrasound is not an uncommon finding as
trans-vaginal sonography can detect as little as 50 ml of
free fluid. The presence of free fluid is not diagnostic of
a leaking ectopic pregnancy but should heighten the
physician’s awareness of the possibility of a leaking ec-
topic pregnancy when the clinical context and other ul-
trasound findings are taken into consideration [16].
The presence of a gestational sac size greater than 5
cm is associated with an increased risk of treatment fail-
ure. Thoen et al found that a gestational sac size of more
than 3.5 cm was associated with treatment failure [11].
Three of 13 patients had a gestational sac size of greater
than 3.5 cm on ultrasound or laparoscopy but no patient
had a sac size greater than 4 cm.
The presence of rebound tenderness is a sign of irrita-
tion of the peritoneal lining, in the case of a patient pre-
senting with an ectopic pregnancy this is usually due to
blood from the site of rupture of the ectopic pregnancy
irritating the peritoneal lining [17]. Patients who were
treated with salpingectomy were more likely to have
adnexal tenderness and this was statistically significant
(p value < 0.013).
The future pregnancy rate was 50% for salpingectomy
and 28.5% for methotrexate treated ectopic pregnancy in
our study. Bouyer et al [17] found the intrauterine preg-
nancy rates to be lower for salpingectomy treatment and
higher for medical treatment. He also found the intrau-
terine pregnancy rates to be lower for conservative sur-
gical treatment than for medical treatment and higher for
conservative surgical than radical surgical treatment [18].
The findings in our study may be out of keeping with
others because of poor follow-up of all the patients.
The rate of repeat ectopic pregnancy was 0% in the
medically treated group and 25% in the salpingectomy
treated group. Bouyer et al [17] found that the rate of
recurrent ectopic was not different based on the treat-
ment but found that other factors including presence of
tubular disease affected reproductive outcome and the
risk of ectopic pregnancy [18].
In this study only 14 of the 18 patients had both base-
line renal and liver function tests done. Serious and po-
tentially fatal side effects can occur in the presence of
liver or renal failure with methotrexate.
This study was limited by the presence of a small
sample size and this may have limited the number of
results that were significant. Another limiting factor was
that this was a retrospective study and hence is more
prone to error as against a prospective study due to con-
founding factors and bias. There was difficulty and in
many cases it was not possible to contact many patients.
This small study however confirms that medical ther-
apy is a viable option in carefully selected patients
however we still have to overcome challenges of fol-
low-up of treatment in our setting.
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