Conservative treatment of unruptured Ectopic pregnancy in Jamaica

doi:10.4236/ojog.2011.11002

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Open Journal of Obstetrics and Gynecology, 2011, 1, 6-11

doi:10.4236/ojog.2011.11002 Published Online March 2011 (http://www.SciRP.org/journal/ojog/

OJOG

Published Online March 2011 in SciRes. http://www.scirp.org/journal/OJOG

Conservative treatment of unruptured ectopic pregnancy in

Jamaica

H. Fletcher, K. Buchanan, L. Jacob

Department of Obstetrics and Gynaecology, University of the West Indies, Mona, Kingston, Jamaica.

Email: [email protected]

Received 15 February 2011; revised 18 March 2011; accepted 25 March 2011.

ABSTRACT

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

1. INTRODUCTION

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.

2. PATIENTS AND METHODS

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.

3. RESULTS

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

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

treatment.

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-

tomy.

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

H. Fletcher et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 6-11

OJOG

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

4. DISCUSSION

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-

nancies.

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-

gery.

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.

REFERENCES

[1] Centers for Disease Control and Prevention (1995) Ec-

H. Fletcher et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 6-11 11

topic pregnancy - United States 1990-1992. Morbidity

and Mortality Weekly Report, 44, 46-48.

[2] Kamwendo, F., Forslin, L., Bodin, L. and Danielsson, D.

(2000) Epidemilogy of ectopic pregnancy during a 28

year period and the role of pelvic inflammatory disease.

Sex Tr ansmitted Infect, 76, 28-32.

doi:10.1136/sti.76.1.28

[3] Lui, A., D’Ottavio, G., Rustico, M.A., Conoscenti, G.,

Fischer Tamaro, F., Meir, Y.J., Maieron, A. and Mand-

ruzzato, G.P. (1997) Conservative management of ectopic

pregnancy. Minerva Ginecologica, 49, 67-72.

[4] Walker, G.J.A., Ashley, D.E.C., McCaw, A. and Bernard,

G.W. (1986) Maternal mortality in Jamaica. Lancet,

486-488. doi:10.1016/S0140-6736(86)92939-9

[5] Yao, M. and Tulandi, T. (1997) Current status of surgical

and non-surgical management of ectopic pregnancy. Fer-

tility and Sterility, 67, 421-433.

doi:10.1016/S0015-0282(97)80064-7

[6] Douglas, C.P. (1963) Tubal ectopic pregnancy. British

Medical Journal, 2, 838. doi:10.1136/bmj.2.5361.838

[7] Landström, G., Thorburn, J. and Bryman, I. (1998) Treat-

ment, failures and complications of ectopic pregnancy:

Changes over a 20 year period. Human Reproduction, 13,

203-207.

[8] Tanaka, T., Hayashi, H., Kutsuzawa, T. and Ichinoe, K.

(1982) Treatment of interstitial ectopic pregnancy with

methotrexate: Report of a successful case. Fertility and

Sterility, 37, 851-852.

[9] Yankowitz, J., Leake, J., Huggins, G., Gazaway, P. and

Gates, E. (1990) Cervical ectopic pregnancy: A review of

the literature and report of a case treated by single dose

methotrexate therapy. Obstetrical & Gynecological Sur-

vey, 45, 405-414.

doi:10.1097/00006254-199007000-00001

[10] Barnhart, K., Gosman, M., Ashby, R. and Sammel, M.

(2003) The medical management of ectopic pregnancy: A

meta-analysis comparing “single-dose” and “multi-dose”

regimens. Obstetrics & Gynecology, 101, 778-784.

doi:10.1016/S0029-7844(02)03158-7

[11] Thoen, L. and Crenin, M.D. (1997) Medical treatment of

ectopic pregnancy with methotrexate. Fertility and Ste-

rility, 68, 727-730. doi:10.1016/S0015-0282(97)00284-7

[12] Tawfig, A., Agameya, A.F. and Claman, P. (2000) Pre-

dictors of treatment failure for ectopic pregnancy treated

with single dose methotrexate. Fertility and Sterility, 74,

877-880. doi:10.1016/S0015-0282(00)01547-8

[13] Dilbaz, S., Caliskan, E., Dilbaz, B., Degirmenci, O. and

Haberal, A. (2006) Predictors of methotrexate treatment

failure in ectopic pregnancy. Journal of Reproductive

Medicine, 51, 87-93.

[14] Stika, C.S., Anderson, L. and Frederiksen, M.C. (1996)

Single dose methotrexate for the treatment of ectopic

pregnancy. North Western Memorial Hospital 3 year ex-

perience. American Journal of Obstetrics & Gynec- ol-

ogy, 174, 1840-1846.

doi:10.1016/S0002-9378(96)70219-3

[15] Erdem, A., Arslam, H., Biberoglu, K. and Gursoy, R.

(2004) Single dose methotrexate for the treatment of un-

ruptured ectopic pregnancy. Archives of Gynecology &

Obstetrics, 270, 201-204.

doi:10.1007/s00404-003-0543-4

[16] Condous, G., Okaro, E., Khalid, A., Lu, C. and Van Huf-

fel, S. (2005) The accuracy of transvaginal ultraso-

nography for the diagnosis of ectopic pregnancy prior to

surgery, Human Reproduction, 20, 1404-1409.

doi:10.1093/humrep/deh770

[17] Bouyer, J., Job-Spira, N., Pouly, J.L., Coste, J., Germaine,

E. and Fernandez, H. (2000) Fertility following radical,

conservative-surgical or medical treatment for tubal preg-

nancy: A population based study. British Journal of Ob-

stetrics & Gynecolog, 107, 714-721.

[18] Kelly, H. and Harvey, D. (2006) A cautionary tale: A fatal

outcome of methotrexate therapy given for management

of ectopic pregnancy. Obstetrics & Gynecology, 107,

439-441. doi:10.1097/01.AOG.0000172374.72125.3e