30/8/2019 Ectopic pregnancy: Choosing a treatment - UpToDate

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Ectopic pregnancy: Choosing a treatment

Author: Togas Tulandi, MD, MHCM
Section Editor: Courtney A Schreiber, MD, MPH
Deputy Editor: Kristen Eckler, MD, FACOG

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jul 2019. | This topic last updated: Jun 13, 2019.

INTRODUCTION

An ectopic pregnancy is a pregnancy outside of the uterine cavity. The majority of ectopic
pregnancies occur in the fallopian tube (96 percent) [1], but other possible sites include cervical,
interstitial (also referred to as cornual, a pregnancy located in the proximal segment of the
fallopian tube that is embedded within the muscular wall of the uterus), hysterotomy scar (eg, in
patient with a previous cesarean delivery), intramural, ovarian, or abdominal. In addition, in rare
cases, a multiple gestation may be heterotopic (include both a uterine and extrauterine
pregnancy).

Ectopic pregnancy is a potentially life-threatening condition. While surgical approaches are the
gold-standard treatment, advances in early diagnosis in the 1980s facilitated the introduction of
medical therapy with methotrexate [2]. With the routine use of early ultrasound, diagnosis of
ectopic pregnancy can be established early and medical treatment can be administered in many
cases. The overall success rate of medical treatment in properly selected women is nearly 90
percent [3-5]. In select cases of early ectopic pregnancy or pregnancy of unknown location,
expectant management is an option.

Guidance regarding how to choose a treatment for ectopic pregnancy will be reviewed here.
Related topics regarding ectopic pregnancy are discussed in detail separately, including:

● Epidemiology, risk factors, and pathology (see "Ectopic pregnancy: Epidemiology, risk factors,
and anatomic sites")

● Clinical manifestations and diagnosis (see "Ectopic pregnancy: Clinical manifestations and
diagnosis")

● Methotrexate therapy (see "Ectopic pregnancy: Methotrexate therapy")

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● Surgical management (see "Ectopic pregnancy: Surgical treatment")

● Expectant management (see "Ectopic pregnancy: Expectant management")

● Diagnosis and management of uncommon sites of ectopic pregnancy (see "Abdominal

pregnancy, cesarean scar pregnancy, and heterotopic pregnancy")

OVERVIEW

The three approaches to the management of ectopic pregnancy are surgery (salpingostomy or
salpingectomy), methotrexate (MTX) treatment, or expectant management (algorithm 1).

Approximately one-third of women with ectopic pregnancies are candidates for MTX treatment [6].
The remaining two-thirds of women will require surgery (eg, due to suspicion of a ruptured tube,
large ectopic pregnancy, inability to comply with the follow-up for MTX therapy) and some patients
may prefer surgical treatment. A limited proportion of patients are eligible for expectant
management. However, with early diagnosis, most patients with ectopic pregnancy may be treated
medically with MTX.

MEDICAL VERSUS SURGICAL TREATMENT

For appropriately selected patients, methotrexate (MTX) therapy is a noninvasive option that has
comparable efficacy, safety, and fertility outcomes with surgery.

The advantages of surgical treatment are less time for resolution of the ectopic pregnancy and
avoidance of the need for prolonged monitoring. Surgery is required when emergency treatment is
indicated or MTX therapy is contraindicated or unlikely to be successful.

For women with tubal pregnancy who are candidates for MTX therapy, we suggest MTX rather
than surgical treatment (algorithm 1). Surgery is required for women who need emergency
surgical treatment (hemodynamically unstable, suspected tubal rupture). Women may reasonably
choose surgery if they need a concurrent surgical procedure or if they value a treatment that is of
shorter duration and involves less follow-up and are willing to take the risks and recovery time
associated with surgery.

There are two choices of surgical approach for tubal pregnancy. Salpingectomy (removal of the
fallopian tube) and salpingostomy (incising the tube to remove the tubal gestation but leaving the
remainder of the tube intact). There is a small risk of retained trophoblastic tissue and an
increased risk of recurrent ectopic pregnancy with salpingostomy, but both procedures appear to
result in similar subsequent fertility. Traditionally, salpingectomy has been the standard procedure,
but salpingostomy is preferred because it is a conservative surgical option. (See "Ectopic
pregnancy: Surgical treatment", section on 'Salpingostomy versus salpingectomy'.)
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Surgical indications — Surgical indications include:

● Emergency surgery is required:

• Hemodynamically unstable

• Signs of symptoms of impending or ongoing rupture of ectopic mass (eg, pelvic or

abdominal pain or evidence of intraperitoneal bleeding suggestive of rupture)

● Indications for a concurrent surgical procedure, which may include:

• Desire for sterilization

• Planned in vitro fertilization (IVF) for future pregnancy with known hydrosalpinx (removal
of hydrosalpinges increase the likelihood of successful IVF) (see "Reproductive surgery
for female infertility", section on 'Salpingectomy before in vitro fertilization')

Alternatively, the ectopic pregnancy may be treated with MTX and surgery for concurrent
conditions may be performed electively at a later date

● Heterotopic pregnancy with coexisting viable intrauterine pregnancy (see "Abdominal

pregnancy, cesarean scar pregnancy, and heterotopic pregnancy", section on 'Heterotopic
pregnancy')

● Contraindications to MTX therapy (see 'Contraindications' below)

● Failed MTX therapy

In hemodynamically stable women, surgical intervention should be performed only if a

transvaginal ultrasound examination clearly shows a tubal ectopic pregnancy or an adnexal mass
suggestive of ectopic pregnancy. If no mass is visualized sonographically, there is a high likelihood
that a tubal pregnancy will not be visualized or palpated at surgery, thus resulting in an
unnecessary surgery.

Surgical contraindications are reviewed in detail separately. (See "Ectopic pregnancy: Surgical
treatment", section on 'Contraindications'.)

Methotrexate therapy — MTX may be a single-dose or multiple-dose protocol. In most cases, it

is given as a single-dose protocol. (See "Ectopic pregnancy: Methotrexate therapy", section on
'Efficacy of single versus multi-dose therapy'.)

Selection criteria — The optimal candidates for a single-dose MTX treatment of ectopic
pregnancy are women with the following characteristics:

● Hemodynamically stable.

● No contraindications to MTX therapy. (See 'Contraindications' below.)

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● Serum beta-human chorionic gonadotropin (hCG) concentration ≤5000 milli-international

units/mL.

● No fetal cardiac activity detected on transvaginal ultrasound (TVUS). Ectopic mass size less
than 3 to 4 cm is also commonly used as a patient selection criterion; however, this has not
been confirmed as a predictor of successful treatment. (See 'Factors that impact efficacy'
below.)

● Willing and able to comply with post-treatment follow-up and with access to emergency
medical services within a reasonable time frame in case of a ruptured fallopian tube.

Factors that impact efficacy

● High hCG concentration – A high serum hCG concentration is the most important factor
associated with MTX treatment failure (table 1). Women with a high baseline hCG
concentration (>5000 milli-international units/mL) are more likely to require multiple courses of
MTX therapy or experience treatment failure [7,8].

A systematic review of observational studies included 503 women and the outcome of single-
dose MTX therapy was stratified according to initial hCG concentration [7]. There was a
statistically significant increase in failure rates in patients with initial hCG levels of >5000 milli-
international units/mL compared with those who had initial levels of less than 5000 milli-
international units/mL (odds ratio [OR] 5.5, 95% CI 3.0-9.8). The failure rate for women who
had an initial concentration between 5000 and 9999 milli-international units/mL was higher
than for those who had initial levels between 2000 and 4999 milli-international units/mL (OR
3.8, 95% CI 1.2-12.3). Multiple-dose regimens were not evaluated. The authors calculated
that for every 10 treatments, there would be one more failure if the hCG level is 5000 to 9999
milli-international units/mL than there would be if it is 2000 to 4999 milli-international units/mL.

● Fetal cardiac activity – The presence of fetal cardiac activity on TVUS is another relative
contraindication to medical treatment [3,8]. In a meta-analysis, sonographic evidence of
cardiac activity was significantly associated with treatment failure (OR 9.1, 95% CI 3.8-22.0)
[3].

● Large ectopic size – Although large size of the ectopic pregnancy (≥3.5 cm) is often used as
a criterion for exclusion in medical treatment regimens, this restriction is based on small
studies with inconsistent protocols and results [8-10]. Studies have generally restricted the
use of MTX to women with an ectopic mass less than 3 to 4 cm [8,9]; thus, there are few
studies of larger masses [11]. As an example, one observational study found that the success
rate for systematic MTX treatment was slightly higher for women with ectopic masses smaller
than 3.5 cm compared with masses between 3.5 and 4 cm (93 versus 90 percent) [9].

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In addition, there are variations within and among studies regarding whether the size used is
the actual gestational mass or the mass and surrounding hematoma [8,9]. Further, ectopic
mass size does not appear to correlate with hCG level [12].

● Peritoneal fluid – The sonographic finding of free peritoneal fluid is another commonly used
exclusion criterion for MTX treatment of ectopic pregnancy. Peritoneal fluid may be blood;
however, this is not diagnostic of tubal rupture: peritoneal blood may also be the result of
tubal abortion. Historically, culdocentesis detected blood in the peritoneal cavity of 70 to 83
percent of women with ectopic pregnancies, but only 50 to 62 percent of them had a ruptured
fallopian tube [13].

In a large case series, free fluid confined to the pelvic cavity was not associated with medical
treatment failure [8]. While surgical treatment of patients with free fluid in the paracolic gutters
or upper abdomen may be prudent, the amount of allowable free fluid confined to the
posterior cul-de-sac (pouch of Douglas) is controversial [14,15].

● Other – Preliminary reports have cited a variety of other factors which may be associated with
treatment failure. These include sonographic evidence of a yolk sac [8,16,17], isthmic location
of ectopic mass (rather than ampullary) [8,18], high pretreatment folic acid level [19], and rate
of hCG rise or fall prior to and within several days following treatment [18,20]. These are
minor factors that require further study.

Contraindications — Some women are not appropriate candidates for MTX therapy and
should be managed surgically, including women with the following characteristics [15,21]:

● Intrauterine pregnancy.

● Ruptured ectopic pregnancy.

● Clinically important abnormalities in baseline hematologic, renal, or hepatic laboratory values

– MTX is renally cleared, and in women with renal insufficiency, a single dose of MTX can
lead to death or severe complications, including bone marrow suppression, acute respiratory
distress syndrome, and bowel ischemia. Dialysis does not provide normal renal clearance
[22,23]. Renal and liver disease may slow metabolism of MTX and result in pancytopenia and
skin and mucosal disorders [24]. MTX, especially with chronic administration such as for
those with psoriasis or rheumatoid arthritis, can be hepatotoxic. Similarly, it can cause
suppression of the bone marrow.

● Immunodeficiency, active pulmonary disease such as tuberculosis, peptic ulcer disease –

MTX could be associated with pulmonary toxicity, and the toxicities of MTX are enhanced in
women with immune impairment. Similarly, in those with peptic ulcers, MTX may worsen the
condition.

● Hypersensitivity to MTX.
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● Breastfeeding.

Outcome — MTX treatment for ectopic pregnancy has comparable efficacy to laparoscopic
salpingostomy, avoids surgical complications, and results in similar fertility outcomes [25,26].
Studies have reported conflicting results regarding whether surgery or medical treatment is more
cost-effective [5,26].

MTX treatment of tubal ectopic pregnancy appears to be as effective as laparoscopic

salpingostomy, if the patient receives multiple MTX doses if necessary. A systematic review of
randomized trials found that a single dose of systemic MTX (50 mg/m2 or 1 mg/kg) was
significantly less successful than laparoscopic salpingostomy (four trials; 71 versus 88 percent;
relative risk [RR] 0.82, 95% CI 0.72-0.94). However, when additional doses were given if a single
dose was unsuccessful, there was comparable efficacy to salpingostomy (RR 1.01, 95% CI 0.92-
1.12) [26]. There was no significant difference between systemic MTX in a fixed multiple-dose
regimen and surgery (one trial; 82 versus 71 percent; RR 1.15, 95% CI 0.93-1.43). In one trial,
health-related quality of life was significantly more severely impaired after MTX than
salpingostomy (eg, more pain, less energy) [27]. The systematic review did not address
complication rates, but the trials were likely underpowered to detect rare surgical complications.

The rate of tubal rupture without treatment is high. This was illustrated in a population-based study
in France that reported an 18 percent rate of tubal rupture among 843 women with ectopic
pregnancy; women treated with MTX were excluded [28]. Reported rates of rupture after MTX
treatment are 7 to 14 percent [29]. The rate of rupture of ectopic pregnancy certainly depends on
the population studied (rural versus urban, availability of early access to the medical facility, the
readily available transvaginal ultrasound and serum hCG measurement and surveillance). With
early detection and close surveillance, the rate of tubal rupture is very low. The estimated death
related to ectopic pregnancy is 31.9 per 100,000 pregnancies [30]. Since most of mortalities is due
to intraperitoneal bleeding of ruptured ectopic pregnancy, one can assume that the rate tubal
rupture is very low. Further, intra-abdominal bleeding could also be due to tubal abortion.

Treatment with MTX does not appear to compromise ovarian reserve [31]. In a study of women
treated with in vitro fertilization, ovarian responses among women with a history of ectopic
pregnancy treated with MTX or salpingectomy were comparable [32,33].

It appears that the fertility rates after treatment of ectopic pregnancy with salpingostomy,
salpingectomy, or MTX are similar. In the systematic review of randomized trials, subsequent
fertility outcomes were reported in 98 women [26]. No significant differences were found between
single-dose MTX and salpingostomy in the number of intrauterine pregnancies (RR 1.01, 95% CI
0.66-1.54) or in recurrent ectopic pregnancy (RR 0.63, 95% CI 0.14-2.77). Ectopic pregnancy is
likely associated with subfertility since extrauterine pregnancy is usually due to altered tubal
function secondary to clinical or subclinical salpingitis. In a subsequent randomized trial of 446
women assigned to salpingotomy or salpingectomy, the cumulative ongoing pregnancy rates after

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36 months were comparable [34]. A study suggested that women with ectopic first pregnancies
had an increased risk of preterm birth (95% CI 1.18-1.37), low birth weight (95% CI 1.10-1.31),
placental abruption (95% CI 1.04-1.41), and placenta previa (95% CI 1.10-1.91) [35]. The risk of
placental abruption was particularly higher in older women with a prior ectopic pregnancy (RR
1.42, 95% CI 1.16-1.69).

The risk of another ectopic pregnancy appears to be the same for both medical and surgical
therapies [36]. (See 'Medical versus surgical treatment' above.)

MEDICAL VERSUS EXPECTANT MANAGEMENT

Expectant management is an option only for a small proportion of patients with ectopic pregnancy
or pregnancy of unknown location and a very low risk of tubal rupture. This includes women with
the following (algorithm 1) (see "Ectopic pregnancy: Expectant management", section on
'Selection criteria'):

● Transvaginal ultrasound (TVUS) does not show an extrauterine gestational sac or

demonstrate an extrauterine mass suspicious for an ectopic pregnancy.

● Serum beta-human chorionic gonadotropin (hCG) concentration is low (≤200 milli-

international units/mL) and declining.

● Willing and able to comply with post-treatment follow-up and with access to emergency
medical services within a reasonable timeframe in case of a ruptured fallopian tube.

Expectant management remains an option only for a small proportion of women. In women with a
strong suspicion of ectopic pregnancy and no possibility of an intrauterine pregnancy, a single
dose of methotrexate has minimal side effects.

NONTUBAL ECTOPIC PREGNANCY

Medical and surgical management of heterotopic, cervical, cesarean scar, or abdominal

pregnancy are discussed separately. (See "Cervical pregnancy" and "Abdominal pregnancy,
cesarean scar pregnancy, and heterotopic pregnancy".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Ectopic pregnancy".)

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INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topics (see "Patient education: Ectopic pregnancy (The Basics)")

● Beyond the Basics topics (see "Patient education: Ectopic (tubal) pregnancy (Beyond the
Basics)")

SUMMARY AND RECOMMENDATIONS

● An ectopic pregnancy is an extrauterine pregnancy. Almost all ectopic pregnancies occur in

the fallopian tube (96 percent). Tubal ectopic pregnancy may be treated with medically
(methotrexate [MTX]), surgically, or with expectant management (algorithm 1). (See
'Introduction' above.)

● For women with tubal pregnancy who are candidates for MTX therapy, we suggest MTX
rather than surgical treatment (Grade 2B). (See 'Medical versus surgical treatment' above.)

● Candidates for MTX treatment are women with ectopic pregnancy who meet the following
criteria (see 'Selection criteria' above):

• Hemodynamically stable

• Have no renal, hepatic, or hematologic disorders

• Able and willing to comply with post-treatment monitoring and have access to medical
care in case of a ruptured fallopian tube

• Pretreatment serum hCG concentration ≤5000 milli-international units/mL

• No fetal cardiac activity on transvaginal ultrasound

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● Other factors that may impact the efficacy of MTX treatment of ectopic pregnancy include
human chorionic gonadotropin (hCG) >5000 milli-international units/mL, large ectopic size
(eg, ≥3.5 cm), and sonographic finding of peritoneal fluid. (See 'Factors that impact efficacy'
above.)

● Surgery is required for women with the following characteristics (see 'Surgical indications'
above):

• Need emergency surgical treatment (hemodynamically unstable, suspected tubal

rupture)
• Heterotopic pregnancy with coexisting viable intrauterine pregnancy
• Contraindications to MTX therapy or failed MTX therapy

Women may also reasonably choose surgery if they need a concurrent surgical procedure or
if they value a treatment that is of shorter duration and involves less follow-up and are willing
to take the risks and recovery time associated with surgery.

● For women with suspected ectopic pregnancy, we recommend against expectant

management if the serum hCG is >200 milli-international units/mL (Grade 1B). We treat these
women with MTX or surgery. (See 'Medical versus expectant management' above.)

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REFERENCES

1. Bouyer J, Coste J, Fernandez H, et al. Sites of ectopic pregnancy: a 10 year population-

based study of 1800 cases. Hum Reprod 2002; 17:3224.

2. Lipscomb GH. Medical therapy for ectopic pregnancy. Semin Reprod Med 2007; 25:93.

3. Barnhart KT, Gosman G, Ashby R, Sammel M. The medical management of ectopic

pregnancy: a meta-analysis comparing "single dose" and "multidose" regimens. Obstet
Gynecol 2003; 101:778.

4. Farquhar CM. Ectopic pregnancy. Lancet 2005; 366:583.

5. Morlock RJ, Lafata JE, Eisenstein D. Cost-effectiveness of single-dose methotrexate

compared with laparoscopic treatment of ectopic pregnancy. Obstet Gynecol 2000; 95:407.

6. Van Den Eeden SK, Shan J, Bruce C, Glasser M. Ectopic pregnancy rate and treatment
utilization in a large managed care organization. Obstet Gynecol 2005; 105:1052.

https://www.uptodate.com/contents/ectopic-pregnancy-choosing-a-treatment/print?search=EMBARAZO ECTOPICO&source=search_result&sel… 9/14

30/8/2019 Ectopic pregnancy: Choosing a treatment - UpToDate

7. Menon S, Colins J, Barnhart KT. Establishing a human chorionic gonadotropin cutoff to guide
methotrexate treatment of ectopic pregnancy: a systematic review. Fertil Steril 2007; 87:481.

8. Lipscomb GH, McCord ML, Stovall TG, et al. Predictors of success of methotrexate
treatment in women with tubal ectopic pregnancies. N Engl J Med 1999; 341:1974.

9. Lipscomb GH, Bran D, McCord ML, et al. Analysis of three hundred fifteen ectopic
pregnancies treated with single-dose methotrexate. Am J Obstet Gynecol 1998; 178:1354.

10. Nazac A, Gervaise A, Bouyer J, et al. Predictors of success in methotrexate treatment of

women with unruptured tubal pregnancies. Ultrasound Obstet Gynecol 2003; 21:181.

11. Tzafettas JM, Stephanatos A, Loufopoulos A, et al. Single high dose of local methotrexate
for the management of relatively advanced ectopic pregnancies. Fertil Steril 1999; 71:1010.

12. Gamzu R, Almog B, Levin Y, et al. The ultrasonographic appearance of tubal pregnancy in
patients treated with methotrexate. Hum Reprod 2002; 17:2585.

13. Vermesh M, Graczykowski JW, Sauer MV. Reevaluation of the role of culdocentesis in the
management of ectopic pregnancy. Am J Obstet Gynecol 1990; 162:411.

14. Lipscomb GH, Puckett KJ, Bran D, Ling FW. Management of separation pain after single-
dose methotrexate therapy for ectopic pregnancy. Obstet Gynecol 1999; 93:590.

15. Practice Committee of American Society for Reproductive Medicine. Medical treatment of
ectopic pregnancy: a committee opinion. Fertil Steril 2013; 100:638.

16. Bixby S, Tello R, Kuligowska E. Presence of a yolk sac on transvaginal sonography is the
most reliable predictor of single-dose methotrexate treatment failure in ectopic pregnancy. J
Ultrasound Med 2005; 24:591.

17. Potter MB, Lepine LA, Jamieson DJ. Predictors of success with methotrexate treatment of
tubal ectopic pregnancy at Grady Memorial Hospital. Am J Obstet Gynecol 2003; 188:1192.

18. Dudley PS, Heard MJ, Sangi-Haghpeykar H, et al. Characterizing ectopic pregnancies that
rupture despite treatment with methotrexate. Fertil Steril 2004; 82:1374.

19. Takacs P, Rodriguez L. High folic acid levels and failure of single-dose methotrexate
treatment in ectopic pregnancy. Int J Gynaecol Obstet 2005; 89:301.

20. da Costa Soares R, Elito J Jr, Camano L. Increment in beta-hCG in the 48-h period prior to
treatment: a new variable predictive of therapeutic success in the treatment of ectopic
pregnancy with methotrexate. Arch Gynecol Obstet 2008; 278:319.

https://www.uptodate.com/contents/ectopic-pregnancy-choosing-a-treatment/print?search=EMBARAZO ECTOPICO&source=search_result&se… 10/14

30/8/2019 Ectopic pregnancy: Choosing a treatment - UpToDate

21. Medical management of ectopic pregnancy. ACOG Practice Bulletin #94. American College
of Obstetricians and Gynecologists, 2008.

22. Kelly H, Harvey D, Moll S. A cautionary tale: fatal outcome of methotrexate therapy given for
management of ectopic pregnancy. Obstet Gynecol 2006; 107:439.

23. Teal SB. A cautionary tale: fatal outcome of methotrexate therapy given for management of
ectopic pregnancy. Obstet Gynecol 2006; 107:1420.

24. Willner N, Storch S, Tadmor T, Schiff E. Almost a tragedy: severe methotrexate toxicity in a
hemodialysis patient treated for ectopic pregnancy. Eur J Clin Pharmacol 2014; 70:261.

25. Hajenius PJ, Mol F, Mol BW, et al. Interventions for tubal ectopic pregnancy. Cochrane
Database Syst Rev 2007; :CD000324.

26. Mol F, Mol BW, Ankum WM, et al. Current evidence on surgery, systemic methotrexate and
expectant management in the treatment of tubal ectopic pregnancy: a systematic review and
meta-analysis. Hum Reprod Update 2008; 14:309.

27. Nieuwkerk PT, Hajenius PJ, Ankum WM, et al. Systemic methotrexate therapy versus
laparoscopic salpingostomy in patients with tubal pregnancy. Part I. Impact on patients'
health-related quality of life. Fertil Steril 1998; 70:511.

28. Job-Spira N, Fernandez H, Bouyer J, et al. Ruptured tubal ectopic pregnancy: risk factors
and reproductive outcome: results of a population-based study in France. Am J Obstet
Gynecol 1999; 180:938.

29. Bachman EA, Barnhart K. Medical management of ectopic pregnancy: a comparison of

regimens. Clin Obstet Gynecol 2012; 55:440.

30. Grimes DA. Estimation of pregnancy-related mortality risk by pregnancy outcome, United
States, 1991 to 1999. Am J Obstet Gynecol 2006; 194:92.

31. Oriol B, Barrio A, Pacheco A, et al. Systemic methotrexate to treat ectopic pregnancy does
not affect ovarian reserve. Fertil Steril 2008; 90:1579.

32. Wiser A, Gilbert A, Nahum R, et al. Effects of treatment of ectopic pregnancy with
methotrexate or salpingectomy in the subsequent IVF cycle. Reprod Biomed Online 2013;
26:449.

33. Gay C, Perrin J, Courbiere B, et al. Impact of salpingectomy for ectopic pregnancy on the
ovarian response during IVF stimulation. J Gynecol Obstet Hum Reprod 2019.

34. Mol F, Strandell A, Jurkovic D, et al. The ESEP study: salpingostomy versus salpingectomy
for tubal ectopic pregnancy; the impact on future fertility: a randomised controlled trial. BMC
https://www.uptodate.com/contents/ectopic-pregnancy-choosing-a-treatment/print?search=EMBARAZO ECTOPICO&source=search_result&se… 11/14
30/8/2019 Ectopic pregnancy: Choosing a treatment - UpToDate

Womens Health 2008; 8:11.

35. Chouinard M, Mayrand MH, Ayoub A, et al. Ectopic pregnancy and outcomes of future
intrauterine pregnancy. Fertil Steril 2019; 112:112.

36. Gervaise A, Masson L, de Tayrac R, et al. Reproductive outcome after methotrexate

treatment of tubal pregnancies. Fertil Steril 2004; 82:304.

Topic 112852 Version 10.0

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GRAPHICS

Algorithm: Choosing a treatment for ectopic pregnancy

hCG: human chorionic gonadotropin; TVUS: transvaginal ultrasound; MTX: methotrexate.

* Severe or persistent lower abdominal pain and/or evidence of hematoperitoneum.
¶ Serum quantitative beta-hCG.
Δ Some clinicians treat with MTX for patients with hCG >5000 to ≤10,000 mIU/mL if the
following criteria are met: no free fluid in the pelvic cul-de-sac or abdomen, pelvic ultrasound
meets criteria for methotrexate, and the patient has minimal pelvic or abdominal pain.
◊ Ectopic mass diameter <3 to 4 cm is also commonly used as a patient selection criterion;
however, this has not been confirmed as a predictor of successful treatment.

Graphic 114571 Version 3.0

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Success of single dose methotrexate for ectopic pregnancy according to hCG

concentration

hCG concentration Number of women successfully Number of women failing

(IU/L) treated (%) treatment (%)

<1000 133 (99) 2 (1)

1000 to 1999 51 (94) 3 (6)

2000 to 4999 106 (96) 4 (4)

5000 to 9999 42 (86) 7 (14)

10,000 to 150,000 18 (82) 4 (18)

hCG: human chorionic gonadotropin; IU: international units.

Adapted from: Menon S, Colins J, Barnhart KT. Establishing a human chorionic gonadotropin cutoff to guide methotrexate
treatment of ectopic pregnancy: A systematic review. Fertil Steril 2007; 87:481.

Graphic 74836 Version 3.0

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