Ectopic Pregnancy: Diagnosis and Management

Jennifer L Kulp; Kurt T Barnhart

Women's Health. 2008;4(1):79-87.

Risk Factors & Pathogenesis

Ectopic pregnancy occurs in the fallopian tube in over 95% of cases.^[3] Other locations for ectopic pregnancies are rare: abdominal, ovarian or cervical. The most common location in the fallopian tube for ectopic pregnancies to occur is the ampulla (70.0%); other locations, such as the isthmus (12.0%), the fimbria (11.1%) and the cornua (2.4%), are less common (Figure 1). The ampullar portion of the fallopian tube is more distendable than other areas. Ectopic pregnancies in this location may result in tubal abortion and not be recognized clinically. The isthmus of the fallopian tube is not able to expand to accommodate a growing ectopic pregnancy and is more prone to rupture.

(Enlarge Image)

Figure 1.

Locations of fallopian tube ectopic pregnancy. Adapted from reference 54.

Patients with certain risk factors are known to be at higher risk of developing ectopic pregnancy. Patients who have had a previous ectopic pregnancy, who have had previous tubal surgery, who have documented tubal pathology, who have known in utero diethystilbestrol exposure or who are undergoing assisted reproductive technologies are at relatively high risk of developing an ectopic pregnancy if they were to become pregnant. Patients with infertility, previous genital infections including gonorrhea and chlamydia, or who have greater than one lifetime sexual partner are at moderately increased risk.^[4] Overall, patients who have an intrauterine device (IUD) or who have had a tubal ligation are at decreased risk of ectopic pregnancy compared with nonpregnant controls. However, if women become pregnant with an IUD in place or after a tubal ligation, they are at increased risk for having an ectopic pregnancy compared with women who conceive without an IUD or tubal ligation ( Table 1 ).^[5]

Ectopic pregnancies may occur owing to impaired migration of the fertilized ovum in the fallopian tube, resulting from inflammation, hormonal or other factors. If the passage of the fertilized ovum is slowed and hatching occurs prior to the ovum reaching the endometrial cavity, the embryo may implant in the fallopian tube. Intrinsic factors to the embryo do not seem to contribute to ectopic pregnancy. In a series analyzing the chromosomes of abnormally implanted embryos, no karyotype abnormalities were noted.^[6,7] Research is now focusing on the molecular signaling at the time of blastocyst implantation and identifying abnormalities in this event that may further explain the etiology of ectopic gestations.^[8]

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Table 1. Risk Factors for Ectopic Pregnancy
Risk factor	Odds ratio*
High risk
Tubal surgery	21.0
Tubal ligation	9.3
Previous ectopic pregnancy	8.3
In uteroexposure to diethystilbestrol	5.6
Use of intrauterine devices	4.2-45.0
Tubal pathology	3.8-21.0
Assisted reproduction	4.0
Moderate risk
Infertility	2.5-21.0
Previous genital infections	2.5-3.7
Multiple sexual partners	2.1
Salpingitis isthmica nodosa	1.5
Low risk
Previous pelvic infection	0.9-3.8
Cigarette smoking	2.3-2.5
Vaginal douching	1.1-3.1
First intercourse <18 years	1.6

*Single values, common odds ratio from homogenous studies; point estimates, range of values from heterogenous studies.
Adapted from reference 55.

Table 2. Methotrexate Protocols
Day	Single-dose protocol	Multidose protocol	Two-dose protocol
0	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 50 mg/m² Rhogam if Rh negative	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 1 mg/kg Rhogam if Rh negative	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 50 mg/m² Rhogam if Rh negative
1		Leucovorin 0.1mg/kg
2		ß-hCG level Methotrexate
3		Leucovorin
4	ß-hCG level	ß-hCG level Methotrexate	ß-hCG level Methotrexate
5		Leucovorin
6		ß-hCG level Methotrexate
7	ß-hCG level, CBC, LFTs, creatinine Repeat methotrexate if <15% decrease in ß-hCG level from day 4	Leucovorin	ß-hCG level, CBC, LFTs, creatinine, Repeat methotrexate if <15% decrease in ß-hCG level from day 4
11	ß-hCG level, if repeat dose is given		ß-hCG level Repeat methotrexate if <15% decrease in ß-hCG level from day 7
14	ß-hCG level, if repeat dose is given		ß-hCG level CBC, LFTs, creatinine, if repeat dose is given
14	Maximum two doses of methotrexate	Continue methotrexate and leucovorin until 15% decrease in hCG levels between two consecutive titers Maximum four doses of methotrexate	Maximum four doses of methotrexate

For all protocols, after initial decline in ß-hCG, check weekly levels until undetectable or, in the multidose protocol, until <15 IU/l.
ß-hCG: ß-human chorionic gonadotropin; CBC: Complete blood count; LFT: Liver-function tests.

Table 2. Methotrexate Protocols
Day	Single-dose protocol	Multidose protocol	Two-dose protocol
0	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 50 mg/m² Rhogam if Rh negative	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 1 mg/kg Rhogam if Rh negative	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 50 mg/m² Rhogam if Rh negative
1		Leucovorin 0.1mg/kg
2		ß-hCG level Methotrexate
3		Leucovorin
4	ß-hCG level	ß-hCG level Methotrexate	ß-hCG level Methotrexate
5		Leucovorin
6		ß-hCG level Methotrexate
7	ß-hCG level, CBC, LFTs, creatinine Repeat methotrexate if <15% decrease in ß-hCG level from day 4	Leucovorin	ß-hCG level, CBC, LFTs, creatinine, Repeat methotrexate if <15% decrease in ß-hCG level from day 4
11	ß-hCG level, if repeat dose is given		ß-hCG level Repeat methotrexate if <15% decrease in ß-hCG level from day 7
14	ß-hCG level, if repeat dose is given		ß-hCG level CBC, LFTs, creatinine, if repeat dose is given
14	Maximum two doses of methotrexate	Continue methotrexate and leucovorin until 15% decrease in hCG levels between two consecutive titers Maximum four doses of methotrexate	Maximum four doses of methotrexate

Table 2. Methotrexate Protocols
Day	Single-dose protocol	Multidose protocol	Two-dose protocol
0	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 50 mg/m² Rhogam if Rh negative	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 1 mg/kg Rhogam if Rh negative	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 50 mg/m² Rhogam if Rh negative
1		Leucovorin 0.1mg/kg
2		ß-hCG level Methotrexate
3		Leucovorin
4	ß-hCG level	ß-hCG level Methotrexate	ß-hCG level Methotrexate
5		Leucovorin
6		ß-hCG level Methotrexate
7	ß-hCG level, CBC, LFTs, creatinine Repeat methotrexate if <15% decrease in ß-hCG level from day 4	Leucovorin	ß-hCG level, CBC, LFTs, creatinine, Repeat methotrexate if <15% decrease in ß-hCG level from day 4
11	ß-hCG level, if repeat dose is given		ß-hCG level Repeat methotrexate if <15% decrease in ß-hCG level from day 7
14	ß-hCG level, if repeat dose is given		ß-hCG level CBC, LFTs, creatinine, if repeat dose is given
14	Maximum two doses of methotrexate	Continue methotrexate and leucovorin until 15% decrease in hCG levels between two consecutive titers Maximum four doses of methotrexate	Maximum four doses of methotrexate

Table 2. Methotrexate Protocols
Day	Single-dose protocol	Multidose protocol	Two-dose protocol
0	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 50 mg/m² Rhogam if Rh negative	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 1 mg/kg Rhogam if Rh negative	Labs (pretreatment) - ß-hCG level, CBC, LFTs, creatinine, type and screen Methotrexate 50 mg/m² Rhogam if Rh negative
1		Leucovorin 0.1mg/kg
2		ß-hCG level Methotrexate
3		Leucovorin
4	ß-hCG level	ß-hCG level Methotrexate	ß-hCG level Methotrexate
5		Leucovorin
6		ß-hCG level Methotrexate
7	ß-hCG level, CBC, LFTs, creatinine Repeat methotrexate if <15% decrease in ß-hCG level from day 4	Leucovorin	ß-hCG level, CBC, LFTs, creatinine, Repeat methotrexate if <15% decrease in ß-hCG level from day 4
11	ß-hCG level, if repeat dose is given		ß-hCG level Repeat methotrexate if <15% decrease in ß-hCG level from day 7
14	ß-hCG level, if repeat dose is given		ß-hCG level CBC, LFTs, creatinine, if repeat dose is given
14	Maximum two doses of methotrexate	Continue methotrexate and leucovorin until 15% decrease in hCG levels between two consecutive titers Maximum four doses of methotrexate	Maximum four doses of methotrexate

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