History and exam

Key diagnostic factors

common

abdominal pain

Common in ectopic pregnancy but also present in other conditions in the differential diagnosis (e.g., miscarriage).

Typically unilateral lower abdominal pain; however, women may present with generalised or upper abdominal pain.

Pain with vomiting may be indicative of tubal rupture.[42]

amenorrhoea

Last menstrual period typically 6-8 weeks before presentation.

vaginal bleeding

Like abdominal pain, also seen in other conditions in the differential diagnosis (e.g., miscarriage, pelvic inflammatory disease and cervicitis).

abdominal tenderness

May also be present in early pregnancy loss; typically lower quadrant with voluntary guarding.

If involuntary guarding, rebound, or other acute abdomen findings present, could be warning sign of rupture.

adnexal tenderness or mass

Presence of adnexal tenderness or mass increases the likelihood of ectopic pregnancy.[45]

blood in vaginal vault

May be present in the absence of rupture.

uncommon

haemodynamic instability, orthostatic hypotension

Bleeding from the implantation site can be haemodynamically significant.

Hypotension and tachycardia are warning signs of possible rupture.

cervical motion tenderness

Often caused by irritation from intraperitoneal bleeding.

Possible warning sign of rupture.

Other diagnostic factors

uncommon

urge to defecate

From pooling of blood in the cul-de-sac.

Warning sign of possible rupture.

referred shoulder pain

Bleeding from the fallopian tube may irritate the diaphragm leading to referred shoulder pain.

Warning sign of possible rupture.

Risk factors

strong

previous ectopic pregnancy

Related to the underlying factor that led to the initial ectopic pregnancy.

Risk increases with the number of previous ectopic pregnancies. Risk of ectopic pregnancy is approximately 10% if the woman has had one previously (OR 3.0; 95% CI 2.1 to 4.4) and 25% with two or more previous ectopic pregnancies (OR 11.17; 95% CI 4.0 to 29.5).[25]

One retrospective review found the rates of recurrence following single-dose methotrexate, salpingectomy, and linear salpingostomy to be 8%, 9.8%, and 15.4% respectively.[26]

previous tubal sterilisation surgery

Believed to be due to possibility of tuboperitoneal fistula formation leading to spermatozoa escape and oocyte fertilisation.

A long-term, multicentre, prospective cohort study showed cumulative rate of 7.3 ectopic pregnancies per 1000 procedures, with bipolar coagulation having the highest incidence at 31.9 per 1000 procedures.[27]

in utero diethylstilbestrol exposure of the mother

Ninefold increase in ectopic pregnancy rate, probably due to altered tubal morphology and possible fimbrial malfunction.[28]

intrauterine device (IUD) use

Copper and levonorgestrel-releasing IUD devices lower the absolute risk of ectopic pregnancy when compared with the non-contraceptive-using general population; however, if a pregnancy occurs with an IUD in situ, there is an increased risk of an ectopic pregnancy.

Progesterone-releasing IUDs show a 50% to 80% higher risk than in the non-contraceptive-using controls, possibly due to action on the endometrium or delayed tubal motility.[29] Odds ratio: 1.1 to 4.5.[2]

previous genital infections

Lead to distortions of tubal anatomy.[30] In one retrospective cohort study, the odds ratio following 2 and ≥3 chlamydial infections was 2.1 and 4.5 respectively.[31]

chronic salpingitis

Syndrome manifesting as diverticuli of the fallopian tubes.

Aetiology unknown; theories include congenital or postinfectious.

salpingitis isthmica nodosa

Nodular scarring of fallopian tubes.

Aetiology of this is unknown; possibly postinfectious.

infertility

May reflect the higher incidence of abnormal fallopian tubes.

multiple sexual partners

Increases risk of pelvic inflammatory disease.

Odds ratio: 1.4 to 4.8.[2]

smoking

Odds ratio of 1.9 to 3.5 in women who smoke, dose-dependent.[32]

Probably due to decreased immunity resulting in higher risk of pelvic infection and impaired tubal motility associated with tobacco smoke.

Cigarettes are the tobacco product used most commonly in pregnancy, but use of alternative forms (e.g., e-cigarettes and vaping products) is increasing. There is likely to still be an increased risk of ectopic pregnancy due to exposure to nicotine and/or flavourants and combustion products with these alternatives, although more evidence is required to confirm this.[33]

race/ethnicity

Black women are at increased risk compared with white women.[18]

weak

assisted reproductive technology (ART)

Increased risk of ectopic and heterotopic pregnancy, with tubal factor subfertility as the most commonly associated risk factor.[34][35]

Increased risk of ectopic pregnancy after ART in women with tubal factor infertility compared with other types of infertility.[36]

There is evidence that frozen-thawed embryo transfer is associated with a lower incidence of ectopic pregnancy compared with fresh embryo transfer.[37]

Increased risk of ectopic pregnancy following transfer of multiple embryos.[36]

first sexual encounter <18 years

Age under 18 years at first sexual encounter is associated with higher rates of ectopic pregnancy.[38]

maternal age >35 years

There is a 4.1% overall rate of ectopic pregnancy among women 35 years of age or older compared with the 1.8% seen in the general population, but this may be due to the cumulative risk factors over a longer time period.[39]

Odds ratio: 1.1 to 4.5.[2]

tubal reconstruction surgery

Thought to be a risk factor, but most of the women receiving this treatment would not have conceived spontaneously, and some of the excess ectopic pregnancies observed in this population may have been caused by the underlying tubal damage that required the surgical intervention.

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