Epidemiology

The rate of ectopic pregnancy in the UK is 11 per 1,000 pregnancies. Although the mortality from ectopic pregnancies in the UK is decreasing, around 0.2 per 100 ectopic pregnancies result in maternal death.^[1] Two thirds of these maternal deaths are associated with substandard care. Women who are less likely to seek medical help have a worse prognosis. These include recent migrants, asylum seekers, refugees and those who have difficulty reading or speaking English.

Anatomy

The majority of ectopic pregnancies occur in the ampullary or isthmic portions of the Fallopian tubes. About 2-5% occur as interstitial (cornual) ectopic pregnancies. The rare remaining locations include cervical, fimbrial, ovarian, and peritoneal sites, as well as previous caesarean section scars. There are a few documented cases of viable pregnancy outside the uterus and tubes but, as a general rule, only an intrauterine pregnancy is viable.

An ectopic pregnancy may also co-exist with intrauterine pregnancy - heterotopic pregnancy - in 1 in 7,000 pregnancies.

Cornual pregnancy

Cornual pregnancy does not represent pregnancy in a rudimentary horn of a bicornuate uterus, but pregnancy in the interstitial rather than extrauterine part of the tube. Cornual pregnancies represent 2-4% of ectopic pregnancies. It can be diagnosed by ultrasound in only 70% of cases. It tends to present early and suddenly and often there is catastrophic haemorrhage before diagnosis is made.

Cornual pregnancies are rare but dangerous types of ectopic pregnancy. Clinicians should be aware of the difficulties with both clinical and ultrasound diagnosis.

Risk factors

NB: one third of women with ectopic pregnancies do not have risk factors.

• Fertility treatments and intrauterine contraceptive devices (IUCDs) are the most important associated risk factors.^[2]
• Pelvic inflammatory disease may cause complete tubal occlusion or delay the transport of the embryo so that implantation occurs in the tube. Adhesions from infection and inflammation from endometriosis may play a part.
• Ectopic pregnancy has been reported in tubes that have been divided in a sterilisation operation and where they have been reconstructed to reverse one.
• Ectopic pregnancy can occur in the treatment of infertility.
• Right-sided tubal pregnancy is more common than left-sided. This is thought to be from spread of infection from appendicitis.
• The ability of the tube to expand increases from medially to laterally. Hence, a more lateral implantation will present later as either pain or rupture.
• Where an IUCD or progestogen-only oral contraceptives, including emergency contraception, fails, the risk of a pregnancy being ectopic is greater than with other forms of contraception. Depot and implant contraception may not have the same risks. Ectopic pregnancy has been reported with implant contraception with etonogestrel (Nexplanon®) but is rare.

Presentation

History

• Symptoms and signs of ectopic pregnancy can resemble those of other more common conditions, including urinary tract infections and gastrointestinal conditions.
• The most common symptoms are:^[3]
  • Abdominal pain.
  • Pelvic pain.
  • Amenorrhoea or missed period.
  • Vaginal bleeding (with or without clots).
• Other symptoms may include:
  • Dizziness, fainting or syncope.
  • Breast tenderness.
  • Shoulder tip pain.
  • Urinary symptoms.
  • Passage of tissue.
  • Rectal pain or pressure on defecation.
• There may be a history of a previous ectopic pregnancy. After one ectopic pregnancy the chance of another in the other tube is much increased.
• If the ectopic pregnancy has ruptured, bleeding is profuse and there may be features of hypovolaemic shock, including feeling dizzy on standing. Most bleeding will be into the pelvis and so vaginal bleeding may be minimal and misleading.
• Diarrhoea and vomiting are possible, atypical clinical features of ectopic pregnancy.

Examination

• There may be some tenderness in the suprapubic region.
• Peritonism and signs of an acute abdomen may occur.
• Women with a positive pregnancy test and any of the following need to be referred immediately to hospital:
  • Pain and abdominal tenderness.
  • Pelvic tenderness.
  • Cervical motion tenderness.

Differential diagnosis

• In threatened miscarriage vaginal bleeding is the predominant feature and pain may come later as the cervix dilates. In ectopic pregnancy, pain usually comes first and if vaginal bleeding occurs it is of much less significance.
• The differential diagnosis is also as for left iliac fossa pain or right iliac fossa pain.

Investigations^[3]

• The most accurate method to detect a tubal pregnancy is transvaginal ultrasound.
• This can identify the location of the pregnancy and also whether there is a fetal pole and heartbeat.
• Human chorionic gonadotrophin (hCG) levels are performed in women with pregnancy of unknown location who are clinically stable.
• hCG levels are taken 48 hours apart. If there is a change in concentration between 50% decline and 63% rise inclusive over 48 hours then the woman should be referred for clinical review in an early pregnancy assessment service within 24 hours.

Management

• Admit as an emergency if the diagnosis of ectopic pregnancy is considered a possibility. A bedside pregnancy test should be performed on all women of childbearing age presenting with lower abdominal pain where pregnancy is even the remotest possibility.
• Anti-D rhesus prophylaxis should be given (at a dose of 250 IU) to all rhesus negative women who have a surgical procedure to manage an ectopic pregnancy. Women who receive medical treatment for their ectopic pregnancy do not need to receive it.
• All women should be given written information which is tailored to their care. They should also be given a 24-hour contact telephone number to use if their symptoms worsen or new symptoms develop.
• Early pregnancy assessment units should accept self referrals from women with a history of ectopic pregnancy.
• Conservative management may be appropriate if the levels of hCG are falling and the patient is clinically well.  Repeat hCG levels are performed in these cases.

Medical management

• Medical management in the form of systemic methotrexate is offered first-line to those women who are able to return for follow-up and who have the following:
  • No significant pain.
  • Unruptured ectopic pregnancy with an adnexal mass <35 mm and no visible heartbeat.
  • No intrauterine pregnancy seen on ultrasound scan.
  • Serum hCG <1500 IU/L.
• Over 75% of patients will complain of abdominal pain 2-3 days after administration of methotrexate.
• Other side-effects include nausea, vomiting and reversible impaired liver function.
• Women should have blood taken for LFTs and to ensure hCG levels are dropping.
• Contraception should be used for 3-6 months as it is teratogenic.
• Clear instruction must be given about the need for follow-up and the ability to return to the ward if there are problems.

Surgical management

• Surgery should be offered to those women who can not return for follow-up after methotrexate or to those who have any of the following:
  • Significant pain.
  • Adnexal mass ≥35 mm.
  • Fetal heartbeat visible on scan.
  • Serum hCG level ≥5000 IU/L.
• A laparoscopic approach is preferable. A salpingectomy should be performed, unless the woman has other risk factors for infertility, in which case a salpingotomy should be undertaken.

Complications

• Nowadays, ectopic pregnancy can often be diagnosed before the woman's condition has deteriorated, resulting in ectopic pregnancy being less of a life-threatening disease and more of a benign condition.^[4]
• Failure to make the prompt and correct diagnosis of ectopic pregnancy can result in tubal or uterine rupture (depending on the location of the pregnancy), which in turn can lead to massive hemorrhage, shock, disseminated intravascular coagulopathy (DIC), and even death.
• Complications of surgery include bleeding, infection, and damage to surrounding organs, such as the bowel, bladder, and ureters, and to the major vessels nearby.

Prognosis

• With accurate determination of very low hCG concentrations and ultrasound, >85% of women are now diagnosed before tubal rupture, which has led to medical therapy and laparoscopic surgery with tubal preservation and the potential for future fertility.^[5]
• The risk of another ectopic pregnancy is about 10-20%.
• The chance of subsequent intrauterine pregnancy is about 55-60%.