An ectopic pregnancy is defined as ‘the implantation of a fertilized ovum outside the endometrial cavity’. Worldwide, ectopic pregnancy is a leading cause of pregnancy-related death in early pregnancy. However, in the developed world there has been a great decline in the incidence rates of rupture of fallopian tubes and associated fatalities.


The presentation of bleeding and pain in the first trimester always generates ectopic pregnancy as an important differential. This is partially due to the fact that ectopic pregnancies still occur in 11.5 per 1,000 pregnancies (1.15%) in the United Kingdom. Occurring so frequently, management of cases and suspected cases is a vital skill for those working in obstetrics and gynaecology departments across the country.


What is an ectopic pregnancy?

Possible anatomical sites of ectopic pregnancies

An ectopic pregnancy is when a fertilized ovum implants outside of the uterus.  The diagram to the left shows possible sites of implantation.  


97% of ectopic pregnancies implant in the fallopian tubes.  



Risk factors

The best way to remember the risk factors for ectopic pregnanay is to understand that ectopic pregnancy shouldn't happen, and the fact that it has, means there must have been some damage or change to the normal environment.


Taking this into account, we can understand the following common causative factors: 


  • Previous history of ectopic pregnancy (12.6% chance of repeat ectopic pregnancy).
  • History of pelvic inflammatory disease / chlamydial infection
  • Tubal disease
  • Previous tubal surgery
  • Use of an intrauterine contraceptive device (when this fails they are much more likely to allow ectopic pregnancies).


      • Tubal ligation (as with intrauterine contraceptive devices)
      • In vitro fertilization (4 - 5% risk of ectopic pregnancy)
      • In utero exposure to diethylstilbestrol
      • Assisted conception
      • History of subfertility



          ‘Classically’ ectopic pregnancy presents as a triad of pain, abnormal vaginal bleeding, and a palpable adnexal mass, most commonly at around 5 weeks gestation. In reality, only 45% of women present in this way and so any woman of reproductive age with acute pelvic / abdominal pain, or vaginal bleeding will be treated as a possible ectopic pregnancy until proven otherwise.  

          Red Flags for ectopic pregnancy presentation



          In 'normal' pregnancy:

          1) βhCG- In early viable intrauterine pregnancies the average βhCG level increases by 66-100% every 48hours.


          2) Trans-vaginal ultrasound- (with or without Doppler flows) can indetify an intrauterine pregnancy from gestations as early as four weeks.


          3) Abdominal ultrasound- identification of a gestational sac in the uterus.




          In ectopic pregnancy:

          1) βhCG - the amount of time taken for βhCG levels to double is increased. (Levels increasing by less than 60% over 48hours but there is no decline= presumed ectopic)

          2) Trans-vaginal Ultrasound- If no intrauterine pregnancy seen by ultrasound at βhCG levels greater than 2000mIU/ml then ectopic pregnancy is assumed. 


          3) Abdominal ultrasound - visualisation of an adnexal mass, haemotoma or extra-uterine gestational sac.

          A note on βhCG

          βhCG is a glycoprotein hormone produced in pregnancy. It helps maintain adequate levels of progesterone production for gestational development. Testing levels of βhCG can be used both as a pregnancy test (from 9days after conception) and as a measure of foetal development.

          Once levels reach 6000mIU/ml levels continue to increase at a slower rate until eight to ten weeks gestation when levels start to decline.

          When βhCG levels are present but less than 2000mIU/ml there are three main possibilities to consider;

          • a normal intrauterine pregnancy that is too early to be detected by ultrasound
          • a failing intrauterine pregnancy
          • an ectopic pregnancy that is resolving spontaneously



          Until recently the standard treatment for ectopic pregnancies was emergency surgery.  Recent developments mean emphasis is now on early diagnosis and non-surgical management.

          Its enough to just know what the options are, so feel free to stop reading here. Congratulations, you have reasonable knowledge on ectopic pregnancies!


          The following sections go into detail about the individual management options.

          Expectant Management

          Around 70% of ectopic pregnancies with βhCG levels <1000mIU/mL resolve spontaneously, or ‘expectantly’.

          The best indicator of spontaneous resolution is βhCG levels that are falling by 15-25% every 48hours.

          If spontaneous resolution is suspected, the patient will be monitored with 48hourly bloods looking for a continuous decline in βhCG of at least 15% each two days. If this rate stops declining or βhCG levels start to rise then medical or surgical treatment should be considered.

          Appropriate Patient Selection:


          • Minimal or no pain                  
          • Vaginal bleeding not excessive
          • βhCG less than 1000mIU/ml
          • Progesterone less than 60nmol/l
          • Willing to undertake repeat follow-up visits




          Methotrexate Treatment

          Methotrexate, given as intramuscular injection or ultrasound guided intra-amniotic injection, is commonly used in treating unruptured ectopic pregnancies.

          Methotrexate is an anti-metabolite that inhibits DNA and RNA synthesis, stopping production of new cells. Methotrexate also kills the rapidly dividing cells at the fallopian tube implantation site. The body should then reabsorb the remaining products of conception and blood clot that made up the ectopic pregnancy.


          Appropriate Patient Selection:

          • Must meet the set criteria (minimal pain and bleeding, no live ectopic, ßhCG less than 5000mIU/ml, adnexal mass less than 4.0cm in diameter.)
          • Must be motivated and compliant (due to need for multiple follow-up appointments)
          • Must have easy access to emergency care
          • Must not want to conceive in next three months
          • Have no contraindications to methotrexate

          Patients must be informed about possible side-effects:

          • Nausea +/- vomiting      
          • Mouth sores (stomatitis)     
          • Bloating
          • Vaginal bleeding
          • Pain lasting a few days to a few weeks      

          Patients must be advised to avoid direct sunlight, alcohol, folic acid and other vitamins, aspirin, non-steroidal anti-inflammatory drugs, and sexual intercourse during the duration of treatment.

          Algorithm for Methotrexate Management

          Surgical Management

          Surgical management is indicated in haemodynamically unstable patients or if the criteria for methotrexate or expectant therapy are not met.  It involves either salpingostomy (incision into the fallopian tube to remove the ectopic) or salpingectomy (removal of the entire fallopian tube).

          The surgery can be carried out laparoscopically or by laparotomy,with laparoscopy preferred.  However, in the event of tubal rupture, laparotomy is more appropriate.

          If the patient has already had infertility problems or the other tube is blocked then salpingostomy has the obvious benefit of saving the tube for future fertility.

          Possible outcomes of ectopic pregnancy

          Even with early screening programmes in place, approximately 25% of ectopic pregnancies rupture, which accounts for 9% of all maternal deaths.  Women who have had a previous ectopic pregnancy have a 12.6% risk of having another.  These patients should have all subsequent pregnancies thoroughly screened regardless of lack of symptoms.



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