Section 1: Epidemiology and aetiology
The incidence of ectopic pregnancy in the UK has remained static for years at one per 100 pregnancies. The incidence in those using assisted reproductive technologies is nearer 4%.
Many ectopic pregnancies follow a benign clinical course and are managed successfully by surgical, medical or conservative approaches. It does however remain a dangerous condition with a significant mortality risk. The Confidential Enquiry into Maternal Death 2015 found that 18 women died from ruptured ectopic pregnancy in the UK between 2009 and 2013.1
The word ectopic comes from the Greek word 'ektopos' meaning out of place. It describes any pregnancy implanted outside the uterine cavity. Around 98% of ectopic pregnancies occur in the fallopian tube. The remainder occur abdominally (1.4%), on the ovary (0.15%) and within the cervix (0.15%).2
The aetiology of ectopic pregnancy is uncertain. It cannot be studied in animals as it is virtually a unique human phenomenon. It seems likely that the main causative factor is a delay in transport of the ovum.3
This means that the ovum becomes too large to travel through the uterotubal junction and so implants in the tube prior to reaching the uterine cavity. In theory, any factors slowing the movement of the ovum may predispose to ectopic pregnancy.
Low oestrogen levels reduce egg movement by smooth muscle within the tube. High progesterone levels, such as in progesterone-only pill users, reduce cilia formation and movement inside the tube.
Sterilisation reduces the risk of pregnancy to 1 in 100 but if it does occur, the risk of ectopic is higher as the pregnancy implants in a tubal stump. Pelvic infection damages the cilia and epithelium inside the tube often causing narrowing. One episode of pelvic infection increases the risk of ectopic pregnancy by six times.3
Progression of pregnancy
The natural progression of an ectopic pregnancy starts with implantation. At this stage there are minimal symptoms and nothing to visualise.
As the pregnancy progresses the fallopian tube becomes distended and discoloured. The fallopian tube is unable to respond to the pregnancy and starts to stretch and thin with local haemorrhage.
As the embryo reaches a critical size tubal integrity is breached and it ruptures, bleeding into the peritoneal cavity. The embryo rarely survives.
Sometimes the rupture releases the pregnancy into the abdomen and if bleeding is minimal, it may be reabsorbed by the surrounding tissues. Alternatively bleeding can be life threatening.
Time of rupture depends on the diameter of the fallopian tube where the pregnancy has implanted but is most commonly seen between 5 and 7 weeks gestation.
Section 2: Making the diagnosis
History taking should focus on risk factors that increase the chance of implantation outside the uterine cavity. These include tubal disease from chlamydia infection, sterilisation or tubal surgery, an intrauterine contraceptive device or progesterone-only pill use, fertility treatment or previous ectopic pregnancy.
Women may present with symptoms of abdominal pain, diarrhoea and vomiting. Pain is usually due to intraperitoneal haemorrhage with or without tubal rupture. Shoulder tip pain occurs when blood irritates the diaphragm and stimulates the phrenic nerve.
There may be amenorrhoea, brown vaginal loss or fresh, light bleeding. Heavy bleeding with clots is more likely to be a miscarriage.
Any woman of reproductive age with a hypotensive, shocked collapse should be assumed to have a ruptured ectopic pregnancy until excluded.
Abdominal examination reveals generalised tenderness and rebound. Vaginal examination rarely elicits additional information.3,4
Important! Any woman of reproductive age with a hypotensive, shocked collapse should be assumed to have a ruptured ectopic pregnancy until excluded.
The two essential tools for diagnosis and management of an ectopic pregnancy are serum beta-hCG and transvaginal ultrasound scanning. Both of these are performed in early pregnancy clinics.
Any woman of reproductive age presenting to her GP with lower abdominal pain, or amenorrhoea with GI symptoms or fainting should have a pregnancy test performed. If this is positive, ectopic pregnancy needs to be ruled out.
If the woman is stable and well, she can be referred to the next available early pregnancy clinic appointment at the nearest hospital. If she is faint, hypotensive or has severe abdominal pain with rebound or guarding, she should be discussed with the on-call gynaecology registrar to decide whether she should be seen that day as an emergency.
If the woman is sure of her dates and is over 10 weeks pregnant or has already had an ultrasound scan confirming intrauterine pregnancy, ectopic pregnancy is extremely unlikely.
At the early pregnancy clinic transvaginal ultrasound is performed for a patient who is sure of the date of her last menstrual period (LMP) and is more than six weeks gestation.4 If she is unsure of her LMP or has an irregular cycle, blood is taken for serum hCG.
If the hCG is less than 1,000IU/L it will be repeated in 48 hours to test whether it is doubling (likely to be a viable intrauterine pregnancy), falling (miscarriage) or achieving a suboptimal rise (probable ectopic).
Once hCG exceeds 1,500IU/L a scan can be performed.2 Ultrasound may show an empty uterus, viable intrauterine pregnancy, sac in the uterus or even an adnexal mass or tubal ectopic with fetal heart beat. Free fluid in the pouch of Douglas may indicate tubal rupture.
Section 3: Managing the condition
If the patient presents collapsed and unstable, management should include resuscitation with an ABC approach, wide bore cannulae, fluid replacement and urgent admission to hospital.
When the patient is haemodynamically stable, management is determined by the early pregnancy clinic. Management can be conservative, surgical or medical. Most ectopic pregnancies will resolve spontaneously and it is thought that the trend towards earlier diagnosis is resulting in over treatment. The key to management is to identify those at risk of rupture.
Expectant management is an option for clinically stable women with minimal symptoms and a pregnancy of unknown location. Where the patient is seen on ultrasound to have an ectopic but is asymptomatic with a decreasing hCG under 1,000IU/L expectant management can also be used.
Five observational studies 7 have demonstrated that more than half will spontaneously resolve. Serum hCG should be monitored in the early pregnancy clinic until below 20IU/L.2,4
Laparoscopy is the gold standard surgical treatment for ectopic pregnancy. It is quicker than laparotomy with less blood loss, less pain and a shorter hospital stay. Diagnostic laparoscopy under general anaesthetic is performed to confirm ectopic pregnancy.
The guideline from the Royal College of Obstetricians and Gynaecologists advises removal of the tube containing the ectopic pregnancy (salpingectomy) when the contralateral tube is healthy.4 This does not compromise the subsequent intrauterine pregnancy rate5 and avoids the complication of persistent pregnancy tissue or future ectopic in the already damaged tube.
If the contralateral tube appears damaged or absent, and future fertility is desired, salpingotomy is performed. An incision is made to remove the ectopic from the tube which is then left to heal by secondary intention. Salpingectomy in this situation would mean IVF treatment would be required for future conception.
Single dose methotrexate injection is the most widely studied medical treatment and its high success rate of 86-90% is not skill dependent. Patients do have to be carefully selected.
Any patient unlikely to comply with follow up, who has an adnexal mass over 4cm, fetal heart seen, hCG over 3000IU/L or who is unstable, in severe pain or collapsed with a suspected ruptured ectopic pregnancy is unsuitable. The patient will be counselled, weighed and then given an IM injection of methotrexate 1mg/kg.
Over 75% of patients will complain of abdominal pain 2-3 days after administration. Fewer than 10% of these will require intervention, but those with severe pain should be referred back to hospital for observation.6 Other side-effects include nausea, vomiting and reversible impaired liver function.
Patients will be followed up in the early pregnancy clinic at day 4, 7 and 14 following methotrexate injection. Blood will be taken for LFTs and to ensure hCG levels are dropping.
The methotrexate may need to be repeated if the drop in hCG is less than 15% of its original value. Contraception should be used throughout and for three months after treatment as it is teratogenic.
Section 4: Prognosis
Having had one ectopic pregnancy the risk of having another is 15%. If there are underlying risk factors for ectopic pregnancy, the risk of recurrence may be higher.
The intrauterine pregnancy rate following salpingectomy is 54-66%. Intrauterine pregnancy rate after salpingotomy is higher at 60-89%, but the risk of recurrent ectopic is higher (18% versus 8%)7,8 and there is a potential need for treatment for persistent pregnancy tissue.
Expectant management in women with a pregnancy of unknown location will be successful in 67-88%. Two thirds of these pregnancies will resolve spontaneously. Compliance with follow up in the early pregnancy clinic is vital to reduce risks to the patient.
In a subsequent pregnancy, GPs can refer patients to the hospital ultrasound department for an early scan. Early pregnancy clinics will not accept patients for reassurance scans.
Section 5: Case study
Alison is a 22-year-old woman who uses the progesterone-only pill for contraception.Her periods are irregular.She is slim and fit and smokes five cigarettes a day.
One evening Alison develops abdominal pain. It is suprapubic and mildly uncomfortable.
When a brownish discharge starts the next day, Alison assumes a period is coming. Two days later the pain is worse and focused on the left side.
The following morning she attends her GP surgery with left-sided abdominal pain and light brown vaginal discharge.
She has no urinary or bowel symptoms but feels slightly nauseous. Alison is unsure of the date of her last period, but is certain she has not forgotten any of her contraceptive pills. Her GP notes a history of previous chlamydia infection.
On examination Alison's abdomen is soft with mild tenderness in the left iliac fossa.
Vaginal examination is not performed.
MSU dipstick is positive for blood. Alison is shocked to hear that a pregnancy test is positive.
The GP is suspicious that Alison may have an ectopic pregnancy so refers her to the local early pregnancy clinic for the next morning as she is generally well. Alison attends the next day and as she is unsure of her dates has a blood test for hCG.
The result is 900IU/L. The clinic decide not to scan Alison but instead make an appointment to see her two days later.
At this appointment the blood test is repeated. The hCG level is now 1,500IU/L. A transvaginal ultrasound scan shows an empty uterus but suspicious mass in the left fallopian tube.
With the suboptimal rise in hCG, suggestive scan and risk factors of previous chlamydia, progesterone-only pill and smoking, Alison is booked for diagnostic laparoscopy.
As she is waiting for surgery, Alison's pain increases in severity. She complains of severe abdominal pain and twinges in her shoulders and requires a dose of morphine. She is found to be tachycardic at 140bpm and hypotensive.
Alison is taken immediately for surgery and is found to have a ruptured left ectopic pregnancy.
There is 1L of blood in her peritoneal cavity. The left tube and embryo are removed laparoscopically and the blood washed out of her abdomen.
Alison makes a good recovery and although she is initially very upset about the unexpected pregnancy and loss of her fallopian tube she has support from a friend who has also had an ectopic pregnancy.
Two years later she is delighted to find she is pregnant again.
Early ultrasound scan confirms an intrauterine pregnancy and she goes on to deliver a healthy baby boy at term.
Section 6: Evidence base
Although there are changing trends in the management of ectopic pregnancy, methods of diagnosis and identification of patients at risk of rupture have remained constant. Recently the acceptable level of HCG for use of methotrexate has been revised down from 6000 to 3000. Above that the rate of treatment failure and subsequent surgery or ‘double treatment’ is too high.
- Royal College of Obstetricians and Gynaecologists. Management of tubal pregnancy. Greentop guideline. No 21, 2004. (Revised version due 2016)
This describes the management guidelines followed by early pregnancy clinics and gynaecologists once the patient has been referred to hospital and lists the evidence it is based upon.
- Mascarenhas LJ. Ectopic pregnancy. In: Luesley D, Baker P, Drife J. Obstetrics and gynaecology; an evidence-based text for MRCOG. London: Hodder Arnold 2004.
These chapters summarise current knowledge and the most recent evidence base for diagnosis and management.
- The Ectopic Pregnancy Trust. www.ectopic.org.uk
This is a charity website with forums for patients affected by ectopic pregnancy and information for patients and professionals.
This is an excellent illustrated information booklet from the RCOG, for patients which can be downloaded. It answers questions including prognosis and risk of recurrence.
- Dr Polly Weston is consultant obstetrician and gynaecologist in Perth, Western Australia
This is an updated version of an article that was first published in March 2011
- MBBRACE Saving lives, improving mothers’ care. December 2015. https://www.npeu.ox.ac.uk/mbrrace-uk/reports
- Mascarenhas LJ. Ectopic pregnancy. In: Luesley D, Baker P, Drife J Obstetrics and gynaecology; an evidence-based text for MRCOG. London: Hodder Arnold 2004
- Klentzeris LD. Ectopic pregnancy. In: Shaw RW, Soutter WP, Stanton SL Gynaecology (third edition). London: Churchill Livingstone 2003
- RCOG. Management of tubal pregnancy. 2004 (reviewed 2010) Greentop guideline No 21
- Dubuisson JB, Morice P, Chapron C, et al. Human Reprod 1996; 11; 1199-203
- Lipscomb GH, Puckett KJ, Brand D, et al. Obstet Gynecol 1999: 93; 590-3
- Mol F, van Mello N et al The Lancet 2014; 383; 1483-9
- Bangsgaard N, Lund C, Otteson B. Br J Obstet Gynaecol 2003; 110; 765-7