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Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
An ectopic pregnancy is one that occurs anywhere outside the uterus. By far the most common place for ectopic pregnancy is the Fallopian tubes.
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. 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.
Rates of ectopic pregnancy after assisted reproduction vary from 0.8-8.6%, although the incidence has decreased over time.
The incidence of heterotopic pregnancy (when both an intrauterine and an ectopic pregnancy are present) varies from 1 in 4,000 women to 1 in 30,000 women in the general population.
97% of ectopic pregnancies occur in the Fallopian tubes. The majority occur in the ampullary or isthmic portions of the Fallopian tubes. About 2-3% occur as interstitial ectopic pregnancies (arising in the part of the tube which goes through the endometrial cavity). 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.
Diagram from The Ectopic Pregnancy Trust, used with permission.
Interstitial, cornual and cervical pregnancy
These terms may be confused, but describe different situations. Cornual pregnancy describes pregnancy in a rudimentary horn of a bicornuate uterus, whilst interstitial pregnancy describes pregnancy in the interstitial rather than extrauterine part of the tube. Interstitial pregnancies represent 2-3% of ectopic pregnancies. Interstitial pregnancy can be misdiagnosed by ultrasound as normal intrauterine pregnancy. It tends to present early and suddenly and often there is catastrophic haemorrhage before diagnosis is made.
Interstitial pregnancies are rare but dangerous types of ectopic pregnancy. Clinicians should be aware of the difficulties with both clinical and ultrasound diagnosis. The rarest of ectopics (<1%) are implanted within the cervical canal below the level of the internal cervical os. Predisposing factors include prior uterine curettage, induced abortion, Asherman's syndrome, leiomyomata and the presence of an intrauterine contraceptive device (IUCD).
One third of women with ectopic pregnancies do not have risk factors. However, the following increase risk of ectopic pregnancy:
- Assisted reproductive treatments such as in vitro fertilisation (IVF).
- History of pelvic infection. 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.
- Previous tubal surgery. Ectopic pregnancy has been reported in tubes that have been divided in a sterilisation operation and where they have been reconstructed to reverse one. A past history of ectopic pregnancy increases the risk.
- IUCD use. IUCDs reduce the risk of ectopic pregnancy compared to using no contraception. The risk of ectopic pregnancy with an IUCD or intrauterine system (IUS) in situ is around 1 in 1,000 over five years. However, where an IUCD fails, the risk of a pregnancy being ectopic is very high, with some studies showing half of pregnancies in this situation being ectopic.
- Women becoming pregnant whilst using progestogen-only contraceptive methods may also have an increased risk of ectopic pregnancy, although a previous history of ectopic pregnancy is not a contra-indication to use. Risks are lowest for depot injection and implants.
Be aware that ectopic pregnancy commonly presents in an atypical way, so consider the possibility in women of reproductive age. Consider the need for a pregnancy test even in women with nonspecific signs.
- 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:
- 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.
- Gastrointestinal symptoms such as diarrhoea and/or vomiting.
- There may be a history of a previous ectopic pregnancy. After one ectopic pregnancy the chance of another 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.
- Pelvic or abdominal tenderness.
- Adnexal tenderness.
Other possible signs:
- Rebound tenderness.
- Cervical tenderness.
- Abdominal distension.
- Enlarged uterus.
- Tachycardia and/or hypotension.
- Shock or collapse.
NB: there is thought to be a possible increased risk of rupture of an ectopic pregnancy following palpation, so internal examination would not normally be performed if ectopic pregnancy is suspected, particularly where there is early access to ultrasound.
Women with a positive pregnancy test and any of the following need to be referred to hospital for urgent assessment via the early pregnancy assessment service or on-call gynaecologist out of hours:
- Pain and abdominal tenderness.
- Pelvic tenderness.
- Cervical motion tenderness.
- Vaginal bleeding.
- 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.
A pregnancy test should be performed on all women of childbearing age presenting with lower abdominal pain where pregnancy is even the remotest possibility.
- 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. In a woman with pregnancy of unknown location, however, clinical symptoms are of more significance than hCG levels.
- 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.
- Admit as an emergency if the diagnosis of ectopic pregnancy is considered a 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.
- Single-dose methotrexate treatment appears to have similar efficacy to surgical treatment. Superiority over expectant management for ceratin patients is less clear. Re-injection may be required.
- 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 methotrexate 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.
- Surgery should be offered to those women who cannot 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.
- Ectopic pregnancy can often be diagnosed before the woman's condition has deteriorated, resulting in ectopic pregnancy being less likely to be life-threatening disease.
- 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 haemorrhage, 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.
- 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.
- The risk of another ectopic pregnancy is about 10-20%.
- The chance of subsequent intrauterine pregnancy is about 64-76%[16, 17].
Further reading and references
Stabile G, Mangino FP, Romano F, et al; Ectopic Cervical Pregnancy: Treatment Route. Medicina (Kaunas). 2020 Jun 1256(6). pii: medicina56060293. doi: 10.3390/medicina56060293.
Szadok P, Kubiaczyk F, Bajorek A, et al; Ovarian ectopic pregnancy. Ginekol Pol. 201990(12):728. doi: 10.5603/GP.2019.0125.
Cali G, Timor-Tritsch IE, Palacios-Jaraquemada J, et al; Outcome of Cesarean scar pregnancy managed expectantly: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018 Feb51(2):169-175. doi: 10.1002/uog.17568.
Ectopic pregnancy; NICE CKS, May 2018 (UK access only)
Saving Lives, Improving Mothers’ Care; Lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2016-18, December 2020
Santos-Ribeiro S, Tournaye H, Polyzos NP; Trends in ectopic pregnancy rates following assisted reproductive technologies in the UK: a 12-year nationwide analysis including 160 000 pregnancies. Hum Reprod. 2016 Feb31(2):393-402. doi: 10.1093/humrep/dev315. Epub 2016 Jan 2.
Maciel N, Lima AF, Cruz R, et al; Advanced abdominal pregnancy in a spontaneous heterotopic pregnancy. BMJ Case Rep. 2017 Dec 132017. pii: bcr-2017-222098. doi: 10.1136/bcr-2017-222098.
Fylstra DL; Ectopic pregnancy not within the (distal) fallopian tube: etiology, diagnosis, and treatment. Am J Obstet Gynecol. 2012 Apr206(4):289-99. doi: 10.1016/j.ajog.2011.10.857. Epub 2011 Oct 20.
Long-acting reversible contraception (update); NICE (September 2014, last updated July 2019)
Intrauterine Contraception; Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit (2015 - last updated September 2019)
Callahan R, Yacobson I, Halpern V, et al; Ectopic pregnancy with use of progestin-only injectables and contraceptive implants: a systematic review. Contraception. 2015 Dec92(6):514-22. doi: 10.1016/j.contraception.2015.08.016. Epub 2015 Sep 10.
Ectopic pregnancy and miscarriage: diagnosis and initial management; NICE Guidance (last updated November 2021)
Lermann J, Segl P, Jud SM, et al; Low-dose methotrexate treatment in ectopic pregnancy: a retrospective analysis of 164 ectopic pregnancies treated between 2000 and 2008. Arch Gynecol Obstet. 2014 Feb289(2):329-35. doi: 10.1007/s00404-013-2982-x. Epub 2013 Aug 3.
Jurkovic D, Memtsa M, Sawyer E, et al; Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial. Ultrasound Obstet Gynecol. 2017 Feb49(2):171-176. doi: 10.1002/uog.17329. Epub 2017 Jan 6.
Inal ZO, Inal HA; Comparison of Four Methods of Treating Ectopic Pregnancy: A Retrospective Cohort Study. Geburtshilfe Frauenheilkd. 2018 Jan78(1):70-77. doi: 10.1055/s-0043-122151. Epub 2018 Jan 22.
Diagnosis and management of ectopic pregnancy; Royal College of Obstetricians and Gynaecologists. Green Top Guideline No 21. November 2016
van Mello NM, Mol F, Ankum WM, et al; Ectopic pregnancy: how the diagnostic and therapeutic management has changed. Fertil Steril. 2012 Nov98(5):1066-73. doi: 10.1016/j.fertnstert.2012.09.040.
Marion LL, Meeks GR; Ectopic pregnancy: History, incidence, epidemiology, and risk factors. Clin Obstet Gynecol. 2012 Jun55(2):376-86. doi: 10.1097/GRF.0b013e3182516d7b.
Fernandez H, Capmas P, Lucot JP, et al; Fertility after ectopic pregnancy: the DEMETER randomized trial. Hum Reprod. 2013 May28(5):1247-53. doi: 10.1093/humrep/det037. Epub 2013 Mar 12.
de Bennetot M, Rabischong B, Aublet-Cuvelier B, et al; Fertility after tubal ectopic pregnancy: results of a population-based study. Fertil Steril. 2012 Nov98(5):1271-6.e1-3. doi: 10.1016/j.fertnstert.2012.06.041. Epub 2012 Jul 18.