Normally, implantation occurs in the uterine cavity. However, about 1% of pregnancies occur outside of the uterus, also known as an ectopic pregnancy.
Pathophysiology
Fertilisation of the egg and sperm occurs in the fallopian tube most commonly. This forms a zygote that then travels down the fallopian tube to become a morula (a 16-32 celled embryo). The blastocyst (32-256 cells) then forms within the uterine cavity. It then implants into the endometrial lining of the uterine wall before burrowing deeper to establish placental circulation through trophoblastic differentiations.
Throughout the initial stages of fertilisation, the tubal epithelium generates a mechanical peristaltic force to push the embryo towards the uterine cavity. Issues throughout this process can result in ectopic pregnancies as implantation subsequently occurs outside of the uterine cavity.
Failed migration of the embryo occurs due to:
- Anatomical abnormalities of the fallopian tube - this may occur due to inflammation (such as salpingitis, PID, endometriosis etc.), which leads to adhesion formation, or surgeries (such as sterilisation or tubal reconstruction)
- Fallopian tube ciliary dysmotility - due to changes to molecular signalling that suppress the ciliary beat frequency in fallopian tubes. This occurs with progesterone, for example.
- Molecular factors - molecules involved in the cellular matrix and extracellular matrix may promote premature implantation.
⚠️ Risk factors
A large proportion of women have no risk factors that are identifiable for their ectopic pregnancy. However, there are certain risk factors associated with an increased risk of ectopic pregnancy. These include:
- History of ectopic pregnancy - there is about a 10% chance of an ectopic if the woman has had one previously. This rises to 25% if they have had 2 or more ectopics.
- History of pelvic surgery - such as tubal reconstruction, sterilization, C-section.
- Pelvic inflammatory disease
- Salpingitis
- Endometriosis
- Black ethnicity
- History of infertility
- History of chlamydial infections
- In vitro fertilization
- Smoking
- Maternal age >35
- Intrauterine contraception - if pregnancy does occur with intrauterine contraception in situ then the risk of ectopic increases greatly.
- Prenatal diethylstilbesterol exposure - diethylstilbesterol (DES) is a synthetic form of oestrogen which was historically given to pregnant women in the 1930s-1980s. It was used to prevent complications in pregnancy. It is associated with abnormal fallopian tube development and as such ectopic pregnancy. It is now used to treat some forms of breast cancer and prostate cancer (although also increases the risk of breast cancer itself too).
- Multiple sexual partners
😷 Presentation
Ectopic pregnancy can present with an array of symptoms which may be similar to other common conditions of the urological and gastrointestinal systems. However, with a woman of childbearing potential there should be a low threshold for suspicion.
It usually presents at around 6-8 weeks gestation.
Some features of ectopic pregnancy are:
- ⭐️ Abdominal/pelvic pain - in the right or left iliac fossa especially. The pain is constant. Rebound tenderness may be present on examination.
- ⭐️ Adnexal mass/tenderness - NICE recommend to not assess for adnexal mass as there is a risk of rupturing the ectopic.
- ⭐️ Vaginal bleeding/discharge - the discharge is described as brown in colour and is described as being similar to prune juice.
- Missed period (amenorrhoea)
- Cervical motion tenderness - on bimanual examination. It is also known as Chandelier sign. It is indicative of
- Shoulder tip pain - due to irritation of the diaphragm by blood within the peritoneal cavity. This is due to the supraclavicular nerves sharing the C3-C5 dermatome.
- Haemodynamic instability - indicative of a ruptured ectopic pregnancy.
- Orthostatic hypotension
- Pallor
- Vomiting and diarrhoea - can often be the presenting symptom of abdominal bleeding.
🔢 Classification
We can classify the ectopic pregnancy based on its anatomical location:
- Tubal ectopic - 97% of ectopic pregnancies are tubal ectopics.
- Ampulla - 73.3%
- Isthmus - 12.5%
- Fimbria - 11.6%
- Interstitium and cornua - 2.6%
- Interstitial ectopic - this is when there is an ectopic at the junction of the fallopian tube and the uterus. Approximately 2% of ectopics are interstitial.
- Ovarian ectopic - 3.2%
- Abdominal ectopic - 1.4%
- Cervical ectopic - <1%
- Caesarean scar ectopic - <1%
🔍 Investigations
- 🥇 Pregnancy test - should be positive.
- 🏆 Transvaginal ultrasound - we can look for a gestational sac with a yolk sac and fetal pole and heartbeat within the fallopian tube.
- Sometimes we may see an empty gestational sac and this is known as the tubal ring sign/bagel sign/blob sign.
- We may see an empty uterus or fluid in the uterus (which can be mistaken for a gestational sac and is known as a pseudogestational sac). These are also indicative of ectopic pregnancy.
- Transabdominal ultrasound - may be done for women with an enlarged uterus, fibroids, ovarian cyst or other cases where transvaginal is not possible.
- 🥈 MRI - can be used as a second-line option
Management
- If the women is stable → pregnancy test to confirm pregnancy → then she must be assessed in an early pregnancy assessment service or out-of-hours gynaecology service immediately if they have any of the following:
- Pain + abdominal tenderness
- Pelvic tenderness
- Cervical motion tenderness
- If haemodynamically unstable → transfer to A&E immediately for urgent assessment and management.
- In women with a pregnancy of less than 6 weeks with bleeding but no pain and no risk factors → perform urine pregnancy test after 7-10 days and return if positive (if negative it means they have miscarried).
Once an ectopic pregnancy has been confirmed, we have 3 options for management:
- Expectant management - i.e. watch and wait.
- Medical management
- Surgical management
- Expectant management involves monitoring the woman over 48 hours and tracking serum ß-hCG levels.
- If they do rise or fail to decrease at an acceptable rate→ active intervention. If symptoms develop then active intervention will be considered too.
Expectant management is considered in women who meet all of the following criteria:
- Clinically stable + pain free
- Ectopic <35mm
- No fetal heartbeat
- Serum hCG <1000
- Able to attend follow up
- Unruptured
- 🥇 IM methotrexate - given in the buttocks. It is highly teratogenic and results in spontaneous termination. Women should also be advised to not get pregnant for the subsequent 3 months.
Adverse effects of methotrexate include: vaginal bleeding, nausea and vomiting, abdominal pain, stomatitis, hepatotoxicity, nephrotoxicity, pulmonary toxicity, myelosuppression.
Medical management is considered in women who meet all of the following criteria:
- No significant pain
- Ectopic <35mm
- Serum hCG <1500
- No fetal heartbeat
- Unruptured
- No simultaneous intrauterine pregnancy
💡 If the serum hCG is >1500 and <5000 and are able to return for follow up then we can choose between medical and surgical management.
There are 2 surgical options we may choose from:
- 🥇 Laparoscopic salpingectomy - this is the first-line option, unless they have other risk factors for infertility. It involves removal of the fallopian tube.
- 🥈 Laparoscopic salpingotomy - is the preferred option if there are other risk-factors for infertility. It involves an incision in the tube and removal of the ectopic but keeping the tube in situ and not removing it entirely as we do in an a salpingectomy. 1 in 5 women who undergo salpingotomy require further treatment such as methotrexate or salpingectomy.
- 🥇 Anti-D immunoglobulin - must be offered to all rhesus-negative women who have had surgical removal of the ectopic.
Surgical management is considered in women who meet all of the following criteria:
- Significant pain
- Ectopic >35mm
- Serum hCG >5000
- Fetal heartbeat visible
- Unable to return for follow up after methotrexate treatment
A pregnancy of unknown location (PUL) is when there is a positive pregnancy test but no evidence of the pregnancy on ultrasound scan.
If this occurs we have to do the following:
- Serial ß-hCGs - serum hCG is taken and then repeated at 48 hours to assess the change. Normally, in intrauterine pregnancies, hCGs should double every 48 hours. This is not the case in ectopic pregnancies or in miscarriages. Let’s take a look at the following scenarios:
- Rise >63% - most likely an intrauterine pregnancy. Repeat ultrasound at 1-2 weeks.
- Rise <63% - most likely an ectopic pregnancy. Monitor and review patient.
- Fall >50% - most likely a miscarriage. Repeat pregnancy test at 2 weeks to confirm miscarriage.
🚨 Complications
- Maternal death
- Recurrent ectopic pregnancy