Ectopic pregnancy

Ectopic pregnancy is a potentially lethal condition due to rupture and haemorrhage and so is an important diagnosis that needs to be considered in any woman of child bearing age who presents with abdominal pain and or vaginal bleeding.

All suspected cases must therefore have a serum beta HCG performed and a pelvic ultrasound.

Pathophysiology

Ectopic pregnancy occurs when the developing blastocyst becomes implanted at a site other than the endometrium of the uterine cavity.

The most common extra-uterine location is the fallopian tube, which accounts for 98 percent of all ectopic gestations but other possible sites include: cervical, cornual, hysterotomy scar, ovarian, or intraabdominal.

Risk Factors

Recognised risk factors include:

1. Previous tubal pathology, including:
   • Previous ectopic pregnancy
   • Previous tubal surgery:
     • Tubal reconstructive surgery
     • Tubal sterilisation – the estimated failure rate during the first year after tubal     sterilisation is < 1 % and approximately one third of these pregnancies are ectopic.
   • Pelvic inflammatory disease
   • Endometriosis
   • Congenital anomalies
2. Increased age, (> 35 years)
3. IUDs
4. Assisted reproduction:
   The incidence of ectopic pregnancy is higher in those who experience infertility, which could reflect:
   • Increased incidence of tubal abnormality
   • An association between fertility drugs and ectopic pregnancy, which may be related to altered tubal function secondary to hormonal fluctuation.
5. Smoking

Heterotopic pregnancy:

The identification of an intrauterine pregnancy does not absolutely exclude the possibility of an ectopic pregnancy.

A twin ectopic pregnancy may rarely co-exist with an intrauterine pregnancy (heterotopic pregnancy).

The incidence of heterotopic pregnancies in the general population is uncommon, approximately 1:4000, however in patients who have undergone assisted reproduction this condition becomes relatively more important as the incidence rises to 1:100 to 1:500.

The Natural History of Ectopic Pregnancy

 If left untreated, an ectopic pregnancy in the fallopian tube can progress to a tubal rupture a tubal abortion, or spontaneous regression.

1.         Tubal Rupture:

• Tubal rupture is usually associated with profound hemorrhage, which can be fatal if surgery is not performed expeditiously to remove the ectopic gestation.
• Salpingectomy is the most common surgical approach when the tube has ruptured.
• Ruptured ectopic pregnancy is the major cause of pregnancy-related maternal mortality in the first trimester

2.         Tubal Abortion:

• Tubal abortion refers to expulsion of the products of conception through the fimbria
• This can be followed by resorption of the tissue or by reimplantation of the trophoblasts in the abdominal cavity (i.e, abdominal pregnancy) or on the ovary (i.e, ovarian pregnancy).
• Tubal abortion may be accompanied by severe intraabdominal bleeding, necessitating surgical intervention, or by minimal bleeding, not requiring further treatment.

3.         Spontaneous resolution:

• The incidence of spontaneous resolution of an ectopic pregnancy is unknown.
• Potential candidates are hemodynamically stable women with an initial hCG concentration less than 2000 IU/L that is declining.

Clinical Features

Although always important, the clinical history and examination cannot make a definitive diagnosis of ectopic pregnancy.

Beta HCG levels and ultrasound examination will be required to do this.

Important points of history:

1.  Pelvic pain:

• This is seen in 90% of cases (usually localised to one side)
• Tubal rupture may be associated with an abrupt onset of severe pain, but rupture may also present with mild or intermittent pain.
• Over 50 percent of women are asymptomatic before tubal rupture occurs.

2. Short period of amenorrhoea:

• Most commonly this will be at around 6-8 weeks after the last normal menstrual period
• Symptoms can occur later however, especially if the pregnancy is in an extrauterine site other than the fallopian tube.

3. Vaginal bleeding:

• Vaginal bleeding is seen in approximately 70% of cases
• Ectopic pregnancies are typically associated with pain first followed by a small bleed compared to spontaneous abortions which tend to present with bleeding first followed by pain.

Important points of examination:

1. Assess the stability of the patient with respect to hemodynamic status.

• This will be the most urgent consideration.
• An ectopic pregnancy may be unruptured or ruptured at the time of presentation to medical care.

2. Adnexal tenderness/ abdominal peritonism:

• Pelvic pain/ tenderness  is typically localized to one side, however  this may not always be present, and may not always be unilateral.
• Significant diffuse abdominal pain/tenderness/ peritonism suggests rupture and bleeding.

3. Detection of an adnexal mass:

• This may be found in some women, but it is a subjective and unreliable sign.

Care should be taken as excessive pressure may rupture an ectopic pregnancy.

Investigations

Blood tests:

1. FBE: hemoglobin and/or hematocrit
2. UECs/ glucose
3. Serum beta HCG
   • A quantitative test is done, giving a beta HCG level. This is useful in enabling serial estimations to monitor pregnancy viability.
   • In urgent cases, a quick qualitative test (i.e positive or negative) may be done rather than a quantitative test.
   • In very urgent cases, a urinary beta HCG, may be quicker however it must be kept in mind that this is less reliable than a serum result.
4. Blood group and cross matching:
   • Blood is grouped and held or cross matched according to clinical necessity
5. The blood group is also required in order to determine the need for anti D

Ultrasound:

If the beta HCG is >1500 IU / L:

• Transvaginal ultrasound should be able to detect an intrauterine pregnancy at these beta HCG levels.
• The ectopic pregnancy itself may be seen within the fallopian tube.
• If the uterine cavity is empty, the diagnosis must remain “ectopic pregnancy till proven otherwise”, even if the adnexal structures appear normal.

If the beta HCG is < 1500 IU / L:

• Transvaginal ultrasonic diagnosis of ectopic pregnancy is more problematic with beta HCG levels that are below 1500 IU / L.
• At these levels a gestational sac cannot be reliably detected even on transvaginal scans.
• An empty uterine cavity or clear adnexa therefore cannot rule out the possibility of an early normal pregnancy or an early ectopic pregnancy.
• A finding of echogenic fluid (consistent with blood) in the pelvic cul-de-sac and/or abdomen is consistent with rupture.

FAST Scan

Unstable patients should never leave the ED for ultrasound examination.

A FAST scan done in the ED may detect intraperitoneal blood, especially in cases of patients who are hemodynamically unstable.

If the beta HCG level is <1500 IU / L then ultrasound confirmation of ectopic pregnancy may be problematic. If the patient is hemodynamically unstable (or has significant adnexal pain or tenderness), then ectopic pregnancy is not ruled out and these patients must be assessed by the obstetric unit.

Laparoscopy:

Occasionally when beta HCG is elevated but ultrasound is non-diagnostic laparoscopic examination may be considered, when clinical suspicion of ectopic pregnancy remains particularly if the patient is unstable.

See also diagnostic flow chart in appendix 1 below.

Management

There are 3 approaches to treatment:

1. Expectant management
2. Medical management
3. Surgical management

Expectant management

In a small number of cases of presumed or possible ectopic pregnancy, in which the risk of tubal rupture is minimal, expectant management can be appropriate.

Criteria that must be met before expectant treatment is considered include:

• An asymptomatic patient.
• The patient is understanding, motivated and reliable and has ready access to the hospital. 
• The beta HCG is < 200 IU/ml (and declining).¹

These cases should be closely monitored by the Obstetric unit.

• Quantitative beta HCG levels are performed at 48-72 hour intervals.
• Women should be followed until the beta HCG level is < 5
• There should be active intervention if:
  • Symptoms of ectopic pregnancy occur
  • Beta HCG levels rise

Medical management

Methotrexate (often abbreviated as MTX) therapy is a noninvasive medical option in carefully selected patients, that has comparable efficacy, safety, and fertility outcomes with surgery.

The advantages of surgical treatment are less time for resolution of the ectopic pregnancy and avoidance of the need for prolonged monitoring.

Surgery is required when urgent treatment is indicated or methotrexate therapy is unlikely to be successful.

Criteria for methotrexate therapy  include:

1. Hemodynamically stable.
2. Pain free
3. Willing and able to comply with post-treatment follow-up
4. Willing to use reliable contraception for 3 months post treatment.
5. Earlier pregnancies:
   • Beta HCG concentration  ≤ 3,500 IU/L.
   • No fetal cardiac activity.
   • Ectopic mass size less than 3.5 cm is also commonly used
6. There is no free fluid on ultrasound
7. There are no medical contraindications:
   • To methotrexate itself, e.g. allergies, hepatic/ renal impairment/immunosuppression.
   • Should have normal baseline blood tests – FBE/ U&S/LFTs

Methotrexate procedure:

• Patients are generally admitted under the Obstetric Unit to have this treatment initiated as it is complex and based on total body surface area
• Methotrexate is usually given as an IM stat dose, (though some centers use different protocols with IV or oral dosing)

Anti-D is given as per protocol for any rhesus negative woman.

Quantitative beta HCG should then be repeated weekly until there are two consecutive negative measurements, (even if this takes longer than 6 weeks).

Surgical management

Surgery may be done via laparoscopy or laparotomy.

Surgical treatment consists of:

• Salpingostomy: incising the tube to remove the tubal gestation but leaving the remainder of the tube intact.
  Or
• Salpingectomy: removal of the fallopian tube. More commonly performed.
  Salpingectomy is the standard procedure if:
  • The condition of the tube is compromised (ruptured or otherwise disrupted)
  • Bleeding is uncontrolled
  • The gestation appears too large to remove with salpingostomy.

Surgery is indicated in:

1. Ruptured (or suspected ruptured) tube:
   • Clinical signs of symptoms of impending or ongoing rupture of ectopic mass (e.g., pelvic or abdominal pain or evidence of intraperitoneal bleeding suggestive of rupture
   • Ruptured mass on ultrasound or moderate to large free peritoneal fluid on ultrasound.
2. Later ectopic pregnancies:
   • Beta HCG > 3,500 IU/L
   • Adnexal mass > 3.5 cm on ultrasound
3. Relative or absolute contraindication to MTX therapy
4. Failed medical therapy
5. Patient preference

In hemodynamically unstable patients ED priorities will include:

1. Initial fluid resuscitation
2. Blood/ blood products as clinically required
3. Titrated IV opioid analgesia, as required
4. Urgent qualitative urine/ serum beta HCG (if pregnancy not already known)
5. Urgent notification of the:
   • Obstetric unit
   • Anaesthetics
6. Though not an urgent priority, anti-D prophylaxis should be given for all Rhesus negative women according to usual guidelines.

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References

FOAMed

• Nickson C. Ectopic Pregnancy. CCC
• Rippey J. Ultrasound case 013. LITFL
• Rippey J. Ultrasound case 013. LITFL
• Rippey J. Ultrasound case 029. LITFL
• Cadogan M. Cullen sign. LITFL

Publications

• Mummert T, Gnugnoli DM. Ectopic Pregnancy. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.