Ectopic Pregnancy

Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Consequently, affected patients may suffer from acute abdominal pain as the developing embryo increases in size. Ectopic pregnancy can be quickly diagnosed by means of an ultrasound and laboratory analysis. Management can be expectant, medical, or surgical. Severe cases involving rupture of the fallopian tube and hemorrhage are considered a medical emergency and require immediate surgery.

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Epidemiology and Etiology

Epidemiology

  • 3rd-leading cause of maternal mortality 
  • 1%–2% of all pregnancies
  • Diagnosed in approximately 10% of patients presenting with vaginal bleeding and abdominal pain in early pregnancy

Etiology

Ectopic pregnancy (EP) can occur when the fertilized egg does not enter the uterine cavity by way of the fallopian tube by the 5th to 6th day of gestation. 

  • Caused by:
    • Disorders of the ovulation mechanism (e.g., as seen in polycystic ovarian syndrome (PCOS))
    • Blockage of the embryo’s tubal passage: Tubal passage may be affected by congenital anomalies, acquired tubal obstructions, and disruption of ciliary activity or tube motility.
  • Risk factors:
    • Pelvic inflammatory disease (50% of cases, increases risk 3-fold) 
    • Adhesions after tubal surgery (25% of cases)
    • Assisted reproduction (e.g., in vitro fertilization (IVF))
    • Prior EP or abortion
    • Abnormal endometrium (e.g., endometriosis or fibroids)
    • Congenital malformation of the uterus (bicornuate uterus)
    • Smoking
    • Advanced age (> 35 years old)
    • Intrauterine device/oral contraceptives (if pregnancy occurs despite their use)
  • Potential locations of implantation: 
    • 95% within the fallopian tube 
    • 3% in the ovary
    • 1% in the peritoneal cavity (abdominal)
    • < 1% in the cervix

Different types of EP according to location

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Clinical Presentation

  • May present as an acute abdomen
    • Severe lower abdominal or pelvic pain
    • Pain may be more diffuse if there is blood in the abdominal cavity.
    • If pain radiates toward the shoulder → sign of tubular rupture
  • Spotting or vaginal bleeding (may lead to hypovolemic shock)
  • General pregnancy symptoms:
    • Breast enlargement and tenderness
    • Secondary amenorrhea 
    • Morning sickness

Diagnosis

History and clinical examination

  • Patients may report a missed or irregular last menstrual period
  • Abdomen: guarding upon palpation of the lower abdomen
  • Pelvis: 
    • Cervical motion tenderness (must differentiate from pelvic inflammatory disease (PID))
    • Closed cervix
    • Adnexal tenderness
    • An adnexal mass may be felt in 10%–20% of cases.
  • Vital signs: tachycardia and hypotension in the case of a ruptured EP

Labs

  • Very important: Perform a pregnancy test on all women of reproductive age who present with abdominal pain! 
  • Urine or serum beta human chorionic gonadotropin (HCG): Elevated level confirms pregnancy.
  • Type and screen: blood type and Rh factor (if negative, RhoGam is required)
  • Complete blood count (CBC): to look for anemia/evidence of hemorrhage
  • Liver function tests (LFTs), basic metabolic panel (BMP), urinalysis (UA): to evaluate for other causes of acute abdomen

Diagnostic studies

  • Ultrasound:
    • Normal pregnancy: At 5–6 weeks’ gestation, a gestational sac and yolk sac are present within the uterus.
    • EP findings: 
      • An empty uterine cavity without an amniotic sac or with a pseudo-gestational sac
      • Enlargement of the fallopian tube with an amniotic sac
    • In the case of tubal rupture, free fluid (blood) is present in the pouch of Douglas.
    • Possible to determine if the embryo is alive by the detection of a fetal heartbeat
  • Diagnosis can be further confirmed by laparoscopy (or pelviscopy). 

Management

An EP must be closely monitored. The management of an EP can be expectant, medical, or surgical depending on the patient’s condition.

Emergency management

  • Assess and stabilize ABCs (airway, breathing, circulation). 
  • Give intravenous fluids to compensate for blood loss.
  • Transfusion if blood loss is significant
  • If the patient has an Rh-negative blood type: Administer RhoGam to prevent Rh incompatibility in future pregnancies.

Medical management

  • Reserved for hemodynamically stable patients and those with a pregnancy sac < 3.5 cm and no fetal cardiac activity on ultrasound
  • Methotrexate (IV or locally applied) to induce a medical abortion
  • Must monitor the patient’s HCG levels to 0

Expectant management

  • Only for patients who meet the following criteria:
    • Asymptomatic
    • No evidence of extrauterine sac/mass on ultrasound
    • Low and decreasing serum HCG (≤ 200 mIU/mL)
    • Agreeable to close follow-up
  • Steps include: 
    • Monitoring the pattern of serial HCG levels (normal pregnancy: doubles approximately every 48 hrs; in EP, values will decline) 
    • Giving strict return-for-followup instructions to ensure that HCG is monitored
    • Abandoning expectant management if significant abdominal pain develops or HCG increases or fails to decline

Differential Diagnosis

There are many differential diagnoses of an ectopic pregnancy. These diagnoses can be categorized into non-gynecological and gynecological causes.

Non-gynecological causes

  • Acute abdomen: severe, acute-onset abdominal pain that can be life-threatening and therefore requires urgent medical attention. Etiologies may be gastrointestinal (e.g., hepatitis), vascular, and/or genitourinary in nature. Diagnosis is often made using various radiographic studies. Depending on the severity of the condition, surgery may be required. Can be distinguished from EP by beta HCG and ultrasound (US).
  • Sigmoid diverticulitis: inflammation of the diverticula (outpouching of the mucosa due to weakness of the muscular layers of the colonic wall) of the sigmoid colon. Erosion of the diverticular wall by thickened food particles can cause inflammation and lower abdominal pain. Often diagnosed via computed tomography (CT) scan, on which colonic outpouchings and wall thickening can be seen. Treated with antibiotics and/or surgery in severe cases. 
  • Appendicitis: inflammation of the appendix caused by obstruction (e.g., by fecaliths or infection). Produces symptoms such as abdominal pain, vomiting, and malaise. Diagnostic findings may include an elevated WBC count and a thickened appendiceal wall on CT scan. Surgery is the recommended treatment, although some patients respond to antibiotics. Unlike in EP, US may reveal an enlarged appendiceal diameter.
  • Kidney stones: urine can become supersaturated with soluble substances (e.g., calcium oxalate), which crystallize and form stones that deposit throughout the urinary tract. Patients may present with colicky flank or abdominal pain. Diagnostic studies reveal hematuria, urinary stones on CT scan, and/or hydronephrosis on US. Management consists of pain control and varies depending on the chemical nature of the stones. 
  • Urinary tract infection (UTI): infection of the urethra, bladder, or kidney most commonly caused by bacteria. Often presents with frequent and painful urination, hematuria, lower abdominal pain, and fever. Diagnosis is with UA showing leukocytes, blood, and nitrite, but no elevated HCG, which helps differentiate this condition from EP. Treatment is conservative, with increased fluid intake and, in severe cases, antibiotics.

Gynecological causes

  • PID: an infectious disease of the upper female reproductive tract (i.e., uterus, fallopian tubes, and/or ovaries) along with its surrounding tissues. Sexually transmitted bacteria are typically the cause, so mucopurulent discharge and a friable cervix may be present on exam. A negative pregnancy test can help distinguish this condition from EP. Antibiotic therapy tailored to the causative agent is the main treatment. 
  • Ovarian cyst rupture: fluid-filled sacs within an ovary or on its surface, which can form as a result of ovulation. If a cyst ruptures, it can cause severe pain and internal bleeding. Diagnostic findings may include an adnexal mass and free fluid within the pelvis on US, along with a negative pregnancy test. Management includes watchful waiting for uncomplicated cysts and surgery for those cysts associated with hemorrhage. 
  • Ovarian torsion: the complete or partial rotation of the ovary around its supporting ligaments. As a result, ischemic injury of the ovarian tissue occurs due to blood supply compromise. Associated with conditions that cause ovarian enlargement (e.g., cysts, tumors). May lead to acute abdominal pain and vomiting; US and pregnancy testing can be used to distinguish this condition from EP. Urgent surgical detorsion is indicated to preserve the ovary.
  • Polycystic ovarian syndrome (PCOS): a multisystem endocrinological disorder characterized by ovulatory dysfunction and hyperandrogenism. Patients may present with obesity and menstrual abnormalities. Rotterdam criteria (oligo- or anovulation, signs of hyperandrogenism, and polycystic ovaries on US) are used to make the diagnosis. Unlike EP, PCOS is associated with infertility. Treatment depends on whether the patient is pursuing pregnancy.
  • Endometriosis: normal endometrial tissue is implanted outside the uterus, triggering an inflammatory response. Common symptoms include pelvic pain, dysmenorrhea, and menorrhagia. Diagnosis is confirmed by post-surgical histologic evaluation of a biopsied lesion. Tends to be associated with infertility and chronic dysmenorrhea, distinguishing the condition from EP. Management can be medical or surgical, depending on the severity of symptoms.
  • Endometrial hyperplasia: abnormal proliferation of the uterine endometrium. Caused by excess estrogen being unopposed by progesterone, which then causes abnormal uterine bleeding. The gold standard for diagnosis is endometrial sampling. Typically managed via surveillance, pharmacotherapy, or surgery. Although endometrial hyperplasia can cause abnormal bleeding as in EP, the condition tends to occur in perimenopausal women and has less of an association with pain.
  • Miscarriage and spontaneous abortion: loss of pregnancy before 20 weeks’ gestation. Causes include maternal reproductive organ abnormalities and chromosomal aberrations. Bleeding and cramping are the most common symptoms. Beta HCG will be positive in both miscarriages and EP, but EP tends to be associated with smaller amounts of vaginal bleeding than miscarriages. Management is expectant, medical, or surgical, depending on the type of miscarriage.

Mnemonic

The mnemonic “HAIKU POEM” can help you remember the many differential diagnoses of an ectopic pregnancy. (A haiku is a traditional Japanese poem.)

Non-gynecological causes: HAIKU

  • H: Hepatitis 
  • A: Acute abdomen
  • I: Intestinal Inflammation (appendicitis, sigmoid diverticulitis)
  • K: Kidney stone 
  • U: Urinary tract infection

Gynecological causes: POEM

  • P: Pelvic inflammatory disease
  • O: Ovarian disease (cyst rupture, torsion, polycystic ovaries)
  • E: Endometrial diseases (endometriosis, hyperplasia)
  • M: Miscarriage/spontaneous abortion

References

  1. Tulandi, T. (2020). Ectopic pregnancy: Expectant management. UpToDate. Retrieved November 22, 2020, from Tulandi, T. (2020). Ectopic pregnancy: Expectant management. UpToDate. Retrieved November 22, 2020, from https://www.uptodate.com/contents/ectopic-pregnancy-expectant-management?search=ectopic%20pregnancy%20expectant%20management&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 
  2. Sherwood, L. Human Physiology: From Cells to Systems. (9th ed., pp. 753, 756). Cengage Learning. 
  3. Marion, L. L., & Meeks, G. R. (2012). Ectopic pregnancy: History, incidence, epidemiology, and risk factors. Clinical obstetrics and gynecology, 55(2), 376–386. https://doi.org/10.1097/GRF.0b013e3182516d7b
  4. Farquhar C. M. (2005). Ectopic pregnancy. Lancet (London, England), 366(9485), 583–591. https://doi.org/10.1016/S0140-6736(05)67103-6
  5. Scibetta, E. W., & Han, C. S. (2019). Ultrasound in Early Pregnancy: Viability, Unknown Locations, and Ectopic Pregnancies. Obstetrics and gynecology clinics of North America, 46(4), 783–795. https://doi.org/10.1016/j.ogc.2019.07.013

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