II. Definition

  1. Implantation of fertilized ovum outside of the Uterus

III. Epidemiology

  1. Incidence: 2% of all pregnancies
  2. Second most common cause of maternal mortality
    1. Accounts for 6% of maternal deaths (as high as 10-15% of maternal deaths in past)
    2. Case fatality rate: 3.8 deaths per 10,000 ectopics

IV. Risk Factors

  1. Highest risk factors
    1. Prior tubal surgery (Odds Ratio 21.0)
    2. Sterilization such as Tubal Ligation (Odds Ratio 9.3)
    3. Prior Ectopic Pregnancy (Odds Ratio 8.3, represents 11% of cases)
    4. Intrauterine Device (IUD) (Odds Ratio 5.0, represents 14% of cases)
    5. In-vitro fertilization
    6. Diethylstilbestrol Exposure (DES Exposure) in utero (Odds Ratio 5.6)
  2. Moderate risk factors
    1. Pelvic Inflammatory Disease or other tubal infection (Odds Ratio 3.4)
    2. Infertility for 2 years or longer (Odds Ratio 2.7, represents 15% of cases)
    3. Multiple sexual partners
    4. Advanced maternal age >40 years old (Odds Ratio 2.9)
    5. Tobacco abuse (via impaired tubal motility, Odds Ratio 3.9 for 1 ppd, 3.1 for 0.5 ppd)
  3. Other risk factors
    1. Endometriosis
    2. Mini Pill use (Progestin only pill)
    3. Vaginal Douching
    4. Early age at first intercourse (age <18 years)

V. Symptoms

  1. Pregnancy Symptoms (e.g. Amenorrhea, Nausea, Fatigue, Urinary Frequency, Breast engorgement)
  2. Onset of symptoms occurs on average ~7 weeks after Last Menstrual Period
  3. Abdominal Pain (>97% of cases)
    1. May be non-specific, sharp or crampy, diffuse or localized
  4. Vaginal Bleeding (75% of cases)
    1. Varies from spotting to heavy bleeding with clots

VI. Signs

  1. Precaution: Exam can not exclude Ectopic Pregnancy
    1. No Vaginal Bleeding in 30% of ectopic pregnancies
    2. Negative pelvic exam in 10% of ectopic pregnancies
    3. Buckley (1999) Ann Emerg Med 34:589-94 [PubMed]
  2. Ectopic likelihood if Abdominal Pain and Vaginal Bleeding
    1. No risk factors: 39%
    2. Risk factors: 54%
    3. Mol (1999) Hum Reprod 14:2855-62 [PubMed]
  3. Classic (15-50% of patients)
    1. Pelvic Pain or Abdominal Pain (97%)
      1. Initially localized pain
      2. Pain later generalizes
    2. Abdominal tenderness (91%)
    3. First Trimester Bleeding (79%)
  4. Commonly associated findings
    1. Adnexal tenderness (54%)
    2. Amenorrhea
    3. Shoulder Pain
      1. Associated with ruptured Ectopic Pregnancy with Hemorrhage that directly irritates the phrenic nerve
    4. BR sign
      1. Patient faints post Bowel Movement
    5. Early Pregnancy Symptoms
    6. Cullen's Sign (Periumbilical Bruising)
    7. Nausea or Vomiting
    8. Diarrhea
    9. Dizziness
    10. Ectopic Pregnancy ruptures between 6 and 12 weeks
  5. Other Signs
    1. Orthostasis
    2. Tachycardia
    3. Low grade fever
    4. Chadwick's Sign (Cervix and vaginal Cyanosis)
    5. Hegar's Sign (softened uterine isthmus)
    6. Hypoactive bowel sounds
    7. Cervical Motion Tenderness
    8. Enlarged Uterus
    9. Tender pelvic or Adnexal Mass
    10. Cul-de-sac fullness
    11. Decidual cast (Passage of Decidua in one piece)
  6. Signs suggestive of ruptured Ectopic Pregnancy
    1. Severe abdominal tenderness with rebound, gaurding
    2. Orthostatic Hypotension

VII. Differential Diagnosis

  1. Most common alternative diagnoses
    1. Appendicitis
    2. Threatened Abortion
    3. Ruptured Ovarian Cyst (corpus luteum)
    4. Pelvic Inflammatory Disease
      1. Salpingitis
      2. Endometritis
    5. Nephrolithiasis
    6. Ovarian Torsion
    7. Intrauterine Pregnancy
  2. Other alternative diagnoses
    1. Heterotopic pregnancy
      1. Rare in general population (1 case in 30,000 women)
      2. Common for those undergoing in vitro fertilization (1 case in 100 women)
    2. Dysmenorrhea
    3. Dysfunctional Uterine Bleeding
    4. Urinary Tract Infection
    5. Diverticulitis
    6. Mesenteric Lymphadenitis

VIII. Labs

  1. See Imaging below
  2. Quantitative hCG
    1. HCG increases by at least 53% (and typically doubles) every 2 days in a normal pregnancy
      1. Levels off after bHCG reaches 100,000 at approximately 8 weeks
    2. bHCG with inadequate increase may suggest ectopic
      1. Test Sensitivity: 36% (some studies report 71%)
      2. Test Specificity: 65%
      3. bHCG also increases inadequately (<50%) in 1% of viable pregancies
      4. bHCG decreases by <35% in up to 7% of 10% of Spontaneous Abortions
    3. bHCG should not be used to defer Ultrasound when Ectopic Pregnancy is considered
      1. Intrauterine pregnancy is first confirmed on Transvaginal Ultrasound at bHCG 1500-2000
      2. However, 40% of ectopic pregnancies are identified at bHCG less than 1000 mIU/ml
      3. Ectopic pregnancies have occurred with bHCG as low as 10 mIU/ml
    4. bHCG level does not predict ruptured ectopic
      1. Ruptured ectopic may occur at any bHCG level
    5. bHCG must be followed serially with all management protocols
      1. Follow bHCG to non-detectable levels (may need as long as 6 weeks)
      2. If bHCG start to rise again after falling, repeat Ultrasound is needed
  3. Blood Type and Rh, hold units
    1. Rh Negative women should be administered 300 mcg (or 50 mcg) RhoGAM if bleeding
  4. Complete Blood Count
    1. Leukocytosis
  5. Urinalysis with microscopic exam
  6. Culdocentesis
    1. Rarely performed now due to Transvaginal Ultrasound
    2. Differentiates ruptured Ovarian Cyst from ectopic
    3. Yield of aspirate with >15% Hematocrit suggests bleed
  7. Tests not recommended for ectopic diagnosis
    1. Serum Progesterone (Test Sensitivity: 15%)

IX. Imaging

  1. Precautions
    1. Transvaginal Ultrasound should be performed regardless of bHCG level when Ectopic Pregnancy is considered
    2. In 40% of Ultrasound diagnosed Ectopic Pregnancy cases, bHCG was below 1000 mIU/ml
    3. Counselman (1998) J Emerg Med 16(5): 699-703 [PubMed]
  2. General
    1. Findings suggestive of intrauterine pregnancy
      1. Intrauterine Gestational Sac suggests intrauterine pregnancy
        1. Central blastocyst
        2. Surrounding double ring of echogenic Decidua and chorionic villi (double Decidua sign, 4.5-5 weeks)
        3. Yolk Sac confirms intrauterine pregnancy wiith PPV 100% (5-6 weeks)
      2. Exceptions
        1. Pseudogestational sac (no true Gestational Sac)
          1. No Echogenic ring
          2. No Yolk Sac or fetal pole seen
        2. Heterotopic pregnancy (Simultaneous intrauterine and Ectopic Pregnancy)
          1. Overall Incidence: 1 in 4000 to 30,000 risk (rare)
          2. Fertility patient Incidence: 1 in 300 (may be 1 in 30 for some types of fertility treatment)
          3. Ultrasound misses heterotopic pregnancy in 50% of cases at 5-6 weeks
    2. Findings suggestive of Ectopic Pregnancy
      1. Absence of Gestational Sac at bHCG 1500-1800
      2. No mass or free fluid seen (20% likelihood)
      3. Free fluid present (71% likelihood of ectopic)
      4. Echogenic mass at Adnexa (85% likelihood)
      5. Moderate to large free fluid in pouch of Douglas (95% likelihood)
      6. Echogenic mass with free fluid (100% likelihood)
      7. False positive (free fluid in pouch of douglas)
        1. Ruptured corpus luteum cyst
        2. Spontaneous Abortion
        3. Menses
  3. Transvaginal Ultrasound (5 MHz or greater)
    1. Test Sensitivity: 90%
    2. Test Specificity approaches 100%
    3. Gestational Sac of 5 mm (Days 35-37 or 4.5 to 5 weeks, bHCG 1500-2000)
      1. Earliest finding in pregnancy, but does not exclude Ectopic Pregnancy
      2. Double Decidual sac sign (2 bright concentric ring around the Gestational Sac)
      3. Case reports of absent Gestational Sac on Ultrasound in viable pregnancies with bHCG as high as 4300 mIU/ml
    4. Yolk Sac (Days 37-40 or 5-6 weeks, gestation sac>10 mm)
      1. Confirms intrauterine pregnancy (100% Positive Predictive Value)
    5. Fetal Pole (Day 40, Gestational Sac>18 mm, bHCG 5000)
    6. Fetal Heart Activity (Day 45 or 6-7 weeks, crown rump length >5 mm, bHCG 17,000)
  4. Transabdominal Ultrasound
    1. Gestational Sac (Day 42, bHCG 6000-6500)
    2. Evaluate pouch of douglas for free fluid (see above)
  5. FAST Exam
    1. Free fluid in Morrison's pouch or in Pelvis on Abdominal Ultrasound may warrant emergent surgery

X. Evaluation

  1. Indications
    1. Positive Pregnancy Test AND
    2. Pelvic Pain or Vaginal Bleeding
  2. Step 1: History and physical
    1. Unstable
      1. Go to emergent protocol below
    2. Stable
      1. Go to step 2
  3. Step 2: Transvaginal Ultrasound
    1. Intrauterine pregnancy
      1. Expectant management
    2. Ectopic Pregnancy
      1. See protocols below
  4. Step 3a: Initial bHCG above discriminatory level (e.g. >1500 mIU on Transvaginal Ultrasound)
    1. Treat suspicious Adnexal Mass as Ectopic Pregnancy
    2. Repeat bHCG and Transvaginal Ultrasound in 2 days if no Gestational Sac or Adnexal Mass identified
      1. Treat as Ectopic Pregnancy if bHCG fails to rise appropriately
      2. Treat as normal pregnancy if Transvaginal Ultrasound confirms IUP
      3. Follow weekly bHCG until 0 mIU/ml if decreases
      4. Repeat bHCG and Transvaginal Ultrasound in 2 days if bHCG has normal rise (but nondiagnostic Ultrasound)
  5. Step 3b: Initial bHCG below discriminatory level (e.g. <1500 mIU on Transvaginal Ultrasound)
    1. Repeat bHCG every 48 hours
    2. bHCG decreasing (intrauterine or ectopic failed pregnancy)
      1. Obtain weekly bHCG levels until falls to <5 mIU/ml
    3. bHCG rises normally
      1. Repeat Transvaginal Ultrasound when discriminatory level reached (e.g. <1500 mIU)
    4. bHCG plateaus or with inadequate rise
      1. Obtain Transvaginal Ultrasound
      2. Manage medically or surgically as failed pregnancy (ectopic or intrauterine)
        1. If Transvaginal Ultrasound negative or with Adnexal Mass

XI. Approach: Ultrasound, bHCG with D&C

  1. Indications
    1. Pregnancy with cramping and Vaginal Bleeding
    2. Patient stable
  2. Step 1: Pelvic Ultrasound
    1. Intrauterine Pregnancy: Routine Prenatal Care
    2. Ectopic Pregnancy
      1. See Ectopic Pregnancy Management below
      2. See Methotrexate Ectopic Protocol
    3. Abnormal Intrauterine Pregnancy: D&C (see Step 3)
    4. Non-Diagnostic Ultrasound: Go to Step 2 below
  3. Step 2: Quantitative hCG
    1. Transvaginal Ultrasound discriminatory HCG: 1500 mIU
    2. HCG less than discriminatory levels: Go to Step 4
    3. HCG exceeds discriminatory levels: Go to Step 3
  4. Step 3: Dilatation and Curettage (if HCG > cutoff)
    1. D&C shows chorionic villi: Routine care for failed intrauterine pregnancy
    2. D&C shows no chorionic villi: Surgery for Ectopic Pregnancy
  5. Step 4: Serial Quantitative hCG (if HCG < cutoff)
    1. Normal fall: Manage as Miscarriage
    2. Abnormal rise or fall in HCG: D&C (see Step 3)
    3. Normal HCG rise
      1. Ultrasound when HCG > cutoff
      2. Go to Step 1
    4. Precaution
      1. Symptomatic Ectopic Pregnancy can occur prior to HCG of 1500 (before discriminatory values)

XII. Approach: Emergent

  1. Indications
    1. Suspected ruptured Ectopic Pregnancy
    2. Hemoperitoneum (significant intraperitoneal fluid presumed to be Hemorrhage)
    3. Hemorrhagic Shock
    4. Abdominal Pain with peritoneal signs
    5. Open cervical os
  2. Evaluation protocol
    1. Consult Ob/Gyn early in suspected Ectopic Pregnancy with hemodynamic instability
      1. Surgical exploration and stabilization is indicated
    2. Obtain IV Access with 2 large bore IVs
    3. Obtain labs as above (including bHCG, Blood Type and Cross)
    4. Fluid Resuscitation and Blood Transfusion for Hemorrhagic Shock
    5. Bedside Transvaginal Ultrasound (if available)

XIII. Management: Treatment protocols

  1. See Approach above
  2. Precautions
    1. Follow bHCG to non-detectable levels regardless of management strategy (up to 6 weeks)
    2. If bHCG start to rise again after falling, repeat Ultrasound is needed
  3. All patients
    1. RhoGAM for Rh negative women with Vaginal Bleeding
  4. Expectant Management indications (counsel regarding tube rupture risk; follow bHCG every 48 hours, then weekly)
    1. Minimal pain or bleeding
    2. Reliable patient with no barriers to follow-up and accessing healthcare
    3. bHCG less than 1000 mIU/ml and falling
    4. No signs of tubal rupture
    5. Ectopic or Adnexal Mass <3 cm or not detected
    6. No Embryonic heart beat
    7. Cohen (1999) Clin Obstet Gynecol 42:48-54 [PubMed]
  5. Medical Management: Methotrexate Indications
    1. See Methotrexate Ectopic Protocol
    2. Reliable patient with no barriers to follow-up and accessing healthcare
    3. Stable Vital Signs with normal LFTs, CBC, platelets
    4. Unruptured Ectopic Pregnancy without cardiac activity
    5. Ectopic mass 3.5 cm or less
    6. bHCG <2000 mIU/ml (or <5000 mIU/ml per some guidelines)
    7. No medical contraindications
      1. Liver, Kidney, lung or hematologic condition
      2. Immunodeficiency
      3. Peptic Ulcer Disease
      4. Alcohol Abuse
      5. Breastfeeding
  6. Surgical Management Indications (Salpingectomy or if desired fertility, and possible, Salpingostomy)
    1. Failed or contraindicated non-surgical management
    2. Nondiagnostic Transvaginal Ultrasound and bHCG >1500
    3. Hemoperitoneum
    4. Diagnosis unclear
    5. Advanced Ectopic Pregnancy (high B-HCG, large mass, Embryonic cardiac activity)
    6. Non-compliant patient
    7. Unstable Vital Signs

XIV. Prognosis: Future conception

  1. Conception rate post-ectopic: 77%
  2. Recurrent Ectopic Pregnancy risk
    1. After first Ectopic Pregnancy: 5-20% risk
    2. After second Ectopic Pregnancy: 32% risk

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Ontology: Ectopic Pregnancy (C0032987)

Definition (MEDLINEPLUS)

The uterus, or womb, is an important female reproductive organ. It is the place where a baby grows when a woman is pregnant. If you have an ectopic pregnancy, the fertilized egg grows in an abnormal place, outside the uterus, usually in the fallopian tubes. The result is usually a miscarriage.

Ectopic pregnancy can be a medical emergency if it ruptures. Signs of ectopic pregnancy include

  • Abdominal pain
  • Shoulder pain
  • Vaginal bleeding
  • Feeling dizzy or faint

Get medical care right away if you have these signs. Doctors use drugs or surgery to remove the ectopic tissue so it doesn't damage your organs. Many women who have had ectopic pregnancies go on to have healthy pregnancies later.

Dept. of Health and Human Services Office on Women's Health

Definition (NCI) An abnormal pregnancy in which the conception is implanted outside the endometrial cavity.
Definition (NCI_NCI-GLOSS) A condition in which a fertilized egg grows outside of the uterus, usually in one of the fallopian tubes. Symptoms include sharp pain on one side of the abdomen and bleeding from the vagina.
Definition (NCI_FDA) The state or condition of having a developing embryo or fetus in the body (outside the uterus), after union of an ovum and spermatozoon, during the period from conception to birth.
Definition (MSH) A potentially life-threatening condition in which EMBRYO IMPLANTATION occurs outside the cavity of the UTERUS. Most ectopic pregnancies (>96%) occur in the FALLOPIAN TUBES, known as TUBAL PREGNANCY. They can be in other locations, such as UTERINE CERVIX; OVARY; and abdominal cavity (PREGNANCY, ABDOMINAL).
Definition (CSP) development of a fertilized ovum outside of the uterine cavity.
Concepts Disease or Syndrome (T047)
MSH D011271
ICD9 633.9, 633
ICD10 O00 , O00.9
SnomedCT 156083001, 198630007, 156080003, 34801009
LNC MTHU015326
English Ectopic Pregnancies, Pregnancies, Ectopic, Pregnancy, Ectopic, Unspecified ectopic pregnancy, EXTRAUTERINE PREGNANCY, PREGNANCY ECTOPIC, Ectopic pregnancy NOS, Ectopic pregnancy, unspecified, PREGN ECTOPIC, ECTOPIC PREGN, ectopic pregnancy (diagnosis), ectopic pregnancy, Pregnancy ectopic, Extra-uterine pregnancy, Extrauterine pregnancy, Ectopic Pregnancy, Pregnancy, Ectopic [Disease/Finding], Pregnancy;ectopic, ectopic pregnancies, Eccyesis, Ectopic pregnancy NOS (disorder), ECTOPIC PREGNANCY, PREGNANCY, ECTOPIC, extrauterine pregnancy, Extrauterine Pregnancy, Extrauterine Pregnancies, Pregnancy, Extrauterine, Pregnancies, Extrauterine, Ectopic pregnancy, EP - Ectopic pregnancy, Ectopic pregnancy (disorder), extrauterine gestation or pregnancy, extrauterine; pregnancy, pregnancy; extrauterine, Ectopic pregnancy, NOS
French GROSSESSE EXTRA-UTERINE, Grossesse extra-utérine non précisée, Grossesse extra-utérine, non précisée, GROSSESSE ECTOPIQUE, Grossesse extra-utérine, Gestation ectopique, Grossesse ectopique
Portuguese GRAVIDEZ ECTOPICA, Gravidez extra-uterina, Gravidez ectópica NE, GRAVIDEZ EXTRA-UTERINA, Ecciese, Gravidez ectópica, Gravidez Ectópica
Spanish EMBARAZO ECTOPICO, Embarazo extrauterino, Embarazo ectópico no especificado, EMBARAZO EXTRAUTERINO, Eccyesis, embarazo ectópico, SAI (trastorno), embarazo ectópico, SAI, Ectopic pregnancy NOS, embarazo ectópico (trastorno), embarazo ectópico, Embarazo ectópico, Embarazo Ectópico
Italian Gravidanza ectopica, Gravidanza ectopica non specificata, Eccyesis, Gravidanza extrauterina
Dutch buitenbaarmoederlijke zwangerschap, extra-uteriene zwangerschap, niet-specifieke ectopische zwangerschap, ectopische zwangerschap, niet-gespecificeerd, eccyesis, extra-uterien; zwangerschap, zwangerschap; extra-uterien, Ectopische zwangerschap, niet gespecificeerd, ectopische zwangerschap, Ectopische zwangerschap, Zwangerschap, ectopische, Zwangerschap, ovariale
German Extrauteringraviditaet, unspezifisch, Schwangerschaft ektopisch, unspezifische ektopische Schwangerschaft, EXTRAUTERINGRAVIDITAET, Extrauteringraviditaet, nicht naeher bezeichnet, SCHWANGERSCH EXTRAUTERIN, Ekkyesis, Extrauteringraviditaet, Extrauterinschwangerschaft, Schwangerschaft, ektopische, Ektopische Schwangerschaft, Extrauteringravidität
Swedish Utomkvedshavandeskap
Finnish Kohdunulkoinen raskaus
Czech Mimoděložní těhotenství, Extrauterinní gravidita, Blíže neurčené mimoděložní těhotenství, Mimoděložní těhotenství, blíže neurčené, Těhotenství mimo dělohu, graviditas extrauterina, těhotenství mimoděložní, mimoděložní těhotenství, GEU, ektopická gravidita, graviditas ectopica
Korean 자궁외 임신, 상세불명의 자궁외 임신
Polish Ciąża ektopowa, Ciąża pozamaciczna, Ciąża szyjkowa
Hungarian Nem meghatározott ectopiás terhesség, Ectopiás terhesség, nem meghatározott, Méhen kívüli terhesség, Ectopiás terhesség, Extrauterin graviditas, Ectopiás graviditas, Graviditas extrauterina
Japanese 子宮外妊娠, 異所性妊娠, シキュウガイニンシン, イショセイニンシンショウサイフメイ, イショセイニンシン, 異所性妊娠、詳細不明, 外妊, 外妊娠, 子宮外妊, 異所妊娠, 妊娠-子宮外, 妊娠-異所性
Norwegian Graviditet utenfor livmoren, Ekstrauterin graviditet, Ekstrauterint svangerskap, Svangerskap utenfor livmoren, Ektopisk svangerskap, Ektopisk graviditet

Ontology: Pregnancy, Tubal (C0032994)

Definition (NCI) An abnormal pregnancy in which the conception is implanted in the fallopian tube.
Definition (MSH) The most common (>96%) type of ectopic pregnancy in which the extrauterine EMBRYO IMPLANTATION occurs in the FALLOPIAN TUBE, usually in the ampullary region where FERTILIZATION takes place.
Concepts Disease or Syndrome (T047)
MSH D011274
ICD9 633.1
ICD10 O00.1
SnomedCT 198622006, 198619009, 156082006, 79586000
English Pregnancies, Tubal, Pregnancy, Tubal, Tubal Pregnancies, Tubal Pregnancy, Tubal pregnancy NOS, PREGN TUBAL, TUBAL PREGN, tubal pregnancy (diagnosis), tubal pregnancy, Pregnancy, Tubal [Disease/Finding], tubal ectopic pregnancy, ectopic pregnancy tubal, fallopian pregnancy tube, pregnancy tubal, Pregnancy;tubal, fallopian tube pregnancy, fallopian pregnancy, tubal pregnancies, pregnancy fallopian, fallopian pregnancies tube, Tubal pregnancy NOS (disorder), Tubal pregnancy, Fallopian pregnancy, Fallopian tube pregnancy, Tubal pregnancy (disorder), tubal; pregnancy
Dutch eileider zwangerschap, tubair; zwangerschap, Tuba Fallopii, zwangerschap, Tubaire zwangerschap, Zwangerschap, tubaire, Zwangerschap, tuba Fallopii
German Tubargraviditaet, Eileiterschwangerschaft, Schwangerschaft, Eileiter-, Tubenschwangerschaft
Portuguese Gravidez tubária, Gravidez Tubária
Spanish Embarazo tubárico, embarazo en trompa de Falopio, embarazo en la trompa de Falopio, embarazo tubárico, SAI (trastorno), embarazo tubárico, SAI, embarazo tubárico (trastorno), embarazo tubárico, Embarazo Tubario, Embarazo Tubárico
Swedish Tubargraviditet
Japanese ランカンニンシン, 卵管妊娠, 妊娠-卵管
Czech těhotenství tubální, Tubární těhotenství
Finnish Munanjohdinraskaus
Korean 자궁관 임신
Polish Ciąża jajowodowa
Hungarian Tuba terhesség
Norwegian Svangerskap i eggleder, Tubarsvangerskap, Tubargraviditet, Graviditet i eggleder
French Grossesse tubaire
Italian Gravidanza tubarica