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Ectopic Pregnancy and Emergencies in the First 20 Weeks of Pregnancy -…

- - - - Appendicitis
      - Inflammatory bowel disease
      - Ovarian pathology
        
        Ovarian cyst
        
        Ovarian torsion
      - Pelvic inflammatory disease
      - Endometriosis
      - Sexual assault or trauma
      - Urinary tract infection
      - Ureteral colic
    - - Normal intrauterine pregnancy
      - Threatened abortion
      - Inevitable abortion
      - Molar pregnancy
      - Heterotopic pregnancy
      - Implantation bleeding
      - Corpus luteum cyst
- - - - Urine: greater than or equal to 20 mIU/mL
      - Serum: greater than or equal to 10 mIU/mL
    - - Urine: not greater than 1%
      - Serum: not greater than 0.5%
  - - - Occurs when hCG levels are generally at concentrations of 1000000 mIU/mL
      - Excess hCG saturates both fixed solid-phase antibody and labeled soluble antibody
      - Causes absence of signal leading to false-negative result
      - Mitigated by diluting the sample
- - - - Ampullary portion of the fallopian tube: vast majority of cases
      - Extratubal sites: abdominal cavity, cervix, or ovary
    - - Damage to tubal mucosa from previous infection preventing transport
      - Tubal surgery
      - Defects in the ovum resulting in premature implantation
      - Elevated estradiol or progesterone levels inhibiting tubal migration
    - - Ovum penetrates into the muscular wall of the tube
      - Maternal blood seeps into tubal tissue causing intermittent distention
      - Blood leaks from fimbriated end into peritoneal cavity
      - Ectopic pregnancy and hematoma can be completely or partially extruded out of fallopian tube end or through tubal wall rupture
      - Death results from maternal exsanguination after tubal rupture
    - - Abdominal ectopic pregnancies
        
        Account for approximately 1% of ectopic pregnancies
        
        Derived from early rupture or abortion of tubal pregnancy with subsequent peritoneal reimplantation
      - Cervical ectopic pregnancies
        
        Account for less than 1% of ectopic pregnancies
        
        Predisposing factors include previous dilatation and curettage, previous cesarean delivery, in vitro fertilization, endometrial adhesions or fibrosis, prior instrumentation, infertility, previous ectopic pregnancy
        
        Clinical presentation involves profuse vaginal bleeding
        
        Bimanual exam reveals soft large cervix compared to uterus or hourglass-shaped uterus
        
        Diagnosis confirmed with US
      - Cesarean scar pregnancy
        
        Rare but can cause massive maternal hemorrhage
        
        Diagnosis confirmed with US demonstrating empty uterine sac and cervical canal with gestational sac in uterine isthmus
  - - - Classic sign of amenorrhea 4 to 12 weeks after last normal period reported in 70% of cases
      - No missed menses reported in 15% of cases
      - Vaginal bleeding is often scant but heavy bleeding does not exclude it
    - - Prior tubal surgery for sterilization assumed to be ectopic pregnancy until proven otherwise
      - Highest risk conditions: laparoscopic partial salpingectomy or electrodestruction tubal ligation at age less than 28 years, especially 5 to 15 years after procedure
      - Hysterectomy with oophorectomy excludes ectopic pregnancy
      - Hysterectomy without oophorectomy makes ectopic pregnancy exceedingly rare with only 27 cases since 1918 due to fistulous tract enabling embryo implantation
    - - Reported in 90% of cases due to tubal distention or rupture
      - Classic pain of rupture is lateralized, sudden, sharp, and severe
      - Shoulder pain can occur due to diaphragmatic irritation from ruptured ectopic pregnancy
      - Lack of pain does not exclude ectopic pregnancy if vaginal spotting or bleeding is present
  - - - Shock
      - Peritoneal signs
      - Adnexal mass and tenderness
      - Cervical motion tenderness
      - Relative bradycardia due to vagal stimulation
      - Normal vital signs may persist due to compensatory mechanisms despite significant hemoperitoneum
      - Fever is rare
    - - Vital signs are likely to be normal
      - Adnexal mass or fullness with tenderness may be present
      - Corpus luteum cyst can mimic presentation with thin-walled unilocular cyst measuring 3 to 11 cm causing pain, tenderness, and menstrual irregularities
      - Cervical motion tenderness may be seen
      - Blood often present in vaginal vault
      - Pelvic exam may be completely normal
      - Cervix may have blue coloration
      - Uterine size most often normal
      - Vaginal examination in stable women with first-trimester bleeding adds little to clinical diagnosis if transvaginal US is obtained
  - - - US
      - Direct visualization by laparoscopy
      - Surgery
    - - Normal pregnancy: rises rapidly until 9 to 10 weeks then plateaus
      - Nonviable or successfully treated ectopic pregnancy: beta-hCG levels decline
      - Pathologic pregnancy: absolute levels tend to be lower and doubling times longer than IUP but with much overlap
      - Rule of thumb: serum concentration approximately doubles every 2 days early in normal pregnancy
      - Minimum hCG rise in normal pregnancy may be as low as 53% in 48 hours
      - Median rise in beta-hCG is 53% in 1 day and 124% in 2 days
      - Spontaneous abortion: hCG expected to decrease by 21% to 35% in 2 days
      - Increase of less than 53% in 2 days suggests but is not diagnostic of ectopic pregnancy or abnormal IUP
      - Increase of greater than 53% does not rule out ectopic pregnancy
      - Serial measurements at least 2 days apart characterize risk in stable patients but are not diagnostic
      - Decrease of less than 21% at 2 days or less than 60% at 7 days suggests retained trophoblasts or ectopic pregnancy
    - - Secreted by ovaries, adrenal glands, and placenta
      - Ovarian production predominates during first 8 to 10 weeks keeping serum levels relatively constant
      - Placental production increases after 10th week causing levels to rise
      - Absolute levels are lower in pathologic pregnancies and fall when pregnancy fails
      - Diagnostic thresholds
        
        Less than or equal to 10 ng/mL: found in most pathologic pregnancies
        
        Less than or equal to 5 ng/mL: nearly 100% of pregnancies will be pathologic
        
        Less than or equal to 2.5 ng/mL: no normal pregnancies reported
        
        Greater than 25 ng/mL: 97% sensitivity for viable IUP
      - Empty uterus or nonspecific fluid collection on US with progesterone less than or equal to 5.0 ng/mL is highly predictive of abnormal IUP or ectopic pregnancy
      - Overlapping values limit usefulness and test is often not routinely available on urgent basis
    - - Primary goals: determine viable IUP and exclude ectopic pregnancy
      - Heterotopic pregnancy incidence
        
        Historical incidence: 1 in 30000 pregnancies
        
        General population incidence: up to 1 in 3000 pregnancies
        
        In vitro fertilization population: 4% are ectopic pregnancies with 2 of 29 heterotopic gestations
      - Sonographic Timing via Transvaginal Scan
        
        Gestational sac: 4.5 weeks
        
        Yolk sac: 5.5 weeks
        
        Fetal pole: 6.0 weeks
        
        Transabdominal scan visualizes these signs approximately 1 week later
      - Fetal Demise Criteria
        
        Embryo without cardiac activity within the uterus provided crown-rump length is at least 5 mm
      - Diagnostic Extrauterine Findings
        
        Empty uterus with embryonic cardiac activity outside uterus is diagnostic and seen in less than 10% of transabdominal and up to 25% of transvaginal scans
        
        Echogenic adnexal mass with free fluid and empty uterus: risk near 100%
        
        Tubal ring: risk greater than 95%
        
        Moderate or large amount of free pelvic fluid alone: risk 86%
        
        Complex pelvic mass alone: risk 72%
        
        Any free pelvic fluid alone: risk 52%
        
        Hepatorenal free fluid: risk approximately 100%
    - - Definition: level of beta-hCG at which findings of an IUP are expected on US
      - Threshold values
        
        Transvaginal scanning: often considered to be 1500 mIU/mL
        
        Transabdominal scanning: expected IUP at about 6000 mIU/mL
      - Interpretation
        
        Beta-hCG higher than discriminatory zone with empty uterus suggests ectopic pregnancy
        
        Beta-hCG below discriminatory zone with empty uterus is indeterminate
        
        Ectopic pregnancy can occur at very low beta-hCG levels less than 500 mIU/mL
        
        Watchful waiting with close follow-up is appropriate for stable patients with beta-hCG greater than discriminatory zone and no visible intrauterine or extrauterine pregnancy
    - - MRI: high sensitivity and specificity but limited by cost, availability, and time
      - Culdocentesis: supplanted by beta-hCG and US due to poor sensitivity and false-positives from technical errors or ruptured corpus luteum cyst
      - Laparoscopy: diagnostic and therapeutic for patients with suspected ectopic pregnancy and nondiagnostic US
  - - - Indicated if laparoscopy is needed for diagnosis
      - Laparoscopic salpingostomy is most frequently used for unruptured ectopic pregnancy
    - - Alternative to surgery with comparable success rates in unruptured ectopic pregnancy
      - Mechanism: folic acid antagonist that inhibits dihydrofolate reductase causing depletion of cofactors needed for DNA and RNA synthesis
      - Ideal Patient Selection
        
        Hemodynamic stability
        
        Minimal abdominal pain
        
        Ability to follow up reliably
        
        Normal baseline liver and renal function tests
      - Absolute Contraindications
        
        Intrauterine pregnancy
        
        Evidence of immunodeficiency
        
        Moderate to severe anemia, leukopenia, or thrombocytopenia
        
        Sensitivity to methotrexate
        
        Active pulmonary disease
        
        Active peptic ulcer disease
        
        Clinically important hepatic or renal dysfunction
        
        Breastfeeding
        
        Hemodynamic instability
      - Relative Contraindications
        
        Embryonic cardiac activity detected by transvaginal US
        
        Human chorionic gonadotropin concentrations greater than 5000 mIU/mL
        
        Ectopic pregnancy greater than 4 cm in size as imaged by transvaginal US
        
        Refusal to accept blood transfusion
        
        Inability to reliably return for follow-up
      - Dosing and Regimen
        
        Single intramuscular dose: 50 mg/m²
        
        Failure rate with single dose if pretreatment beta-hCG greater than 5000 mIU/mL: 14.3% or higher
        
        Failure rate with single dose if pretreatment beta-hCG less than 5000 mIU/mL: 3.7%
        
        Multiple-dose regimen success rate is higher than single dose: 92.7% versus 88.1%
      - Side Effects and Separation Pain
        
        Most common side effect: abdominal pain up to 75% followed by flatulence and stomatitis
        
        Lower abdominal pain lasting up to 12 hours is common 3 to 7 days after treatment
        
        Caused by methotrexate-induced tubal abortion or tubal distention due to hematoma formation
        
        Responds to NSAIDs
        
        Evaluation of post-treatment pain requires CBC and abdominopelvic US to rule out tubal rupture and hemoperitoneum
        
        Surgical intervention considered for hemodynamic instability, falling hematocrit, moderate to severe pain, free fluid in the cul-de-sac, or rebound tenderness
      - Prognostic Factors for Medical Treatment Failure
        
        Larger tubal diameter
        
        Higher initial beta-hCG levels
        
        Severe abdominal pain
        
        Fetal cardiac activity
      - Discharge Instructions
        
        Treatment failure occurs in up to 36% of cases
        
        Surgical treatment necessary if medical therapy fails or tubal rupture occurs in approximately 5% of cases
        
        Immediate evaluation needed for vaginal bleeding, abdominal pain, weakness, dizziness, or syncope
        
        Refrain from sexual intercourse for 14 to 21 days until beta-hCG levels are undetectable to decrease tubal rupture risk
        
        Keep post-treatment pelvic examinations to a minimum
    - - Rho(D) antigen can be detected as early as 5.5 weeks and by 6 weeks of gestation
      - Alloimmunization can occur with 0.1 mL of fetal blood admixing with mother's
      - Recommended treatment for Rh-negative women with ectopic pregnancy diagnosed prior to 12 weeks of gestation: 50 micrograms of RhoGAM
      - Administration of full dose of 300 micrograms is acceptable
- - - - Pregnancy-related bloody vaginal discharge or frank bleeding during first half of pregnancy without cervical dilatation
    - - Vaginal bleeding and dilatation of the cervix
    - - Passage of only parts of the products of conception
      - More likely to occur between 6 and 14 weeks of pregnancy
    - - Passage of all fetal tissue including trophoblast and all products of conception before 20 weeks
    - - Fetal death at less than 20 weeks without passage of any fetal tissue for 4 weeks after fetal death
    - - Evidence of infection during any stage of abortion
  - - - History of bleeding quantified as pads used per hour
      - Pelvic examination to check for cervical dilatation and tissue passage
    - - Quantitative serum beta-hCG level
      - CBC to evaluate blood loss
      - Blood type, Rh factor, and antibody screen
      - Urinalysis
    - - Gestational age 4 to 5 weeks
        
        Beta-hCG: less than 1000 mIU/mL
        
        Transvaginal US findings: intradecidual sac
        
        Transabdominal US findings: N/A
      - Gestational age 5 weeks
        
        Beta-hCG: greater than 2000 mIU/mL
        
        Transvaginal US findings: yolk sac with or without embryo
        
        Transabdominal US findings: gestational sac
      - Gestational age 6 weeks
        
        Beta-hCG: 10000 to 20000 mIU/mL
        
        Transvaginal US findings: embryo with cardiac activity
        
        Transabdominal US findings: yolk sac with or without embryo
      - Gestational age 7 weeks
        
        Beta-hCG: greater than 20000 mIU/mL
        
        Transvaginal US findings: embryonic torso or head
        
        Transabdominal US findings: embryo with cardiac activity
  - - - Safe to discharge if follow-up is ensured
      - Bed rest and low activity have no proven effectiveness
      - Patients should avoid intercourse and tampons to minimize infection risk
    - - Requires uterus evacuation
      - Medical treatment: PO misoprostol 600 micrograms
      - Surgical treatment: dilatation and curettage
    - - Safe to discharge if complete passage is confirmed by US
      - Obtain obstetrics consultation if any doubt exists
    - - Admission or discharge to follow up within 1 week
      - Strict return precautions for heavy bleeding defining as more than one pad per hour for 6 hours, pain, or fever
    - - Treat with Rho(D) immunoglobulin before discharge or within 72 hours
- - - - Fluid resuscitation
      - Early obstetric consultation for uterine evacuation
      - Broad-spectrum IV antibiotic regimens
        
        Ampicillin/sulbactam: 3 grams IV
        
        Clindamycin 600 mg plus gentamicin 1 to 2 mg/kg IV
- - - - Complete mole: more common with no actual fetus present
      - Partial mole: deformed nonviable fetus is present
- - - - Cholecystitis or cholelithiasis
      - Gastroenteritis
      - Pancreatitis
      - Appendicitis
      - Hepatitis
      - Peptic ulcer
      - Pyelonephritis
      - Ectopic pregnancy
      - Fatty liver of pregnancy
      - HELLP syndrome
  - - - Brand Name: Phenergan
      - FDA Category: C
      - Dosing: 12.5-25 mg PO or PR every 4 h
      - IV Dosing: 12.5-25 mg IM or IV every 4 h
      - Note: IV extravasation causes tissue injury
    - - Brand Name: Compazine
      - Dosing: 5-10 mg PO every 3-4 h or 25 mg PR every 12 h
      - IV Dosing: 10 mg over 2 min with maximum of 40 mg every 24 h
    - - Brand Name: Thorazine
      - FDA Category: C
      - Dosing: 10-25 mg PO every 4-6 h or 100 mg PR every 6-8 h
      - IV Dosing: 25 mg in 500 mL NS at 250 mL/h
    - - Brand Name: Zofran
      - FDA Category: B
      - Dosing: 4-8 mg PO every 8 h
      - IV Dosing: 8 mg IV over 5 min
      - Disadvantages: cost and insufficient evidence to support or refute teratogenicity
    - - Brand Name: Reglan
      - FDA Category: B
      - Dosing: 10 mg PO every 6-8 h
      - IV Dosing: 10 mg over 1-2 min every 6-8 h
    - - Doxylamine with pyridoxine
        
        Brand Name: Diclegis or Diclectin
        
        FDA Category: A
        
        Dosing: 2 tablets PO every evening
      - Vitamin B6
        
        Dosing: 25 mg PO every 8 h
      - Ginger
        
        Dosing: 500-1000 mg PO daily
      - Diphenhydramine
        
        Brand Name: Benadryl
        
        FDA Category: B
        
        Dosing: 25-50 mg PO every 6 h
  - - - Uncertain diagnosis
      - Intractable vomiting
      - Persistent ketone or electrolyte abnormalities after volume repletion
      - Weight loss of greater than 10% of prepregnancy weight
- - - - Initial requirement in first trimester: 0.7 unit/kg/d
      - Late pregnancy requirement: 1 unit/kg/d
    - - NPH insulin: historically first-line therapy and widely studied
      - Insulin detemir
        
        Brand Name: Levemir
        
        FDA Category: B
        
        Improves fasting plasma glucose and decreases hypoglycemic events compared to NPH
      - Insulin glargine
        
        Brand Name: Lantus
        
        Labeled as "No human pregnancy data" since 2015 FDA pregnancy class category phase-out
        
        Reasonable to initiate or continue if successful in maintaining excellent control
    - - Rapid-acting insulin analogues do not cross the placenta
      - Insulin lispro and insulin aspart are used preferentially over regular insulin due to rapid onset
    - - Metformin is a reasonable alternative in women who decline, cannot safely administer, or cannot afford insulin