Ectopic pregnancy

Ectopic pregnancy occurs when an embryo attaches outside of the uterus, most commonly in the fallopian tubes. It is frequently associated with pelvic inflammatory disease (PID), which may lead to stenosis of the fallopian tubes. This prevents the fertilized egg from passing through to the uterus, instead causing it to attach to the tube itself. In addition to signs of pregnancy, symptoms include abdominal pain and vaginal bleeding. The first diagnostic step is to confirm the pregnancy with a β-hCG test, which should be followed by a transvaginal ultrasound to determine the location of the pregnancy and the fetal heartbeat. Uncomplicated ectopic pregnancies often resolve spontaneously and are usually difficult to diagnose. Patients are typically hemodynamically stable with low, declining hCG concentrations (< 5000 IU/L). Complicated cases may involve tubal abortion or rupture, which can lead to intraabdominal bleeding and shock. Whereas uncomplicated cases are treated conservatively (e.g., methotrexate or expectant management), complicated ectopic pregnancy requires surgical removal. In cases of abdominal pain in women of reproductive age, it is therefore important to rule out ruptured ectopic pregnancy.

Localization

1. Fallopian tube (96% of cases): ampulla >> isthmus > fimbriae > interstitial pregnancy : e.g., cornual pregnancy
2. Ovary (3% of cases)
3. Abdomen (1% of cases)
4. Cervix (very rare)

Risk factors

• Anatomic alteration of the fallopian tubes is the main cause of ectopic pregnancy. It may be due to:
  • A history of PID
  • Previous ectopic pregnancy
  • Past surgeries involving the fallopian tubes
  • Endometriosis
  • Exposure to DES (diethylstilbestrol) in utero
  • Bicornuate uterus
• Non‑anatomical risk factors
  • Intrauterine device (IUD)
  • History of infertility
  • Hormone therapy

References:^{[1][2][3][4][5][6][7][8][9]}

General symptoms of ectopic pregnancy

Patients usually present with signs and symptoms 4–6 weeks after their last menstrual period.

• Lower abdominal pain and guarding
• Vaginal bleeding
• Signs of pregnancy: amenorrhea, nausea, breast tenderness, frequent urination
• Tenderness in the area of the ectopic pregnancy
• Cervical motion tenderness, closed cervix
• Enlarged uterus
• Interstitial pregnancies tend to present late, at 7–12 weeks of gestation, because of myometrial distensibility.

Right lower quadrant pain may indicate appendicitis! Cervical motion tenderness may be a sign of PID!

Tubal rupture

• Acute course with sudden and severe lower abdominal pain (acute abdomen)
• Signs of hemorrhagic shock: e.g., tachycardia, hypotension, syncope
• More common in interstitial pregnancy

References:^[10][11][12]

• Positive pregnancy test: ↑ β-hCG
  • Serum test: β-hCG verifiable from the 8^th day after ovulation
  • Follow-up measurements are required to monitor the increase of β‑hCG levels over time.
• Transvaginal ultrasound (TVUS)
  • Best initial imaging test for determining the localization of the pregnancy and finding a heartbeat
  • Ultrasound findings in ectopic pregnancy (see also ultrasound findings in normal pregnancy)
    • Empty uterine cavity in combination with a thickened endometrial lining
    • Tubal ring sign: echogenic ring that surrounds an unruptured ectopic pregnancy .
    • Possibly free fluid within the pouch of Douglas
    • Interstitial pregnancy
      • Gestational sac appears separately, < 1 cm from the lateral edge of the uterine wall
      • Thin myometrial layer (< 5 mm) surrounding sac seen on ultrasound
• Transabdominal ultrasound (TAUS):
  • Provides a general picture of the pelvic anatomy and the upper abdomen
• Endometrial biopsy; : shows decidualization of the endometrium without chorionic villi or fetal parts

Every woman of reproductive age with abdominal pain should undergo a pregnancy test!

References:^{[13][14][15][16][17][18][19]}

Differential diagnoses of abnormal vaginal bleeding in women of reproductive age

Painful vaginal bleeding

Differential diagnosis	Description of pain	Findings
Ectopic pregnancy	Lower unilateral abdominal pain and guarding	Amenorrhea Positive pregnancy test Ultrasound shows echogenic mass.
Benign neoplasms (e.g., adenomyosis, uterine leiomyoma)	Adenomyosis: chronic pelvic pain Uterine leiomyoma: back or pelvic pain/discomfort	Adenomyosis: dysmenorrhea, menorrhagia, uniformly enlarged uterus Uterine leiomyoma: menorrhagia, dysmenorrhea, irregularly enlarged uterus, infertility
Ovarian cyst rupture	Sudden onset of unilateral abdominal pain	Onset usually during physical activity (exercise, sexual intercourse)
Infection/Inflammation (e.g, PID, cervicitis)	PID: lower bilateral abdominal pain Cervicitis: lower abdominal or pelvic pain	PID: fever, menorrhagia and metrorrhagia, dyspareunia, purulent cervical discharge Cervicitis: intermenstrual bleeding, vaginal discharge, dyspareunia, usually no fever
Endometriosis	Chronic pelvic pain that worsens before the onset of menses	Dysmenorrhea, premenstrual or postmenstrual bleeding Dyspareunia Infertility
Trauma (e.g., foreign body, sexual abuse)	Pelvic pain	Bruising, hematoma, possible accompanying injuries

Painless vaginal bleeding

Differential diagnosis	Findings
PCOS	Amenorrhea, oligomenorrhea, as well as breakthrough bleeding and hypermenorrhea Hirsutism, obesity, acne vulgaris, infertility Ultrasound shows enlarged ovaries with numerous anechoic cysts.
Endometrial hyperplasia	Constant bleeding, intermenstrual bleeding Ultrasonography shows endometrial thickening.
Endometrial polyp	Irregular menstrual bleeding, spotting, menorrhagia
Malignant neoplasms (e.g., cervical cancer, endometrial cancer)	Cervical cancer: menometrorrhagia, postcoital spotting, abnormal vaginal discharge Endometrial cancer: metrorrhagia, menometrorrhagia
Iatrogenic (e.g., anticoagulants, oral contraceptives, intrauterine devices)	Anticoagulants: easy bruising, bleeding tendency

References:^{[20][21][22][23][24][25][26][27][28]}

The differential diagnoses listed here are not exhaustive.

Management may be conservative or surgical, depending on the severity of the condition. Unstable patients require immediate hemodynamic support.

Conservative management

• Indications
  • Uncomplicated ectopic pregnancies
  • Hemodynamic stability
  • β-hCG ≤ 5000 mlU/mL
  • No renal, hepatic, or hematologic diseases
  • No fetal heartbeat and ectopic mass size < 4 cm
• Treatment of choice: methotrexate (MTX)
  • Outcome comparable to surgery
  • A decrease in β-hCG levels should occur within a week of MTX administration.
• Anti-D immunoglobulin (RhoGAM)
• Alternative: expectant management

Surgery

• Indications
  • Hemodynamic instability, impending rupture
  • Risk factors for rupture
  • Contraindications for MTX treatment: e.g., renal insufficiency
  • If conservative treatment is unsuccessful
  • If a concurrent surgical procedure is required, e.g., permanent sterilization
  • Patient's desire for a short duration of treatment and less follow-up
• Laparoscopic removal
  • Salpingostomy (tube‑conserving operation)
    • Risk of persistent ectopic pregnancy
    • Patients with unruptured tubal pregnancy who do not meet the criteria for conservative treatment
  • Salpingectomy (not function-preserving)
    • Ruptured tube, heavy bleeding, large ectopic mass
    • If the patient does not desire future pregnancies → bilateral salpingectomy

References:^{[29][30][31][32][33][34][35][36]}