Gestational Trophoblastic Disease

• Gestational Trophoblastic Disease (GTD)


  A diverse group of interrelated diseases resulting in the abnormal proliferation of trophoblastic (placental) tissue
• Major classifications of GTD

  • Molar pregnancies (80%)
  • Persistent/invasive moles (10% to 15%)
  • Choriocarcinoma (2% to 5%)
  • Placental site trophoblastic tumors (very rare)
• GTD tumors


  • They share the ability to produce human chorionic gonadotropin (hCG), which serves as a tumor marker and a tool for measuring treatment effects
  • They are extremely sensitive to chemotherapy and are the most curable gynecologic malignancy and one of the few that allow for the preservation of fertility
• Molar pregnancy


  Also known as hydatidiform mole, a type of benign GTD
• Types of molar pregnancies

  • Complete/classic moles (90%)
  • Partial/incomplete moles (10%)
• Complete moles


  • Result from the fertilization of an enucleate ovum (empty egg) by one normal sperm which then replicates itself, so all chromosomes are paternally derived
  • Characterized by noninvasive trophoblastic proliferation and diffuse swelling of the chorionic villi, giving the appearance of grape-like vesicles filling the uterus in the absence of a fetus
• Partial moles


  • Result from the fertilization of a normal egg by two sperm, so there is an extra paternal chromosome set
  • Have a coexistent abnormal fetus and some normal chorionic villi
• Risk factors for molar pregnancy

  • Extremes in age (under 20 and over 35)
  • Prior history of GTD
  • Nulliparity (over 70% of women with GTD have never given birth)
  • Low dietary intake of beta-carotene, folic acid, and animal fat
  • Smoking
  • Infertility
  • Spontaneous abortion
  • Blood group A
  • History of oral contraceptive pill use
• Complete moles


  • Have a higher malignant potential than partial moles
• Symptoms associated with molar pregnancy

  • Vaginal bleeding (90-97%)
  • Passage of molar vesicles (80%)
  • Anemia (50%)
  • Uterine size greater than dates (30-50%)
  • Bilateral theca lutein cysts (25%)
  • Hyperemesis gravidarum (10-25%)
  • Preeclampsia before 20 weeks (10-15%)
  • Hyperthyroidism (10%)
  • Trophoblastic pulmonary embolic (2%)
• In the absence of chronic hypertension, preeclampsia occurring prior to 20 weeks' gestation is pathognomonic for molar pregnancy
• Physical examination findings in molar pregnancy

  • Sequelae of preeclampsia (hypertension) or hyperthyroidism (tachycardia, tachypnea)
  • Absence of fetal heart sounds
  • Uterine size greater than anticipated "gestational age"
  • Expulsion of grape-like molar clusters into the vagina
  • Palpable large bilateral theca lutein cysts
• Quantitative serum hCG levels

  Can be extremely high (>100,000 mIU/mL) in molar pregnancy, reflecting the amount of tumor volume
• Ultrasound findings in complete molar pregnancy

  • No fetus or amniotic fluid present
  • Intrauterine tissue appears as a "snow-storm" pattern due to swelling of chorionic villi
  • May reveal bilateral theca lutein cysts
• Differential diagnosis for GTD

  • Multiple gestation pregnancy
  • Erythroblastosis fetalis
  • Intrauterine infection
  • Uterine fibroids
  • Threatened abortion
  • Ectopic pregnancy
  • Normal intrauterine pregnancy
• Treatment for molar pregnancy

  1. Immediate removal of uterine contents with suction curettage (D&C)

  2. Prior to evacuation: baseline hCG, CBC, coagulation studies, renal/thyroid/liver function tests, maternal blood type and antibody screen

  3. If preeclampsia: use antihypertensives

  4. If hyperthyroidism: use beta blockers

  5. Rh immunoglobulin (RhoGAM) for Rh-negative women

  6. Expectant management of theca lutein cysts

  7. Hysterectomy as alternate therapy if patient has completed childbearing
• The prognosis for molar pregnancy is excellent, with 95% to 100% cure rates after suction curettage
• Persistent disease will develop in 15% to 25% of complete moles and 2% to 4% of partial moles
• Dilation and suction curettage (D&C) is the definitive treatment for most patients with complete molar pregnancy
• After the uterine contents have been removed, IV oxytocin can be administered to stimulate uterine contraction and minimize blood loss
• Even though no fetal tissue is present, Rh immunoglobulin (RhoGAM) should be given to all Rh-negative women
• Patients with theca lutein cysts should be managed expectantly. In general, the cysts will spontaneoulsy involute as the hCG levels decrease following the procedure
• If the patient with a molar pregnancy has completed childbearing, hysterectomy is an alternate therapy
• Although hysterectomy will eliminate the risk of local invasion, it does not prevent metastasis of the disease
• Prognosis for molar pregnancy


  Excellent, with 95% to 100% cure rates after suction curettage
• Persistent disease will develop in 15% to 25% of patients with complete moles and in 4% of patients with partial moles
• After evacuation of a molar pregnancy

  1. Serial hCG titers should be monitored to ensure complete resolution of the disease

  2. Levels should be measured within 48 hours and then weekly until negative for 3 consecutive weeks

  3. Levels should then be followed monthly for 6 months
• The average time to normalization of hCG levels is 14 weeks for a complete mole compared to 2 to 4 weeks following a normal pregnancy, miscarriage, or termination
• A plateau or rise in hCG levels during monitoring or the presence of hCG greater than 6 months after the D&C is indicative of persistent/invasive disease
• OCPs are typically used to prevent pregnancy during the follow-up period, given their low failure rate and low risk of irregular bleeding
• Patients who are cured of the disease can have normal pregnancies after treatment with no increase in the rate of spontaneous abortion, complications, or congenital malformations
• All subsequent pregnancies should be closely monitored with early ultrasound and hCG levels to exclude recurrent disease
• The risk of developing recurrent GTD is approximately 1% to 2% after one molar pregnancy (compared to 0.1% in the general population), but as high as 16% to 28% after two molar pregnancies
• This holds true even after hysterectomy
• Partial molar pregnancy


  Formed when a normal ovum is fertilized by two sperm simultaneously, resulting in a triploid karyotype with 69 chromosomes, of which two sets are paternally derived
• The most common karyotype in partial moles is 69,XXY (80%)
• Partial moles


  • Placental abnormality characterized by focal hydropic villi and trophoblastic hyperplasia primarily of the cytotrophoblast
  • hCG levels are normal or only slightly elevated compared to the extreme elevations seen in complete moles
• Partial moles are the only histologic type of GTD associated with the presence of a fetus
• Most fetuses associated with partial moles survive only several weeks in utero before being spontaneously aborted in the late first or early second trimester
• Partial moles are almost always benign and have a much lower malignancy potential than complete moles