Gestational trophoblastic disease is proliferation of trophoblastic tissue in pregnant or recently pregnant women. Manifestations may include excessive uterine enlargement, vomiting, vaginal bleeding, and preeclampsia, particularly during early pregnancy. Diagnosis includes measurement of the β subunit of human chorionic gonadotropin, pelvic ultrasonography, and confirmation by biopsy. Tumors are removed by suction curettage. If disease persists after removal, chemotherapy is indicated.
Gestational trophoblastic disease is a tumor originating from the trophoblast, which surrounds the blastocyst and develops into the chorion and amnion (see Amniotic sac and placenta). This disease can occur during or after an intrauterine or ectopic pregnancy. If the disease occurs during a pregnancy, spontaneous abortion, eclampsia, or fetal death typically occurs; the fetus rarely survives. Some forms are malignant; others are benign but behave aggressively.
Classification is morphologic:
Hydatidiform moles are most common among women < 17 or > 35 and those who have previously had gestational trophoblastic disease. They occur in about 1/2000 gestations in the US. For unknown reasons, incidence in Asian countries approaches 1/200. Most (> 80%) hydatidiform moles are benign. The rest may persist, tending to become invasive; 2 to 3% of hydatidiform moles are followed by choriocarcinoma.
Symptoms and Signs
Initial manifestations of a hydatidiform mole suggest early pregnancy, but the uterus often becomes larger than expected within 10 to 16 wk gestation. Commonly, women test positive for pregnancy have vaginal bleeding and severe vomiting, and fetal movement and fetal heart sounds are absent. Passage of grapelike tissue strongly suggests the diagnosis. Complications may include uterine infection, sepsis, hemorrhagic shock, and preeclampsia, which may occur during early pregnancy.
Placental site trophoblastic tumors tend to cause bleeding.
Choriocarcinoma usually manifests with symptoms due to metastases.
Gestational trophoblastic disease does not impair fertility or predispose to prenatal or perinatal complications (eg, congenital malformations, spontaneous abortions).
Gestational trophoblastic disease is suspected in women with a positive pregnancy test and any of the following:
If gestational trophoblastic disease is suspected, testing includes measurement of serum β-hCG and, if not previously done, pelvic ultrasonography. Findings (eg, very high β-hCG levels, classic ultrasonographic findings) may suggest the diagnosis, but biopsy is required. Invasive mole and choriocarcinoma are suspected if biopsy findings suggest invasive disease or if β-hCG levels remain higher than expected after treatment for hydatidiform mole (see below).
Hydatidiform mole, invasive mole, and placental site trophoblastic tumor are evacuated by suction curettage. Alternatively, if childbearing is not planned, hysterectomy may be done.
After tumor removal, gestational trophoblastic disease is classified clinically to determine whether additional treatment is needed. The clinical classification system does not correspond to the morphologic classification system. Invasive mole and choriocarcinoma are classified clinically as persistent disease. The clinical classification is used because both are treated similarly and because exact histologic diagnosis may require hysterectomy.
A chest x-ray is taken, and serum β-hCG is measured. If the β-hCG level does not normalize within 10 wk, the disease is classified as persistent. Persistent disease requires CT of the brain, chest, abdomen, and pelvis. Results dictate whether disease is classified as nonmetastatic or metastatic. In metastatic disease, prognosis (including risk of death) may be poor or good (see Table 4: WHO Scoring System in Metastatic Gestational Trophoblastic Disease). Poor prognosis is suggested by the following (National Institutes of Health [NIH] criteria):
Persistent disease is usually treated with chemotherapy. Treatment is considered successful if at least 3 consecutive serum β-hCG measurements at 1-wk intervals are normal. Typically, oral contraceptives (any is acceptable) are given for 6 to 12 mo; alternatively, any effective contraceptive method can be used.
Nonmetastatic disease can be treated with a single chemotherapy drug (methotrexate or dactinomycin). Alternatively, hysterectomy is considered for patients > 40 or those desiring sterilization and may be required for those with severe infection or uncontrolled bleeding. If single-drug chemotherapy is ineffective, hysterectomy or multidrug chemotherapy is indicated. Virtually 100% of patients with nonmetastatic disease can be cured.
Low-risk metastatic disease is treated with single-drug or multidrug chemotherapy. High-risk metastatic disease requires aggressive multidrug chemotherapy. Cure rates are 90 to 95% for low-risk and 60 to 80% for high-risk disease.
Hydatidiform mole recurs in about 1% of subsequent pregnancies. Patients who have had a mole require ultrasonography early in subsequent pregnancies, and the placenta should be sent for pathologic evaluation.
Last full review/revision May 2013 by Pedro T. Ramirez, MD; David M. Gershenson, MD
Content last modified September 2013