After fertilization the embryo differentiates into fetal and placental tissue. The fetal tissue develops into the baby and the placental tissue provides nourishment for the baby from the mother. During the first trimester, the placenta or trophoblast, is many times larger than the fetus and has the ability to grow independently. The placenta may continue to grow even without a viable fetus present. In rarer cases a pregnancy consists of abnormal placental tissue, called a molar pregnancy, which can have the potential for uncontrolled growth, like a tumor or cancer. These tumors are also called gestational trophoblastic disease. Molar pregnancy, or hydatidiform mole, is a pregnancy which has defective growth patterns. The placental tissue grows abnormally appearing as multiple cysts that have been classically described as a "bunch of grapes". There are two subtypes of moles: complete and partial. Complete moles have no fetal tissue present while partial moles have some fetal tissue and some normal placental tissue. The chromosomal make up of molar pregnancies is quite interesting. Complete moles arise from fertilization of an "empty egg" i.e. an egg which has lost its genetic material. All the genetic material arise from the father by fertilization of either two sperm at once or one sperm which duplicates its genes within the egg. A partial mole also has a duplicate paternal genetic material though the maternal chromosomal complement is intact and therefore the genetic material is in triplicate. Molar pregnancy is a clinical problem not only because it produces an abnormal pregnancy which in most cases needs to be terminated but also because of its ability to have residual disease and, in severe cases, result in metastasis. The malignant form of the disease is called an invasive mole or choriocarcinoma. EPIDEMIOLOGY The incidence of molar pregnancy varies greatly by region, with a higher rate in Asian countries. In Taiwan the incidence is 1/125 live births while the incidence in the United States is 1/1500. The main risk factor is advanced maternal age. Women over age 40 have a 5-10 fold greater chance of molar pregnancy. Other possible risk factors are related to poor nutrition, particularly a low intake of carotene (Vitamin A precursor). However the association is poor. SYMPTOMS & SIGNS Almost all patients with a complete molar pregnancy have vaginal bleeding in the first trimester. For the most part the symptoms mimic those of a miscarriage. 50% of patients with a complete mole have uterine enlargement which is advanced for their gestational age. As is true in normal pregnancy, nausea and vomiting are common complaints. The disease toxemia, marked by high blood pressure, swelling and protein in the urine, which is for the most part limited to the third trimester can be seen before 20 weeks in patients with a complete mole. A few patients can have findings of hyperthyroidism such as a fast heart beat, tremulousness, and feeling warm. Patients with partial moles in general have fewer symptoms. They rarely have uterine enlargement, hyperthyroidism or toxemia of pregnancy. DIAGNOSIS A complete molar pregnancy has characteristic findings on ultrasound. The placental tissue is swollen into cyst-like structures and there is the absence of a fetus. A partial mole is much harder to delineate from an early miscarriage in which the pregnancy is no longer viable. Another tool to help diagnose a molar pregnancy is the beta HCG levels. This is a protein produced by the placenta which is used in pregnancy tests. It can be measured in both the urine and blood. The blood test has the advantage of giving a quantitative level which corresponds to the gestational age of the pregnancy. In a complete mole the level of beta HCG can be abnormally high, >100,000 mIu/ml. A partial mole may have beta HCG levels in a high to normal range. More specific tests to delineate a molar pregnancy from an early pregnancy are being developed which measure different subunits of the HCG protein. MANAGEMENT Once the diagnosis of a molar pregnancy or a non viable pregnancy suspicious for a partial mole is made, evacuation of the uterus is recommended with termination of the pregnancy. The products of conception are sent to pathology for a final diagnosis. A pre-operative work up should be performed to rule out any spread of the disease such as a chest x-ray and liver function tests. FOLLOW-UP Because 20% of patients with a complete mole and 5-7% with a partial mole may have residual disease, close follow up is necessary. Beta HCG levels are monitored weekly until two normal values are obtained and then monthly for 6 months. It is important for the patient to use contraception for 6 months so that rising HCG levels while normal for pregnancy are not confused with residual disease. The birth control pill does not increase the risk of post-molar disease. After normal HCG values are obtained for 6 months pregnancy is considered safe. Persistent molar disease is assumed if the HCG levels plateau or rise, are still elevated 6 months after the termination of the pregnancy, or are >20,000 mIu/ml four weeks after the termination. If choriocarcioma, a malignant form of the disease, is found on the pathology specimen, or if metastasis are found on physical exam or chest X-ray further treatment is also necessary. TREATMENT Persistent disease is characterized as local or metastatic (spread to other organs). Metastatic disease is divided into two subgroups, called good and poor-prognosis, based on how long the disease is present, the pre treatment beta HCG level, location of the spread and if the patient failed prior chemotherapy. For local spread and good-prognosis metastatic disease the cornerstone of therapy is single agent chemotherapy such as methotrexate. This drug kills rapidly dividing cells and is used for treatment of early ectopic pregnancies as well. The cure rate for this low risk group approaches 100%. The treatment of poor-prognosis metastatic disease is multiple chemotherapeutic agents. If brain metastasis are found then local radiation therapy is needed. The cure rates for the poor prognosis group is more than 70%. FUTURE FERTILITY |