Approach

Although there are several classic symptoms and signs typical of molar pregnancy, such as vaginal bleeding, hyperemesis, or hyperthyroidism, most women with molar pregnancy in modern clinical practice are diagnosed incidentally at histologic exam of the products of miscarriage or on findings from early maternal ultrasound.[30][31]

History

Women with molar pregnancy typically present in the first trimester of pregnancy with a history of a missed menstrual period, and are found to have positive urine test for pregnancy and elevated serum human chorionic gonadotropin (hCG) levels on laboratory evaluation. Women are commonly at the extremes of reproductive life (younger than 20 years of age or over 35 years of age), and may relate a history of prior MP.​[8]​​​[9][10][11][12]​​​[13][14][15]​​​[32]

The most common presenting symptom is vaginal bleeding.[33][34] This may vary in its degree from light spotting to heavy bleeding, and may even include passage of hydropic villi. Heavy or persistent bleeding can lead to anemia, with symptoms of dizziness and fatigue.

Women may report exacerbated symptoms of pregnancy (as a result of abnormally high serum hCG levels) that include severe nausea and emesis (hyperemesis gravidarum), palpitations, insomnia and diarrhea (from thyrotoxicity), and headache and photophobia (from early-onset preeclampsia).[24][25]​​[35] High-output cardiac failure from hyperthyroidism, severe preeclampsia and, less commonly, anemia may lead to dyspnea and respiratory distress. Dyspnea may also indicate trophoblastic emboli or pulmonary metastases. Because it is accompanied by significantly higher levels of serum hCG, complete hydatidiform mole is more likely to be associated with these symptoms than partial molar pregnancy.[23]​ Women with molar pregnancies may also experience pelvic pain secondary to ovarian theca lutein cysts. 

Hydatidiform moles with severe medical complications occur less frequently because of early diagnosis from the widespread use of ultrasound in the first trimester of pregnancy. About 50% of women with molar pregnancies are diagnosed while still asymptomatic. However, earlier diagnosis has not been associated with a lower occurrence of postmolar gestational trophoblastic neoplasia (GTN), and prognosis is still a clinical challenge.[24][25]

Physical exam

The uterine size is greater than expected for gestational age in approximately 25% of complete molar pregnancies.[36][37]​​ There may be active bleeding from the cervical os, and there may be spontaneous evacuation of hydropic vesicles from the cervix.[4]

Other signs include pallor, tachycardia, tremor, hypertension, and respiratory distress. Because of the molecular homology between subunits of thyroid-stimulating hormone and hCG, serum hCG may stimulate the production of thyroid hormone with the clinical symptoms and signs of thyrotoxicosis.[26][38]​​​[39]​ However, the absence of ophthalmopathy differentiates molar pregnancy from thyrotoxicosis due to Graves disease.[40]

Laboratory investigations

Most molar pregnancies (MPs) are diagnosed incidentally at pathologic evaluation of a suction evacuation (electrical or manual) specimen for missed abortion or from early maternal ultrasound screening in the first trimester of pregnancy.[31] Many women who are diagnosed with MP at an early maternal ultrasound screening in the first trimester of pregnancy terminate pregnancy before the development of the classic signs and symptoms.​[24][25]​​​[35] For this reason, most authorities consider it mandatory to conduct histologic exam of miscarriage tissue.[4][34]

hCG is secreted by syncytiotrophoblasts, which proliferate excessively in molar pregnancy, and so it is a sensitive biomarker for diagnosis of MP, response to treatment and follow-up monitoring for GTN.[22]​ Normal pregnancies are associated with a peak serum hCG level of <100,000 mIU/mL.[23]​ However, hCG levels alone should not be used to infer the presence of a molar pregnancy because greater than expected hCG levels may be seen in multiple gestations. Serum hCG acts as a tumor marker to follow postmolar regression and to identify postmolar gestational trophoblastic neoplasia. In the absence of histopathology, post-treatment measurement of hCG levels should be performed weekly until normalization of hCG levels or diagnosis of GTN. The duration of monitoring varies by country.[3] The International Federation of Gynecology and Obstetrics recommends monitoring hCG every 1-2 weeks post-treatment until levels return to normal, followed by a single confirmatory normal measurement within a month for partial hydatidiform moles and monthly hCG measurements for 6 months for complete hydatidiform moles.[4][41]​​​ 

Anemia may result from heavy or persistent vaginal bleeding and the dilutional effects of increased blood volume. There is a greater risk for serious bleeding at the time of evacuation for MP, with a risk of disseminated intravascular coagulation from blood loss or trophoblastic embolism, although these are the rarest complications of molar pregnancy.

About 15% to 20% of women with complete molar pregnancies and 0.5% to 5% of women with partial molar pregnancies develop GTN and require chemotherapy.[4][42] These chemotherapy agents require normal liver and renal function for optimal dosing. Women undergoing evacuation of molar pregnancies are at increased risk of bleeding significant enough to require a blood transfusion. Blood typing ensures that type-appropriate blood can be made available in the event of hemorrhage.

Imaging

Pelvic ultrasound is the mainstay of diagnosis and an essential component in the evaluation of suspected GTN.[31][43]​​​ Typical ultrasound findings for a complete molar pregnancy include a diffuse echogenic pattern described as a snow-storm pattern, which is created by intermingling of hydropic villi and blood clots.[3][42]​​ The presence of a smaller volume of abnormal placenta with partial fetal development, without fetal cardiac activity, is characteristic of a partial molar pregnancy.[3][42]​​​ Cystic enlargement of the ovaries may represent theca lutein cysts.[3][Figure caption and citation for the preceding image starts]: Ultrasound showing multiple cystic areas in the uterine cavity giving a "snowstorm appearance" suggestive of molar pregnancy.Nigam A, Kumari A, Gupta N. Negative urine pregnancy test in a molar pregnancy: is it possible? Case Reports 2014;2014:bcr2014206483. [Citation ends].com.bmj.content.model.Caption@21eb127d

Advanced imaging, such as CT scan or MRI, is not typically required for benign moles, unless the woman has signs or symptoms of pulmonary or brain metastases.[4]

Women with an established diagnosis of gestational trophoblastic neoplasia (GTN)

The FIGO diagnostic criteria for postmolar GTN without symptoms are based on surveillance of hCG levels and histopathology:[4]

  • Four or more measurements of plateaued hCG levels over a 3-week period (on days 1, 7, 14, and 21).

  • An increase in hCG levels for three or more consecutive weekly measurements over a period of at least 2 weeks (on days 1, 7, and 14).

  • A histopathologic diagnosis of choriocarcinoma.

Women with an established diagnosis of GTN following molar pregnancy should be evaluated with a pelvic exam and chest x-ray.[3] Pulmonary congestion, edema, alveolar infiltrates, and metastatic nodules may be visible on the chest radiograph. If the chest x-ray is inconclusive, if there are metastases ≥1 cm or the woman has a signs or symptoms of metastatic disease, computed tomography scans of the chest, abdomen, and pelvis should be performed and magnetic resonance imaging of the brain should be obtained to further evaluate and stage metastases.[3][4]​​

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