The established risk factors for complete mole are pregnancy at extremes of maternal age and prior molar pregnancy. Compared to the risk for the 21–35 years age group, risk for complete mole is nearly twice for women younger than 21 years and older than 35 years, and 7.5 times higher for women over 40 years. This suggests increased risk of abnormal gametogenesis and fertilization of the ovum produced at extremes of reproductive age. Prior molar pregnancy increases the risk to 10 times for sporadic complete moles, while familial clustering and recurrent mole is the rule in familial biparental recurrent moles due to mutations of NLRP7 and KHDC3L genes. Other risk factors include: cigarette smoking, family history of GTD, Asian race and history of miscarriages.

Grossly, CHM consists of hydropic villi to semitransparent vesicles of variable sizes with absence of normal placenta. Early CHM may have minimal or no gross evidence of abnormal villi. Differential diagnoses of CHM include PHM, hydropic abortion, and early non-molar gestation with florid trophoblastic hyperplasia.  

Histologically, complete mole has florid cistern formation, trophoblastic proliferation, and absence of fetal parts. Significant cytological atypia and mitotic figures may be seen. In the first trimester, CHM villi may not be markedly enlarged but have a distinct polypoid appearance with abnormal villous stromal changes and mild to moderate trophoblastic hyperplasia. In contrast, such histologic features are less marked in partial mole, and fetal parts or cells are present. Hydropic spontaneous abortion may mimic the appearance of partial mole. 

A cyclin-dependent kinase inhibitor p57 is encoded by the paternally imprinted and maternally expressed gene and hence is absent in the villous cytotrophoblasts and stromal cells of CHM without the maternal genome. In contrast, PHM and non-molar abnormal gestations with maternal genome have strong nuclear p57 staining, which can be used to exclude complete mole. However, p57 cannot differentiate PHM from non-molar gestations. The cytogenetics of CHM, PHM, and hydropic spontaneous abortion are different. Typically, CHM is diploid and has 46, XX chromosomes with both X chromosomes from paternal origin, whereas PHM is triploid with maternal and paternal genetic origin. Hydropic spontaneous abortion normally has 46, XX or XY from both parents. Microsatellite short tandem repeat (STR) genotyping enables precise diagnosis of CHM and PHM by identifying the absence of maternal genetic contribution and diandric triploidy, respectively.

Grossly, the tumor is bulky with hemorrhagic and necrotic areas. Apart from the uterus, it can be found in tubes, ovaries, lung, liver, spleen, kidneys, bowel, or brain. 

Histologically, choriocarcinoma shows absence of chorionic villi and presence of abnormal intermediate trophoblast and cytotrophoblast, rimmed with syncytiotrophoblasts with areas of necrosis and hemorrhage. Genotyping analysis can identify unique paternal alleles and confirm the choriocarcinoma or germ cell origin and somatic carcinoma with trophoblast differentiation.

Patient may present with abnormal bleeding per vagina which is a common presenting feature. Other features may include passage of grape like vesicles, uterus larger than expected for gestational age, abdominal pain, vomiting. Features may mimic hyperthyroidism and hyperemesis gravidarum. In cases of GTN, the features may include those associated with metastases eg seizures and hemoptysis.

This includes full blood count, electrolyte, urea and creatinine, quantitative beta hCG test, ultrasound scan and chest xray. Histology is necessary for definitive diagnosis.

Suction curettage is the method of choice for removal of molar pregnancies except in cases when the size of fetal parts (for partial mole) may deter the use of suction curettage and then medical removal can be considered. 

Women with GTN may be treated with single-agent or multi-agent chemotherapy depending on the severity of the disease. The severity of the disease can be assessed using the FIGO 2000 prognostic scoring system. A score of 6 or less suggest low grade disease and can be managed using single agent chemotherapy. A score of more than 7 suggest high grade disease and will require multi-agent chemotherapy.

PSTTs and ETTs are rare forms of GTD diagnosed by histological examination of retained pregnancy tissue. They are less chemo sensitive and their presentation and behavior are different and less predictable. Hysterectomy is curative in many cases with localized disease. 

This is achieved primarily with serial measurement of beta hCG levels. It is important that women who had a removal of a molar pregnancy are advised not to become pregnant until they have completed their hCG follow-up. Women who undergo chemotherapy are advised not to conceive for 1 year after completion of treatment, as a precautionary measure. The use of exogenous estrogens and other fertility drugs can be considered once hCG levels have returned to normal. The risk of recurrence in a later pregnancy is low (0.6%–2%)

The outlook however for women properly treated is generally excellent with an overall cure rate close to 100%.