What is a molar pregnancy in women of childbearing age, particularly those under 20 or over 35 years old with a history of previous miscarriages or fertility issues?

What is Molar Pregnancy

A molar pregnancy is a benign premalignant tumor arising from abnormal fertilization of placental tissue that results in a non-viable pregnancy, with potential to progress to life-threatening complications including hemorrhage and malignant transformation requiring chemotherapy. 1

Types and Genetic Origins

Molar pregnancy presents as two distinct entities with different genetic mechanisms and clinical implications:

Complete Hydatidiform Mole (CHM)

• Accounts for approximately 80% of all gestational trophoblastic disease and results from fertilization of an ovum that has lost its maternal chromosomes before or shortly after fertilization 2, 3
• All nuclear DNA is entirely paternal in origin, with 80% arising from duplication of a single sperm's haploid genome and 20% from fertilization by two sperm (dispermy) 2
• Contains no fetal tissue or normal embryonic structures, only abnormal placental tissue with characteristic vesicular appearance 2, 1
• Mitochondrial DNA remains maternal despite the absence of maternal nuclear chromosomes 2

Partial Hydatidiform Mole (PHM)

• Almost always triploid, resulting from fertilization of a normal ovum by two sperm or occasionally a diploid sperm 2
• May contain abnormal fetal tissue that ultimately dies, distinguishing it from complete moles 1, 4
• The existence of diploid partial moles is unlikely, with most reported cases representing misdiagnosed conditions 2

Clinical Presentation

Complete Mole Presentation

• Vaginal bleeding is the most common presenting symptom, typically occurring between 6-16 weeks of gestation 2, 5, 3
• Markedly elevated hCG levels, often exceeding 100,000 IU/L, far beyond expected levels for gestational age 2, 1
• Uterine enlargement beyond expected gestational age due to exuberant trophoblastic growth 1, 4
• Additional signs may include preeclampsia, hyperemesis, anemia, and theca lutein ovarian cysts, though these are less common with early diagnosis 2, 4

Partial Mole Presentation

• Tends to present later in the first or early second trimester with symptoms mimicking incomplete or missed abortion 2
• Smaller uterine size and lower hCG levels compared to complete moles 4
• Grows more slowly than complete moles 2

Diagnostic Approach

Ultrasound Findings

• Characteristic "snowstorm" appearance with heterogeneous mass without fetal development for complete mole 2, 5, 1
• Patchy villous hydropic change with scattered abnormally shaped irregular villi for partial mole 5
• Ultrasound has high false positive and negative rates, especially for partial moles, making it unreliable as the sole diagnostic method 2, 5

Definitive Diagnosis

• Histological examination following evacuation is essential for definitive diagnosis and classification, as ultrasound alone is insufficient 2, 5, 3
• All products of conception from non-viable pregnancies must undergo histological examination regardless of ultrasound findings 2
• Reference pathology review in a Gestational Trophoblastic Disease center within 2 weeks is considered best practice 5

Risk of Malignant Transformation

Post-Molar Gestational Trophoblastic Neoplasia (GTN)

• Post-molar GTN develops in approximately 15-20% of complete moles, significantly higher than the 1-5% risk following partial moles 2, 3, 1
• Malignant change is indicated by plateaued hCG on three consecutive samples or rising hCG on two consecutive samples 2, 5, 1
• Cure rates approach 100% with appropriate treatment and surveillance, with fertility preservation generally possible 2, 3, 1

Epidemiology and Risk Factors

• Affects approximately 1 in 500 to 1,000 pregnancies globally, with an estimated 220,000 women diagnosed with gestational trophoblastic disease annually worldwide 3
• Maternal age is a primary risk factor, with higher incidence in women under 20 or over 35 years old 6
• History of previous molar pregnancy increases recurrence risk to 1.0-2.0% in subsequent pregnancies, compared to the general population 6
• Incidence varies geographically, with higher rates in certain populations 3

Special Genetic Considerations

Familial Recurrent Hydatidiform Mole (FRHM)

• Some patients with recurrent complete moles have diploid biparental CHM rather than typical androgenetic CHM, due to an autosomal recessive condition 2, 5
• Associated with mutations in NLRP7 and, more rarely, KHDC3L genes 2, 5
• Women with FRHM are unlikely to achieve a normal pregnancy except through ovum donation from an unaffected individual, unlike women with recurrent androgenetic CHM who can have normal live births 2, 5, 3

Life-Threatening Complications

Molar pregnancy can rapidly progress to severe complications including:

• Life-threatening hemorrhage during evacuation or from invasive disease 1
• Acute respiratory distress syndrome 4
• Thyroid storm from hyperthyroidism 4
• Preeclampsia 4
• Invasive moles can extend into myometrium via venous channels, with approximately 15% metastasizing to lung or vagina 2