What is gestational trophoblastic disease (GTD) in a female of reproductive age with a history of in vitro fertilization (IVF)?

What is Gestational Trophoblastic Disease?

Gestational trophoblastic disease (GTD) is a group of rare pregnancy-related tumors that develop from placental trophoblastic tissue, ranging from benign premalignant conditions (hydatidiform moles) to malignant tumors (gestational trophoblastic neoplasia), with an incidence of approximately 1 in 500-1,000 pregnancies and cure rates approaching 100% when treated appropriately. 1, 2

Classification and Types

GTD encompasses both premalignant and malignant entities that arise from abnormal trophoblastic proliferation 1:

Premalignant Forms (Benign GTD)

• Hydatidiform moles (HM) comprise approximately 80% of all GTD cases and include 1:
  • Complete hydatidiform mole (CHM): Results from abnormal fertilization of an ovum lacking nuclear DNA, with 80% arising from duplication of a single sperm's haploid genome and 20% from fertilization by two sperm (dispermy); contains no fetal tissue 1
  • Partial hydatidiform mole (PHM): Occurs when a normal ovum is fertilized abnormally, either by a single sperm with subsequent chromosome duplication or by two sperm; can contain fetal tissue 1
• Atypical placental site nodules (APSNs) represent non-neoplastic trophoblastic lesions 1

Malignant Forms (Gestational Trophoblastic Neoplasia - GTN)

• Invasive mole (15% of GTD): Arises from HM extending into the myometrium, with approximately 15% metastasizing to lung or vagina 1
• Choriocarcinoma (part of the remaining 5%): The most potent hCG producer, developing after hydatidiform mole (50%), term/preterm gestation (25%), or ectopic pregnancy/abortion (25%) 1, 3
• Placental site trophoblastic tumor (PSTT): Rare tumor that secretes hCG at significantly lower levels than other GTN forms 1, 3
• Epithelioid trophoblastic tumor (ETT): Another rare form with lower hCG production 1, 3

Epidemiology and Risk Factors

• The global incidence is approximately 1 in 500-1,000 pregnancies, translating to an estimated 220,000 women diagnosed annually worldwide, including 22,000 with GTN 1, 2
• Geographic variation exists, with higher incidence in Asia compared to Europe and North America, attributed to differences in diagnostic criteria, reporting practices, and nutritional factors 1
• Malignant transformation risk varies significantly by mole type 1, 2:
  • Post-molar GTN develops in 15-20% of complete moles
  • Only 1-5% of partial moles progress to GTN
  • Overall reported incidence of GTN after molar pregnancy ranges from 18-29%

Pathogenesis and Genetic Basis

• GTD is unique because maternal tumors arise from gestational tissue with locally invasive or metastatic potential 1
• Complete moles have characteristic genetic patterns: most (80%) contain two identical paternal chromosome complements from a single sperm, while 20% result from dispermy 1
• Partial moles retain maternal chromosomes and result from either single sperm fertilization with paternal chromosome duplication or dispermy 1
• The parental origin of chromosomes determines whether triploidy produces molar changes: diandric triploidy (extra paternal genome) creates partial moles, while digynic triploidy results in non-molar hydropic abortion 4

Clinical Presentation and Diagnosis

• Vaginal bleeding is the most common presenting symptom, typically occurring between 6-16 weeks of gestation 2
• Serum β-hCG levels are typically elevated beyond expected levels for gestational age 2
• Ultrasound examination serves as the primary imaging modality for initial detection 2
• Definitive diagnosis requires histological examination following evacuation, with ancillary techniques including p57KIP2 immunostaining, ploidy analysis, or molecular genotyping needed for accurate classification 4
• Partial moles show patchy villous hydropic change with scattered irregular villi, trophoblastic pseudoinclusions, and patchy trophoblast hyperplasia 4

Prognosis and Treatment Outcomes

• Cure rates approach 100% when treated adequately, with treatment typically allowing fertility preservation 1, 2
• Suction dilation and curettage under ultrasound guidance is the safest evacuation method 2
• All women with molar pregnancy require careful hCG monitoring to detect malignant transformation 2
• The distinction between molar and non-molar pregnancy matters clinically because partial moles carry a 0.5-1% risk of persistent GTD requiring hCG surveillance, while non-molar triploid pregnancies lack this malignant potential 4

Special Considerations for IVF Patients

• Women with recurrent androgenetic complete hydatidiform mole are likely to have normal live births in subsequent pregnancies and benefit from conventional in vitro fertilization 2
• Twin pregnancies with a coexistent normal twin and complete mole result in healthy babies in approximately 40% of cases, without obvious increase in risk of malignant transformation 2