From the Guidelines
Molar pregnancies are primarily caused by chromosomal abnormalities, including diandry, where 80% of complete hydatidiform moles (CHM) result from duplication of a single sperm's haploid genome, and 20% from dispermic fertilization of an ovum, while partial hydatidiform moles (PHM) are almost always triploid, resulting from fertilization of a normal ovum by two sperm or a diploid sperm 1.
Etiology of Molar Pregnancies
The etiology of molar pregnancies can be understood by examining the genetic origin of these conditions. Complete molar pregnancies typically have 46 chromosomes, all of paternal origin, resulting from either the duplication of a single sperm's chromosomes or the fertilization of an empty egg by two sperm. This lack of maternal genetic material renders the development of a viable fetus impossible. On the other hand, partial molar pregnancies usually have 69 chromosomes (triploidy), with one set of maternal chromosomes and two sets of paternal chromosomes, typically arising from the fertilization of a normal egg by two sperm.
Chromosomal Abnormalities
Chromosomal abnormalities play a crucial role in the development of molar pregnancies. Diandry, or the presence of two sets of paternal chromosomes, is a common cause of complete molar pregnancies. In contrast, partial molar pregnancies are often the result of triploidy, where there is an extra set of paternal chromosomes. Less commonly, molar pregnancies can result from digyny, where there is excess maternal genetic material.
Risk Factors and Clinical Implications
Risk factors for molar pregnancies include extremes of reproductive age, previous molar pregnancy, and certain geographic or ethnic backgrounds. The abnormal chromosomal composition of these pregnancies leads to dysfunctional placental development, characterized by grape-like vesicles and excessive production of human chorionic gonadotropin (hCG). These genetic abnormalities disrupt normal embryonic development and placentation, resulting in the characteristic pathological features of molar pregnancies and creating a risk for persistent trophoblastic disease. Therefore, monitoring of hCG levels after evacuation is essential to detect any potential malignant transformation 1.
Genetic Analysis and Diagnosis
Genetic analysis can be helpful in the diagnosis and management of molar pregnancies. In cases where tissue is available from gestational trophoblastic neoplasia (GTN), the genotype will reflect that of the causative pregnancy. This information can be particularly useful in patients with multiple pregnancies, where the interval from the causative pregnancy to the time of GTN diagnosis carries prognostic information 1. Additionally, genetic analysis can aid in the differential diagnosis between gestational and non-gestational tumors, which is critical for guiding treatment and predicting outcomes.
From the Research
Molar Pregnancy Etiology
- Molar pregnancy is a type of gestational trophoblastic disease, which is a spectrum of interrelated conditions originating from the placenta 2
- The etiology of molar pregnancy is complex and involves chromosomal abnormalities, including diandry (fertilization of an egg by two sperm) and digyny (fertilization of an empty egg by a single sperm) 3
Chromosomal Abnormalities
- Complete hydatidiform mole (CHM) is typically characterized by diandry, where a single egg is fertilized by two sperm, resulting in a 46,XX karyotype 4
- Partial hydatidiform mole (PHM) is typically characterized by digyny, where an empty egg is fertilized by a single sperm, resulting in a 69,XXX or 69,XY karyotype 4
Pathogenesis
- Dysregulation of parentally imprinted genes is important in the pathogenesis of complete hydatidiform mole (CHM) 3
- The risk of developing gestational trophoblastic neoplasia (GTN) remains unchanged, even with earlier diagnosis of molar pregnancy in the first trimester 3
Diagnosis and Management
- Accurate diagnosis of molar pregnancy relies on expert histopathology coupled with ancillary molecular and genetic techniques 4
- Close surveillance with serial human chorionic gonadotropin (hCG) monitoring is essential to diagnose GTN and identify the need for chemotherapy 5, 4
- Selection of single-agent or multiagent chemotherapy depends on accurate assignment of the clinical stage and risk stratification by the International Federation of Gynecology and Obstetrics (FIGO) prognostic scoring system 4