Gestational Trophoblastic Neoplasia From Genetically Confirmed Hydatidiform Moles: Prospective Observational Cohort Study.

OBJECTIVE: The aim of this study was to evaluate the incidence and risk factors of gestational trophoblastic neoplasia (GTN) from hydatidiform moles (HMs) cytogenetically diagnosed in a prospective cohort setting. METHODS: The prospective observational cohort study included cases of cytogenetically defined molar pregnancies, which were diagnosed by a multiplex short tandem repeat polymorphism analysis. Cases were classified as androgenetic complete HMs (CHMs), diandric monogynic triploid partial HMs (PHMs), or biparental abortion. Gestational trophoblastic neoplasia was diagnosed according to the International Federation of Gynecology and Obstetrics 2000 criteria. Incidences for each category, that is, CHM, PHMs, and biparental abortion, were calculated. Clinical variables (age, partner age, gravidity, parity, height, weight, BMI, and gestational age) and laboratory data (serum human chorionic gonadotropin [hCG], white blood cell count, hemoglobin, and platelet count) were compared between spontaneous remission cases and GTN cases in androgenetic CHMs. RESULTS: Among 401 cases, 380 were classified as follows: 232 androgenetic CHMs, 60 diandric monogynic PHMs, and 88 biparental abortions. A total of 35 cases (15.1%) of CHMs, but only 1 case of PHM (1.7%) and no biparental abortions, exhibited progression to GTN. The hCG value before evacuation was significantly higher in GTN cases than in spontaneous remission cases (P = 0.001, Kruskal-Wallis test). Patient age was also significantly higher in GTN cases than in spontaneous remission cases (P = 0.002, Student t test). CONCLUSIONS: Under the cohort cytogenetic diagnosis setting, the traditional risk factors for GTN after molar pregnancy, hCG value before evacuation and age, were confirmed in androgenetic CHMs. The risk of GTN was lower for PHMs than for CHMs. However, 1 patient with cytogenetic PHMs developed into GTN.

Complete hydatidiform moles are composed of paternal chromosomes and maternal mitochondria.

Mitochondrial DNA (mtDNA) and genomic DNA are produced in separate subcellular compartments. Human mtDNA is transmitted via maternal transmission in general. Complete hydatidiform moles (CHMs) represent major trophoblastic diseases that are cytogenetically exceptional because the chromosomal genomic DNA is derived only from sperm cells, making them strikingly different from normal concepti. However, few reports have described the mtDNA-transmission pattern in hydatidiform moles. To evaluate mtDNA transmission in androgenetic CHMs, we compared the sequences of hypervariable regions in 16 trios sets of mtDNAs from maternal, paternal, and villous samples of androgenetic CHMs diagnosed by short tandem repeat-polymorphism analysis. All mtDNAs in androgenetic CHMs were maternally derived, in line with the general human inheritance pattern. Three maternal mtDNAs were heteroplasmic. The heterozygous status of maternal mtDNA was reflected in villous tissue, in which variants status was also heterozygous. CHMs are composed of paternal chromosomes and maternal mitochondria.