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Diagnosis of hydatidiform moles using circulating gestational trophoblasts isolated from maternal blood

Introduction: Identifying hydatidiform moles (HMs) is crucial due to the risk of gestational
trophoblastic neoplasia. When a HM is suspected on clinical findings, surgical termination is
recommended. However, in a substantial fraction of the cases, the conceptus is actually a nonmolar miscarriage. If distinction between molar and non-molar gestations could be obtained
before termination, surgical intervention could be minimized.

Methods: Circulating gestational trophoblasts (cGTs) were isolated from blood from 15 consecutive
women suspected of molar pregnancies in gestational week 6 to 13. The trophoblasts were
individually sorted using fluorescence activated cell sorting. STR analysis targeting 24 loci was
performed on DNA isolated from maternal and paternal leukocytes, chorionic villi, cGTs, and

Results: With a gestational age above 10 weeks, cGTs were isolated in 87% of the cases. Two
androgenetic HMs, three triploid diandric HMs, and six conceptuses with diploid biparental
genome were diagnosed using cGTs. The STR profiles in cGTs were identical to the profiles in DNA
from chorionic villi. Eight of the 15 women suspected to have a HM prior to termination had a
conceptus with a diploid biparental genome, and thus most likely a non-molar miscarriage.

Discussion: Genetic analysis of cGTs is superior to identify HMs, compared to analysis of cfDNA, as
it is not hampered by the presence of maternal DNA. cGTs provide information about the full
genome in single cells, facilitating estimation of ploidy. This may be a step towards differentiating
HMs from non-HMs before termination.