TY - JOUR

T1 - Diagnosis of hydatidiform moles using circulating gestational trophoblasts isolated from maternal blood

AU - Ravn, Katarina

AU - Hatt, Lotte

AU - Singh, Ripudaman

AU - Schelde, Palle

AU - Hansen, Estrid Stæhr

AU - Vogel, Ida

AU - Uldbjerg, Niels

AU - Niemann, Isa

AU - Sunde, Lone

PY - 2023/4

Y1 - 2023/4

N2 - 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 non-molar 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 6–13. 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 cfDNA. 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.

AB - 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 non-molar 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 6–13. 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 cfDNA. 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.

KW - Cell-based non-invasive prenatal testing

KW - Circulating gestational trophoblasts

KW - Gestational trophoblastic disease

KW - Hydatidiform mole

KW - Liquid biopsy

UR - http://www.scopus.com/inward/record.url?scp=85149759412&partnerID=8YFLogxK

U2 - 10.1016/j.placenta.2023.02.012

DO - 10.1016/j.placenta.2023.02.012

M3 - Journal article

C2 - 36889013

AN - SCOPUS:85149759412

VL - 135

SP - 7

EP - 15

JO - Placenta

JF - Placenta

SN - 0143-4004

ER -