Usefulness of combined NGS and QF‐PCR analysis for product of conception karyotyping

<jats:title>Abstract</jats:title><jats:sec><jats:title>Purpose</jats:title><jats:p>Since chromosomal abnormalities can be detected in more than half of miscarriages, cytogenetic testing of the product of conception (POC) can provide important information when preparing for a subsequent pregnancy. Conventional karyotyping is the common diagnostic method for a POC but can be problematic due to the need for cell culture.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We here conducted shallow whole‐genome sequencing (sWGS) using next‐generation sequencing (NGS) for alternative POC cytogenomic analysis. Since female euploidy samples can include 69,XXX triploidy, additional QF‐PCR was performed in these cases.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We here analyzed POC samples from miscarriages in 300 assisted reproductive technology (ART) pregnancies and detected chromosomal abnormalities in 201 instances (67.0%). Autosomal aneuploidy (151 cases, 50.3%) was the most frequent abnormality, consistent with prior conventional karyotyping data. Mosaic aneuploidy was detected in seven cases (2.0%). Notably, the frequency of triploidy was 2.3%, 10‐fold lower than the reported frequency in non‐ART pregnancies. Structural rearrangements were identified in nine samples (3%), but there was no case of segmental mosaicism.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>These data suggest that NGS‐based sWGS, with the aid of QF‐PCR, is a viable alternative karyotyping procedure that does not require cell culture. This method could also assist with genetic counseling for couples who undergoes embryo selection based on PGT‐A data.</jats:p></jats:sec>