Nikhil S Sahajpal, Ashis K Mondal, Sudha Ananth, Chetan Pundkar, Kimya Jones, Colin Williams, Timothy Fee, Amanda Weissman, Giuseppe Tripodi, Eesha Oza, Larisa Gavrilova-Jordan, Nivin Omar, Alex Hastie, Barbara R DuPont, Lawrence Layman, Alka Chaubey, Ravindra Kolhe.
Conventional cytogenetic analysis of products of conception (POC) is of limited utility because of failed cultures, microbial and maternal cell contamination (MCC). Optical genome mapping (OGM) is an emerging technology that has the potential to replace conventional cytogenetic methods. The use of OGM precludes the requirement for culturing (and related microbial contamination). However, a high percentage of MCC impedes a definitive diagnosis, which can be addressed by an additional pre-analytical quality control step that includes histological assessment of H&E stained slides from FFPE tissue with macro-dissection for Chorionic villi to enrich fetal tissue component for Single nucleotide polymorphism (SNP) microarray analysis. An internal audit of POC cases subjected to karyotype-only analysis showed a low yield on clinically actionable information that contributed to patient care. To improve the diagnostic yield, an integrated workflow was devised that included MCC characterization of POC tissue, followed by OGM for MCC negative cases or SNPM with histological assessment for MCC positive cases. A result was obtained in 93% (29/31) cases with a diagnostic yield of 45.1% (14/31) with proposed workflow compared to 9.6% (3/31) and 6.4% (2/31) with routine workflow, respectively. The integrated workflow with these technologies demonstrates the clinical utility and higher diagnostic yield in evaluating POC specimens.