Introduction The ability to combine whole genome amplification (WGA) with gene-specific primers in a single PCR reaction to allow both aneuploidy detection (PGT-A) and monogenic disease detection (PGT-M) is an advantage of DOPlify® and the RHS targeted sequence enrichment (TSE) protocol. This study aims to compare Allele Drop-Out (ADO) rates by comparing three different approaches; gene specific PCR only, WGA and WGA with TSE. Material and Methods Thirty 5-cells aliquots were manually sorted from a cell line containing a 2bp heterozygous BRCA1 mutation (GM14090, Coriell Institute). To allow an assessment of aneuploidy detection, thirty 5-cell aliquots from an aneuploid cell line (GM04965, 48,XXY,+21, Coriell Institute) were also used. In the TSE approach, cells were amplified using DOPlify® (RHS Ltd) with the inclusion of three BRCA1 primers. One BRCA1 primer set was designed to specifically amplify the region on chromosome 17 containing the deletion site in GM14090 and other two primer sets to amplify BRCA1 linker markers. The resulting WGA-TSE product was diluted 1/10 and used as template for a second gene specific multiplex PCR (Qiagen) containing the same BRCA1 primers. The BRCA1 PCR products were then pooled back into the WGA-TSE product before library preparation and analysed using a single library index (WGA-TSE+GS). Secondly, for PGT-M only, cells were subjected to two rounds of gene specific PCR using multiplex PCR (Qiagen) and the same BRCA1 primers (GS+GS). Lastly, cells were amplified according to standard DOPlify® protocol (RHS Ltd) with no BRCA1 primers added. The resulting WGA product was diluted 1/10 and seeded into the BRCA1 multiplex PCR reaction (Qiagen) (WGA+GS). PCR products from the WGA-TSE+GS condition were sequenced according to standard PG-Seq™ protocol (RHS Ltd). Amplicons from the GS+GS and WGA+GS conditions were diluted 1/10 before final library pooling then were sequenced with the Illumina MiSeq. Results The 2bp heterozygous BRCA1 deletion was accurately detected in 10/10 of the WGA-TSE+GS samples, 10/10 of the GS+GS samples and 7/10 of the WGA+GS samples with average allele frequencies of 41%, 47% and 53%, respectively. The average read depth across the 2bp deletion site was 120, 129 and 138, respectively. One GM04965 sample from the GS+GS condition failed to amplify the region. Correct aneuploidy results were obtained for 9/9 BRCA1 cells and 10/10 GM04965 cells processed with the WGA-TSE+GS protocol with one BRCA1 sample excluded after failing quality control (weak amplification). The GS+GS protocol does not allow for PGT-A assessment. Conclusions The DOPlify® TSE protocol is able to reliably generate both PGT-A and PGT-M results from a cell sample representing a single embryo biopsy. The PGT-A results were not compromised, and PGT-M results showed no ADO and were comparable to the gene specific PCR protocol. These results highlight the benefit of the DOPlify® TSE protocol, which is now being clinically validated.