Modern techniques have made misdiagnosis uncommon, and data from a large European consortium tracking outcomes over many years has reported no confirmed cases of misdiagnosis when linkage-based testing is used correctly. That said, no laboratory test on a handful of cells is ever presented as absolutely perfect, and every reputable program discusses a small, quoted margin of error before testing begins.

Several factors can reduce the reliability of an individual result. Allele dropout, where one copy of a gene fails to be detected during the laboratory amplification process, is the most significant technical risk; combining direct variant testing with linkage analysis substantially lowers this risk compared with either method alone. Recombination, a natural process in which chromosome segments swap between generations, can occasionally interfere with the genetic markers being tracked. Poor-quality DNA from the biopsy sample, laboratory contamination, and certain difficult categories of genetic change, including repeat-expansion disorders such as fragile X syndrome, large deletions, and changes affecting genes with similar-looking backup copies elsewhere in the genome, also pose extra technical challenges. A variant that arose new in a family member, rather than being inherited from a parent, can be harder to track with certainty because there is no established family pattern of markers to follow.

Because of these limitations, every major professional body, including the American College of Obstetricians and Gynecologists, recommends that a pregnancy resulting from an embryo identified as unaffected still be offered confirmatory testing, through chorionic villus sampling or amniocentesis, once the pregnancy is established. This step provides a far higher level of diagnostic certainty than testing a few cells from an early embryo ever can, and it remains the safety net that makes the overall approach dependable.