While PGD is an important diagnostic tool, it is not without limitation. Genetic analysis of single cells is technically demanding and prone to errors of various kinds. PGD-FISH (fluorescent in-situ hybridization) can only test for a limited number of chromosomes. Abnormalities in the remaining chromosomes cannot be detected. PGD-PCR (polymerase chain reaction) can sometimes fail to detect single gene defects. For chromosomal translocations, PGD cannot detect abnormalities in chromosomes other than the one known to be involved in the translocation. The error rate for PGD in detecting chromosomal abnormalities is approximately ten percent. In cases of genetic mosaicism, where a given genetic abnormality may exist in one cell of an embryo but not in another, PGD if often is inadequate for diagnostic purposes. On the other hand, because of the limitations of PGD, it is possible that no embryo will appear normal, while an embryo may in fact be normal, so PGD can create both false positives and false negatives.

One concern many couples have is whether or not the procedure will affect their chances of pregnancy or, more importantly, the health of their embryo. Because the procedure is done so early in the developmental process, at a time when any cell from the embryo can potentially be removed, PGD does not cause any harm to the developing embryo. More debatable is, however, is the degree to which PGD affects your chances of a successful pregnancy. Studies on PGD and pregnancy success rates have reported conflicting findings, with some studies suggesting that it lessens the chances of pregnancy and others finding it increases those chances.

In rare cases, it is possible that an embryo may be accidentally damaged during biopsy, resulting in developmental arrest. Embryo biopsy may delay cell division by a few hours, and some embryos fail to recover from biopsy and fail to result in a live birth. In other cases, embryo biopsy and/or genetic analysis may fail due to technical problems.

Despite these risks and limitations, PGD is an important diagnostic tool for many couples with a family history of genetic defects.