Cytogenetic diagnosis of "normal 46,XX" karyotypes in spontaneous abortions frequently may be misleading

To use the molecular identification of Y chromosome material in products of conception cytogenetically diagnosed as "46,XX" to confirm the occurrence of inaccurate cytogenetic test results most likely attributable to maternal cell contamination.

Retrospective analysis.

Academic medical center.

Thirty-four archival tissues from cases of spontaneous abortion with a "46,XX" karyotype based on cytogenetic analysis.

Maternal and villus DNA were extracted from microdissected, formalin-fixed, paraffin-embedded archival tissues. The presence of the X and Y chromosomes was detected with the use of polymerase chain reaction assays and confirmed with fluorescence in situ hybridization.

Accuracy of cytogenetic evaluation of products of conception.

Four (29%) of 14 first trimester and 1 (5%) of 20 second trimester "46,XX" pregnancy losses contained Y chromosome-specific DNA and demonstrated a single X chromosome-specific allele by polymerase chain reaction analysis consistent with an "XY" karyotype. Fluorescence in situ hybridization was confirmatory in 4 of 5 samples that demonstrated single X and Y signals in villus cells.

Inaccuracy exists in the cytogenetic analysis of early products of conception that most likely is due to maternal cell contamination. In the absence of confirmatory testing, such as with a "DNA fingerprinting" assay, reports of a "46,XX" karyotype should be used cautiously in patient counseling and management.