Algorithms to minimize the effect of maternal contamination in non-invasive chromosome screening.

RESEARCH QUESTION: Can algorithms be developed to assess maternal contamination in the embryo spent culture medium without parental samples and correct copy number variations (CNV)?

DESIGN

An algorithm was developed to confirm the proportion of maternal contamination based on the mosaic ratios of X and Y chromosomes and an algorithm to correct copy number variation (CNV) in embryos with maternal contamination. Performance of algorithms was tested in 317 culture medium samples. A prospective clinical study was then conducted to validate the accuracy.

RESULTS

Among 55 male embryos with maternal contamination, the consistency of the corrected CNV results with the whole embryo results was higher than that of the CNV results before correction (69.1% versus 10.9%, P < 0.001). Among the 317 embryo culture medium samples, maternal contamination was identified in 88 (27.8%) samples through the algorithm based on the mosaic ratios of X and Y chromosomes and quantitative parental contamination test. Upon re-assessment using the CNV correction algorithm, two and five of the 19 samples deemed as euploid initially were re-classified as mosaic and aneuploid, respectively; 23 and three of the 36 samples deemed as mosaic initially were re-classified as aneuploid and euploid, respectively. In the clinical study, the live birth rate was 44.7%. Accuracy of the algorithms was assessed in 25 donated embryos and 47 cases with prenatal testing. The overall concordance rate was 95.8% (69/72).

CONCLUSIONS

The CNV correction algorithm could be used to minimize the effect of maternal contamination in culture medium and enhance the accuracy of non-invasive chromosome screening.