Molecular karyotype analysis of spontaneous abortion products

Molecular karyotype – aCGH is able to detect all chromosomal aneuploidies and imbalances revealed by ‘classic’ karyotype analysis, such as trisomy 13, 18, 21, etc., while it additionally allows the investigation of other chromosomal imbalances (deletions and/or duplications), undetectable by classic karyotype, at an analytical level of about 10-100 times higher resolution than classic karyotype analysis.

Spontaneous abortions, which mostly occur in the first trimester of pregnancy, is a relatively common reproductive problem, affecting 10-15% of all pregnancies. It is known that chromosomal abnormalities are responsible for >60% of fetal losses and their detection provides valuable information regarding the genetic causes of miscarriage but also the risk for subsequent pregnancies.

Application of classic karyotype analysis is based on the successful culturing of embryonic tissue/cells; however, due to in utero embryo demise and tissue necrosis, as well as other technical problems relating to the culture or bad morphology of the chromosomes, successful analysis rates range internationally from 60 to 90%. Furthermore, the information provided by the classice karyotype is limited to microscopically visible numerical chromosomal abnormalities and major structural rearrangements with a size >10MB.

Recently, several studies, as well as our own considerable experience, have demonstrated that application of molecular karyotype-aCGH analysis in spontaneous abortion samples has a 10-15% increase in detection rate compared to classic karyotype for uncovering pathological chromosomal abnormalities. Furthermore, molecular karyotype detected successfully chromosomal abnormalities in ~50% of the samples in which classic karyotype analysis failed to produce a final result by (mainly due to culture problems).

Finally, the application of molecular karyotype in spontaneous abortion samples does not require the time-consuming sample culturing, thus the test is completed in 4-5 days.

If the karyotype is found to be that of a normal female, we also perform, free of charge, further DNA analysis for the exclusion of maternal cell contamination and to ensure that the karyotype truly reflects the aborted fetus. Therefore, a small amount of peripheral blood from the mother is requested to accompany each spontaneous abortion sample.

Karyotype analysis of spontaneous abortion samples is preferably carried out from chorionic villi tissue through a sampling process which takes care to minimize maternal contamination.