Chromosomal aberrations in pregnancy loss: insight on the effect of consanguinity, review of 1625 cases, comparison with karyotype

Background: Pregnancy loss affects 10-15% of pregnancies and is caused by several factors, maternal and fetal. Traditionally karyotype was used to detect the cause of abortion. Recently with the advent of array comparative genomic hybridization (a-CGH) has become a more accurate alternative for the detection of fetal chromosome anomalies. We are reporting the results of our 7-year experience and a comparison of the results from a-CGH with our twenty-year experience with karyotypingObjective: In addition, we are comparing the rate and frequency of chromosomal aberrations in consanguineous couples with non-consanguineous couples.Materials and Methods: DNA was extracted from 1625 product of abortions. In 1104 of cases both quantitative fluorescent-polymerase chain reaction (QF-PCR) and a-CGH and in 521 cases only a-CGH was performed.Results: Detection rate using QF-PCR and a-CGH is 20% compared to 12.7% overall and 15.7% excluding failed samples by karyotypes in our center. QF-PCR and a-CGH failed in 1.9% of cases, while the failure rate for karyotypes was 20.1%. The difference of detection rate and failure rate is significant (p<0.001 and p<0.001 respectively). Unexpectedly we found a significant difference in frequency of imbalances in related vs. unrelated couples (p<0.001).Conclusion: It is highly likely that the pregnancy loss in the consanguineous couples is caused by other genetic and immune mechanisms. It is plausible through the same mechanism by which single gene disorders have a higher prevalence of manifesting disease in consanguineous couples; they can cause lethal genetic disorders leading to pregnancy loss in these couples. We propose that further study and reports of other cohorts with similar consanguinity frequency is necessary to verify these findings.

Keywords:

Miscarriage , Array comparative genomic hybridization , Consanguinity , Chromosomal abnormality , Recurrent abortion