Chromosomal aberrations in pregnancy and fetal loss: Insight on the effect of consanguinity, review of 1625 cases

Abstract

Background: Pregnancy loss affects 10%–15% of pregnancies and is caused by several factors, maternal and fetal. Most common cause is chromosomal aneuploidy and has traditionally been detected by karyotyping product of conception and/or fetal tissue. In recent years, array comparative genomic hybridization (a-CGH) has been used because of its higher detection and lower failure rates. Methods: DNA was extracted from 1625 products of abortion or fetal tissue. In 1,104 cases both quantitative fluorescent-polymerase chain reaction (QF-PCR) and a-CGH, and in 521 cases only a-CGH, was performed. Results: The 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 and failure rates is significant (p-value < 0.001 and p-value < 0.001 respectively). Unexpectedly we also found a significant difference in frequency of imbalances in related versus unrelated couples. (χ2 = 11.4926, p-value < 0.001). Conclusion: It is highly likely that the pregnancy loss in consanguineous couples is caused by other genetic and immune mechanisms. It is plausible that, 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 and intra-uterine fetal death (IUFD) in these couples. Our findings suggest that this is a matter for further study as it will greatly influence the approach to counseling and managing consanguineous couples with pregnancy loss.