Molecular Analysis of Chromosomal Abnormalities in Products of Conception (POCs)

Miscarriages are the most common complication during the first trimester of pregnancies, approximately 15-25% of the cases are clinically recognized pregnancy losses and in about 60% of cases a chromosomal abnormality is observed. Recurrent pregnancy loss (RPL) has been recently defined as two or more consecutive pregnancy losses in the first or early second trimester. Although the overall incidence of RPL is low and estimated at less than 5% of women, it presents a significant diagnostic and treatment challenge for both patients and clinicians

Cytogenetic analysis of POC is essential to determine the cause of sporadic and recurrent pregnancy loss and allows the risk of recurrence to be estimated for future pregnancies, thus improving the chances of subsequently producing a healthy full-term pregnancy.

POCs analysis has traditionally been performed using Giemsa banding (G-banding) on cultured cells in metaphase, and it is considered the gold standard detection method. However, it has many limitations in the analysis of miscarriage. It relies on the successful culture of fetal tissue and preparation of metaphase cells, yet the successful rate of conventional karyotyping of miscarriage tissue is relatively low, ranging from 60 to 90% because of the in vivo death of tissue associated with spontaneous abortion, technical problems with culture growth or poor chromosome morphology.

Currently POC chromosome status assessment could be determined by genetic molecular methods, more efficient since direct DNA extraction from the tissue can be performed avoiding cell culture. In the current lecture the results of our laboratory in the molecular analysis if POCs by array CGH and Next Generation Sequencing will be presented. Aditionally, in a subset of patients, hysteromebryoscopy was performed and we were able to infer the real incidence of feto-placental mosaicism.