Recurrent Pregnancy Loss Associated Cytogenetic and Genetic Anomalies – Study from Eastern India

Recurrent early pregnancy loss (REPL) refers to loss (2 or more) of pregnancy within the first trimester of the gestation period. Reports of REPL cases are significantly increasing along with idiopathic or enigmatic REPL because associated clinical parameters in such cases remain within normal range and diagnosis remains odyssey. Genetic factors like single nucleotide variations (SNV) and altered heterochromatin and/or satellite content, as chromosomal aberrations like translocation, deletion and inversions have reportedly remained associated with many diseases. The present study aimed to find any structural and single nucleotide variations associated with idiopathic REPL. Three thousand six hundred twelve (3612) couples with history of 2 or more pregnancy losses or neonatal death were subjected to clinical investigations, karyotype analyses and Whole Exome Sequence analyses as per requirement to identify the underlying cause(s). More than 14% of the idiopathic REPL cases were found to carry chromosomal heteromorphisms. Among these, 9qh+ was predominant, followed by 21ps+, 15ps+, 14ps+ and others. Heteromorphies were significantly higher in females than males except for 14ps+. Along with some single nucleotide variations were also found among the subjects, though compound heterozygosity or allelic homozygosity were major causal factors. Idiopathic REPL cases were found to carry genetic variations, as per the present study, with a prevalence of more than 10% among RPL cases with yet unknown molecular mechanisms of damage. A further thorough study to unveil the underlying molecular pathology is strongly recommended.