Abstract
Genetic alterations significantly contribute to the aetiology of reproductive failure and comprise monogenic, chromosomal and epigenetic disturbances. The implementation of next-generation sequencing (NGS) based approaches in research and diagnostics allows the comprehensive analysis of these genetic causes, and the increasing detection rates of genetic mutations causing reproductive complications confirm the potential of the new techniques. Whereas mutations affecting the fetal genome are well known to affect pregnancies and their outcome, the contribution of alterations of the maternal genome was widely unclear. With the recent mainly NGS-based identification of maternal effect variants, a new cause of human reproductive failure has been identified. Maternal effect mutations affect the expression of subcortical maternal complex (SCMC) proteins from the maternal genome, and thereby disturb oocyte maturation and progression of the early embryo. They cause a broad range of reproductive failures and pregnancy complications, including infertility, miscarriages, hydatidiform moles, aneuploidies and imprinting disturbances in the fetus. The identification of women carrying these molecular alterations in SCMC encoding genes is therefore essential for a personalised reproductive and genetic counselling. The diagnostic application of new NGS-based assays allows the comprehensive analysis of these factors, and helps to further decipher these functional links between the factors and their disturbances. A close interdisciplinary collaboration between different disciplines is definitely required to further decipher the complex regulation of early embryo development, and to translate the basic research results into clinical practice.