Genetic and Epigenetic Profiling of Embryos in Assisted Reproduction Technologies

Abstract

Preimplantation genetic testing improves assisted reproductive technology outcomes in high-resource settings, yet implementation in genetically diverse African populations remains virtually absent despite elevated genetic disease burden. This study aimed to characterise the genetic and epigenetic profiles of embryos from Nigerian couples undergoing assisted reproductive technology and assess clinical outcomes following genetic selection. We conducted a prospective, multicentre study across 30 fertility clinics in Nigeria's six geopolitical zones between January 2023 and June 2024, enrolling 246 couples and yielding 1,248 embryos for comprehensive genetic analysis. Embryos underwent next-generation sequencing for chromosomal assessment, targeted testing for monogenic disorders, and epigenetic profiling using bisulfite sequencing and chromatin immunoprecipitation. Statistical analysis employed generalised linear mixed models with random intercepts for clinic clustering using R version 4.3.0. Overall, the aneuploidy rate was 48.6% (95% CI: 45.8-51.4%), increasing from 35.4% in women under 35 years to 78.2% in those over 40 years. Single euploid embryo transfers achieved significantly higher implantation rates than morphology-selected transfers: 42.8% versus 26.3% (OR = 2.09, 95% CI: 1.47-2.97, p < 0.001). Preimplantation genetic testing for sickle cell disease demonstrated a diagnostic accuracy of 98.2%. Nigerian embryos exhibited 1,203 differentially methylated regions compared to European populations and 3-fold greater mitochondrial haplogroup diversity. Genetic embryo selection substantially improves Nigerian assisted reproductive technology outcomes but requires population-specific protocols rather than direct application of international standards.