Assisted reproductive technology results: why are live-birth percentages so low?

The present bioessay aims to analyze the impact of parental age, cause of infertility, embryo chromosomal anomalies, assisted reproduction technology (ART) treatments, and environmental and occupational exposures to xenobiotics on ART results, particularly on live-birth percentages per transfer. Special attention is paid to analyzing the effects of these factors on the mitochondrial, genetic, and epigenetic traits of gametes and embryos to ascertain the molecular/cellular mechanisms responsible for the relatively low percentages of live births reported year after year in ART cycles. The bias of age distribution of women attending fertility clinics toward the late thirties and beyond and the high incidence of mosaicism found in pre-implantation embryos emerge as the two biggest players in this scenario. Parental reproductive aging and some causes of infertility are associated with mitochondrial, genetic, and epigenetic alterations to gametes. ART treatments such as ovarian stimulation, gamete/embryo cryopreservation, oocyte in vitro maturation, intracytoplasmic sperm injection, in vitro culture system, and embryo biopsy may also induce epigenetic changes in gametes and/or pre-implantation embryos. Finally, exposure to numerous environmental chemicals is linked to sperm genetic and epigenetic defects. Whereas the selective transfer of euploid blastocysts may improve implantation and pregnancy percentages, especially in reproductively older women, it does not guarantee the total absence of mitochondrial and/or epigenetic defects in embryos. The presence of induced and/or inherited DNA epigenetic disturbances in ART offspring is unlikely to be prevented, even by replacing the whole cytoplasm of oocytes using nuclear-genome-transfer technology.