Contemporary Use of ICSI and Epigenetic Risks to Future Generations.

Since the birth of Louise Brown in 1978 via IVF, reproductive specialists have acquired enormous knowledge and refined several procedures, which are nowadays applied in assisted reproductive technology (ART). One of the most critical steps in this practice is the fertilization process. In the early days of IVF, a remarkable concern was the unpleasant outcomes of failed fertilization, overtaken by introducing intracytoplasmic sperm injection (ICSI), delineating a real breakthrough in modern ART. ICSI became standard practice and was soon used as the most common method to fertilize oocytes. It has been used for severe male factor infertility and non-male factors, such as unexplained infertility or advanced maternal age, without robust scientific evidence. However, applying ICSI blindly is not free of potential detrimental consequences since novel studies report possible health consequences to offspring. DNA methylation and epigenetic alterations in sperm cells of infertile men might help explain some of the adverse effects reported in ICSI studies on reproductive health in future generations. Collected data concerning the health of ICSI children over the past thirty years seems to support the notion that there might be an increased risk of epigenetic disorders, congenital malformations, chromosomal alterations, and subfertility in babies born following ICSI compared to naturally conceived children. However, it is still to be elucidated to what level these data are associated with the cause of infertility or the ICSI technique. This review provides an overview of epigenetic mechanisms and possible imprinting alterations following the use of ART, in particular ICSI. It also highlights the sperm contribution to embryo epigenetic regulation and the risks of in vitro culture conditions on epigenetic dysregulation. Lastly, it summarizes the literature concerning the possible epigenetic disorders in children born after ART.