Assisted reproductive technologies and pregnancy outcomes: mechanistic insights from animal studies

Modern techniques in assisted reproduction have become a common and accepted form of clinical care benefiting an estimated 1 in 10 people of reproductive age who are subfertile or infertile. The success of these technologies relies, to large extent, on the remarkable tolerance of mammalian gametes and the preimplantation embryo to physical manipulations and alterations to their chemical environment. Recent reports from both human and animal studies, however, suggest that our faith in the ability of these "germ cells" to accurately recapitulate the normal process of early development under such conditions may be misplaced. While acknowledging the recognized risk factors of increased maternal age and infertility in human assisted reproductive technology (ART) subjects and the transfer of supernumerary embryos, evidence from animal studies indicates that ART procedures can directly contribute to the variable perinatal outcomes observed and imprinting disorders recently recognized. Controversy surrounds the specific nature and extent of these contributions; however, ovarian stimulation, in vitro maturation and embryo culture, intracytoplasmic sperm injection, and gamete/embryo cryopreservation have all been implicated. These issues are considered in detail in this article, which evaluates the insights that can be gained from studies with animals.