Association Between Human Embryo Culture Conditions, Cryopreservation, and the Potential Risk of Birth Defects in Children Conceived Through Assisted Reproduction Technology.

Assisted reproduction technology (ART) has advanced significantly over the past four decades, leading to improved pregnancy outcomes and a reduction in complications, particularly those associated with multiple pregnancies. These improvements largely stem from advances in understanding embryonic physiology, which has enabled better culture conditions. As a result, embryologists can now efficiently culture embryos to the blastocyst stage and successfully cryopreserve them for future use. However, while incubators aim to replicate the maternal environment of the oviduct and uterus, embryos in vitro are cultured in static conditions, unlike the dynamic, constantly changing environment they experience in vivo. Key factors such as pH, temperature, osmolality, and gas concentrations are crucial for establishing optimal embryo development and implantation potential. Moreover, the vitrification procedure for gametes or embryos can introduce oxidative stress, as well as osmotic shock and cryoprotectant toxicity, which may affect embryo viability and increase the risk of birth defects. Since the first successful ART birth in 1978, over 10 million babies have been conceived through these techniques. Although most of these children are healthy, concerns exist about potential birth defects or changes linked to the handling of gametes and embryos. The preimplantation period is marked by significant epigenetic reprogramming, which can be influenced by ART procedures such as ovarian stimulation, in vitro fertilization, embryo culture, and cryopreservation. However, the long-term health implications for offspring remain uncertain. Epigenetic reprogramming during early embryogenesis is essential for proper embryo development and can be changed by ART-related conditions. These concerns have raised questions about the possible connection between ART and a higher risk of birth defects or other changes in children born through these methods. Therefore, we conducted a scoping review following PRISMA-ScR guidelines to map evidence on ART-related risks, including epigenetic and birth defect outcomes.