risk of imprinting disorders in children born by IVF compared to children born by natural conception: a narrative review

Assisted reproductive technologies, especially in vitro fertilisation (IVF) and Intracytoplasmic Sperm Injection (ICSI), have revolutionised the management of infertility, leading to the birth of millions of children worldwide. However, concerns have arisen regarding the long-term safety of Assisted Reproductive Technology (ART), specifically its potential to disrupt epigenetic processes, such as genomic imprinting. This narrative review explores whether children conceived via ART face a higher risk of imprinting disorders (IDs) than those conceived naturally.Through a literature review conducted via PubMed, Cochrane Library and EMBASE, current evidence was generated on the association between ART and specific imprinting syndromes, such as Angelman Syndrome (AS), Prader-Willi Syndrome (PWS), Silver-Russell Syndrome (SRS), and Beckwith-Wiedemann Syndrome (BWS). These findings suggest a slight but important increase in the incidence of certain imprinting disorders, particularly BWS, in ART-conceived children. Key mechanisms are associated with aberrant DNA methylation patterns during gametogenesis and early embryo development, which are potentially influenced by hormonal stimulation, embryo culture conditions, cryopreservation, and embryo transfer. Data from large cohort studies emphasise the increased risk, especially in protocols involving ICSI and frozen embryo transfer (FET). However, the absolute risk remains low, and most ART-conceived children are born healthy. Confounding factors, including subfertility, parental age, and environmental influences, complicate the understanding of these procedures’ effects. Further research is needed to understand the specific contributions of ART procedures to epigenetic dysregulation and to optimise protocols for minimising this risk. Increased awareness among physicians, genetic counsellors, and parents is warranted to enable the early diagnosis and appropriate management of IDs in ART offspring.