Long-term follow-up of intra-cytoplasmic sperm injection-conceived offspring compared with in vitro fertilization-conceived offspring: a systematic review of health outcomes beyond the neonatal period

Summary The use of intra-cytoplasmic sperm injection (ICSI) has increased significantly worldwide, often chosen instead of in vitro fertilization (IVF), yet long-term health outcomes are unknown and health differences between ICSI and IVF conceptions have not been comprehensively assessed. A systematic review of health outcomes of ICSI-conceived offspring beyond the neonatal period compared to IVF-conceived offspring was carried out. PubMed, OVID Medline/Embase, Informit, Web of Science and Proquest databases were searched on 9 November 2016 for studies reporting on health outcomes in ICSI-conceived offspring beyond 28 days after birth. Physical and psychosocial health were the main outcome measures. The search strategy yielded 2781 articles; 2539 were not relevant or did not meet inclusion criteria and 137 were duplicates. One hundred and five full-text papers were evaluated further and 34 satisfied the inclusion criteria. Studies comparing ICSI- and IVF-conceived children suggest their neurodevelopment is comparable. Growth and aspects of physical health are also similar; however, studies are few and limited to childhood. ICSI-conceived children may be at increased risk of autism and intellectual impairment. No difference in risk of childhood cancer was reported in one study. Whilst the neurodevelopment of ICSI-conceived children appears comparable to those of IVF conception, data relating to neurodevelopmental disorders, growth, physical health and childhood cancer are inconclusive. Further research into health outcomes in adolescence and adulthood is required before conclusions can be drawn about the long-term safety of ICSI compared to IVF. Until then, ICSI might be better reserved for its original intended use, male-factor infertility.