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The reasons for increased birth defect prevalence following in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are largely unknown. Classification of birth defects by pathology rather than organ system, and examination of the role of embryo freezing and thawing may provide clues to the mechanisms involved. This study aimed to investigate these two factors.Data on 6946 IVF or ICSI singleton pregnancies were linked to perinatal outcomes obtained from population-based data sets on births and birth defects occurring between 1991 and 2004 in Victoria, Australia. These were compared with 20 838 outcomes for singleton births in the same population, conceived without IVF or ICSI. Birth defects were classified according to pathogenesis.Overall, birth defects were increased after IVF or ICSI [adjusted odds ratio (OR) 1.36; 95% CI: 1.19–1.55] relative to controls. There was no strong evidence of risk differences between IVF and ICSI or between fresh and thawed embryo transfer. However, a specific group, blastogenesis birth defects, were markedly increased [adjusted OR 2.80, 95% CI: 1.63–4.81], with the increase relative to the controls being significant for fresh embryo transfer (adjusted OR 3.65; 95% CI: 2.02–6.59) but not for thawed embryo transfer (adjusted OR 1.60; 95% CI: 0.69–3.69).Our findings suggest that there is a specific risk of blastogenesis birth defects arising very early in pregnancy after IVF or ICSI and that this risk may be lower with use of frozen-thawed embryo transfer.