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Additional file 1. Supplementary Tables S1���S3.

Key Points Question Are children conceived with assisted reproductive techniques at risk of poor psychiatric health owing to adverse effects of the treatment or parental background factors? Findings In this long-term follow-up of a Swedish birth cohort of 1 221 812 children, those conceived with assisted reproductive techniques had an elevated risk of obsessive-compulsive disorder (OCD) but not of any other types of anxiety, depression, or suicide compared with all other children. The risk of OCD was no longer present in comparison with children born to couples with infertility. Meaning These findings suggest that adolescents conceived with ART are not at risk of poor psychiatric health compared with the general population, except for an elevated risk of OCD that may be explained by differences in parental characteristics., This cohort study quantifies the occurrence of psychiatric disorders, use of antidepressants, and suicidal behavior among children and adolescents in Sweden who were conceived by assisted reproductive techniques and assesses whether outcomes are associated with parental characteristics., Importance Individuals conceived with assisted reproductive techniques (ARTs) could be at elevated risk of psychiatric disorders owing to potential adverse effects of the procedures themselves, or because such traits or their risk factors may be more common in couples with infertility. Objective To investigate the risk of psychiatric disorders in adolescents and young adults conceived with ARTs and to evaluate the role of treatment-related parental characteristics. Design, Setting, and Participants This prospective follow-up of a nationwide birth cohort used linkage of Swedish population registers with coverage through 2018. All children born in Sweden from January 1, 1994, to December 31, 2006, were included in the analysis. Follow-up was completed on December 31, 2018, when participants were 12 to 25 years of age, and data was analyzed from March 17, 2020, to September 10, 2021. Exposures In vitro fertilization with or without intracytoplasmic sperm injection and transfer of fresh or frozen-thawed embryos. Main Outcomes and Measures Clinical diagnoses of mood disorder, including major depression, anxiety, obsessive-compulsive disorder (OCD), or suicidal behavior, were identified from hospital records and outpatient specialist care. Suicide was additionally identified from death certificates. Antidepressant use was identified from dispensations of prescribed medications. Results A total of 1 221 812 children (48.6% female, 51.4% male) born between 1994 and 2006 were followed up to a median age of 18 (IQR, 15-21) years. Among these participants, 31 565 (2.6%) were conceived with ART. Compared with all others, adolescents conceived with ART had an elevated risk of OCD (hazard ratio [HR], 1.35 [95% CI, 1.20-1.51]), but the association was attenuated and no longer statistically significant after adjustment for parental characteristics (adjusted HR [aHR], 1.10 [95% CI, 0.98-1.24]) and was no longer present when restricted to individuals born to couples with known infertility (aHR, 1.02 [95% CI, 0.89-1.17]). Adolescents conceived with ARTs were not at elevated risk of depression or suicidal behavior compared with other adolescents (irrespective of parental infertility). Type of fertilization (standard in vitro fertilization or intracytoplasmic sperm injection) had no association with outcomes. Compared with non–ART-conceived children of couples with infertility, fresh, but not frozen, embryo transfer was associated with a lower risk of mood disorders (aHR, 0.90 [95% CI, 0.83-0.97]), making frozen embryo transfer appear less advantageous when directly contrasted with fresh embryo transfer. Conclusions and Relevance These findings suggest that adolescents conceived with ARTs around the millennium are not at risk of poor psychiatric health compared with the general population, except for an elevated risk of OCD that may be explained by differences in parental characteristics.

Additional file 13: Figure S13. Kaplan-Meier curves by IHC subtype and pTN status with and without age-standardisation. Restricted to M0.

Additional file 4: Figure S4. Distributions of grade and Ki67 by IHC subtype in women diagnosed 2011–2015.

Additional file 3: Figure S3. Distributions of Ki67 by grade for women diagnosed 2011–2015.

Additional file 10: Table S10. Adjusted hazard ratios (HR) of BC death with and without adjustment for adjuvant therapy, in subset of patients with adjuvant treatment available.

Additional file 12: Figure S12. Kaplan-Meier curves by IHC subtype and grade with and without age-standardisation.

Additional file 2: Figure S2. Definition of IHC subtype by grade.

Additional file 5: Figure S5. Box plot of Ki67 by grade in women diagnosed 2011–2015.

Additional file 1: Figure S1. Included patients in the analyses.

Additional file 8: Figure S8. Distributions of TNM stage by IHC subtype and grade.

Additional file 6: Table S6. Chi-square tests of clinicopathological characteristics by IHC subtype.

Additional file 7: Figure S7. Distributions of pTN status by IHC subtype and grade. Restricted to M0.

Additional file 11: Table S11. Adjusted hazard ratios (HR) of BC death by IHC subtype with adjustment (rather than stratification) for grade.

Additional file 9: Table S9. Adjusted hazard ratios (HR) of BC death for early (0-5y) and late (5-13y) follow-up.