Fertility treatment and the risk of childhood and adolescent mental disorders: a register-based cohort study

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Study question We compared the risk of mental disorders in childhood and adolescence between children born after fertility treatments with in vitro fertilization (IVF), intra cytoplasmic sperm injection (ICSI) or ovulation induction (OI) with or without insemination (IUI) and children born after spontaneously conception.

Summary answer We found an increased risk of mental disorders in children born after OI/IUI, while children born after IVF/ICSI were found to have overall comparable risk with children conceived spontaneously.

What is known already Several follow-up studies have been investigating potentially adverse effects of fertility treatment, mostly focusing on perinatal outcomes. Any risks are generally considered related to the parental sub fertility or the risk of multiplicity and not to the procedures. However, much fewer and smaller studies have been conducted on the long-term development, very few have included children born after OI, and finally, the comparison of the previous studies is restricted by methodological shortcomings.

Study design, size, duration We designed a historical cohort and included children born between 1st of January 1995 and 31st of December 2003 (N = 588,967) with follow-up in 2012 when the children were between 8 and 17 years old.

Participants/materials, setting, methods Using Danish national health registers we assessed information about conception method, diagnoses of mental disorders and important covariates for all children born in Denmark in the inclusion period. With time to event analyses we compared the risk of mental disorders while adjusting for potential confounding variables.

Main results and the role of chance The risk of mental disorders in children born after in vitro fertilization or intra cytoplasmic sperm injection compared to spontaneous conceived children was not increased, except for a borderline significantly increased risk of tic disorders (HR 1.4 (1.0-1.9)). In contrast, children born after ovulation induction with or without insemination had significantly increased risks of any mental disorder (HR 1.2 (1.1-1.3)), autism spectrum disorders (HR 1.2 (1.1-1.5)), hyperkinetic disorders (HR 1.2 (1.1-1.4)), conduct, emotional, or social disorder (HR 1.2 (1.0-1.5)), and tic disorders (HR 1.5 (1.2-2.0)). The risk was not systematically related to type of hormonal medication, etiology of infertility or whether fresh or frozen embryos were used in the treatments.

Limitations, reason for caution The study did not include information on parental psychiatric history and since it is well known that mental disorders run in families, this could explain our findings if children conceived after OI/IUI were born by parents with a higher prevalence of mental disorders.

Wider implications of the findings We found no relation with IVF/ICSI but an association with OI/IUI. Hormonal stimulation is used in most fertility treatments and between IVF/ICSI and OI the hormonal treatments differ mainly by the use of Clomiphene Citrate in OI. Since we found no association with the use of this medicament, we believe that the reasons for the association most likely do not originate from the treatments but rather from underlying causes of parental infertility or residual confounding.

Study funding/competing interest(s) This study was funded by a fellow-ship granted by Aarhus University and The Augustinus Foundation, Denmark.

Trial registration number Register-based studies do not require ethical approval in Denmark, but was approved by the Danish Data Protection Agency (2012-41-1045).
Original languageEnglish
Article numberp575
JournalHuman Reproduction
Issue numberSuppl. 1
Pages (from-to)i357
Publication statusPublished - 2013

ID: 118447706