Fertility Treatment & Epilepsy of Genetic Origin

Parental infertility or fertility treatment may be linked to idiopathic generalized epilepsy, which is thought to have a genetic etiology, according to a study published in Paediatric and Perinatal Epidemiology.¹

The study found, however, no link between infertility or fertility treatment and overall increased risk for epilepsy in offspring.

“We found no association between parental infertility or fertility treatment, and the overall risk of childhood epilepsy. However, the results indicate that fertility treatment is associated with idiopathic generalised epilepsy in the offspring and that this association may be attributable to characteristics of the infertile couple,” wrote first author Laura Kettner, MD, of Aarhus University Hospital (Aarhus, Denmark), and colleagues.

The study is the first to evaluate the link between parental infertility or fertility treatment and idiopathic generalized epilepsy. 

Past studies have suggested that assisted reproductive technology (ART) is associated with increased risk of some childhood diseases, including certain infections, asthma, and epilepsy.² However, whether or not this increased risk is due to characteristics of the infertile couple or to ART is unknown.  Few studies have looked at the effect of ART on the neurological development of offspring.

The cohort study included all live single births between 1995-2013 in the Aarhus Birth Cohort, Denmark, an ongoing study of children born at Aarhus University Hospital, Denmark. Researchers used questionnaires to obtain information on fertility treatment (artificial insemination, hormonal treatment, and in vitro fertilization), and time to pregnancy. A couple with 12 or more months time to pregnancy was considered infertile. They identified children with epilepsy in 2013 from the Danish National Patient Register and the Danish National Prescription Registry.

Key results:

• Of 60,440 pregnancies, 0.8% (n=473) offspring developed epilepsy

• Primary analyses: no link between parental infertility or fertility treatment and overall risk of childhood epilepsy (HR: 1.08 [0.73, 1.60] and 1.04 [0.71, 1.52], respectively)

• Secondary analyses: parental infertility and fertility treatment linked to increased risk of idiopathic generalised epilepsy (HR: 2.25 [1.10, 4.58] and 2.45 [1.26, 4.75], respectively)

• No link between parental infertility and fertility treatment and focal epilepsy

The authors emphasized that the results of the subgroup analyses rely on only a few children exposed to ART who developed epilepsy. Other limitations include self-report of time to pregnancy and fertility treatment. Also, the study relied on ICD-10 codes which cannot clearly distinguish between epilepsy of genetic origin and that of structural origin. Because misclassification of epilepsy subtypes could have weakened the results, the link between parental infertility or fertility treatment and epilepsy of genetic origin may be stronger than the results indicate, they pointed out.

“Further studies are required ideally including more accurate information on the exposures and on epilepsy of genetic origin,” they concluded.

Take-home Points

• A Danish cohort study suggests link between parental infertility and fertility treatment and increased risk of generalized idiopathic epilepsy in offspring.

• Generalized idiopathic epilepsy is thought to have a genetic etiology, and these results suggest that parental characteristics may be involved. 

• Results showed no link between parental infertility and fertility treatment and overall epilepsy risk in offspring.   

• The study used self-reported questionnaires to assess parental infertility and fertility treatment, and more studies are needed to more accurately evaluate factors related to exposure and epilepsy of genetic etiology.

Aarhus University, the Aase and Ejnar Danielsen Foundation, Helsefonden, and the Danish Council for Independent Research funded the study.

References:

1. Kettner LO, et al. Parental infertility, fertility treatment, and childhood epilepsy: a population-based cohort study. Paediatr Perinat Epidemiol. 2016 May 30. [Epub ahead of print]

2. Kettner LO, et al. Assisted reproductive technology and somatic morbidity in childhood: a systematic review. Fertil Steril. 2015 Mar;103(3):707-719.