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Study of Assisted Reproductive Technology (START) – epigenic mechanisms - project description

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The main aim of the project is to understand health consequences of subfertility in women and men, and to examine how genetic influences and epigenetic differences are associated with subfertility and the use of assisted reproductive technologies (ART).


As mothers’ and fathers’ age at first birth have increased, we have also witnessed increased fecundity problems in the population. There has been a steady increase in the use of assisted reproductive technology (ART) since its introduction in Norway in 1984. Because the total number of births per woman has also decreased, the proportion of children conceived in this way has increased. Today, around 2500 children are born in Norway each year through ART, which is about 4% of all births, and around 7 million children have been born through ART worldwide.  Moreover, as in other countries, there has been an increase in childlessness in Norway, from 10% in 1985 to 13% in 2015 for women and much more pronounced in men, from 14% 1985 to 23% in 2015.

Whilst most mothers treated with ART and children born through ART are healthy, there is some evidence pointing to adverse effects. ART has been associated with adverse pregnancy outcomes and increased risk of congenital malformations, infant morbidity and mortality. ART is also associated with several childhood diseases as well as cardiovascular diseases and cancer in mothers. One proposed mechanism for the detrimental effects of ART procedures is epigenetic modifications of the DNA during gametogenesis, fertilisation, and early embryonic development. However, it is not clear whether the observed adverse effects of ART are caused by the procedure itself or if it is caused by the underlying subfertility itself or higher age of the mother.

Our Centre of Excellence funding has permitted us to initiate an analysis of epigenetic signatures (e.g. DNA methylation) and potential epigenetic effects in subfertility and ART. In 2019, 6048 samples from the biobank of the Norwegian Mother and Child Cohort Study has been analysed for DNA methylation with the new EPIC array covering more than 850 000 methylation sites across the genome. The samples include 1000 trios of mother-father-children born after ART and 1000 control trios (naturally conceived children).

Data sources

In this project we make use biosamples obtained in the Norwegian Mother and Child Cohort Study. Consent is obtained from each participant and the Regional Committee for Medical and Health Research Ethics has approved the project.

The data will be stored at the Service for Sensitive Data (TSD), a service provided by the University of Oslo. The Service for Sensitive Data is a platform to collect, store, analyse and share sensitive data in compliance with Norwegian data protection regulations to protect the individual’s privacy. No information or biological samples are made available to researchers before names and personal identity numbers (fødselsnummer) are removed.

See the full project description at Cristin for more information about results, researchers, contact information etc.

Project participants

Project leader

Siri Håberg, Norwegian Institute of Public Health

Project participants

Per Magnus, Senter for fruktbarhet og helse, Norwegian Institute of Public Health
Håkon Gjessing, Senter for fruktbarhet og helse, Norwegian Institute of Public Health
Inger Johanne Landsjøåsen Bakken, Senter for fruktbarhet og helse, Norwegian Institute of Public Health
Maria Christine Magnus, Senter for fruktbarhet og helse, Norwegian Institute of Public Health
Miriam Gjerdevik, University of Bergen
Julia Romanowska, University of Bergen
Haakon Egdetveit Nustad, Universitetet i Oslo, University of Oslo
Siri Håberg, Norwegian Institute of Public Health

About the project