Exploring genetic and environmental influences on miscarriage rates: a twin study

Abstract Miscarriage is the most common type of pregnancy loss, occurring in up to 15% of clinically recognized pregnancies. Our understanding of the etiology is still limited but is believed to be multifactorial, including endocrine and anatomical abnormalities, immunologic, genetic and lifestyle factors. The aim of this study was to explore whether genetic variability in miscarriage is under any genetic influence. 3234 MZ and DZ female twins completed postal self-completion questionnaires on pregnancies. Rates were adjusted for total number of pregnancies. The relative contribution of genetic and environmental factors to variation in miscarriage was assessed using twin intra-pair correlations and quantified using a variance components model fitting approach. We found 22.7% of our twins reporting having suffered at least one miscarriage. Current age, age at first pregnancy and higher number of pregnancies all had a significant influence on reported miscarriage. The concordance of miscarriage was similar in identical and non-identical twins, 26% and 27%, respectively. Shared environment and predominantly random error and unique environment rather than genetic factors best explained the total variation of miscarriage. To our knowledge, this is the first large twin study exploring heritability of miscarriage which unlike the vast majority of common variable traits, shows no significant genetic influence. In the absence of clear environmental factors, these results suggest the influence of random factors.