Heritability of Subfertility Among Danish Male and Female Twins

Causes behind low male and female fecundity have been suggested to be initiated in foetal life. However, fecundity is also affected by environmental exposures later in life, and genetic factors are known to play a role. Using survey data on Danish twins, the aim of this study was to quantify the relative contribution of genetic and environmental effects on fecundity, measured as waiting time to the first attempt to achieve a pregnancy.

In 1994, a population-based survey was conducted among twins born 1953-1982. Another survey was carried out in 1998 among twins born 1931-1952. We restricted the study population to twins 18 years or older. All analyses were performed both separately for the two surveys and combined. We used a quantitative genetic liability threshold model, splitting the variation of subfertility risk into A (additive genetic effects), D (dominant genetic effects), C (common environmental effects) and E (individual environmental effects) and calculated tetrachoric correlations by zygosity. The analyses were performed both crude and univariately adjusted for age at first attempt to become pregnant, smoking, years in school, age at menarge, oral contraceptives and survey. Waiting time was included as a binary outcome, with cut point at 10 months.

Based on the Akaike Information Criterion the model including dominant genetic and unique environmental factors (DE model) gave the best fit in most cases. Adjusted results for all females (746 MZ and 831 DZ twin pairs) showed that the relative contribution of dominant genetic factors to subfertility was 30% (95% CI 16-44%) and the remainder 70% (95% CI 56-84%) was explained by environmental factors specific for each twin individual, with a tetrachoric correlation of 0.30 (0.15-0.43) for MZ and 0.09 (-0.06-0.24) for DZ. For males (531 MZ and 610 DZ twin pairs), the adjusted results showed that dominant genetic factors explained 6% (95% CI 0-26%) and the remainder 94% (95% CI 74-100%) was due to unique environmental factors, with a tetrachoric correlation of 0.08 (-0.12-0.28) for MZ and -0.04 (-0.21-0.14) for DZ. All results were consistent across surveys and almost similar for the crude and adjusted models.

In conclusion, our results suggest that environmental factors specific for each twin individual explained the largest part (app. 70%) of subfertility for females and almost 100% for males.