Intergenerational fecundity and infertility: a cohort study

To investigate whether parental time to pregnancy (TTP) and maternal history of infertility were associated with higher risk of infertility in adult sons and daughters.

Cohort study.

A total of 11,144 adult sons and daughters born to mothers participating in the Danish birth cohort, Health Habits for Two, when pregnant in 1984-1987.

Parental TTP was reported by the mothers approximately at gestational week 36 and categorized as 1-6 (reference), 7-12, and >12 months. Maternal history of infertility was defined as either self-reported examination or treatment for infertility or a registered infertility diagnosis from a nationwide register at any point before the index pregnancy, and was dichotomized (infertility: yes/no [reference]).

We defined infertility in sons and daughters as having received an International Classification of Diseases 10th revision diagnosis of infertility or been treated by assisted reproductive technology using information from two nationwide registers on the index person and their partners. The combined outcome is referred to as infertility. Associations were analyzed using Cox regression models estimating adjusted hazard ratios (HRs). Dose-response associations were investigated across categories of parental TTP. All analyses were conducted accounting for competing risks of infertility.

Sons born to parents with TTP of >12 months had higher risk of infertility (HR = 1.25 [95% confidence interval {CI}: 0.92-1.71]), although TTP of 7-12 months was not associated with infertility (HR = 1.00 [95% CI: 0.66-1.50]). Dose-response analyses indicated a modest trend (HR = 1.10 [95% CI: 0.95-1.29]). Daughters born to parents with TTP of 7-12 months and >12 months had higher risk of infertility (HR = 1.43 [95% CI: 1.06-1.94]; HR = 1.41 [95% CI: 1.11-1.79]), with a dose-response trend (HR = 1.20 [95% CI: 1.07-1.35]). Maternal history of infertility was associated with higher risk of infertility for both sons (HR = 1.81 [95% CI: 1.26-2.59]) and daughters (HR = 1.49 [95% CI: 1.10-2.01]).

Longer parental TTP and maternal history of infertility were associated with higher risk of infertility among adult sons and daughters. These findings suggest potential intergenerational transmission of low fecundity and infertility. Further research is needed to replicate the results and clarify underlying mechanisms.