Intrauterine Growth and Male Reproductive Health: A Follow-up Study From the Danish National Birth Cohort

Reduced intrauterine growth might affect male reproductive health later in life, however, existing research remain inconclusive.

To investigate the association between placental weight and birthweight Z-scores and semen characteristics, testes volume, and reproductive hormone levels in young men.

We conducted a follow-up study of 1058 young men, born 1998 to 2000, from the Fetal Programming of Semen Quality (FEPOS) cohort, Denmark. Information on placental weight and birthweight was obtained from the Danish Medical Birth Registry. Semen and blood samples, the latter for reproductive hormone analysis, were obtained at a clinical examination, where the men additionally self-measured their testes volume. Relative percentage differences in semen characteristics, testes volume, and reproductive hormone levels were estimated according to placental weight and birthweight Z-scores in categories, continuously and as restricted cubic splines using adjusted regression models.

Overall, estimates for the associations between placental weight and birthweight Z-scores and male reproductive health were small and mostly consistent with no association. However, lower placental weight and birthweight Z-scores were associated with lower testes volume of -4% (95% CI: (-6%; -1%)) and -4% (95% CI: (-6%; -2%)), respectively per Z-score lower weight. Moreover, FSH and LH were higher per Z-score lower birthweight (5% (95% CI: 1%; 8%) and 2% (95% CI: 0%; 4%), respectively).

Testes volume is an important and stable marker of male reproductive capacity. Still, the observed associations for this marker did not correlate with any detectable changes in semen characteristics, potentially reflecting that the elevated FSH observed may compensate to maintain spermatogenesis.

No strong association between reduced intrauterine growth and semen characteristics, and reproductive hormone levels was observed. However, the association between lower placental weight and birthweight Z-scores and lower testes volume, somewhat supported that reduced intrauterine growth may be associated with later reproductive health.