Semen quality and reproductive hormones in sons of subfertile couples: a cohort study

We found no evidence to support that parental subfecundity negatively affects male reproduction. If this finding is replicated in future research, it is reassuring for couples worldwide struggling with subfecundity.

VOLUME 118, ISSUE 4, P671-678


Linn H. Arendt, Ph.D., Anne Gaml-Sørensen, cand. scient. san., Andreas Ernst, Ph.D., Nis Brix, Ph.D., Gunnar Toft, Ph.D., Sandra S. Tøttenborg, Ph.D., Karin S. Hougaard, Ph.D., Jens Peter E. Bonde, Ph.D., Cecilia H. Ramlau-Hansen, Ph.D.



To study the associations between parental subfecundity, assessed by time to pregnancy and use of medically-assisted reproduction, and reproductive health of young men.


Cohort study.




A total of 1,058 men in the Fetal Programming of Semen quality cohort, a subcohort of the Danish National Birth Cohort.


From 2017–2019, men were recruited and provided semen and blood samples. Information on parental time to pregnancy and use of medically-assisted reproduction (including type of treatment) as well as demographic, health, and lifestyle factors were available. We estimated the crude and adjusted relative percentage differences with 95% confidence intervals (CIs) in the outcomes according to time to pregnancy and use of medically-assisted reproduction, using multiple adjusted negative binomial regression analysis.

Main Outcome Measure(s)

Semen characteristics (semen volume, sperm concentration, total sperm count, sperm motility, and morphology), testicular volume, and reproductive hormone levels (follicle stimulating hormone, luteinizing hormone, testosterone, estradiol, sex hormone-binding globulin, and free androgen index).


Overall, semen quality and levels of reproductive hormones were not lower among sons of subfecund parents reporting a time to pregnancy >6 months or use of intrauterine insemination. Sons conceived after in vitro fertilization or intracytoplasmic sperm injection, had a higher semen concentration (29%; 95% CI, −7%–79%) and a higher percentage of sperm with normal morphology (20%; 95% CI, −8%–56%), but with 95% CI overlapping the null. Moreover, these sons had slightly higher estradiol levels (30%; 95% CI, 7%–57%). The absolute differences seen were small, and the clinical significance of these differences are unknown.


We found no major difference in semen quality or reproductive hormones in sons conceived by subfertile couples or with the use of medically-assisted reproduction.

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