Characterisation and comparison of semen microbiota and sperm function in men with infertility, recurrent miscarriage, or proven fertility

Abstract

Poor semen quality increase risks of infertility and recurrent pregnancy loss (RPL) in couples. Global, reported sperm counts have more than halved since the 1970s. Canonical genitourinary microbes such as gonorrhoea are known to impair semen quality. Furthermore, several recent, small studies have highlighted trends in semen microbiome characteristics associated with semen quality in asymptomatic men. However, the semen microbiota during recurrent pregnancy loss (RPL) has not been investigated. Herein we combine metataxonomic profiling of semen microbiota by16S rRNA amplicon sequencing, semen analysis, terminal-deoxynucleotidyl-transferase-mediated-deoxyuridine-triphosphate-nick-end-labelling, Comet DNA fragmentation and luminol ROS chemiluminescence to holistically describe the human seminal microbiome in a total 223 men within a cross-sectional ethics-approved study (healthy men with proven paternity, n=63; male partners of women with RPL, n=46; men with male factor infertility, n=58; men in couples unexplained infertility, n=56). We describe seminal microbiome clusters which are common both healthy men and those with infertility and RPL. Furthermore, specific microbiota perturbation is associated with impaired semen quality irrespective of reproductive disorder.