The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Reversing decreased gamete quality and altered embryogenesis caused by advanced paternal age (#110)

Macarena Gonzalez 1 , Rebecca Robker 1
  1. Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, SA, Australia

Men are seeking fatherhood later in life, yet aging is associated with decreased sperm quality.  Men >40 years old undergoing autologous IVF cycles have lower pregnancy and live birth rates than young men. The increased use of ART to treat age-related infertility necessitates a better understanding of how male age impacts sperm quality and IVF outcomes, and new therapeutic strategies to improve success rates. Chaperone-inducing drugs improve oocyte quality and embryo development in obese mice, but the potential to improve sperm quality has not yet been investigated. The aim of this study was to determine whether treatment of sperm from aged male mice with a chaperone-inducing drug prior to IVF can improve gamete quality and embryo development.

Sperm from C57BL6J male mice that were either “old” (>1-year-old), or “young” (<8 months old) was collected and treated in vitro during capacitation. Sperm quality assessments included motility, zona-binding capacity and mitochondrial activity by flow cytometry. In parallel, sperm was used for IVF and embryo development was analyzed by timelapse imaging.

Old males had ~15% reduction in pregnancy rates compared to young males. Sperm from old males had reduced motility (N=9-12; P=0.03), lower mitochondrial membrane potential (N=6-11; P=0.04) and impaired zona-binding capacity (N=4-6; P=0.02) compared to young males. Each of these sperm quality parameters was improved by in vitro drug treatment. When sperm was used for IVF, morphokinetic analysis showed that embryos from old males had delayed time to first cleavage (N=21-27; P=0.01). Sperm from older males gave decreased 2-cell (N=7-12; P=0.04) and blastocyst rates (N=7-12; P=0.003).  Drug treatment of ‘old’ sperm restored embryo development rates to those of sperm from young males. These results demonstrate that male age negatively impacts the earliest stages of embryo development but that treating sperm in vitro prior to IVF normalises sperm quality and improves embryogenesis.