Oct 30, 2017
Origin: ASRM Press Release
HIGHLIGHTS FROM THE AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE’S 2017 SCIENTIFIC CONGRESS & EXPO
San Antonio, TX – Older men may have a more difficult time conceiving children, whether naturally or with assisted reproductive technology. Several groups presented their findings at the American Society for Reproductive Medicine’s Scientific Congress and Expo. Their investigations look at chromosomal imbalances, accumulated genetic mutations and epigenetic alterations in the sperm of older males.
In Boston, researchers found that embryos created with sperm from men over the age of 50 divide more slowly and take longer to reach the early blastocyst stage. In a retrospective cohort study, they examined time-lapse data for 3,532 embryos from 527 couples. When all embryos were considered, those created with sperm from men over 50 developed 35% more slowly than embryos created with sperm from men under 35. Considering only embryos that reached the blastocyst stage, time-to-blastocyst was 4.3% slower for the embryos of men over 50 than for the embryos of men under 35.
At the Colorado Center for Reproductive Medicine, mice were used to investigate the alterations that individual males’ gametes undergo over the course of a lifetime. From youth to old age, a male’s sperm will accumulate both mutations in the genetic code and serious methylation alterations. Male mice were tracked over their natural lifetimes, with their fecundity confirmed monthly by breeding with young females, from youth (5 months) to old age (15 months). At the 5-month and 15-month marks, testicular sperm was collected from the mice to sequence DNA and perform genetic and methylation analyses. All the male mice ceased producing viable offspring by the time they were 12 months old. Sperm from the older mice exhibited 625 de novo point mutations, never observed when the mice were younger. These mutations resulted in amino acid changes that likely influence protein-enzyme function; pathway analysis of the 625 mutations found genes involved in neurological systems pathways were enriched.
Men with sperm aneuploidy, an incomplete or damaged complement of chromosomes or extra chromosomes in their sperm, are at increased risk of having abnormal embryos. At Baylor College of Medicine in Houston, Taylor Kohn and Alex Pastuszak performed a retrospective cohort study in which they reviewed the records of, and interviewed 99 couples in which the male partner had undergone sperm fluorescent in situ hybridization (FISH) testing for aneuploidy to find relationships between sperm aneuploidies and miscarriage, PGS and amniocentesis results, and live birth. In the study group, most miscarriages occurred at 7.2 weeks gestation. Fewer genetic abnormalities were seen after 15 weeks gestation; all 6 amniocenteses were normal. Fifty-two live births were reported for the 99 couples.
Researchers from Weill Cornell Medicine in New York, showed that as men age, their sperm becomes more prone to the effects of meiotic errors and aneuploidy and this affects its function. In a genetic study on sperm from men in couples experiencing recurrent pregnancy loss or failed IVF, men were divided into seven age groups: the youngest group- 25 to 30, the oldest- over 55. Their sperm was tested via FISH for aneuploidy and DNA sequencing for CNVs- copy number variation, both types of defects were highest in the oldest age group. Fertilization rate was 87.7% in the youngest age group and declines to 46% in the oldest group.
ASRM Vice President, Peter Schlegel commented, “These studies make it clear that for men as well as women it may be difficult to have a child at an advanced age. Older men and their partners should be counseled about the risks of poor pregnancy outcomes and the potential for neurodevelopmental problems in offspring.”