Sperm DNA fragmentation

When in vitro fertilisation was first introduced, it was believed that semen quality as judged by light microscope was able to predict the generation of viable embryos and when the sperm quality was below a certain threshold it would affect the the outcome of IVF techniques. In due course increasing evidence suggested that the basic semen parameters where not enough to predict the fertility potential of spermatozoa and advanced sperm function tests were introduced. Though introduction of ICSI reduced the importance of these tests by achieving fertilisation and development of embryos using subnormal spermatozoa, it became evident that in spite of generating embryos with icsi many of them were not viable and resulted in repeated implantation failures.

One of the main paternal-derived causes of repeated reproduction failure is sperm DNA fragmentation. Approximately 20-30% of men attending an infertility clinic have a level of sperm DNA fragmentation that can cause pregnancy failure. In many patients where the routine semen analysis shows normal sperm morphology, concentration and motility an estimation of sperm DNA integrity may predict male infertility.

Sperm DNA fragmentation is completely independent of the count, motility or morphology. DNA is arranged in a double helix or ladder configuration with side rails and rungs. If the rungs are broken, the ladder becomes unsteady and does not function properly. Several studies have proven that parameters like count, motility or morphology have no correlation to the DNA fragmentation.

Men with otherwise normal semen analyses may have a high degree of DNA damage and men with very poor sperm quality can have very little DNA damage. More importantly what has also been demonstrated is that the degree of DNA fragmentation correlates very highly with the inability of the sperm to initiate a birth regardless of the technology used to fertilize the egg such as insemination, IVF or ICSI. Sperm with high DNA fragmentation may fertilize an egg and embryo development stops before implantation or even if implantation occurs there is a significantly higher likelihood that the pregnancy might result in miscarriage. By testing for sperm DNA fragmentation, many cases of formally "unexplained" infertility can now be explained.