Science and Philosophy
The primary function of a sperm is to deliver male DNA to the egg, and therefore the quality of the DNA delivered is of clear importance to the developing embryo and pregnancy success. Standard semen analysis generally provides information about the quality of sperm as a delivery vessel (i.e., motility, concentration, morphology) but does not directly assess what is being delivered, namely the DNA. One way of assessing the quality or “integrity” of sperm DNA is by measuring the fragmented sperm DNA (DNA breaks). The quantity of breaks is reflected by the amount of DNA that exists as a single strand (ssDNA) rather than in the intact double strand form (dsDNA).
DNA Fragmentation Index (DFI)
Sperm quality is dependent on the amount of damage to the sperm DNA or DNA fragmentation. Sperm DNA fragmentation has little or nothing to do with the parameters that we measure on the routine semen analysis. However, 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.
By testing for sperm DNA fragmentation, many cases of formally “unexplained” infertility can now be explained. To test for sperm DNA fragmentation; we use the Sperm Chromatin Dispersion Assay (SCD). SCD uses the process of controlled DNA denaturation process to remove the protein contained in sperm by making use of heat and other reagents. After the completion of the fixation of various slides to achieve denaturation, normal sperm creates halo while the fragmented sperms are the ones without a Halo.
A normal sample has less then 15% of the sperm with DNA damage. Men with poor fertility potential have greater then 30% of their sperm damaged. The causes of high DNA fragmentation are those same causes of male factor infertility that we have known about for years such as chemical/toxin exposure, heat exposure, varicocele, infection, age, smoking, testicular cancer, radiation, and anything that increases the free radical levels in the semen among a list of many other things. It is very important to understand that sperm DNA fragmentation can change with time and it can be improved in many cases. The goal of a male factor evaluation is to seek out the causes of poor sperm quality and try to correct them so conception can occur naturally or to improve the sperm quality for IVF and maximize the chances of success. In situations where DFI can’t be improved there is evidence to suggest that removing the sperm directly from the testicle via biopsy and using it with ICSI may lead to better outcomes then using poor quality ejaculated sperm.
All men with an abnormal semen analysis are candidates for this test as well as men with normal semen analyses who have failed IVF for unexplained reasons. Those couples using egg donors or surrogates may also benefit from screening prior to going thru the procedures because the effort and costs are so great. Men with poor DFI should have a male factor evaluation including a physical examination by a male reproductive specialist.