DNA fragmentation is when bits of DNA on chromosomes separate or pieces of them break off, which causes disorganization within cells as DNA is the coding on our genes that “programme” all bodily functions. Having a complete and well-organised genetic code on chromosomes is crucial for health, and when two sets of chromosomes join at fertilisation is a crunch moment.
All sperm in every sample have some DNA fragmentation; however, the greater the level of fragmentation, the more disorganised the DNA coding is, and the more difficult it is to repair that damage. There have been DNA fragmentation tests since the 1980s, but more recent advances in vitro fertilization (IVF) have highlighted the importance of the issue.
Sperm with high levels of DNA fragmentation tends to cause problems in the embryo’s cells when they divide and multiply (rather than very early on after fertilisation). All health ultimately depends on the genetic material in the cells, and DNA fragmentation reduces organisation in an embryo’s cells as it grows, which will compromise the health of the pregnancy at some point.
The DNA inside sperm are especially vulnerable to damage from the environment:
- Sperm are by far the smallest of cells, with little material around their DNA to protect them from toxins or damage
- Sperm and egg DNA are especially vulnerable to damage as their structure on chromosomes is less stable than normal cells
- DNA in normal cells is on pairs of chromosomes, and the DNA in eggs and sperm are on half of a pair of chromosomes
- Damage to DNA happens in all cells on a daily basis, but the damage is usually repaired relatively easily. Repair is possible because the two strands of DNA provide greater stability, and each side acts as a ‘template’ to repair any damage
- Eggs and sperm DNA is on single chromosome strands, without the option of repair until they join during fertilisation
Diagram of DNA in a eukaryotic cell
About DNA Fragmentation
- The standard semen analysis measures sperm concentration, motility and morphology but can’t detect DNA fragmentation
- DNA fragmentation doesn’t much affect fertilization or the early stages of embryo development but becomes more of an issue at implantation and beyond
- Sperm DNA fragmentation tests detect the percentage of sperm affected and the risk of unhealthy pregnancies
- Embryos from sperm with high DNA fragmentation are more likely to have implantation failure, miscarriage, abnormalities in the babies and childhood cancer i
- DNA fragmentation levels are closely linked to IUI, IVF and ICSI success and miscarriage rates ii
- Fragmentation levels over 30% significantly reduce the possibility of successful pregnancy with IVF
- DNA fragmentation is much higher in subfertile men, but high rates are sometimes found in men with normal semen
- There are several tests available: the “Comet assay”, the “sperm chromatin dispersion test” (SCD), the “TUNEL assay”, or the “sperm chromatin structural assay” (SCSA)
The causes of sperm DNA fragmentation
The biggest causes of sperm DNA fragmentations are oxidative stress and abnormalities in the immune system. However, high levels are also found with:
- Urogenital infections
- Leucocytospermia (white blood cells in the semen sample)
- Sperm cytoplasmic droplets iii
- Febrile (fever-producing) illnesses
- Elevated testicular temperature
- Diet (especially low antioxidant diets)
- Drugs (both prescribed and recreational)
- Smoking cigarettes
- Exposure to environmental and occupational pollutants
- Advanced age
- Varicoceles iv
DNA fragmentation test results
The DNA Fragmentation Index (DFI) is the percentage of sperm cells containing damaged DNA:
- Below 15% DFI = Excellent fertility potential
- Above 15 to 30% DFI = Good fertility potential
- Above 30% DFI = Fair to poor fertility potential
Men with high DFI values can father healthy children, although the chances reduce to rising DFI values.
Treatments for high DNA fragmentation levels
- Changes in lifestyle and diet to protect against oxidative stress and damage by free radicals help reduce DNA fragmentation v vi
- Infections causing DNA fragmentation need treatment with antibiotics
- Varicocoele repair may improve sperm DNA integrity
- There’s evidence that sperm in the testes have greater DNA integrity than ejaculated sperm
- Studies have shown that ICSI may be more effective than standard IVF for sperm with high DNA fragmentation vii
- There is evidence that young eggs offer a level of protection against sperm DNA fragmentation as they are more efficient at repairing DNA than older eggs. Couples coming for ART with a high DFI have a better prognosis if the female partner is young or they use donor eggs from a young woman
- Some causes of DNA fragmentation are untreatable
- Re-testing 3-6 months after the first test will show if changes in diet and lifestyle have improved DNA fragmentation levels
- Upgrade your morefertile package to get more personalised support and more control of your fertility
ii‘Clinical relevance of sperm DNA damage in assisted reproduction.’ Tarozzi N, Bizzaro D, Flamigni C and Borini A (2007) Reprod Biomed Online 14(6):746-57.
iii‘Human sperm DNA integrity: correlation with sperm cytoplasmic droplets.’ Fischer MA, Willis J, Zini A. Urology [2003, 61(1):207-211]
iv‘Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress.’ Smith R, Kaune H, Parodi D, Madariaga M, Rios R, Morales I and Castro A (2006) Human Reprod. 21(4):986-993.
v ‘Cause-specific treatment in patients with high sperm DNA damage resulted in significant DNA improvement.’ Moskovtsev SI, Lecker I, Mullen, JB, Jarvi k, Willis J, White J and Lo KC (2009) Syst. Biol. Reprod. Med. 55(2):109-15
vi‘Improvement in sperm DNA quality using an oral antioxidant therapy.’ Tunc O, Thompson J and Tremellen K (2009) Reprod Biomed Online 18(6):761-8.
vii ‘Full-term pregnancies achieved with ICSI despite high levels of sperm chromatin damage.’ Gandini L, et al. (2004) Hum Reprod. 2004 Jun;19(6):1409-17
