Information about Sperm DNA Fragmentation


The genetic integrity of the spermatozoan is essential for normal embryo development. A high level of DNA fragmentation in sperm cells may represent a cause of male infertility that conventional examinations - sperm concentration, motility analysis, morphology assessment - cannot detect.  Results reported in the scientific literature show regardless of the assisted reproductive technology used, elevated levels of DNA fragmentation above the critical threshold will significantly compromise the possibility of a successful pregnancy. 

  • high sperm DNA fragmentation does not appear to affect fertilisation or the first or second embryo cleavage stages 
  • high sperm DNA fragmentation can affect embryo cleavage once the paternal genome is switched on, and subsequent blastocyst development 
  • DNA fragmentation levels are closely correlated with IUI, IVF and ICSI miscarriage and pregnancy rates 
  • DNA fragmentation is significantly higher in subfertile men. 
  • men with poor semen parameters are more likely to have high DNA fragmentation 
  • high sperm DNA fragmentation is also found in men with normal semen parameters

Advantages of the Sperm DNA Fragmentation test

This test provides a reliable analysis of sperm DNA integrity that may help to identify men who are at risk of failing to initiate a healthy ongoing pregnancy. Information about sperm DNA integrity may help in the clinical diagnosis, management and treatment of male infertility and may be of prognostic value in assessing outcome of assisted conception treatment.

 

High Rates of Sperm DNA Fragmentation and Pregnancy

Normal, healthy pregnancies do occur in couples where the male partner has a high percentage of sperm with fragmented DNA, although the chances are significantly reduced, as the percentage of sperm bearing low levels of DNA fragmentation is much lower. Embryos derived from sperm whose DNA is highly fragmented have a poor prognosis. Evidence suggests that this could result in initiation of apoptosis and mutations resulting in blastocyst arrest, miscarriage, abnormalities in the offspring and an increased susceptibility to childhood cancer. Protection against high DNA fragmentation may be afforded by younger oocytes which are much more efficient at DNA repair of defective sperm than older oocytes. Couples undergoing fertility treatment where sperm DNA fragmentation is high have a better prognosis if the female partner is young. 

 

Causes of Sperm DNA Fragmentation

A major causative factor for sperm DNA damage is oxidative stress. Other factors include abnormalities in the regulation of apoptosis, or defects in topoisomerase activity. Increased sperm DNA fragmentation is also associated with:

  • infection
  • leucocytospermia
  • sperm cytoplasmic droplets
  • febrile illness
  • elevated testicular temperature
  • diet
  • drug use
  • cigarette smoking
  • exposure to environmental and occupational pollutants
  • advanced age
  • varicocoele

Indications for male patients who may benefit from the Test

  • unexplained infertility
  • arrested embryo development
  • poor blastocyst development
  • multiple failed IVF/ICSI treatment
  • recurrent miscarriage in partner
  • advanced age
  • varicocoele
  • poor semen parameters
  • exposure to harmful substances

 

Treatment

Some causes of DNA fragmentation cannot be treated, but if the damage is caused by free radicals, then a change in lifestyle and a diet designed to protect against oxidative stress may help reduce the levels of DNA fragmentation in some of these cases. Treatment of infection with antibiotics would also be expected to reduce DNA fragmentation. There is some evidence to show that varicocoele repair may improve sperm DNA integrity.  Initiatives to reduce the levels of fragmentation can be assessed by undertaking a second test three months after the first. Initial reports suggest that DNA damage occurs at the post-testicular level, so that testicular sperm may have a healthier DNA integrity than ejaculated sperm. Furthermore, studies show that ICSI may be a more effective treatment than IVF for sperm with a high DNA fragmentation. 

 

What is the DNA fragmentation test?

This test is an effective method for measuring thousands of sperm in an ejaculate. Sperm are stained with a fluorescent probe that interacts with the DNA molecule. The fluorescence signal changes when the DNA is fragmented, and this is monitored using a flow cytometer. The SCSA® test has been developed over the last 20 years and is one of the most robust tests available for sperm DNA fragmentation. It is CLIA approved. 

 

Results

The results are reported showing 4 statistical categories of fertility potential :

 

DNA Fragmentation Index (%DFI; % sperm cells containing damaged DNA)

≤ 15% DFI = excellent to good sperm DNA integrity 


> 15 to < 25% DFI = good to fair sperm DNA integrity


> 25 to < 50% DFI = fair to poor sperm DNA integrity


≥ 50% DFI = very poor sperm DNA integrity

 

Note: The above values relate to natural and IUI conceptions 


The statistically significant DFI threshold for subfertility has been established at > 25 %.Normal full-term pregnancies are possible with an elevated DFI, but the higher the level of fragmentation, the greater the incidence of reduced term pregnancies and miscarriage. The above values relate to natural and IUI conceptions. When % DFI is above 25 %, current literature suggests that the patient either try to reduce the DFI by medical intervention or change of lifestyle, or skipping IUI and go on to IVF ICSI for greatest success (www.scsatest.com for details)


Hypothesis: A high ratio of moderate DFI to high DFI sperm may be the most negative since moderate DFI sperm have normal nuclear morphology and will likely fertilise but may have DNA damage beyond the repair capacity of eggs.
 

 

High DNA stainability (HDS): % sperm with immature chromatin and abnormal proteins. Levels in the > 25% range are considered negative for pregnancy outcome


Additional information downloads:
Sperm DNA Fragmentation and Aneuploidy/Sample Information Sheet and Request Form (Word doc, 56Kb)


 

REFERENCES

 

Osman A, Alsomait H, Seshadri S, El-Toukhy T, Khalaf Y (2014) The effect of sperm DNA fragmentation on live birth rate after IVF or ICSI: a systematic review and meta-analysis. Reprod Biomed Online. Nov 13. pii: S1472-6483(14)00603-8. doi: 10.1016/j.rbmo.2014.10.018. [Epub ahead of print] Review.


Zhao J, Zhang Q, Wang Y, Li Y (2014) Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Fertil Steril 102(4):998-1005


Wright C, Milne S, Leeson H (2014) Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility. Reprod Biomed Online 28:684-703


Evenson DP (2013) Sperm chromatin structure assay (SCSA®). Methods Mol Biol. 927:147-64.


Smit M, Romijn JC, Wildhagen MF, Veldhoven JL, Weber RF, Dohle GR. (2013) Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate. J Urol. 189 (1 Suppl):S146-50.


Humm KC and Sakkas D (2013) Role of increased male age in IVF and egg donation: is sperm DNA fragmentation responsible? Fertil Steril 99 (1):30-6.


Wang YJ, Zhang RQ, Lin YJ, Zhang RG, Zhang WL. (2012) Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis. Reprod Biomed Online. 25 (3):307-14


Kumar K, Deka D, Singh A, Mitra DK, Vanitha BR, Dada R. (2012) Predictive value of DNA integrity analysis in idiopathic recurrent pregnancy loss following spontaneous conception. J Assist Reprod Genet. 29 (9):861-7.


La Vignera S, Condorelli R, D'Agata R, Vicari E, Calogero AE (2012) Semen alterations and flow-citometry evaluation in patients with male accessory gland infections. J Endocrinol Invest. 35(2):219-23


Robinson L, Gallos ID, Conner SJ, Rjkhowa M, Miller D, Lewis S, Kirkman-Brown J and Coomarasamy A (2012) The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis Hum. Reprod. 27 (10): 2908-2917


Gharagozloo P, Aitken RJ.(2011) The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod. 26 (7):1628-40


Zini A and Dohle G (2011) Are varicoceles associated with increased deoxyribonucleic acid fragmentation? Fertil Steril. 96 (6):1283-7


Speyer BE, Pizzey AR, Ranieri M, Joshi R, Delhanty JD and Serhal P (2010) Fall in implantation rates following ICSI with sperm with high DNA fragmentation. Hum Reprod. 25 (7):1609-18.


Brahem S, Mehdi M, Landolsi H, Mougou S, Elghezal H and Saad A. (2011) Semen parameters and sperm DNA fragmentation as causes of recurrent pregnancy loss. Urology. 2011 Oct;78(4):792-6


Aitken RJ, De Iuliis GN and McLachlan RI (2009). Biological and clinical significance of DNA damage in the male germ line. Int J Androl 32 (1):46-56


Armand Zini, Jason M. Boman, Eric Belzile and Antonio Ciampi (2008) Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis Human Reproduction  23 (12):2663-2668