Dr Anupa Nandi
Sperm may be defective even if the routine semen analysis is normal – Role of DNA fragmentation test
Updated: Dec 18, 2019
The main investigation performed for male infertility is semen analysis. It looks mainly at three parameters – sperm count, motility and normal forms. The values that are considered as normal are as follows:
These parameters were decided based on semen analysis of fertile men (defined as men with partners who conceived within 12 months of stopping contraception). They were introduced as a guide to compare fertility.
Men, whose semen parameters fall short of these, are not necessarily infertile and on the other hand, normal parameters do not guarantee fertility.
However, it has limitations:
1. The parameters can vary between two samples. Hence it is always advisable to perform a repeat sample in 3-4 months if the first sample is suboptimal.
2. Depends largely on who is analysing it: High intra- and inter-observer variability in reporting parameters from the same specimen
3. It says nothing about the sperm function.
Semen parameters can vary between two samples. Routine semen analysis does not say anything about sperm function.
What can affect the sperm function?
Sperm is a highly specialised to perform one function- deliver the DNA to the egg and fertilise it. Factors that would cause damage to this DNA will undoubtedly impair its ability to fertilise the egg and reduce chances of natural conception.
Various factors can cause DNA damage in the sperm:
1. Ageing – men over 40 years
2. Diet and Lifestyle factors: smoking, alcohol, obesity,
3. Infection – sexually transmitted infections like chlamydia, general systemic infections, febrile illness
4. Environmental factors- toxins, pollutants, pesticides
5. Injury to testes, torsion
6. Occupational – exposure to high heat due to specific jobs
8. Testicular heat – even 2-3 degrees rise in temperature has been shown to increase DNA fragmentation.
Some amount of DNA damage is always present in any semen sample, which can be repaired by the egg. However, if the level of DNA damage becomes excessive, then it can lead to infertility.
The difficulty is to know what level of DNA damage is detrimental to fertility.
Some DNA damage is always present in any semen sample. It is difficult to know above what level pregnancy is impossible.
Can DNA damage be there if the semen analysis is normal?
DNA damage can be there in both normal and abnormal semen parameters.
Studies have shown that men diagnosed with unexplained infertility with otherwise normal semen parameters have higher DNA fragmentation than fertile men (ref). It has also been found to be high in cases with recurrent early pregnancy miscarriages. It is now considered a part of recurrent miscarriage investigations as per ESHRE guideline.
When DNA fragmentation tests should be done?
Routine use of DNA fragmentation is not recommended. If used in selected cases, it can be beneficial.
Its use has been shown to be of benefit in following cases:
1. Unexplained infertility, especially if there are risk factors as above.
2. Recurrent miscarriages
3. Recurrent IUI/IVF failure.
Why routine use of DNA fragmentation is not recommended?
1. One of the greatest challenge is to identify the threshold of DNA fragmentation which is detrimental for pregnancy
2. Multiple ways to assess DNA fragmentation like SCSA (sperm chromatin structure assay), TUNEL, COMET, and SDA. Each test has its own threshold and they are not interchangeable.
3. Different assays and cut offs are used in different studies. It is difficult to interpret the available evidence due to this.
4. DNA fragmentation can vary considerably in the same man over the time.
Routine use of DNA fragmentation test is not recommended. However, if used in selected cases, it can be beneficial.
What can be done if DNA fragmentation is found to be raised?
High DNA fragmentation is a curable condition. Since sperm are continually being made every 3 months, it is possible to improve the DNA fragmentation by making life style adjustments:
The first line approach should be to stop smoking, alcohol, recreational drugs and eating healthy balanced diet containing antioxidants, minerals and vitamins.
Mild to moderate exercise to reduce weight for obese men.
Clinical examination to detect varicocele and infection. Variocelectomy and treatment of infection will improve DNA fragmentation.
Avoidance of exposure to excessive heat, like avoiding sauna, occupational exposure, radiation from mobile phones.
Taking anti-oxidants has been shown to improve live birth rates in a Cochrane review of low quality evidence.
Most of the causes for high DNA fragmentation are modifiable by lifestyle adjustments. Hence a healthy lifestyle is the first recommendation before considering DNA fragmentation test.
Would I need IVF if my DNA fragmentation is high?
IUI success rate has been found to be lower in presence of high DNA fragmentation. ICSI success has been found to be better compared to IVF if DNA fragmentation is very high. So if DNA fragmentation were high it would be better to have ICSI instead of IUI or IVF.
Those undergoing ICSI due to high DNA fragmentation should also undertake above discussed measures to reduce the DNA fragmentation to reduce the risk of miscarriage.