DNA fragmentation explained

Sperm DNA fragmentation and has certainly gained more interest and attention over recent years despite it being around within andrology for over 20 years.


More couples are becoming aware of it and are looking to find out whether it’s something they should consider yet the information and provision of testing is still inconsistent.


Interestingly, in 2021 the sixth edition of the World Health Organisation’s guidance on Semen analysis testing and processing was published which included more details and recommendations for the use of DNA fragmentation in extended examinations but we’re yet to see any significant change around this in the UK.



Semen analysis vs DNA fragmentation test, what’s the difference?


For pretty much any man trying to conceive a semen analysis will be offered as standard but not a lot else. Where a man’s results are sub optimal he may be advised to improve his diet, exercise or lose weight but if a couple still don’t fall pregnant they’ll eventually end up in the queue for IVF. Very little further help, guidance or investigations are offered to a man; it’s assumed that IVF will be the answer.


A semen analysis is a basic first test, but it doesn’t really tell you much about the integrity and quality of the sperm. It will tell you how many sperm you have, whether they’re swimming in the right direction and what shape they are, but it doesn’t tell you a thing about the genetic quality of the sperm.


A sperm DNA fragmentation test will give you a far better picture of a man’s sperm health and the genetic quality of his sperm.



What is DNA fragmentation and why is it so important?


Regardless of whether you have a medical background or not most of us understand that DNA is the blueprint for life and when it comes to conception it’s the DNA of the woman and man coming together that makes a baby.


The DNA from a man’s perspective is all contained within the head of the sperm. The mid piece and tail are just part of the propulsion and energy system to get the sperm to the egg. If there is a high level of fragmentation going on in a man’s sample, then this is going to have a serious impact on a couples ability to conceive both naturally or through assisted treatment techniques.


DNA fragmentation testing allows us to look at the level of damage that’s occurring to the DNA in the head of the sperm. The damage we are referring to is in relation to the strands that connect the DNA molecules together. You can get single or double strand breaks and the greater the number of breaks the less likely it is that you will conceive or maintain pregnancy.  


If the blueprint isn’t right, then no matter what you do it’s highly unlikely that things will go to plan.


When might DNA fragmentation be affecting your chances?


There are some very definite indications as to when DNA fragmentation may be a factor in your ability to conceive. All too often this is overlooked and not considered until couples are much further down the line with multiple failures behind them.


Certainly, if you fall into any of these categories then it could be worth considering a DNA fragmentation test.


Repeated failure during IVF or ICSI cycles especially if fertilisation rates and embryo development are poor


If the guy has sub optimal sperm despite living a healthy lifestyle


Recurrent miscarriage


A diagnosis of unexplained infertility after TTC for 2 years or more


If the man experiences any aching, dragging or heaviness in his testicles (although an ultrasound may be the cheaper and easier first option here)



One really important thing to note is that DNA fragmentation can still be present despite a man having a perfectly normal semen analysis. So just bear that in mind even if things look good on paper.



What are the causes of DNA fragmentation?


DNA fragmentation is usually a by-product of something else within the body or that the man is doing to put his body into a state of high oxidative stress.


As the smallest cells in the body, we know that sperm are particularly sensitive and vulnerable to heat and oxidative stress. Oxidatvie stress is where the balance between free radicals (cells that damage other cells) and anti-oxidants (free radical neutralisers) is working against sperm quality.


When oxidative stress is high it leads to greater levels of DNA fragmentation. What’s important is getting to the bottom of why there’s high oxidative stress and / or high DNA fragmentation.


A few of the main culprits are:


​​Varicocele

Infection

Lifestyle and diet



How to get tested?


Currently there is no provision for DNA fragmentation testing on the NHS and it’s likely to be some time until this changes. Much as there are recommendations within the latest WHO guidance for DNA fragmentation testing it’s not being offered as standard. There is also still some controversy around the value of the test. This comes down to lack of research, confusion over standardised results and tests and what the appropriate treatment pathway is once you have your results.


This means for many couples they will have to find a clinic privately that can offer this test. It is our vision with testhim to make comprehensive testing for men more easily available and affordable.


Certainly, some IVF clinics now offer advanced male fertility testing that will include a DNA fragmentation test. Where possible we believe that men should be getting full comprehensive testing ahead of IVF treatment rather than after multiple failed cycles so if you can push to get this done, we would strongly encourage it.



What to do if you have high levels of DNA fragmentation?


First of all, it’s important that if you get tested you have someone to help you interpret the results. DNA fragmentation testing is an important part of the jigsaw but what’s also important is that you know what to do with the information you’ve got from the test. We’ve spoken to couples who’ve had a DNA fragmentation test with poor results only to be told that ICSI is the answer with no further investigation or explanation as to what was causing the DNA fragmentation. ICSI doesn’t fix DNA fragmentation!


If you have high level DNA fragmentation then it’s important to make sure you’re doing all you can around lifestyle, diet and stress management.


However, it’s equally as important, to go and see an Andrologist. This is a medical professional who specialises in male reproductive health. They will want to get to the bottom of what’s causing the fragmentation and will be able to run further tests to ascertain the likely cause. Once they’ve done this, they’ll be able to suggest potential treatment options because importantly, there are fixes for some causes of DNA fragmentation.



In summary


DNA fragmentation is a very important part of the jigsaw and well worth considering either as a reassurance check before trying to conceive, as an IVF preparation test or to just discount any other problems if you’re not managing to conceive naturally or through IVF.


The other important consideration is the fact that high level DNA fragmentation is just an outcome and it needs further investigation to find out why it’s occurring.  Further medical investigations are absolutely key when it comes to DNA fragmentation so find yourself a good Andrologist who can properly assess you and treat you accordingly.