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Share your experiences by joining our Patient Engagement Forum.Sperm DNA fragmentation
For most patients, having a routine cycle of proven fertility treatment is effective without using any treatment add-ons.
Our ratings indicate whether the evidence from studies shows that a treatment add-on is effective at improving treatment outcomes for someone undergoing fertility treatment. Our rating does not tell you how much that treatment add-on improves your chances of having a baby – please discuss this with your clinic.
What is sperm DNA fragmentation testing?
It takes around three months for mature sperm to be made. The genetic material called DNA is packaged within the sperm. The DNA is composed of strands of genes which carry a genetic code. During sperm maturation the DNA may be susceptible to factors which may cause the DNA strands to break or fragment. This may cause the failure of a natural pregnancy, failed IVF cycles or miscarriage.
Sperm DNA fragmentation (SDF) testing is a method of testing the sperm and looks for damage or breaks (fragmentation) in the DNA (genetic materials) of sperm. Sperm DNA damage is assessed by non-invasive tests that look at the patient’s sperm. These tests do not involve procedures being performed on the patient’s body. The tests measure how many sperm have damaged DNA and report it as a percentage known as the DNA fragmentation index (DFI).
Several different tests might be used in your clinic to assess the level of DNA damage in your sperm. The results of a sperm DNA damage test are unlikely to impact on the management of your fertility treatment.
There are several different types of sperm DNA fragmentation tests used in the UK:
- Terminal deoxynucleotidyl transferase dUTP Nick End Labelling (TUNEL) test
- Sperm chromatin structure assay (SCSA) test
- Sperm chromatin dispersion (SCD) test
- Comet assay test (not commonly used in UK fertility clinics)
Sperm DNA fragmentation testing may be offered to patients in the following situations:
- Recurrent pregnancy loss (miscarriage) following natural conception or IVF
- IVF failure
- Where the male patient has unexplained infertility
There is no standardisation of sperm DNA fragmentation testing, which means there are no commonly agreed ways to carry out the various DNA fragmentation tests. This can result in the same patient having very different test results due to the way the tests are carried out by different laboratories.
There is also no agreement in the UK or internationally for deciding what is a normal versus a high level of DNA damage in the sperm.
Where sperm DNA fragmentation takes place and the result is considered “high” (typically a DNA fragmentation index (DFI) above 25%), the patient may then be advised to have one of the following interventions:
- To take an antioxidant (a supplement) containing ingredients like vitamins, minerals and micronutrients for a period of time before undergoing IVF (in vitro fertilisation)
- To use a sperm sorting method before undergoing IVF or ICSI (intracytoplasmic sperm injection).
- The use of testicular sperm extraction (TESE) or testicular sperm aspiration
This review rates the interventions advised following sperm DNA fragmentation (SDF) testing. The review does not assess or rate the tests themselves.
| Rated outcomes for antioxidants following SDF testing | |
|---|---|
| Rated grey for increasing the chances of having a baby for patients with male factor infertility
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The use of antioxidants following sperm DNA fragmentation testing is rated GREY for improving the chances of having a baby for patients with male factor infertility. This is because there is insufficient moderate/high quality evidence investigating the effectiveness of the use of antioxidants following SDF testing in patients with male factor infertility. |
| Rated grey for increasing the chances of having a baby for patients with repeated pregnancy loss (RPL)
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The use of antioxidants following sperm DNA fragmentation testing is rated GREY for improving the chances of having a baby for patients with repeated pregancy loss. This is because there were no research studies addressing the use of antioxidants following SDF testing for this patient group. |
| Rated outcomes for sperm selection and ICSI or PICSI following SDF testing | |
|---|---|
| Rated grey for increasing the chances of having a baby for patients with male factor infertility
Grey traffic light
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The use of density gradient centrifugation (DGC) or or magnetic-activated cell sorting (MACS) with ICSI or physiological intracytoplasmic sperm injection (PICSI) for patients with male factor infertility is rated GREY for improving the chances of having a baby. This is because there is insufficient moderate/high quality evidence investingating the effectiveness of the use of DGC or MACS and ICSI or PICSI following SDF testing in patients with male factor infertility. |
| Rated grey for increasing the chances of having a baby for patients with repeated pregnancy loss (RPL)
Grey traffic light
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The use of sperm selection and ICSI, or PICSI following sperm DNA fragmentation (SDF) testing is rated GREY for improving the chances of having a baby for patients with repeated pregancy loss. This is because there were no research studies addressing the use of use of sperm selection and ICSI, or PICSI following SDF testing for this patient group. |
| Ratings for TESE or TESA and ICSI following SDF testing | |
|---|---|
| Rated red for increasing the chances of having a baby for patients with male factor infertility
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The use of testicular sperm extraction (TESE) or testicular sperm aspiration (TESA) and ICSI following sperm DNA fragmentation (SDF) testing is rated RED for improving the chances of having a baby for patients with male factor infertility. This is because there is insufficient moderate to high quality evidence that TESE or TESA improve the chances of having a baby and some risks are associated with these procedures. |
What do ratings mean?
There are five ratings that indicate whether a treatment add-on is effective at improving treatment outcomes for someone undergoing fertility treatment, according to the evidence from studies. To make it easier to understand the scientific evidence for each treatment add-on, we have a range of symbols and colours for each rated add-on below.
Green traffic light
On balance, findings from high quality evidence shows this add-on is effective at improving the treatment outcome.
Yellow traffic light
On balance, it is not clear whether this add-on is effective at improving the treatment outcome. This is because there is conflicting moderate/high quality evidence – in some studies the add-on has been found to be effective, but in other studies it has not.
Grey traffic light
We cannot rate the effectiveness of this add-on at improving the treatment outcome as there is insufficient moderate/high quality evidence.
Black traffic light
On balance, the findings from moderate/high quality evidence shows that this add-on has no effect on the treatment outcome.
Red traffic light
There are potential safety concerns and/or, on balance, the findings from moderate/high quality evidence shows that this add-on may reduce treatment effectiveness.
All treatment add-ons on our list will have a rating to indicate whether the evidence shows that the treatment add-on is effective at improving the chances of having a baby for most fertility patients. Some treatment add-ons on our list may also have additional ratings for specific treatment outcomes. For example, whether the evidence shows that the treatment add-on reduces miscarriage. There may also be further ratings for specific patient groups, for example whether the evidence shows that the treatment add-on is effective for those who are aged over 40. Please see the individual webpages for each treatment add-on for their ratings.
An agreement between the HFEA and other professional and patient bodies (the 19th October 2023 consensus statement) states that treatments that have no strong evidence of their safety and/or effectiveness should only be offered in a research setting. Patients should not be charged extra to take part in research, including clinical trials.
What’s the evidence for sperm DNA fragmentation testing?
There is inconclusive evidence to show that where sperm DNA fragmentation tests result in a DNA fragmentation index (DFI) considered high (typically 25% or above), this is associated with reduced fertility and increased risk of miscarriage. Furthermore, DFI can differ according to the type of test used. Reduced fertility in this context refers to taking longer to conceive naturally or having a lower chance of achieving pregnancy through IUI (intrauterine insemination) IVF or ICSI.
While there is some evidence of a link between high sperm DNA damage and fertility treatment outcomes, there is not enough high or moderate quality evidence on the impact of interventions recommended following testing on fertility treatment outcomes.
Seven clinical studies on antioxidants were examined. The studies used different combinations of antioxidants including but not limited to L-carnitine, folic acid, zinc, selenium, vitamin E, and vitamin C. Three high or moderate quality studies looked at the chance of having a baby but found no improvement for antioxidant use. Six studies found a slight (non-significant) improvement in pregnancy rates, but several had limitations including being small, and having a study design that may have influenced the findings.
Three clinical studies looked at sperm sorting methods including magnetic-activated cell sorting (MACS) or density gradient centrifugation (DGS) with ICSI, PICSI, and testicular sperm extraction (TESE) or testicular sperm aspiration (TESA) with ICSI. The studies were considered of moderate or high quality and reported that the different sperm sorting methods showed no significant impact on pregnancy rates or the chance of having a baby.
Is this treatment add-on safe?
Sperm DNA fragmentation (SDF) testing is a non-invasive process and does not carry any additional risks to the patient compared to having a routine semen test.
The research studies looking at the use of antioxidants in men assessed as having “high” sperm DNA damage (usually DNA fragmentation index (DFI) of 25% or higher) did not report any safety concerns.
Sperm sorting methods like gradient centrifugation (DGS) and magnetic-activated cell sorting (MACS) are procedures carried out on ejaculated sperm and do not carry any risks to the (male) patient. Intracytoplasmic sperm injection (ICSI) and physiological intracytoplasmic sperm injection (PICSI) are methods of IVF that do not pose any additional risks to the health of the male or female patient, but have an increased risk of egg damage and may be associated with long-term health issues for any resulting children. More information about ICSI including its safety can be found here.
MACS is a magnetic sperm sorting technique which is used to separate healthy sperm from damaged sperm. This is done by identifying a warning signal on the surface of sperm that is associated with damaged or dying sperm, which are more likely to have DNA damage.
DGC is a technique used to separate high-quality sperm from lower quality sperm including sperm with DNA damage. This is done by placing sperm in a tube with different density media so the best quality sperm can reach the bottom of the tube.
Although testicular sperm retrieval, either through testicular sperm extraction (TESE) or testicular sperm aspiration (TESA), is recommended for some medical conditions like azoospermia, they are invasive procedures carried out on the (male) patient’s body and not without risks.
TESA is a needle aspiration procedure (a needle is placed in the patient’s scrotum) and is considered minimally invasive. TESA carries a small risk of bleeding, infection or testicular injury and common side effects for the patient include temporary soreness and swelling. TESA is usually carried out under a local anaesthetic and intravenous sedation, both of which carry potential risks for the patient.
TESE is a surgical procedure that involves the removal of small amounts of testicular tissue. The risks of the procedure to the patient include bleeding, bruising, infection, and testicular injury, and common side effects include post-surgery pain and swelling. TESE can be carried out under local anaesthetic, general anaesthetic or sedation, all of which carry risks for the patient.
If you have any questions about the safety and risks, your clinic will be able to discuss whether a treatment add-on would be safe for you to use considering your specific medical history and circumstances.’
Studies reviewed for this treatment add-on
| Intervention | Study | DOI/Reference |
|---|---|---|
| Antioxidants | Barekat, 2016 | https://doi.org/10.22074/ijfs.2016.4777 |
| Habibi, 2022 | https://doi.org/10.22074/cellj.2022.8273 | |
| Lahimer, 2023 | https://doi.org/10.3390/antiox12111937 | |
| Matthieu d'Argent, 2021 | https://doi.org/10.3390/jcm10091876 | |
| Schisterman, 2020 | https://dx.doi.org/10.1001/jama.2019.18714 | |
| Steiner, 2019 | https://doi.org/10.1016/j.fertnstert.2019.11.008 | |
| Stenqvist, 2018 | https://doi.org/10.1111/andr.12547 | |
| Considered, but did not meet inclusion criteria. | De Ligny, 2025 | https://dx.doi.org/10.1001/jamanetworkopen.2025.32405 |
| Sperm Selection (MACS or DGC with ICSI, PICSI or TESE/TESA with ICSI) | Hasanen, 2020 | https://dx.doi.org/10.1007/s10815-020-01913-4 |
| Hozyen, 2022 | https://doi.org/10.1007/s43032-021-00642-y | |
| Mantravadi, 2024 | https://dx.doi.org/10.1007/s10815-024-03128-3 | |
| Ejaculatory Abstinence | Kabukcu, 2021 | https://dx.doi.org/10.1007/s00404-020-05783-0 |
| Other Reviews | ||
| Cochrane review | de Ligny, 2022 | https://dx.doi.org/10.1002/14651858.CD007411.pub5 |
| NICE guideline | NICE (2026) NG257 | Fertility problems: assessment and treatment: Sperm DNA fragmentation |
What are treatment add-ons?
In vitro fertilisation (IVF) and intrauterine insemination (IUI) are established treatments that have been proven effective for most patients. Treatment add-ons are optional non-essential treatments or tests that may be offered in addition to such proven fertility treatment. Treatment add-ons are:
- Additional treatments (to the core treatment e.g. IVF or IUI) or tests that are being offered to the general patient population in licensed fertility clinics in the UK,
- where there is published scientific literature which claims to demonstrate that the add-on improves live birth rates or other treatment outcomes rated by the HFEA; but
- where evidence of effectiveness for the use of the treatment or test in a clinical setting is lacking or absent; and
- where patients need unbiased information about the effectiveness and risks of this treatment or test
It is important to keep in mind that for most patients, having routine cycles of proven fertility treatment are effective without using any treatment add-ons. If you are paying for your own treatment, you may want to think about whether it might be better to pay for multiple cycles of IVF or IUI, rather than spending large sums of money on a single treatment cycle with treatment add-ons that haven’t been proven to be effective.
We aim to publish clear and reliable information about some of the treatment add-ons that don’t have enough evidence to show that they improve your chances of having a baby and other relevant treatment outcomes. This provides useful information to patients and allows them to question the use of add-ons.
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