For many couples in India, the fertility journey begins with a semen analysis. When the report comes back “normal,” there is a natural sense of relief, an assumption that the male partner is not the issue. Yet months pass, treatments are attempted and conception continues to elude them. The diagnosis they often receive is one of the most frustrating in reproductive medicine: unexplained infertility.
What a growing body of research now confirms is that standard semen parameters sperm count, motility and morphology tell only part of the story. Beneath these surface-level metrics lies a deeper dimension of sperm health that conventional testing simply cannot detect: the integrity of sperm DNA. As the field of fertility tests for men continues to advance, the sperm DNA fragmentation test is emerging as a vital diagnostic tool, one that bridges the gap between a “normal” semen report and persistent infertility.
What Standard Semen Analysis Measures And Where It Falls Short
Semen analysis has long been a fundamental part of assessing male fertility. Based on the World Health Organisation’s reference values, it assesses sperm concentration, total motility, progressive motility and morphology. These parameters provide a useful initial overview and remain an essential first step among fertility tests for men.
However, clinical experience and published research consistently demonstrate that a normal semen report does not guarantee fertility. A notable proportion of infertile men present with entirely normal semen parameters. Conversely, men with borderline results sometimes conceive without difficulty. The reality is that semen analysis evaluates what sperm looks like and how it moves but it cannot assess what it carries.
The genetic material within sperm DNA is arguably the most critical component for successful fertilisation and healthy embryo development. And this is precisely where many cases of so-called unexplained infertility find their explanation.
Understanding Sperm DNA Fragmentation
Sperm DNA fragmentation describes the presence of breaks or impairment within the genetic material contained in sperm cells. Unlike the physical characteristics measured during semen analysis, DNA damage occurs at a molecular level invisible under the microscope and can significantly impair fertility outcomes even when all visible parameters appear normal.
The DNA within sperm is responsible for half of the genetic blueprint passed to offspring. When this genetic material is fragmented, the consequences can be far-reaching:
- Reduced fertilisation rates, even with assisted reproductive technologies
- Higher rates of early pregnancy loss and miscarriage
- Significantly lower implantation rates during IVF and ICSI cycles
- Compromised embryo quality and developmental potential
- Potential long-term impact on offspring health.
Three primary mechanisms contribute to DNA damage in sperm: defective apoptosis during spermatogenesis, DNA strand breaks during chromatin remodelling and post-testicular oxidative stress. Importantly, each of these pathways can be influenced by lifestyle, environmental and medical factors making DNA fragmentation both identifiable through testing and, in many cases, reversible.
The Unexplained Infertility Connection
Unexplained infertility is a diagnosis that essentially reflects the limitations of conventional testing rather than the true absence of a cause. It is one of the most common diagnoses in fertility clinics and, for many couples, it is also the most disheartening because without a clear cause, there is no clear treatment path.
Research now offers compelling evidence that sperm DNA fragmentation is a hidden contributor in a substantial proportion of these cases. Multiple clinical studies have shown that a significant number of men diagnosed with unexplained infertility carry elevated DNA fragmentation despite their semen reports appearing completely normal. Notably, research from India published in 2025 found that men with unexplained infertility had dramatically higher DNA fragmentation levels compared with fertile controls, even though both groups had normal semen profiles.
These findings carry important clinical implications. They suggest that for many couples labelled as having unexplained infertility, there is indeed an identifiable cause – one that standard fertility tests for men simply cannot capture. The sperm DNA fragmentation test fills this diagnostic gap, offering couples and clinicians the clarity they need to move forward with targeted treatment.
Why DNA Fragmentation Testing Matters for Fertility Outcomes
The clinical significance of sperm DNA fragmentation extends across the full spectrum of reproductive approaches. Whether a couple is trying to conceive naturally, through IUI, or via IVF and ICSI, elevated DNA fragmentation has been consistently linked to poorer outcomes including lower pregnancy rates, increased miscarriage risk and reduced implantation success.
For couples experiencing recurrent pregnancy loss, the evidence is equally persuasive. Research has shown that men whose partners suffer repeated miscarriages tend to have significantly higher DNA fragmentation than fertile controls, with a clear relationship between the number of pregnancy losses and the severity of DNA damage. This makes the sperm DNA fragmentation test a particularly valuable investigation when couples face repeated failed cycles or unexplained losses, and one that deserves a place alongside other essential fertility tests for men.
Risk Factors Relevant to Indian Men
India’s unique occupational, environmental and lifestyle landscape presents specific challenges for male reproductive health. IT professionals and businessmen form a large proportion of affected individuals, driven by prolonged screen exposure, sedentary work patterns, disrupted sleep cycles and chronic stress. The expanding corporate sector, irregular meal timings and late-night work shifts are all contributing to a noticeable rise in male fertility concerns across urban India.
Key risk factors for elevated sperm DNA fragmentation include:
- Advanced paternal age, particularly relevant as many Indian men now delay fatherhood for career and financial reasons
- Alcohol consumption, identified in recent research as one of the strongest lifestyle-associated predictors of elevated DNA fragmentation
- Smoking and tobacco use, which introduce toxins that directly damage sperm DNA
- Obesity and metabolic conditions such as varicocele and impaired glucose tolerance
- Occupational stress, prolonged sitting and exposure to high temperatures
- Unsupervised use of gym supplements, anabolic steroids and protein powders
- Urban air pollution, with emerging research linking higher PM2.5 exposure to increased DNA damage in sperm.
When to Consider Sperm DNA Fragmentation Testing
Andrology Center recommends sperm DNA fragmentation testing as part of a comprehensive panel of fertility tests for men in the following clinical scenarios:
- Instances of unexplained infertility where the female partner has completed a thorough evaluation
- Recurrent pregnancy loss or repeated IVF/ICSI failure
- Normal semen analysis with persistent difficulty conceiving
- Advanced paternal age
- Clinical varicocele with borderline semen parameters
- Significant lifestyle risk factors or environmental exposures.
Among available testing methods, the Sperm Chromatin Structure Assay (SCSA®) is widely regarded as the gold standard. This flow cytometry-based method provides a precise DNA Fragmentation Index that is well correlated with fertility potential and has been validated across thousands of clinical studies worldwide. Andrology Center is the only laboratory in India licensed to perform the SCSA® test, in partnership with SCSA Diagnostics USA.
The Path Forward: From Diagnosis to Improvement
Encouragingly, sperm DNA fragmentation is often reversible. Evidence consistently shows that addressing modifiable risk factors can lead to meaningful improvements over a period of three to six months. Effective strategies include dietary changes emphasising antioxidant-rich foods, regular moderate exercise, smoking cessation, limiting alcohol intake and actively managing psychological stress. Targeted supplementation with nutrients such as Coenzyme Q10, zinc, Vitamin E and selenium under medical guidance can further support sperm DNA integrity.
For men diagnosed with elevated DNA fragmentation, varicocele repair has demonstrated clear benefits in reducing DNA damage. When natural conception remains challenging despite intervention, assisted reproductive technologies can be tailored based on fragmentation results. For instance, the use of testicular sperm rather than ejaculated sperm may offer advantages for men with high fragmentation, as testicular sperm typically exhibits better DNA integrity.
Conclusion
A normal semen analysis report, while reassuring, does not provide a complete picture of male fertility potential. For the many couples facing unexplained infertility, sperm DNA fragmentation represents a clinically meaningful and often treatable factor that standard testing overlooks.
As the landscape of fertility tests for men continues to evolve, the sperm DNA fragmentation test has moved from a research curiosity to an essential clinical investigation. By identifying DNA-level damage that semen analysis cannot detect, it empowers couples with the information they need to make informed decisions and pursue the right treatment path.
If you and your partner have been diagnosed with unexplained infertility, or if previous treatments have not yielded the expected results, seeking a comprehensive fertility evaluation that includes sperm DNA fragmentation testing is a proactive and evidence-based next step. Andrology Center offers advanced diagnostic services, including the SCSA® test, to help you understand the full picture of your reproductive health and chart a clear path forward.
