What Is Sperm DNA fragmentation?

As the term itself suggests, DNA fragmentation is defined as the breaking of one’s sperm DNA into separate (fragmented) pieces. It is one of the most common DNA abnormalities observed in male gametes. Sperm DNA fragmentation is known to be linked with low fertilization rates, poor quality semen, reduced success in assisted reproduction procedures as well as impaired development of embryo after a pregnancy is achieved.

Sperm DNA Fragmentation & Its Impact On The Process Of Reproduction

According to WHO, sperm motility, morphology, concentration, and semen volume are the most significant parameters when it comes to analysing the former’s quality2. Although DNA fragmentation is a less tested parameter, sperm damage as a result of its fragmented DNA is very common. In fact, too much fragmented DNA in sperm has been observed to have a negative impact on implantation, development of the embryo, as well as pregnancies (both natural and assisted). This is because your body cannot repair the damage caused by DNA fragmentation, and as a result, it accumulates. When the level of sperm DNA fragmentation goes beyond a certain threshold, it leads to fertility problems and reduces one’s chance of conceiving naturally as well as via assisted reproductive techniques like IVF (In Vitro Fertilization).3

You must already know that the genetic makeup of a newborn is a result of fusion of the DNA information in a male’s sperm and a female's egg or oocyte. However, any type of damage or abnormalities in the DNA of the male or female gamete can interrupt the process of reproduction2.

Among males, sperm DNA fragmentation is one of the most common types of defect in the DNA  to be transmitted to their offsprings. Although it’s normal to have some degree of fragmented DNA in one’s sperm, when the level of fragmentation goes beyond a certain threshold, male fertility problems tend to occur. Thus, this is how sperm DNA fragmentation is found widely among both subfertile as well as infertile men2.

Measuring Sperm DNA Fragmentation

DNA fragmentation is often measured via DNA fragmentation index (also known as DFI). This value is referred to as the percentage of fragmented sperm (sperm observed to have fragmented DNA) found in a semen sample. A higher DFI is directly proportional to the amount of damaged sperm in an individual’s sample.

In general, DFI of more than 30% is regarded as quite high and has less chances of achieving pregnancy naturally or via insemination. Even 20% DFI is considered to be quite high and the chances of achieving a natural pregnancy with it is substantially reduced4.

What Causes Sperm DNA Fragmentation?

DNA fragmentation is mostly known to be caused by 3 common triggers. They are:

  • Apoptosis:

Sperm apoptosis (programmed cell death of impaired sperm) helps regulate over synthesis of sperm cells and also helps in discarding abnormal cells. However, some defective sperm cells that have a normal morphology but an abnormal genetic makeup (DNA fragmentation) can still be found in male ejaculate (the white fluid - semen - discharged from the male reproductive tract)2.

  • Sperm Chromatin Damage:

The sperm chromatin is mainly composed of a complex of DNA and nuclear proteins (forming the chromosomes). This genetic material might undergo DNA fragmentation while being packed into the extremely small sperm head during spermiogenesis (the final stage of spermatogenesis that results in the formation of matured sperm)5.

  • Damage By Oxygen Radicals: 

Radiation from electromagnetic sources as well as toxins from industrial and other by-products can all produce free radicals, which, in turn, induces sperm DNA fragmentation6.

Risk Factors For Sperm DNA Fragmentation

Here are some common factors that have been associated with an increase in Sperm DNA fragmentation.

1. Advancing Paternal Age:

Increased paternal age is linked to various reproductive issues in males and females alike. Older men are found to have lower semen volume and motility. Beginning at 40 years old, an increased incidence of sperm DNA fragmentation has also been observed in males7.

2. Low Sperm Quality:

Abnormalities in normal sperm morphology, low motility, and low sperm concentration have been observed to cause higher levels of sperm DNA fragmentation5.

Sperm DNA Fragmentation & Assisted Reproduction Outcomes

High DNA fragmentation has been observed to have a negative impact on the outcomes of assisted reproductive techniques like IVF (In Vitro Fertilization) and ICSI (Intracytoplasmic Sperm Injection). 

The chances of successfully carrying a pregnancy to term, growth and development of the embryo, the probability of a live birth during assisted reproduction, are all significantly lowered when the sperm is subjected to DNA fragmentation. However, the chances of an early pregnancy loss are quite high in spouses of males with high levels of fragmented DNA in their sperm2.

Sperm DNA Fragmentation & Increased Risk Of Miscarriages

Multiple studies have linked damaged sperm DNA to early pregnancy loss and also as a potential cause of recurrent miscarriages8 9

In a study comprising couples who opted for IVF, more miscarriages were observed when the male partners had increased levels of sperm DNA fragmentation. The same study also concluded that there was a drop in pregnancy rate with increased incidence of sperm DNA fragmentation among the patients7.

Conclusion

Men who are sub fertile or infertile should be educated and guided on their chances of having fragmented DNA in their sperm. In many instances, men with normal sperm parameters have fragmented DNA2. Thus, irrespective of the results of a classic semen analysis, males who have been facing repeated reproductive failure with their spouses (with an unidentified cause) must also be made to undergo sperm DNA fragmentation tests to get a clear cut picture on the root cause of their inability to embrace parenthood.

References

  1. https://rbej.biomedcentral.com/articles/10.1186/s12958-018-0369-3 
  2. https://www.intechopen.com/chapters/48736 
  3. https://examenlab.com/news/the-2021-who-manual-includes-sperm-dna-fragmentation-testing-in-its-extended-examination-list/ 
  4. https://pubmed.ncbi.nlm.nih.gov/23596042/ 
  5. https://pubmed.ncbi.nlm.nih.gov/19264700/ 
  6. https://rbej.biomedcentral.com/articles/10.1186/1477-7827-9-47 
  7. https://www.researchgate.net/profile/Javier-Garcia-Ferreyra/publication/262601398_High_Levels_of_DNA_Fragmentation_Observed_in_an_Infertile_Population_Attending_a_Fertility_Center_are_Related_to_Advanced_Paternal_Age/links/0f317539eee26591cd000000/High-Levels-of-DNA-Fragmentation-Observed-in-an-Infertile-Population-Attending-a-Fertility-Center-are-Related-to-Advanced-Paternal-Age.pdf 
  8. https://academic.oup.com/humrep/article/21/11/2876/2939172?login=false 
  9. https://www.fertstert.org/article/S0015-0282(07)01361-1/fulltext 

References