Fragmentation of the DNA of the sperm

Definition of spermatic DNA fragmentation

What is spermatic DNA fragmentation and what is its significance?

Spermatic DNA fragmentation, as its name indicates, refers to breakage or lesions in the genetic material of the sperm.

The larger the number of lesions, the lower will be the integrity of the genetic material and the probabilities of producing a full-term pregnancy.

Can these DNA lesions be repaired?

In some cases the oocyte can repair the damage to the DNA of the sperm that has fertilised it. This will depend on various factors:

• The type of DNA lesion.
• The percentage of DNA of the affected sperm.
• The quality of the oocyte, since it will depend on it whether or not it can repair the DNA damage in the sperm. This parameter is generally linked to the age of the patient.

Is it possible that differences exist between one sample and another from the same patient?

Yes, the levels of DNA fragmentation can differ from one sample to another obtained one or several weeks later.

Is there any treatment that improves spermatic DNA fragmentation levels?

In these cases the recommended practice would be the use of sperm coming from the testicle, since it has already been observed that its degree of fragmentation is usually significantly less.

Differences between the seminogram and the test to detect fragmentation

Can a seminogram detect the lesions in the genetic material of sperm?

No, the seminogram evaluates other parameters of the semen sample such as the concentration of sperm, their motility or the morphology, but it does not take into account the integrity of the genetic material.

Causes

What causes damage in the DNA of the sperm?

The causes are several and can be intrinsic or induced by external factors.

The intrinsic factors include:

• Inefficient selection: Sperm production is localised in the seminiferous tubules (testicles) and in some cases the sperm and their progenitor cells suffer disorders of a genetic type that result in breakage of the DNA. These damaged sperm are generally selected and eliminated, but if the selection mechanism fails, sperm appear with the fragmented DNA in the ejaculate.
• Incorrect maturation: The sperm undergo a process of maturing in the epididymis that is known as epididymal maturation.

This maturation process entails nuclear chromatin packaging and the acquisition of the spermatic motility. If this process is not carried out correctly, lesions can occur in the spermatic DNA.

The external factors include:

• Damage induced by radio-chemotherapy.
• Varicocele.
• Episode of high fever.
• Exposure to high temperatures.
• Acute and chronic inflammatory disease.
• Post-testicular oxidative stress : During the transport of sperm through the epididymis, fragmentation of the spermatic DNA can occur. One of the principal mechanisms is that related to the production of free radicals, either because of immature sperm or because of the epithelial cells of the epididymis, which directly damage the genetic material of the sperm. In addition, the activation of caspases and spermatic endonucleases by toxic factors and high temperatures also induce DNA fragmentation.

Detection methods for spermatic DNA fragmentation

How is spermatic DNA fragmentation detected?

There are various methods for measuring the fragmentation levels. In our centre we use the TUNEL test, which is the test recommended by opinion leaders in studies of DNA fragmentation.

The majority of the fragmentation tests, including the SCSA test and the SCD test, measure potential damage and susceptibility to the denaturalisation of the DNA and, therefore, they have a lower predictive level. On the contrary, the TUNEL test measures real damage and has a high predictive value in assisted reproduction techniques. Currently, the cut-off value of normality recommended by the TUNEL test is less than 15%. To conduct the TUNEL test, the sperm react with an enzyme and the sperm with fragmented DNA show either microscopic coloration of a clear field or fluorescence of a green colour if viewed through a fluorescence microscope.

Clinical indications

In what cases is the spermatic DNA fragmentation test advised?

This test is recommended in the following cases:

• Idiopathic infertility (of unknown cause).
• After repeated failures in assisted reproduction techniques.
• Cases where poor embryonic quality has been observed.
• Patients that have suffered repeated miscarriages.
• Varicocele.
• Feverish episode in the last 3 months.

How do we select the best sperm in cases of spermatic DNA fragmentation?

In cases of spermatic DNA fragmentation, when embarking on an In Vitro Fertilisation treatment, Institut Marquès uses the FERTILE® chip, the latest technology in sperm analysis, that allows choosing the best spermatozoon to ensure treatment success.