Sperm DNA fragmentation refers to breaks in the genetic material contained within the sperm. This fragmentation can be single-stranded or double-stranded, depending on the DNA strands affected by the break.
Any alteration in the male's sperm DNA can be a cause of male infertility, since the integrity of the genetic material is essential for embryonic development to occur normally.
Therefore, with a high number of lesions in the sperm DNA, the probability of achieving a pregnancy and carrying it to term may be reduced.
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Sperm DNA fragmentation
Male fertility and seminal quality are assessed through the seminogram (semen analysis) test. This is an analysis of the semen that evaluates macroscopic parameters (such as volume or seminal viscosity) and microscopic parameters (such as concentration, motility, and sperm morphology).
However, there are other sperm parameters that are not evaluated in this exam and that can influence the male's fertile potential.
This would be the case of sperm DNA fragmentation. Furthermore, this alteration in the genetic material of the male gamete can be present even when the parameters of concentration, motility, and sperm morphology are normal in the seminogram results.
Nevertheless, sperm motility and morphology parameters can be affected and related to sperm DNA fragmentation.
Implications for male fertility
High levels of sperm DNA fragmentation have been associated with male infertility. In addition, sperm DNA fragmentation has been extensively studied in relation to assisted reproduction techniques, where it can have the following implications:
- Lower fertilization rate.
- Poorer embryo quality.
- Lower implantation rate.
- Higher rate of miscarriages.
However, it is important to clarify that the relationship between high sperm DNA fragmentation and these parameters is still a matter of controversy.
Diagnosis with fragmentation test
As we have mentioned, it is possible for men with normal seminogram values to have a high fragmentation index in their sperm DNA. However, the fragmentation level is most likely to be elevated when seminal parameters are altered.
In any case, to evaluate the integrity of the sperm DNA, it is necessary to perform complementary tests known as fragmentation tests.
There are several methods to measure the degree of sperm DNA fragmentation in the laboratory, but the most widely used are the following:
SCD Test
The Sperm Chromatin Dispersion (SCD) test consists of decondensing the sperm DNA.
As a consequence, sperm with intact DNA will show large dispersion halos, while those with fragmented DNA will have small or absent dispersion halos around the head.
TUNEL Assay
The TUNEL (Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick-End Labeling) assay is a technique that typically uses flow cytometry to evaluate DNA integrity.
It involves staining with fluorescent markers that will only bind to broken DNA strands. Then, as the sample passes through the flow cytometer, the fluorescence signal will indicate when the DNA is fragmented.
In addition, the TUNEL test allows the simultaneous detection of both types of sperm DNA breaks (single and double-strand), which is why this test is widely used.
How are the results interpreted?
To determine if seminal quality is compromised, it is essential to compare the percentage of sperm DNA fragmentation obtained with reference values. The most common reference ranges when interpreting the results of the sperm fragmentation study are detailed below:
- Low or normal fragmentation (< 15-20%): the seminal sample is considered to be of good quality. With these levels, the oocyte is usually able to repair the genetic damage of the sperm after fertilization, allowing the development of a healthy embryo.
- Intermediate fragmentation (20% - 30%): there is moderate damage. In these cases, the probability of natural pregnancy or through artificial insemination may be reduced, and evaluating other techniques or antioxidant treatments is recommended.
- High or pathological fragmentation (> 30%): indicates severe damage to the genetic material. These values are frequently associated with low fertilization rates, poor embryo quality, and an increased risk of miscarriage. In this scenario, advanced sperm selection techniques or the use of testicular sperm are usually recommended.
It is important to emphasize that the interpretation of the results of the sperm fragmentation analysis should always be performed by a specialist, as a high fragmentation index does not necessarily make pregnancy impossible. However, it will be necessary to propose the most appropriate treatment options.
Indications for the fragmentation study
Normally, these tests to assess sperm DNA fragmentation are done when the couple fails to conceive after having undergone several fertility treatments, although there are also other indications:
- Unexplained sterility.
- Repeated implantation failures.
- Poor quality embryos.
- Varicocele.
- Recurrent miscarriages.
- Men over 45 years old.
- Chronic diseases such as diabetes.
- Men who smoke.
- Altered seminogram results.
Causes
There are various factors that can cause an increase in sperm DNA breaks, but among the most frequent causes are the following:
- High testicular temperature
- due to episodes of high fever, the presence of a varicocele, or even wearing tight clothing.
- Pharmacological treatments
- certain medications can lead to sperm DNA fragmentation.
- Exposure to pollutants
- pesticides and certain chemical compounds can cause sperm DNA damage.
- Smoking
- male smokers have poorer seminal quality and, in addition, smoking can increase the number of sperm with fragmented DNA.
- Advanced age
- sperm DNA fragmentation increases with age, especially after 45 years.
In addition to these, there are other intrinsic causes of fragmentation that occur during sperm production, due to alterations that leave the sperm DNA vulnerable to damage by oxidative stress.
Treatment
Some of the causes that provoke sperm DNA fragmentation cannot always be treated. In other cases, a change in lifestyle or treatment with antioxidants may be useful to improve seminal quality.
As we have mentioned, oxidative stress caused by the increase of free radicals in the male's body causes damage to the sperm DNA. Therefore, it will be necessary to lead a healthy lifestyle and a varied and balanced diet to be able to decrease these fragmentation levels in the sperm DNA.
Antioxidant treatments for approximately 3 months can reduce sperm DNA fragmentation, although this is not always possible.
On the other hand, varicocele surgery, if applicable, can also help improve DNA integrity and the male's fertile potential.
Achieving pregnancy
The fact that a man has a high sperm DNA fragmentation rate does not mean he cannot achieve a natural pregnancy with his partner. However, the probability of achieving it may be reduced due to what has been discussed throughout this article.
If the fragmentation index is low, the egg may be able to repair this damage on its own after fertilization.
How this mechanism works is not very well known, but its success may depend on the type and extent of the sperm DNA lesions and the quality of the oocyte.
Regarding assisted reproduction treatments, sperm DNA fragmentation can also affect the results in the manner previously explained. However, there are sperm selection techniques such as the Fertile Chip to improve the seminal quality of men with elevated levels of sperm DNA fragmentation, especially when it is double-stranded.
On the other hand, it has been seen that sperm obtained directly from the testicle via testicular biopsy can have better DNA quality than ejaculated sperm, making this management possible in certain cases of men with high sperm DNA fragmentation and previous ICSI failures.
If you need to undergo IVF to become a mother, we recommend that you generate your Fertility Report now. In 3 simple steps, it will show you a list of clinics that fit your preferences and meet our strict quality criteria. Moreover, you will receive a report via email with useful tips to visit a fertility clinic for the first time.
FAQs from users
How does MACS in sperm selection work?
MACS stands for Magnetic-activated cell sorting and consists of discarding apoptotic sperm, or select sperm that do not have fragmented DNA.
It can be used in seminal samples of patients who are going to perform both in vitro fertilization (IVF), intracytoplasmic microinjection (ICSI) and artificial insemination (AI), although its limitation is that it must be used in samples with sufficient seminal quality for the result to be optimal, as the seminal concentration decreases.
It is indicated for patients with a high percentage of spermatozoa with fragmented DNA, repeated miscarriages, poor embryo quality and low fertilization rates.
How much does a sperm fragmentation test cost?
The cost of this test is not covered by insurance and is $300, plus the home collection kit that cost $150.
Are tests of sperm DNA damage clinically useful?
Absolutely, especially in cases of pregnancy loss by IVF and ICSI, as well as to increase IUI pregnancy rates. However, the true clinical utility of these tests is still to be established, as available studies are still small and few in number.
Can sperm DNA fragmentation be improved?
Yes, it is possible. A man with high sperm DNA fragmentation can improve his semen quality by taking antioxidants and vitamin supplements that include vitamins C, E, and A.
However, it is important to note that the likelihood of success with these supplements will also depend on the degree of sperm DNA fragmentation. If the percentage of DNA fragmentation exceeds 30%, pregnancy can only be achieved through IVF/ICSI.
Can sperm with DNA fragmentation fertilize an egg?
Sí, es posible lograr, especialmente cuando el grado de fragmentación espermática es bajo o moderado.
Si el índice de fragmentación es bajo, es posible que el óvulo compense esta alteración y repare el daño tras la fecundación. Esto daría lugar a un embrión viable y, por tanto, a un embarazo que puede evolucionar favorablemente.
What is the price of the sperm DNA fragmentation test?
The sperm fragmentation test is not included in the price of the semen analysis; it is considered an additional test. The price of the sperm fragmentation study is approximately 80-120 euros, although it may vary depending on the clinic or laboratory where the test is performed.
Since the price of the semen analysis is also around 70-130 euros, if a complete semen study is done with both tests, the cost can rise to between 150-250 euros.
Does sperm DNA fragmentation cause birth defects?
Actually, there is no human study showing a direct relationship between birth defects and sperm DNA fragmentation. However, damage in the sperm DNA increases the risks increases the risk of genetic mutations, thereby increasing the risk of miscarriage.
Suggested for you
In addition to this test, there exist other male fertility tests that can be done prior to starting a fertility treatment. Find them all in the following post: Male Fertility Testing – How Do You Know if a Man’s Sperm Is Fertile?
As explained above, IVF with ICSI is the most adequate fertility treatment for those couples who are trying to conceive without luck and testing has show high levels of sperm DNA fragmentation. Check out this for information: What Is ICSI Technique? – Process, Success Rates & Cost.
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References
Agarwal A, Cho CL, Esteves SC. Should we evaluate and treat sperm DNA fragmentation? Curr Opin Obstet Gynecol. 2016 Jun;28(3):164-71 View
Esteves SC, Santi D, Simoni M. An update on clinical and surgical interventions to reduce sperm DNA fragmentation in infertile men. Andrology. 2020 Jan;8(1):53-81 (View)
Esteves SC, Zini A, Coward RM, Evenson DP, Gosálvez J, Lewis SEM, Sharma R, Humaidan P. Sperm DNA fragmentation testing: Summary evidence and clinical practice recommendations. Andrologia. 2021 Mar;53(2):e13874 (View)
Evenson DP. The Sperm Chromatin Structure Assay (SCSA(®)) and other sperm DNA fragmentation tests for evaluation of sperm nuclear DNA integrity as related to fertility. Anim Reprod Sci. 2016 Jun;169:56-75 (View)
Muratori M, Marchiani S, Tamburrino L, Baldi E. Sperm DNA Fragmentation: Mechanisms of Origin. Adv Exp Med Biol. 2019;1166:75-85 (View)
Qiu Y, Yang H, Li C, Xu C. Progress in Research on Sperm DNA Fragmentation. Med Sci Monit. 2020 Apr 22;26:e918746 (View)
Sharma R, Iovine C, Agarwal A, Henkel R. TUNEL assay-Standardized method for testing sperm DNA fragmentation. Andrologia. 2021 Mar;53(2):e13738 (View)
Simon L, Emery B, Carrell DT. Sperm DNA Fragmentation: Consequences for Reproduction. Adv Exp Med Biol. 2019;1166:87-105 (View)
FAQs from users: 'How does MACS in sperm selection work?', 'Is it better to study single-stranded or double-stranded DNA breaks? And why?', 'How much does a sperm fragmentation test cost?', 'Are tests of sperm DNA damage clinically useful?', 'Can sperm DNA fragmentation be improved?', 'Can sperm with DNA fragmentation fertilize an egg?', 'What is the price of the sperm DNA fragmentation test?' and 'Does sperm DNA fragmentation cause birth defects?'.
