DNA FRAGMENTATION, SPERM MORPHOLOGY AND MALE INFERTILITY

The assessment of male infertility is often a complex procedure which covers the investigation of manifold disorders that impair man's ability to fertilize. Usually, the starting point for this investigation is the semen analysis, whose results may help in the diagnosis. Low sperm counts (oligozoospermia), poor vitality and poor sperm progression (asthenozoospermia) and changes in the sperm structure (teratozoospermia) are findings that are indicative of disorders affecting male fertility.

Since the 1990s, experts in human reproduction and andrology have also emphasized that DNA fragmentation is a cause of male infertility. Sperm DNA is a double helix molecule, which breaks in some instances (fragmentation) impairing the chances of conception. Many infertile patients have high rates of DNA fragmentation. Among the most common causes of this disorder are mentioned genital infections causing leukocytospermia (increased leukocytes in the semen) and the excess of abnormal spermatozoa in the ejaculate, especially in varicocele patients. Recently, we have observed that Candida sp also cause increased sperm DNA fragmentation. Apart from male infertility, many studies published in this century also showed a relationship between increased sperm DNA fragmentation and recurrent pregnancy loss.

In this Lisalab Reports we will present two cases, in which we detected abnormal sperm morphology (severe teratozoospermia) and increased rates of DNA fragmentation. In addition, we report a third case with normal DNA fragmentation. These patients sought the laboratory with a history of male infertility around 3 years. In Table 1 we present some clinical data of the patients and in Table 2 we report some records of the Advanced Seminal Analysis and of DNA Fragmentation Test.

Tabela 1

Clinical data	Patient 1	Patient 2	Patient 3
Age	40 years old	56 years old	39 years old
Infertility time	3 years	3 years	3 years
Children	None	one daughter*	one son*
Varicocele	bilateral	not investigated	not detected
Varicocele (surgery)	yes (2019)	No	No

* of prior marriage

Tabela 2

Parameter	Patient 1	Patient 2	Patient 3	References
Sperm count/mL	390 x 10(6)	158 x 10(6)	104 x 10(6)	>15 x 10(6)/mL
Vitality	67%	50%	72%	>58%
Total motility	44%	24%	33%	>40%
Progressive motility	43%	23%	32%	>32%
Normal morphology	0.24%	0.28%	18.6%	>4%
Tapered	15%	9%	0	<5%
Germinal integrity*	44/1	150/1	52/1	>40/1
Leukocytes/mL	0.92 x 10(6)	0.07 x 10(6)	2.97 x10(6)	<1.0 x 10(6)
DNA fragmentation**	51.9%	74.1%	27.3%	<30.0%

*Index developed in our laboratory for measuring the germinal epithelium integrity (no increased dequamation of immature germinal cells). The higher the index, the greater is the integrity of the germinal epithelium

**DNA fragmentation index (SCSA)

The tables show some interesting data, as follows:

• Three patients are practically age grouped from 40 to 60 years old.
• Patient 1 reported having done bilateral varicocele surgery in 2019. Severe teratozoospermia is associated with an increase in tapered sperm and a high index of DNA fragmentation, in spite of having normal vitality and motility and polyzoospermia.
• Patient 2 also had severe teratozoospermia, with a slight increase of tapered sperm. These data are indicative that he may be a carrier of varicocele. Note that it also has a DNA fragmentation index higher than patient 1 and both abnormal sperm vitality and motility.
• Patient 3 has normal sperm count, vitality, morphology and DNA fragmentation index, mild asthenozoospermia and leukocytospermia. In addition, he complained of pelvic and perineal pain in lab anamnesis and low levels of both calcium and zinc, markers of prostatic function. In lab practice of advanced semen analysis, these findings suggest the presence of non-bacterial symptomatic prostatitis (no bacteria was detected in semen bacterioscopy), although it is less than 50 years old (CAP / CPPS IIIA according to NIH-USA ?). Since we do not perform the semen culture, this prostatitis can also be chronic bacterial Type II according to NIH-USA. However, only a more detailed clinical evaluation and the patient submitting a Mears-Stamey routine, the type of prostatitis present can be correctly diagnosed. It is still worth noting that, despite the likelihood of prostatitis, it presented a normal DNA fragmentation index.

The three cases reported here show different results and interpretations, although the Advanced Seminal Analysis carried out, as well as the DNA fragmentation tests were requested with the same purpose, namely the investigation of male infertility. It is noticed that the data of tables 1 and 2 were meaningful on this investigation leading at some conclusions for helping in the diagnosis.

In summary, this publication once again shows how Advanced Seminal Analysis gives multifarious information and ways of investigation of any disturbance affecting the functional capacity of the male genital organs apart from its main clinical setting.