Effect of Prostate Inflammation on Ejaculate Indicators in Men of Various Ages from Infertility Couples

The question of the impact of chronic prostatitis on male fertility remains debatable. In our study, we proved that inflammation of the prostate affects the characteristics of a man’s ejaculate. The inflammatory process negatively affects the reproductive characteristics of men of all ages, however, in the older age group, its clinical and laboratory manifestations are most pronounced.

Male fertility requires not only full-fledged spermatogenesis, but also coordinated functions of the genitourinary system organs and all accessory glands of the male genital tract [7]. However, the question of the relationship between genitourinary system diseases, in particular, between chronic inflammation of the prostate and impaired fertility, remains controversial [8] [9].
There are works that dispute the relationship between prostatitis and sperm characteristics [10]. According to several experts from the European Association of Urology [11], there is no convincing evidence that chronic prostatitis negatively impacts the sperm quality and causes male infertility.
On the contrary, according to other experts, the idea of the negative impact of inflammation of the prostate and other accessory glands of male urogenital tract on the ejaculate quality and, as a result, fertility, is completely justified [12]. The prevalence of male infertility associated with infection of the male genital tract ranges from 10% to 35% of the total number of infertile men [13]. If we include those men who have suffered from prostatitis at some point in their lives, the prevalence of infertility increases to 50%, and the condition becomes chronic in 10% of cases [14]. It can be assumed that for the diseases such as orchitis, epididymitis [15], and prostatitis [16], due to the prolonged infection and inflammation of the male genital tract, the spermatozoa are directly exposed to activated leukocytes and their products during a long period of their maturation. It is likely that leukocytes in seminal fluid not only impair spermatozoa motility and reduce their ability to fertilize, but also can induce apoptosis in human spermatozoa [14]. The inflammation can disrupt the physiological functions of the prostate, and change the properties of the secret produced by its epithelial cells that make up about 30% of the ejaculate volume [17]. According to Robertson et al. [18], the key contribution of prostatic fluid to the maintenance of male fertility is related to its role as a trigger of molecular pathways involved in ejaculation, sperm activation and capacitation, as well as in the stimulation of gene expression, cellular changes and tissue remodeling in the female reproductive tract and the immune system.
The effect of inflammation on the ejaculate characteristics in the age aspect has not been sufficiently studied, although it appears to be important in connection with the trend towards late fatherhood: over the past few decades the age of fathers increased in many countries [19]. For example, in Russia, according to RosStat, the proportion of fathers aged 35 to 45 increased from 25% in 1999 to 40% in 2009 [20].
The aim is to study the effect of inflammation of the prostate gland on the ejaculate characteristics of men of different ages from infertile couples.

Materials and Methods
The work performed was based on the informed consent of the subjects and in

Methods of Statistical Data Processing
The Shapiro-Wilk test was used to assess the type of parameters distribution.

Results
For all examined infertile men the average percentage of viable spermatozoa was 60%, and the average percentage of spermatozoa with normal Kruger morphology was 2%.
At the first stage of the study all men (n = 266) were divided into 2 groups: under 35 years old (n = 133) and older than 35 years old (n = 133). Further, each group was divided into subgroups, considering the number of leukocytes in the ejaculate: with laboratory signs of the inflammatory process of the gonads in the form of leukospermia (>1 million/ml) and without these signs (leukocytes < 1 million/ml).
In Characteristics of the spermogram for all four subgroups are presented in Table 1. The volume of ejaculate did not differ between subgroups with/without leukospermia in the group of younger men, and in the group of older men the presence of leukospermia was associated with a decrease in ejaculate volume. The decrease in ejaculate volume was most noticeable in the subgroup of older men with leukospermia relative to the same subgroup of younger men.
Total sperm count also did not differ significantly between the subgroups with/without leukospermia in the younger group, although in the leukospermia subgroup this value tended to decrease; in the subgroup of older men the presence of leukospermia was associated with an almost threefold decrease in the total number of spermatozoa relative to the subgroup without leukospermia of the corresponding age. As a result, the sperm concentration was reduced in the subgroups with leukospermia relative to the corresponding subgroups without leukospermia in men of both groups.
For total sperm motility, as in the case of concentration, the value tended to decrease in subgroups with leukospermia relative to subgroups without leukospermia in the corresponding age groups. A similar situation was noticed in relation to the values of progressively motile spermatozoa, and in the subgroup with leukospermia of the older age group, this decrease was 60% and was found statistically significant. Note. L-number of leukocytes in seminal fluid, mln/ml.
The values of such characteristics as viability (%) and Kruger morphology did not differ between subgroups with/without leukospermia in men of different age groups.  Table 2). The growth of opportunistic pathogens in the titer >/= 10 4 KOE was significantly higher in both subgroups of men with leukospermia.
Opportunistic pathogenic microflora was presented by Enterococcus faecalis-28% in the group of men under 35 y.o. and 31% in the group over 35 y.o., there were no significant differences between the subgroups. The growth of  Table 3.
According to the results of the survey on the NIH-CPSI scale, clinical symptoms of chronic prostatitis were found only in men older than 35 years with leukospermia. The average total score in this group was 10.5 [0; 16].

Discussion
In the course of the study the aims of the research were achieved, namely, additional data were obtained on the effect of prostate inflammation on the ejaculate characteristics of men of different age groups in infertile couples. In this study, the inflammatory process was not accompanied by clinical complaints specific for chronic prostatitis and its exacerbation in young men. Similar results were described in Frungieri M. B. et al. [24], where the authors showed that chronic inflammation was not always accompanied by clinical symptoms.
The inflammatory process had a negative effect on fertility in all subjects, but in the older age group, its clinical and laboratory manifestations were most pronounced. These manifestations may be indicators of aging, which, according to some researchers, is usually characterized by a chronic pro-inflammatory state and is considered a predictor of the pathogenesis and development of age-related diseases. The term "inflammation" is currently used to describe the increased inflammatory response that occurs with age. Aging and inflammation are two closely related processes. Many theories have been developed to establish whether inflammation is a cause of aging, or its consequence. However, no theory explains all aspects of aging, leading to the assumption that all multiple processes (i.e., oxidative stress, mitochondrial damage, immune aging, endocrine aging, epigenetic modifications, and age-related diseases) contribute and that they are all interrelated with inflammatory processes [24].
Our results are also consistent with those of Yamamichi F. et al. (2017): in older patients, inflammation of the reproductive organs, pyuria and fever is observed more often than in younger patients [25].
Leukospermia reduces the number of progressively motile spermatozoa in men in the group over 35 years old, but we did not notice its significant effect on the viability and morphology of spermatozoa. In young men, the severity of the inflammatory process is clinically significantly lower than in men of the older group, and the negative consequences on ejaculate parameters in the older age group are more severe and statistically significant in terms of ejaculate volume, the total number of spermatozoa, their progressive motility, as well as the DNA fragmentation index in spermatozoa. The growth of opportunistic microflora was found in a third of infertile men without leukospermia and significantly increased in its presence, regardless of age.

Conclusion
The results of the study demonstrate the negative impact of the inflammatory process on the fertility of men of all ages, however, in the older age group its manifestations are significantly more severe.