Determination of sperm acrosin activity for evaluation of male fertility

Aim: To investigate a simple method for assaying acrosin activity for the evaluation of male fertility. Methods:The acrosin activity of 7.5 × 10~6 sperm without seminal plasma and acrosin activity inhibitors was assayed using N-α-benzoyl-DL-arginine-p-nitroanilide (BAPNA) and detergent (Triton X-100) as substrate. Results: The acrosin ac-tivity of 60 normal fertile men (35 ± 10 μIU/10~6 sperm ) was higher than that of 168 infertile men ( 16 ± 8 μIU/10~6sperm) (P <0.01). It was indicated that there was a significant positive correlation between the acrosin activity andthe sperm motility ( r ≥ 0.6534, P < 0.01) and a significant negative correlation between the sperm malformed rateand the WBC number ( r ≤ -0.5426, P < 0.01). The temperature and time of incubation and the sperm concentrationcould influence the assay results. Conclusion: Acrosin activity is an important index for the evaluation of male fer-tility. The approach developed by the authors is a simple method for the determination of acrosin activity.

Diagnostic tools in male infertility--the question of sperm dysfunction

Sperm dysfunction is the single most common cause of infertility, yet what is remarkable is that, there is no drug a man can take or add to his spermatozoa in vitroto improve fertility. One reason for the lack of progress in this area is that our understanding of the cellular and molecular workings of the mature spermatazoon is limited. However, over the last few years there has been considerable progress in our knowledge base and in addressing new methods to diagnose sperm dysfunction. We review the current state of the field and provide insights for further development. We conclude that： （i） there is little to be gained from more studies identifying/categorizing various populations of men using a basic semen assessment, where an effort is required in making sure the analysis is performed in an appropriate high quality way; （ii） technological development is likely to bring the reality of sperm function testing closer to implementation into the clinical pathways. In doing this, these assays must be robust, cheap （or more appropriately termed cost effective）, easy to use and clinically useful; and （iii） clinical necessity, e.g., the need to identify the highest quality spermatozoon for injection is driving basic research forward. This is an exciting time to be an andrologist and, likely, a fruitful one.

Leukocytes and oxidative stress： dilemma for sperm Function and male fertility

Spermatozoa are constantly exposed to the interphase between oxidation through high amounts of reactive oxygen species （ROS） and leukocytes, and reduction by means of scavengers and antioxidants. Considering the very special functions as being the only cells with such high polarization and exerting their functions outside the body, even in a different individual, the female genital tract, the membranes of these cells are chemically composed of an extraordinary high amount of polyunsaturated fatty acids. This in turn, renders them very susceptible to oxidative stress, which is defined as an imbalance between oxidation and reduction towards the oxidative status. As a result, ROS deriving from both leukocytes and the male germ cells themselves cause a process called ＇lipid peroxidation＇ and other damages to the sperm cell. On the other hand, a certain limited amount of ROS iS essential in order to trigger vital physiological reactions in cells, including capacitation or the acrosome reaction in sperm. The treatment of patients with antioxidants to compensate the oxidative status caused by oxidative stress is highly debated as uncontrolled antioxidative treatment might derail the system towards the reduced status, which is also unphysiological and can even induce cancer. This paradox is called the ＇antioxidant paradox＇. Therefore, a proper andrological diagnostic work-up, including the evaluation of ROS levels and the antioxidant capacity of the semen, has to he carried out beforehand, aimed at keeping the fine balance between oxidation and scavenging of vital amounts of ROS.

The comparative effects of aqueous extract of Tetracarpidium conophorum seeds and Proviron on the sperm parameters of male guinea pigs

Objective:To investigation the comparative effects of the aqueous extracts of the seeds of Tetracarpidium conophorum (T.conophorum) and Proviron on the sperm parameters of male guinea pigs,and screen phytochemical constituents of the seeds of T.conophorum.Methods:The sperm count,motility and morphology of the male guinea pigs were done using Neubauer chamber(Haemocytometer),light microscope and dilute carbol Fuchsin(1:20) method,respectively.Phytochemical screening was done by standard procedures.Results: The aqueous extract of the T.conophorum seeds(100 -400 mg/kg) caused statistically significant increase (P 【 0.05,ANOVA) in the sperm count and motility,from 67.7±2.10 and 56.5±2.40 to 78.0±3.5 and 75.0±2.8,respectively.The highest effect was obtained at 300 mg/kg of T.conophoru.At this dose, the sperm count and motility of the male guinea pigs administered with T.conophorum were the same with the group administered 12.5 mg/kg Proviron.The values were 78.0±3.50 and 75.0±2.80,respectively for sperm count and motility(P 【0.001,ANOVA).At 400 mg/kg,T.conophorum caused a slight decline in sperm count and motility.These effects were dose-dependent and comparable to the observed effects of Proviron (12.5 mg/kg) on sperm parameters of male guinea pigs.In time-dependent study,the observed effect of T. conophorum(300 mg/kg) and Proviron on the values of sperm count and motility at 14th day were almost the same.These values are 58.0±1.80 and 70.0±2.60,respectively for sperm motility and count.However, on the 7th day of treatment,T.conophorum exhibited highest effect which was higher than that of Proviron. These effects decreased progressively from the 14th to the 28th day.But Proviron showed the highest effect on the 28th day.These effects were all time-dependent and statistically significant at P 【 0.05(ANOVA).Finally, the phytochemical screening of the seeds of T.conophorum revealed the presence of flavonoids,tannins, alkaloids,terpenoids,carbohydrates,volatile oils,steroids,saponins and cardiac glycosides.Conclusion: This study shows that the seeds of T.conophorum possess some active principles that can contribute positively on male fertility.This therefore,supports the claims on the use of the seeds of this plant by traditional medicine practitioners to increase/improve libido in men.However,further studies need to be done to investigate the mechanism of this action and also to isolate and characterize the active principles responsible for this effect in the extracts of this plant.

New insights in sperm biology:How benchside results in the search for molecular markers may help understand male infertility

The male factor is responsible for about 40% of couple infertility cases and such percentage is expected to increase in the future because of several likely factors including the presence of endocrine disruptors in the environment,changes in lifestyle habits and advanced couple aging.How such factors affect male fertility status,however,should be clarified.Most studies on male fertility status have focused on parameters analyzed using a spermiogram test,the primary diagnostic tool in the routine assessment of male infertility,which is,however,poorly predictive of both natural and medically assisted conception.For these reasons it is mandatory for the scientific community to identify new molecular markers to incorporate into the existing diagnostic tests of male fertility.Ideally,such markers would be detected in mature spermatozoa to avoid invasive procedures for the patient.This review summarizes the recent advancements in benchside approaches that appear most promising for the development of new diagnostic sperm fertility tests,or identification of therapeutic targets,and,illustrates their advantages and limits.

Low Sperm Counts: Biophysical Profiles of Oligospermic Males in Sub-Saharan Africa

Introduction: Male infertility is a public health burden and a psychological dilemma in the life of the affected man. Subjects and Methods: A total of 911 men were studied retrospectively, from 2010 to 2015. Among these, 49.7% had normal sperm count, 39.3% were oligospermic and 12.0% were azoosper-mic. Azoospermic men were withdrawn from this study solely to investigate the seminal fluid parameters and the biophysical characteristics of oligospermic men in contrast to those with normal sperm count. Age was stratified into <30, 30 - 39.9, 40 - 49.9, 50 - 59.9 and ≥60 years;body mass index was categorized into underweight (<18.5), normal (18.5 - 24.9), overweight (25.0 - 29.9) and obese (≥30) and standard semen analysis was performed. Results: The means (±sd) of age and of BMI of the 802 subjects of the study were 42.7 (±7.0) years and 26.9 (3.9) kg/m2 respectively. There was no significant difference in the age or BMI of normal and oligospermic men. A total of 453 (56.5%) had normal sperm count while 349 (43.5%) were oligospermic. Compared to normal weight men, those overweight and those obese were, respectively, 1.11 (χ2 = 0.44, P-value = 0.51, OR = 1.11, 95% CI = 0.81, 1.54) and 1.56 times (χ2 = 4.50, P-value = 0.03, OR = 1.56, 95% CI = 1.03, 2.36) more likely to be oligo-spermic. The mean of normal oval head sperms was significantly higher (t = -7.31, P-value = 0.00001) in normal men (47.8 ± 8.9) than in oligospermic men (43.0 ± 10.7). Oligospermic men were over 4 times as likely to produce progressive sperm motility of <32% (χ2 = 70.90, P-value = 0.000001, OR = 4.24, 95% CI = 2.99, 6.02) than men with normal sperm count. Multivariate regression analysis shows negative but significant correlations between age and semen volume (coef. = - 0.04, Std Err. = 0.01, t = - 4.01, P-value = 0.0001, 95% CI: - 0.06, - 0.02) and between BMI and sperm count (coef. = - 0.18, Std Err. = 0.06, t = - 3.26, P-value = 0.001, 95% CI: - 0.29, - 0.07). Conclusion: Our findings suggest that overweight and obesity are associated with oligospermia and oligospermia is significantly linked with low progressive motility, and various sperm cell defects.

A Study on Infertility of Males Infected with <i>Mycoplasma hominis</i>with Reference to Sperm Morphology

Objectives: The main objective of this study was to investigate the effect of Mycoplasma hominis infection on the morphology of sperms and its association with the infertility of men. The patients were referred to the Urology Departments of Mosul General Hospital and Soran Hospital in Mosul and Erbil respectively. Methods: The present study was carried out from April 2019 to March 2020 and the number of the patients group was 108. The patients aged 20 to 60 years. Semen was collected from infertile men of a couple that female failed to become pregnant after one year of regular and unprotected intercourse of marriage and submitted for seminal fluid analysis as well as for bacteriological investigations Results: M. hominis was detected in 14 semen specimens (12.9%) from the infertile men. The teratozoospermia, normozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia and leukospermia were seen among patients examined. Statistically, there were no significant differences between these forms of infected infertile men and non-infected infertile men (P > 0.05). Conclusions: The results of present study demonstrated that the genital Mycoplasma hominis seems to be widespread among male partners of infertile couples in Iraq. The present data did not show any significant differences between forms of the sperm concentration and sperm morphology related to the infection by M. hominis.

Intracytoplasmic sperm injection in the treatment of male infertility due to obstructive or non-obstructive azoospermia

Objective: To evaluate the effects of intracytoplasmic sperm injection (ICSI) ontreatment of infertility due to obstructive and non-obstructive azoospermia..Methods: A retrospective analysis of fertilization, cleavage, embryo implantationand pregnancy rates was done in 158 ICSI cycles including 112 obstructive azoospermiaand 46 non-obstructive azoospermia. Ovarian hyperstimulation and ICSI procedureswere performed by conventional protocol. The sperm was collected by percutaneous epi-didymal sperm aspiration (PESA) or testicular sperm extraction (TESE).Results:The fertilization rate (73.1% vs. 67.0%), cleavage rate (88.6% vs. 86.3%), embryo implantation rate (20.7% vs. 11.4%), clinical pregnancy rate per trans-fer cycle (35.7% vs. 19.6%) were obtained for obstructive and non-obstructiveazoospermia, respectively.Conclusion: The results revealed that in the cases of obstructive azoospermia, ferti-lization rate, embryo implantation rate and clinical pregnancy rate were significantlyhigher than those of non-obstructive azoospermia. But there was no significant differ-ence of the cleavage rate between two groups.

Evaluation of the Concentration of Anti-Spermatozoa Antibodies in Seminal Plasma of Normozoosperms and Azoosperms of Patients at the Pasteur Institute of Cote d’Ivoire

Under normal circumstances, spermatozoa are protected from the immune system by the blood-testis barrier. The breakdown of this barrier is the origin of the synthesis of antisperm antibodies (ASA). The presence of sperm agglutinates in semen is characteristic of ASA. But is the presence of agglutinates in semen necessarily linked to the level of ASA in semen? The objective of this study was to assess the concentration of anti-sperm antibodies (ASA) in normozoosperms and infertile men with azoospermia. The biological material consisted of samples of human sperms: 30 samples with azoospermia and 32 with normozoospermia. The ASA assay was performed in seminal plasma using the DRG® Sperm Antibody ELISA (seminal plasma) kit (EIA-4249). The reading was carried out using a microplate reader at 450 nm. Data analysis was performed using Graph Pad Prism 7 software. The results obtained showed that the difference in ASA concentration between these two categories of sperm was not significant, with an average ASA level of 31.54 ± 2.45 U/mL in azoospermic ejaculate and 27.63 ± 1.51 U/mL in normozoosperms. Statistical analysis showed higher ASA concentrations in azoosperms with 6.67% of these declared positive. The ASA positivity rate made it possible to distinguish secretory azoospermias from obstructive ones. Also, the presence of ASA is not necessarily linked to the presence of agglutinates in the semen.

Male factor infertility and ART

For years, the management and treatment of male factor infertility has been ‘experience＇ and not ‘evidence＇ based. Although not evidence-based, current clinical practice involves extensive use of assisted reproductive techniques （ART）. Where specific treatments are not indicated or have failed, ART have become popular adjunctive treatments for alleviating male factor infertility. According to the limited evidence available, intrauterine insemination （IUI） may be considered as a first-line treatment in a couple in which the female partner has a normal fertility status and at least 1 × 10^6 progressively motile spermatozoa are recovered after sperm preparation. If no pregnancy is achieved after 3-6 cycles of IUI, optimized in vitro fertilization （IVF） can be proposed. When less than 0.5× 106 progressively motile spermatozoa are obtained after seminal fluid processing or sperm are recovered surgically from the testis or epididymis, intracytoplasmic sperm injection （ICSI） should be performed. Although the outcome of no other ART has ever been scrutinized as much before, no large-scale ‘macroproblems＇ have as yet been observed after ICSI. Yet, ICSI candidates should be rigorously screened before embarking on IVF or ICSI, and thoroughly informed of the limitations of our knowledge on the hereditary aspects of male infertility and the safety aspects of ART.

Sperm DNA damage and its clinical relevance in assessingreproductive outcome

The routine examination of semen, which assesses sperm concentration, percentage motility and morphology, does not identify subtle defects in sperm chromatin architecture. The focus on the genomic integrity of the male gamete has intensified recently due to the growing concern that genetic diseases may be transmitted via assisted reproductive techniques (ART). Accordingly, the intent of this review is to describe the details of the information pertaining to mitochondrial/nuclear sperm DNA damage with an emphasis on its clinical significance and its relation ship with male infertility. Assessment of sperm DNA damage appears to be a potential tool for evaluating semen samples prior to their use in ART. Testing DNA integrity may help select spermatozoa with intact DNA or with the least amount of DNA damage for use in assisted conception. In turn, this may alleviate the financial, social and emotional problems associated with failed ART attempts.

Preparation and incubation conditions affect the DNA integrity of ejaculated human spermatozoa

Appropriate semen processing and assessment are critical for successful infertility treatment. We investigated whether laboratory procedures including semen preparation and incubation affect sperm DNA integrity. A total of 153 infertile men were involved. Conventional semen parameters and sperm chromatin structure assay （SCSA） parameters, that is, DNA fragmentation index （%DFI） and high DNA stainability （%HDS）, were assessed on the flesh ejaculated semen samples, which were treated and incubated under different conditions. Negative correlations were identified between the %DFI and sperm concentration, motility, progressive motility and morphology. A lower percentage of DFI was detected in spermatozoa when density gradient centrifugation （DGC） was followed by swimup treatment in comparison with DGC alone （P 〈 0.01）. Although the %DFI increased in a time-dependent manner with incubation both at room temperature （RT） and at 37℃ in air, the %DFI after 24 h at RT was significantly lower than that at 37℃ （P 〈 0.05）. Incubation with 5% CO2 was effective in maintaining sperm motility （P 〈 0.01）; however, it induced further elevation of %DFI （P 〈 0.001）. Thus, sperm DNA damage was associated with longer incubation periods. Interestingly, common culture conditions, such as maintaining pH and temperature, compromised the sperm DNA integrity.

Obesity leads to higher risk of sperm DNA damage in infertile patients

There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be altered in case of high body mass index （BMI）. A few studies assessing the impact of BMI on sperm DNA integrity have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI, through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling （TUNEL） assay, we observed an increased rate of sDerm DNA damage in obese men （odds ratio （95% confidence interval）： 2.5 （1.2-5.1））.

The impact of male overweight on semen quality and outcome of assisted reproduction

It is well-documented that male overweight and obesity causes endocrine disorders that might diminish the male reproductive capacity; however, reports have been conflicting regarding the influence of male body mass index （BMI） on semen quality and the outcome of assisted reproductive technology （ART）. The aim of this study was to investigate whether increased male BMI affects sperm quality and the outcome of assisted reproduction in couples with an overweight or obese man and a non-obese partner. Data was prospectively collected from 612 infertile couples undergoing ART at a Danish fertility center. Self-reported information on paternal height and weight were recorded and BMI was calculated. The men were divided into four BMI categories： underweight BMI 〈 20 kgm^-2, normal BMI 20-24.9 kg m^-2, overweight BMI 25-29.9 kgm^-2 and obese BMI 〉 30 kgm^-2. Conventional semen analysis was performed according to the World Health Organization guideline and sperm DNA integrity was analyzed by the Sperm Chromatin Structure Assay （SCSA）. No statistically significant effect of male BMI was seen on conventional semen parameters （sperm concentration, total sperm count, seminal volume and motility） or on SCSA-results. Furthermore, the outcome of ART regarding fertilization rate, number of good quality embryos （GQE）, implantation and pregnancy outcome was not influenced by the increasing male BMIo

Medical therapy for spermatogenic failure

Medical treatment of men with primary spermatogenic failure remains largely ineffective in contrast to those with secondary testicular failure. Treatment has been attempted with a multitude of agents ranging from hormones to nutritional supplements （antioxidants）. While some studies have demonstrated benefit to some treatments, no treatments have consistently demonstrated efficacy nor has it been possible to reliably identify patients likely to benefit. Idiopathic spermatogenic failure likely results from multiple discrete defects in sperm production that are as yet unidentified. A better understanding of these defects will yield more effective treatment options and appropriate triage of patients to specific therapeutic regimens. This review focuses on the rationale and current evidence for hormonal and antioxidant therapy in medical treatment of male infertility, spermatogenic failure in particular. Although empiric medical therapy for spermatogenic failure has been largely replaced by assisted reproductive techniques, both treatment modalities could play a role, oerhaos as combination therapy.

No relationship between biopsy sites near the main testicular vessels or rete testis and successful sperm retrieval using conventional or microdissection biopsies in 220 non-obstructive azoospermic men

In 220 consecutive patients with non-obstructive azoospermia, sperm retrieval was attempted by a combination of conventional and microdissection testicular sperm extraction （TESE）. For sperm retrieval, 2-3 conventional biopsies were performed followed by a microdissection TESE in cases of negative conventional biopsies. During the surgery, the vasculature of the testis was assessed using the operative microscope, and the location of positive biopsies was registered in relation to the blood supply. The overall sperm retrieval rate was 58.2%. From the initial conventional biopsies, sperm could be retrieved in 46.8% of the patients. With microdissection TESE, sperm could be retrieved from an additional 11.4% of the patients. The further use of microdissection TESE improved the sperm retrieval rate significantly （P=0.017）. No significant accumulation of positive biopsies was found towards the rete testis or the main testicular vessels.

Dimensions of human ejaculated spermatozoa in Papanicolaou- stained seminal and swim-up smears obtained from the Integrated Semen Analysis System （ISAS）

Objective measurements are required for computer-aided sperm morphometric analysis （CASMA） machines to distinguish normal from abnormal sperm heads. The morphometric characteristics of spermatozoa in 72 samples of semen and of spermatozoa from 72 other semen samples after swim-up were quantified by the semi-automated Integrated Sperm Analysis System （ISAS） computer-aided system, which measured the sperm head parameters length （L）, width （W）, area （A）, perimeter （P）, acrosomal area （Ac）, and the derived values L/W and P/A. For each man a homogeneous population of distributions characterized seminal spermatozoa （7 942 cells： median values L 4.4 μm, W 2.8μm A 9.8 μm^2, P 12.5 μm, Ac 47.5%, L/W 1.57, P/A 1.27）, and there was no significant difference in within- and among-individual variation. Different men could have spermatozoa of significantly different dimensions. Head dimensions for swim-up spermatozoa from different men （4 812 cells） were similar to those in semen, differing only by 2%-5%. The values of L, Wand L/W fell within the limits given by the World Health Organization （WHO）. Although these samples were not biologically matched, linear mixed-effects statistical analyses permitted valid comparison of the groups. A subpopulation of 404 spermatozoa considered to fit the stringent criteria of WHO ‘normal＇ seminal spermatozoa from both semen and swim-up were characterized by median values （and 95% confidence intervals） of L, 4.3 μm （3.8-4.9）, W, 2.9 μm （2.6-3.3）, A, 10.2μm^2 （8.5-12.2）, P, 12.4μm （11.3-13.9）, Ac, 49% （36-60）, L/W, 1.49 （1.32-1.67） and P/A, 1.22 （1.11-1.35）. These median values fall within the 95th centile confidence limits given by WHO, but the confidence intervals for L and W were larger. Although these differences in head dimensions among men and after swim-up could be detected by CASMA, the small differences make it unlikely that technicians would be able to distinguish them. The values could be used as default sperm head values for the CASMA machine used here.

Can DNA fragmentation of neat or swim-up spermatozoa be used to predict pregnancy following ICSI of fertile oocyte donors？

This study compared the potential of assessing sperm DNA fragmentation （SDF） from neat semen and the subsequent swim-up （SU） procedure to predict pregnancy when conducting ICSI of fertile donor oocytes. Infertile females （n=81） were transferred embryos resulting from intracytoplasmic sperm injection （ICSI） of their partner＇s spermatozoa and proven donor oocytes. This model normalized the impact of female factor in putative sperm DNA repair. Semen was blindly assessed for SDF using Halosperm immediately following ejaculation （NS） and after swim-up at the time of ICSI fertilisation. There was a decrease in SDF values of the ejaculated semen sample following the swim-up protocol （P=0.000）. Interestingly, pregnancy could be equally predicted from SDF values derived from either neat or swim-up semen samples. Receiver operator curves and the derived Youden＇s indices determined SDF cutoff values for NS and SU of 24.8% and 17.5%, respectively. Prediction of pregnancy from NS SDF had a sensitivity of 75% and a specificity of 69%, whereas for SU SDF was 78% and 73%, respectively. While increased levels of SDF negatively impact reproductive outcome, we have shown that a reduction in SDF following sperm selection using ICSI with proven donor oocytes is not mandatory for achieving pregnancy. This suggests that a certain level of DNA damage that is not detectable using current technologies could be impacting on the relative success of assisted reproductive technology （ART） procedures. Consequently, we propose a modification of the so called ＇iceberg model＇ as a possible rationale for understanding the role of SDF in reproductive outcome.

The effectiveness and safety of acupuncture for poor semen quality in infertile males： a systematic review and meta-analysis

The aim of this review is to evaluate the effectiveness and safety of acupuncture for poor semen quality in infertile men. We searched for relevant trials registered up to May 2013 in 14 databases. We selected randomized controlled trials （RCTs） that compared acupuncture, with or without additional treatment, against placebo, sham, no treatment, or the same additional treatment. Two reviewers independently performed the study selection, data extraction, risk of bias and reporting quality appraisal. Risk of bias and reporting quality were appraised by the Cochrane risk of bias tool, the consolidated standards of reporting trials and Standards for Reporting Interventions in Clinical Trials of Acupuncture. The outcomes were sperm motility, sperm concentration, pregnancy rate, and adverse events. Pregnancy was defined as a positive pregnancy test. Four RCTs met the eligibility criteria. Acupuncture increased the percentage of sperm with rapid progression （mean difference - 6.35, 95% confidence interval （CI）. 4.38-8.32, P〈 0.00001） and sperm concentration （mean difference - 6.42, 95% CI. 4.91-7.92, P〈 0.00001）, but these two outcomes were substantially heterogeneous among the studies （F = 72% and 58%, respectively）. No differences in pregnancy rate were found between acupuncture and control groups （odds ratio 1.60, 95% CI. 0.70-3.69, P= 0.27, F = 0%）. No participants experienced adverse events. The current evidence showing that acupuncture might improve poor semen quality is insufficient because of the small number of studies, inadequacy of procedures and/or insufficient information for semen analysis, high levels of heterogeneity, high risk of bias, and poor quality of reporting. Further large, well-designed RCTs are required.

Antioxidant therapy in male infertility： fact or fiction？

Infertile men have higher levels of semen reactive oxygen species （ROS） than do fertile men. High levels of semen ROS can cause sperm dysfunction, sperm DNA damage and reduced male reproductive potential. This observation has led clinicians to treat infertile men with antioxidant supplements. The purpose of this article is to discuss the rationale for antioxidant therapy in infertile men and to evaluate the data on the efficacy of dietary and in vitro antioxidant preparations on sperm function and DNA damage. To date, most clinical studies suggest that dietary antioxidant supplements are beneficial in terms of improving sperm function and DNA integrity. However, the exact mechanism of action of dietary antioxidants and the optimal dietary supplement have not been established. Moreover, most of the clinical studies are small and few have evaluated pregnancy rates. A beneficial effect of in vitro antioxidant supplements in protecting spermatozoa from exogenous oxidants has been demonstrated in most studies; however, the effect of these antioxidants in protecting sperm from endogenous ROS, gentle sperm processing and cryopreservation has not been established conclusively.