Proteomics,oxidative stress and male infertility

Oxidative stress has been established as one of the main causes of male infertility and has been implicated in many diseases associated with infertile men. It results from high concentrations of free radicals and suppressed antioxidant potential, which may alter protein expression in seminal plasma and/or spermatozoa. In recent years, proteomic analyses have been performed to characterize the protein profiles of seminal ejaculate from men with different clinical conditions, such as high oxidative stress. The aim of the present review is to summarize current findings on proteomic studies performed in men with high oxidative stress compared with those with physiological concentrations of free radicals, to better understand the aetiology of oxidative stress-induced male infertility. Each of these studies has suggested candidate biomarkers of oxidative stress, among them are DJ-1, PIP, lactotransferrin and peroxiredoxin. Changes in protein concentrations in seminal plasma samples with oxidative stress conditions were related to stress responses and to regulatory pathways, while alterations in sperm proteins were mostly associated to metabolic responses (carbohydrate metabolism) and stress responses. Future studies should include assessment of post-translational modifications in the spermatozoa as well as in seminal plasma proteomes of men diagnosed with idiopathic infertility.Oxidative stress, which occurs due to a state of imbalance between free radicals and antioxidants, has been implicated in most cases of male infertility. Cells that are in a state of oxidative stress are more likely to have altered protein expression. The aim of this review is to better understand the causes of oxidative stress-induced male infertility. To achieve this, we assessed proteomic studies performed on the seminal plasma and spermatozoa of men with high levels of oxidative stress due to various clinical conditions and compared them with men who had physiological concentrations of free radicals. A variety of sperm and seminal plasma proteins were found to be expressed either in abundance (over-expressed) or in a lesser amount (underexpressed), while other proteins were found to be unique either to men with oxidative stress or to men with a balanced ratio of antioxidants/free radicals. Each study included in this review suggested several proteins that could possibly act as biomarkers of oxidative stress-induced male infertility, such as protein DJ-1, PIP, lactotransferrin and peroxiredoxin. Pathway analysis performed in these studies revealed that the changes in seminal plasma proteins in men with oxidative stress could be attributed to stress responses and regulatory pathways, while changes in sperm proteins were linked to stress responses and metabolic responses. Subsequent studies could look into post-translational modifications in the protein profile of men with idiopathic infertility. We hope that the information in this review will contribute to a better understanding of the main causes of idiopathic male infertility.     

The role of free radicals and antioxidants in reproduction

PURPOSE OF REVIEW: This review summarizes the role of free radicals and oxidative stress in the pathophysiology of human reproduction. RECENT FINDINGS: An extensive review of the literature on the role of oxidative stress in influencing assisted reproduction and its outcome is described in this article. Free radicals or reactive oxygen species mediate their action through many of the proinflammatory cytokines and this mechanism has been proposed as a common underlying factor for endometriosis, ovarian cancer, polycystic ovary disease, and various other pathologies affecting the female reproductive process, as highlighted in this review. Oxidative stress, sperm DNA damage, and apoptosis have been implicated in male infertility. Elevated reactive oxygen species levels correlate with the poor fertility outcomes seen in the assisted reproductive technology setting. SUMMARY: Oxidative stress has been implicated in male and female infertility, including fetal dysmorphogenesis, abortions, and intrauterine growth restriction. Accurate evaluation of seminal oxidative stress by standardized assays may help in the diagnosis and management of male infertility. There is evidence in the literature on the beneficial effects of oral antioxidant supplementation in male infertility. Current ongoing trials will provide answers on the safety and effectiveness of antioxidants in improving maternal and fetal outcomes. Further studies need to be conducted to determine if antioxidant supplementation will prevent fetal developmental defects in high-risk pregnancy with diabetes.     

Role of free radicals in female reproductive diseases and assisted reproduction

Infertility is a common problem experienced by many couples. Numerous treatments are available for female infertility. However, in some cases, the treatment is empirical in nature because the aetiology of infertility is not fully understood. Recently, reactive oxygen species (ROS) have been shown to have an important role in the normal functioning of reproductive system and in the pathogenesis of infertility in females. Reactive oxygen species may also play a role in other reproductive organ diseases of women such as endometriosis. Oxidative stress develops when there is an imbalance between the generation of ROS and the scavenging capacity of antioxidants in the reproductive tract. It affects both natural and assisted fertility. Because assisted reproductive techniques are used extensively in the treatment of infertility, it is critical to understand the in-vitro conditions that affect fertilization and embryo development. Treatments that reduce oxidative stress may help infertile women with diseases that are caused by this imbalance. Such strategies include identifying the source of excessive generation of ROS, treating the primary cause, and in-vitro and in-vivo supplementation of antioxidants. Research is in progress to identify the mechanisms that are involved in the aetiology of female reproductive diseases caused by ROS, and to create effective strategies that can counteract oxidative stress.     

Free radical and superoxide reactivity detection in semen quality assessment: past,present, and future

Oxidative stress is a well-established cause of male infertility, with reactive oxygen species (ROS) impairing sperm production, motility, membrane, and DNA integrity. Currently, most clinics do not test infertile patients for the imbalance between ROS generation and the ability of the antioxidants to scavenge them, although there is a clear need for andrology laboratories to be able to identify and/or quantify seminal oxidative stress. As such there is a clinical urgency for an inexpensive and easy-to-perform assay able to identify oxidative stress in semen. The aim of this review is to provide information on the currently available methods to assess and quantify ROS and particularly superoxide in male reproductive cells, tissues, and fluids which may have a significant clinical utility in identifying men with impaired fertility associated with oxidative stress. Through a deeper understanding of oxidative stress and its assessment options, clinical andrology labs may better assist patients to achieve increased rates of fertility and pregnancy.     

The role of lipid oxidation and oxidative lipid derivatives in the development of preeclampsia

Preeclampsia develops as a consequence of an exceptionally complex interaction between a multiplicity of factors that originate in 2 genetically different individuals (the mother and the fetus). Oxidative stress/oxidative lipid derivatives may represent one group of such factors. The evidence for a role of oxidative stress/oxidative lipid derivatives in the pathogenesis of preeclampsia may be summarized as follows: In women with established preeclampsia there is good evidence of increased oxidative stress/oxidative lipid derivatives in the decidual-placental tissues. Likewise, in the systemic circulation of women with established preeclampsia most of the studies although not all, indicate elevated levels of oxidative lipid derivatives and reduced anti-oxidative capacity. Because almost all studies on the role of oxidative stress in the pathogenesis of preeclampsia have been among women with established preeclampsia, it remains uncertain whether enhanced oxidative stress is present before clinical signs of preeclampsia develops. One controlled randomized study in which antioxidants were used to treat severe preeclampsia showed nonsignificant differences in clinical outcomes in favor of antioxidants. Controlled studies on the effectiveness of antioxidants in preventing preeclampsia are lacking. Such studies are of major interest in order to evaluate more definitely the role of oxidative stress/oxidative lipid derivatives in the pathogenesis of preeclampsia.     

Oxidative stress and male infertility

BackgroundBetween 30% and 80% of patients with male infertility produce excessive reactive oxygen species (ROS) in their ejaculate even though the cause of male infertility is unexplained in approximately half of cases. The strong connection between oxidative stress (OS) and male infertility has led recent investigators to propose the term “Male Oxidative Stress Infertility (MOSI)” to describe OS‐associated male infertility.MethodsWe searched the PubMed database for original and review articles to survey the effects of OS on male infertility, and then verified the effects and treatments.Main findingsSeminal plasma contains many antioxidants that protect sperm from ROS, because low amounts of ROS are required in the physiological fertilization process. The production of excessive ROS causes OS which can lower fertility through lipid peroxidation, sperm DNA damage, and apoptosis. Several assays are available for evaluating OS, including the MiOXSYS® analyzer to measure oxidation‐reduction potential. Several measures should be considered for minimizing OS and improving clinical outcomes.ConclusionAccurately diagnosing patients with MOSI and identifying highly sensitive biomarkers through proteomics technology is vital for better clinical outcomes.     

The role of the oxidative-stress in the endometriosis-related infertility

Endometriosis is a common gynecological disorder of the reproductive age characterised by pelvic pain, dysmenorrhea and infertility. Classic theories have failed to propose a precise pathogenetic mechanism. Recent studies have investigated the role of the immune system and oxidative stress in the development of endometriosis as well as the identification of biomarkers for a non-invasive diagnosis of the disease. At endometriotic sites, inflammatory cells including eosinophils, neutrophils and macrophages generate reactive oxygen species that contribute to the development of oxidative stress in the peritoneal cavity. Oxidative stress further augments immune response in affected sites. The oxidants exacerbate the development of endometriosis by inducing chemoattractants and endometrial cell growth-promoting activity. The oxidative proinflammatory state of the peritoneal fluid is an important mediator of endometriosis. Many studies investigate the correlation of endometriosis and oxidative stress but the results are discrepant. Furthermore, oxidative stress has been implicated in unexplained infertility and has been associated with some of its causative factors. Oxidative stress influences womens reproductive capacity. The association between endometriosis and infertility is described in several studies and still remains debated.     

Relationship between oxidative stress, varicocele and infertility: a meta-analysis

Varicocele is one of the leading causes of male infertility, and is present in almost 40% of infertile males. Recent understanding of the role of oxidative stress in male reproduction has led some researchers to postulate oxidative stress as the possible cause of sperm dysfunction in varicocele patients. The objective of the present study was to examine the published literature on the role of oxidative stress in patients with varicocele as the aetiology of their infertility. Twenty-three human studies were identified after an extensive search dealing with the role of oxidative stress in varicocele-associated infertility. Out of these studies, four were selected that measured similar types of reactive oxygen species (ROS) by a similar method of measurement. The data were then entered in the RevMan software for analysis. The overall estimate showed that patients have significantly higher concentrations of ROS than controls, with the mean difference being 0.73 (95% CI 0.40, 1.06, P < 0.0001). This translated to an ROS concentration of 4.37 x 10(4) cpm/20 x 10(6) spermatozoa/ml on the linear scale. Total antioxidant capacity levels were found to be significantly lower in the infertile varicocele patients, with 386 fewer trolox equivalents than the controls (95% CI -556.56-216.96, P < 0.00001). From the results, it can be concluded that there is increased oxidative stress in varicocele patients; however, more studies are needed to confirm this finding.     

Oxidative stress and medical antioxidant treatment in male infertility

Oxidative stress (OS) has been recognized as one of the most important cause of male infertility. Despite the antioxidant activity of seminal plasma, epididymis and spermatozoa, OS damages sperm function and DNA integrity. Since antioxidants suppress the action of reactive oxygen species, these compounds have been used in the medical treatment of male infertility or have been added to the culture medium during sperm separation techniques. Nevertheless, the efficacy of such a treatment has been reported to be very limited. This may relate to: (i) patient selection bias; (ii) late diagnosis of male infertility; (iii) lack of double-blind, placebo-controlled clinical trial; and/or (iv) use of end-points that are not good markers of the presence of OS. This review considers the effects of the main antioxidant compounds used in clinical practice. Overall, the data published suggest that no single antioxidant is able to enhance fertilizing capability in infertile men, whereas a combination of them seems to provide a better approach. Taking into account the pros and the cons of antioxidant treatment of male infertility, the potential advantages that it offers cannot be ignored. Therefore, antioxidant therapy should remain in the forefront of preventive medicine, including human reproductive medicine.     

Differences in blood and semen oxidative status in fertile and infertile men,and their relationship with sperm quality

Oxidative stress plays a fundamental role in the aetiology of male infertility by negatively affecting sperm quality and function. Assessment of blood and seminal plasma oxidative profiles might be a valuable tool to improve evaluation of sperm reproductive capacity and functional competence. This study examined the lipid-soluble antioxidant profile and levels of lipid peroxidation both in blood and seminal plasma samples of infertile and fertile males, in relation to semen parameters. Total antioxidant capacity (TAC) and vitamin E concentrations were significantly (P < 0.05) lower in seminal plasma of infertile men compared with fertile subjects; concurrently, a significant accumulation of malondialdehyde was found in infertile patients (P = 0.032 compared with controls), which was negatively correlated with sperm motility and morphology. In blood samples, infertile men presented lower concentrations of TAC, carotenoids and vitamin E than fertile subjects; TAC and carotenoids were positively correlated with sperm motility, morphology and concentration. Finally, blood TAC and vitamin E concentrations were positively correlated with the corresponding seminal values, confirming the close relationship between blood and semen antioxidants. All these results indicated the possibility of using not only seminal antioxidants but also blood antioxidants as biochemical markers to support sperm quality evaluation.Oxidative stress induced by reactive oxygen species (ROS) has been widely recognized as one of the major causes of male infertility; indeed, excessive ROS production can negatively impact sperm quality and function. The assessment of blood and seminal plasma oxidative profiles has been suggested as a valuable tool to improve the evaluation of sperm reproductive capacity and functional competence in infertile men. With this in mind, in the present study we examined the lipid soluble antioxidant profile (carotenoids and vitamins A and E) and the levels of lipid peroxidation (malondialdehyde; MDA) both in blood and seminal plasma samples of infertile and fertile males, in correlation with semen parameters namely motility, morphology and concentration. As a result, we obtained evidence that the total antioxidant capacity (TAC) and the concentrations of vitamin E of seminal plasma samples were significantly lower in infertile men than in fertile subjects; at the same time, a significant accumulation of MDA was found in infertile patients. MDA, in turn, negatively correlated with sperm motility and morphology, thus confirming that oxidative damage to lipids impairs sperm quality. In blood samples, infertile men presented lower TAC and lower concentrations of carotenoids and vitamin E than fertile subjects; interestingly, TAC and carotenoid concentrations were positively correlated with sperm motility, morphology, and concentration, confirming the close relationship between blood antioxidants and sperm quality. In conclusion, all these results suggested that the examination of blood and semen oxidative profiles might furnish useful information on sperm quality and function in infertile men.     

Oxidative stress-mediated essential polyunsaturated fatty acid alterations in female infertility

Prostaglandins are exclusively synthesized in vivo from cell membrane essential fatty acids and together are known to regulate many aspects of reproductive processes. The objective of the study was to examine whether disturbances in fatty acid profile as a result of increased oxidative stress could be one of the causes of female infertility. Forty-five infertile and 30 control women were enrolled via the Department of Obstetrics and Gynecology of Bharati Medical College Hospital, Pune, India. Essential polyunsaturated fatty acids, malondialdehyde (MDA; oxidative stress-marker) levels and antioxidants (vitamins E and C) were measured in both groups. Results show that plasma eicosapentaenoic acid and erythrocyte docosahexaenoic acid levels were reduced (p < 0.05) in infertile women as compared to controls. Likewise, levels of MDA, a peroxidative product of essential fatty acids, were increased (p < 0.05) and vitamin E concentrations were decreased (p < 0.05) in infertile women, suggesting that increased oxidative stress and consequent altered essential polyunsaturated fatty acids are associated with infertility. Our study indicates, for the first time, the cause and effect relationship between oxidative stress and membrane essential polyunsaturated fatty acids in infertile women. These data have important implications for the supplementation of a combination of omega-3 fatty acids and antioxidants in the successful management of female infertility.     

Reactive oxygen species measurement in neat and washed semen: comparative analysis and its significance in male infertility assessment

Purpose  

Oxidative stress (OS) is a major concern in idiopathic male infertility as elevated levels of reactive oxygen species (ROS) in the semen is believed to adversely affect sperm functional competence and damage both nuclear and mitochondrial DNA. Therefore, identifying infertile men with seminal OS may be used as a valuable tool in the assessment of male infertility. Semen is a complex mixture of spermatozoa and seminal plasma which is rich in enzymatic and non-enzymatic antioxidants. However, the measurement of ROS in the semen and its application in male infertility assessment is poorly understood.     

The role of antioxidant therapy in the treatment of male infertility

Oxidative stress contributes to defective spermatogenesis leading to male factor infertility. The aim of this study was to review the current literature on the effects of various antioxidants to improve fertilisation and pregnancy rates. The sources of literature were Pubmed and the Cochrane data base. Reviewing the current literature revealed that Carnitines and vitamin C and E have been clearly shown to be effective by many well-conducted studies and may be considered as a first line treatment. The efficacy of antioxidants, such as glutathione, selenium and coenzyme Q10 has been demonstrated by few, but well-performed studies, and may be considered second line treatment. There is, however, a need for further investigation with randomised controlled studies to confirm the efficacy and safety of antioxidant supplementation in the medical treatment of idiopathic male infertility as well as the need to determine the ideal dose of each compound to improve semen parameters, fertilisation rates and pregnancy outcomes.     

DNA damage and health in pregnancy

In healthy pregnancy reactive oxygen species and antioxidants remain in balance and DNA damage is repaired effectively. However, pregnancy is an inflammatory state exhibiting increased susceptibility to oxidative stress such that this balance can be easily disrupted. Increased DNA damage has been shown to be involved in many pathological states including pregnancy complications. Modern lifestyles including exposure to pollutants, poor diet, and lack of exercise cause excess inflammation, oxidative stress, and ultimately DNA damage. There is a growing body of literature providing evidence that these lifestyle changes are increasing our risk of infertility, miscarriage, and late-gestation pregnancy complications. Moreover, baseline DNA damage rises with age and couples in developed societies are delaying childbirth, placing them at further risk. In order to understand the effect of lifestyle and DNA damage on pregnancy health we require large prospective studies, with the collection of samples prior to conception and endpoints of time-to-pregnancy, early pregnancy loss, and late-gestation maternal and fetal health.     

Rôles des dérivés actifs de l’oxygène (DAO) sur les spermatozoïdes humains et infertilité masculine

Pro- and antioxidant are balanced in the sperm environment. Reactive Oxygen Species (ROS) are essential to the acquisition of fertilizing ability and contribute to chromatin condensation, membrane remodeling and activation of intracellular signaling pathways, during epididymal maturation, capacitation, and acrosome reaction. However, endogenous and exogenous factors can upset that balance by stimulating ROS production and/or decreasing antioxidant defenses, a situation called oxidative stress. Oxidative stress is described as a major cause of male infertility. It induces membranes and nucleus alterations, resulting in loss of mobility and decline in sperm fertilizing ability. Those are risk factors for low fertility, abnormalities of preimplantation development, and miscarriages. Various methods exist for measuring the pro- and antioxidants status of sperm, yet are little used in routine for diagnostic purposes. Meanwhile, many studies have shown the beneficial effects of oral antioxidants supplementation, or addition to semen freezing medium, to prevent in vivo and limit in vitro the deleterious effects of ROS, respectively.     

Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation

OBJECTIVE: To determine whether particular semen characteristics in various clinical diagnoses of infertility are associated with high oxidative stress and whether any group of infertile men is more likely to have high seminal oxidative stress. Reactive oxygen species (ROS) play an important role in sperm physiological functions, but elevated levels of ROS or oxidative stress are related to male infertility. DESIGN: Measurement of sperm concentration, motility, morphology, seminal ROS, and total antioxidant capacity (TAC) in patients seeking infertility treatment and controls. SETTING: Male infertility clinic of a tertiary care center. PATIENT(s): One hundred sixty-seven infertile patients and 19 controls.Intervention(s): None. MAIN OUTCOME MEASURE(s): Semen characteristics, seminal ROS, and TAC in samples from patients with various clinical diagnoses and controls. RESULT(s): Fifteen patients (9.0%) were Endtz positive and 152 (91.0%) Endtz negative. Sperm concentration, motility, and morphology were significantly reduced in all groups compared with the controls (P =.02), except in varicocele associated with infection group. Mean (+/-SD) ROS levels in patient groups ranged from 2.2 +/- 0.13 to 3.2 +/- 0.35, significantly higher than controls (1.3 +/- 0.3; P<.005). Patient groups had a significantly lower mean (+/-SD) TAC from 1014.75 +/- 79.22 to 1173.05 +/- 58.07 than controls (1653 +/- 115.28, P<.001), except in the vasectomy reversal group (1532.02 +/- 74.24). Sperm concentration was negatively correlated with ROS both overall and within all groups (P相似文献   

Relationship between male reproductive hormones, sperm DNA damage and markers of oxidative stress in infertility

This study investigated the relationship between male reproductive hormones and sperm DNA damage and markers of oxidative stress in men undergoing infertility evaluation for male factor (n = 66) and non-male factor (n = 63) infertility. Semen samples were analysed for DNA fragmentation index (DFI). Serum samples were analysed for FSH, inhibin B, anti-Müllerian hormone (AMH), testosterone and total antioxidant capacity (TAC). Serum inhibin B was significantly lower in the male factor group compared with the non-male factor group. Inhibin B showed a positive correlation with sperm concentration and motility, and serum AMH showed a positive correlation with sperm concentration and semen volume. DFI was 3-fold higher in the male factor group and showed a negative correlation with sperm motility. Blood plasma TAC was negatively related to sperm concentration. The results confirm that AMH and inhibin B are markers of Sertoli cell function. Sperm DNA damage is moderately increased in male factor infertility, and is negatively associated with sperm motility. A negative association between antioxidant activity and sperm concentration suggests that even minimal oxidative stress may influence sperm concentration. However, there was no significant relationship between hormone concentrations, sperm DNA damage and total antioxidant capacity, suggesting other mechanisms for sperm dysfunction.     

Role of varicocele repair for male infertility in the era of assisted reproductive technologies

Varicocele is an abnormal condition characterized by dilatation of the pampiniform plexus veins draining the testis and is present in 15 % of men. Varicoceles have an adverse effect on spermatogenesis and are the most common cause of male infertility. Approximately 35 % of infertile men and more than 70 % of men with secondary infertility were reported to have varicoceles. Although data on methods of varicocele repair are accumulating, there remains controversy regarding the indications and techniques for varicocele repair. In addition, the role of varicocele repair in this era of assisted reproductive technologies continues to be debated. In this study, we performed a comprehensive PubMed search in order to review the current status of varicocele repair for male infertility. We reviewed English‐language studies published from 1992 through 2013. After reviewing the articles, we identified a recent meta‐analysis of four randomized controlled trials, which found that varicocele repair for oligozoospermic men was associated with better pregnancy rates as compared with observation. Our review of prospective studies showed that all semen parameters, including sperm concentration, motility, and progressive motility, were significantly improved after varicocele repair. We also summarize the findings of recent studies reporting beneficial effects of varicocele repair, i.e., decreased oxidative stress and sperm DNA fragmentation after varicocele repair and superior cost effectiveness versus in vitro fertilization/intracytoplasmic sperm injection alone, which may be important in the era of assisted reproductive technologies. Varicocele repair is a widespread, well‐established procedure that can improve semen parameters in men with infertility. The effect of such treatment on the pregnancy rate is unclear because evidence is limited due to difficulties in recruiting patients for studies. Among the repair techniques, microsurgical repair using a subinguinal approach is potentially the best practice, although this procedure requires training in microsurgery. All these topics require further research in studies with sufficient patient enrollment and follow‐up.     

No increase in sperm DNA damage and seminal oxidative stress in patients with idiopathic infertility

The most common cause of male infertility is idiopathic. Standard investigations reveal no abnormality in such cases. The aim of the study was to investigate the levels of sperm DNA damage and seminal oxidative stress and their relationships with idiopathic infertility. The study included 30 normozoospermic infertile men seeking infertility treatment and 20 fertile donors. Semen analysis was performed according to the World Health Organization guidelines. Sperm DNA damage was assessed by alkaline single cell gel electrophoresis (comet assay) after preparation with two-step discontinuous Percoll gradient. Seminal oxidative stress was measured by a novel automated method. DNA damage score, total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) were not different in idiopathic infertile men compared with controls. No correlations were also found between DNA damage score and TAS, TOS levels and OSI in idiopathic infertile group. We did not find any relationship between sperm DNA damage and oxidative stress in normozoospermic infertile men. We think that the pathophysiology of idiopathic infertility cannot be explained by sperm DNA damage or seminal oxidative stress.     

Role of reactive oxygen species in the pathophysiology of human reproduction

OBJECTIVE: To summarize the role of reactive oxygen species (ROS) in the pathophysiology of human reproduction. DESIGN: Review of literature. SETTING: Fertility research center and obstetrics and gynecology department in a tertiary care facility. RESULT(S): ROS plays an essential role in the pathogenesis of many reproductive processes. In male-factor infertility. oxidative stress attacks the fluidity of the sperm plasma membrane and the integrity of DNA in the sperm nucleus. Reactive oxygen species induced DNA damage may accelerate the process of germ cell apoptosis, leading to the decline in sperm counts associated with male infertility. ROS mediated female fertility disorders share many pathogenic similarities with the ones on the male side. These similarities include a potential role in the pathophysiology of endometriosis and unexplained infertility. High follicular fluid ROS levels are associated with negative IVF outcomes, particularly in smokers. Moreover, oxidative stress may be responsible in hydrosalpingeal fluid mediated embryotoxicity as well as poor in vitro embryonic development. CONCLUSION(S): High levels of ROS are detrimental to the fertility potential both in natural and assisted conception states.