Total antioxidant status and lipid peroxidation with and without in vitro zinc supplementation in infertile men

The aim of this study was to assess the total antioxidant capacity (TAC) and malondialdehyde (MDA) level in infertile men with asthenozoospermia and asthenoteratozoospermia compared to fertile donors, and to examine the effect of zinc on sperm lipid peroxidation and antioxidant status in infertile and fertile men. Semen samples provided by infertile men (n = 38) and fertile donors (controls; n = 12) were exposed to 6 mmol/L of zinc for 2 hr at 37°C. After semen analysis, lipid peroxidation was detected by MDA assay and seminal TAC was assessed by colorimetric method using TAS (total antioxidant status) Kit. TAC was significantly lower in infertile group compared to controls (p = .037). However, lipid peroxidation did not alter in infertile patients compared to controls (p > .05). After in vitro incubation of samples with zinc, a significant increase in TAC level was found only in infertile men (p < .001). Meanwhile, zinc had no effect on sperm lipid peroxidation in both fertile and infertile men (p > .05). Our data indicate that antioxidant treatment based on zinc in vitro supplementation may be helpful to enhance the rate of seminal antioxidant status in infertile men; however, it does not prevent sperm lipid peroxidation.     

Seminal plasma oxytocin and oxidative stress levels in infertile men with varicocele

This study aimed to assess seminal plasma oxytocin (OT) and oxidative stress (OS) levels in infertile men with varicocele (Vx). A total of 131 men were divided into fertile men (n = 20), fertile men with Vx (n = 17), infertile men without Vx (n = 40) and infertile men with Vx (n = 54). OT, malondialdehyde (MDA) and glutathione peroxidase (GPx) were estimated in seminal plasma. Mean levels of seminal OT, MDA were significantly decreased, and the mean level of GPx was significantly increased in fertile men with/without Vx compared with infertile men with/without Vx. Mean levels of OT, MDA were increased, and mean level of GPx was significantly decreased in Vx grade III cases compared with Vx grades I, II cases and in bilateral Vx cases compared with unilateral Vx. There was significant negative correlation between seminal OT with sperm count, sperm motility, seminal GPx and significant positive correlation with sperm abnormal forms, seminal MDA. It is concluded that seminal OT is significantly decreased in fertile men with/without Vx compared with infertile men with/without Vx. Seminal OT demonstrated significant negative correlation with sperm count, sperm motility, seminal GPx and significant positive correlation with sperm abnormal forms, seminal MDA. Seminal OT is associated with Vx grade and its bilaterality.     

Seminal cyclooxygenase relationship with oxidative stress in infertile oligoasthenoteratozoospermic men with varicocele

This study aimed to assess the relation of seminal cyclooxygenase COX‐1, COX‐2 with oxidative stress in infertile oligoasthenoteratozoospermic (OAT) men with varicocele (Vx). In all, 128 men were allocated into fertile men, fertile men with Vx, infertile OAT men without Vx and infertile OAT men with Vx. They were subjected to history taking, clinical examination and semen analysis. Also, seminal COX‐1, COX‐2, malondialdehyde (MDA) and glutathione peroxidase (GPx) were estimated. Mean levels of seminal COX‐1, COX‐2 were over‐expressed, the mean level of seminal MDA was significantly increased, and the mean level of seminal GPx was significantly decreased in infertile OAT men with Vx compared with other groups. Seminal COX‐1 and COX‐2 were over‐expressed in cases with Vx grade III compared with Vx grades I, II cases and in cases with bilateral Vx compared with unilateral Vx. There was significant negative correlation between seminal COX‐1 and COX‐2 with sperm concentration, sperm motility, sperm normal morphology, seminal GPx and significant positive correlation with seminal MDA. It is concluded that seminal COX‐1 and COX‐2 are over‐expressed in infertile OAT men with Vx compared with fertile men with/without and infertile OAT men without Vx being associated with oxidative stress, Vx grade and Vx laterality.     

Normal sperm parameters per se do not reliably account for fertility: A case–control study in the real-life setting

A proportion of men are infertile despite having normal medical history/physical examination and normal semen analysis. We aimed to assess whether normal sperm parameters per se account for male factor fertility. 1,957 infertile men were compared with 103 age-comparable fertile controls. Semen analysis was based on 2010 World Health Organization reference criteria. Of all, 12.1% of infertile men and 40.8% of fertile men presented with normal sperm parameters. Among fertile men, 36.9% had isolated sperm abnormalities and 22.3% men showed two or more concomitant sperm abnormalities. Serum total testosterone was higher in infertile men with normal sperm parameters compared to those with ≥2 sperm abnormalities or azoospermia, but similar to those with isolated sperm abnormalities (p ≤ .001). Circulating hormones were similar among sperm parameters groups in fertile men. At multivariable analyses, testicular volume (OR 1.12, p ≤ .001) and FSH (OR 0.8, p ≤ .001) were associated with normal sperm parameters. Overall, the longer the infertility period, the greater the number of sperm parameters abnormalities (p < .01). In conclusion, we found that 12% of infertile men and only 41% of fertile men present with normal sperm parameters. Normal sperm parameters per se do not reliably account for fertility in the real-life setting.     

Association between seminal granulysin and malondialdehyde in infertile men with varicocele and the potential effect of varicocelectomy

This study assessed the seminal plasma granulysin and malondialdehyde (MDA) levels in patients suffering from varicocele-associated infertility prior to and after varicocelectomy. This study was conducted on 34 infertile men with varicocele (group A) and same patients after varicocelectomy (group B) and 32 fertile normozoospermic males (group C). A detailed history taking, clinical examination, scrotal doppler ultrasound for varicocele diagnosis and grading, semen analysis and estimation of seminal granulysin and MDA before and after varicocelectomy were done to all participants. The mean (SD) granulysin and MDA levels in patients with varicocele were higher than in controls with highly significant differences. Post-operatively, there was a significant reduction in mean (SD) granulysin and in MDA level. Basal seminal granulysin positively correlated with basal seminal MDA, abnormal forms and negatively correlated with basal sperm count, concentration, and progressive motility. The receiver operating characteristic curve of seminal granulysin and MDA levels were conducted for discrimination between infertility cases with varicocele and control groups. Excellent AUCs were found for both markers (AUC = 0.971, 0.991 respectively). We concluded that high levels of granulysin and MDA in the semen of infertile males with varicocele negatively impact their spermatogenesis. Varicocelectomy leads to the improvement of semen parameters and significantly decreases seminal plasma granulysin and MDA levels. Hence, seminal granulysin and MDA could be used as a prognostic test in infertile patients with varicocele.     

Seminal SIRT1-oxidative stress relationship in infertile oligoasthenoteratozoospermic men with varicocele after its surgical repair

This work assessed seminal SIRT1-oxidative stress (OS) relationship in infertile oligoasthenoteratozoospermic (OAT) men after varicocele repair. Overall, thirty OAT men with varicocele were investigated. Inclusion criteria were infertile males (males who were unable to initiate a pregnancy within 1 year of regular unprotected intercourse), confirmed OAT and normal female factor. These cases were subjected to history taking, clinical checkup and semen analysis. In their semen, seminal SIRT1, malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were assessed. These men were subjected to varicocele surgical repair and were followed up for 3 months. Post-operatively, the mean seminal SIRT1, GPx levels showed significant increases and the mean MDA level showed significant decrease compared to the pre-operative levels linked to improved sperm parameters. The mean seminal SIRT1, GPx, MDA levels showed more significant improvement in grade III varicocele cases compared to grade II cases after surgical repair. Seminal SIRT1 levels showed significant positive correlations with sperm concentration, sperm motility, sperm normal morphology, seminal GPx levels and a significant negative correlation with seminal MDA levels. It could be concluded that seminal SIRT1 is significantly decreased in infertile OAT men with varicocele after its surgical repair linked to improved sperm parameters as well as seminal OS.     

Relationship between the G protein–coupled oestrogen receptor and spermatogenesis,and its correlation with male infertility

The aim of this study was to investigate the diagnostic value of serum G protein–coupled oestrogen receptor (GPER) levels and their correlation with semen parameters in men with infertility. The participants were divided into two groups as follows: 76 fertile control men (Group 1) and 77 infertile men (Group 2). Semen analysis, hormonal evaluation, serum GPER level and scrotal ultrasound of the participants were evaluated. Follicle-stimulating hormone and total testosterone levels were not significantly different between the groups (p = .413 and p = .535 respectively). The oestradiol level in Group 1 was significantly lower than that in Group 2 (p < .001). The serum GPER level was found to be significantly higher in Group 1 than that of Group 2 (p < .001). GPER levels were positively correlated with the total sperm count, sperm concentration, motility and morphology in Group 2 (r = 0.303, 0.345, 0.260 and 0.322, respectively, p < .001). In this study, GPER levels were positively correlated with sperm parameters, and it was hypothesised that the decrease in GPER expression might be associated with male infertility by adversely affecting spermatogenesis.     

Seminal plasma reactive oxygen species-antioxidants relationship with varicocele grade

This work aimed to assess seminal plasma reactive oxygen species (ROS)-antioxidants relationship with varicocele grade in infertile men with oligoasthenoteratozoospermia (OAT). The study included 89 infertile OAT men with varicocele divided into grade I (n = 22) and grade II (n = 43), grade III (n = 24) and compared with 20 healthy fertile controls. In their seminal plasma, two ROS parameters (malondialdehyde [MDA], hydrogen peroxide [H(2) O(2) ]) and four antioxidants (superoxide dismutase [SOD], catalase [Cat], glutathione peroxidase [GPx], vit.C) were estimated. There was significant increase in seminal MDA, H(2) O(2) and significant decrease in seminal SOD, Cat, GPx, vit.C in varicocele-associated OAT cases when compared with the controls. Compared with grade I cases, varicocele cases with grades II, III demonstrated significant increase in estimated seminal MDA, H(2) O(2) and significant decrease in seminal SOD, Cat, GPx, vit.C. It is concluded that seminal oxidative stress (OS) is related to increased varicocele grade in infertile OAT men associated with varicocele.     

Cytosolic phospholipase A2 and F2 isoprostanes are involved in semen quality and human infertility—A study on leucocytospermia,varicocele and idiopathic infertility

Phospholipase A₂ (PLA₂) is involved in eicosanoid release, and F₂-isoprostanes (F₂-IsoPs), as free radical-generated eicosanoids released by PLA₂, are indicators of oxidative stress in different human conditions. This study investigated the interplay between cytosolic PLA₂ (cPLA₂), F₂-IsoPs and sperm features in male infertility, when the involvement of oxidative stress has been reported. Semen evaluation was performed following WHO guidelines, sperm ultrastructure was detected by transmission electron microscopy indicating a fertility index, and the percentages of sperm immaturity, apoptosis and necrosis. In sperm cells and seminal plasma, cPLA₂ levels were determined by immunological method, whereas F₂-IsoPs by mass spectrometry. Sperm concentration, morphology, vitality and fertility index values were significantly lower in infertile groups compared with fertile men. An increase in sperm apoptosis and necrosis (p < .01), apoptosis (p < .01) and immaturity (p < .001) was detected in leucocytospermia, idiopathic infertility and varicocele, respectively. Seminal cPLA₂ showed the highest value in varicocele group (p < .05), whereas seminal F₂-IsoPs increased in varicocele (p < .001) and leucocytospermia (p < .05) groups. In the whole population, F₂-IsoP and cPLA₂ levels were positively correlated (p < .05). On the contrary, F₂-IsoPs and cPLA₂ were not significantly different when investigated in sperm cells. Our data indicate that fatty acid oxidation/metabolism plays a role in different male reproductive pathological conditions.     

Influence of prenatal waterpipe tobacco smoke exposure on reproductive hormones and oxidative stress of adult male offspring rats

Male infertility is adversely affected by tobacco cigarette smoking. Herein, the effects of prenatal waterpipe tobacco smoke (WTS) exposure on reproductive hormones and oxidative stress of adult offspring rats were evaluated. Pregnant rats received either fresh air or mainstream WTS (2 hr daily). Pregnancy outcomes, circulatory levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin, testicular levels of oestrogen, testosterone and oxidative stress biomarkers [catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS)] were assessed in their adult male offspring rats. Prenatal WTS exposure reduced the number of born offspring, female to pups ratio and birthweight (p < 0.05). Prenatal WTS exposure increased the circulatory levels of FSH and the testicular levels of oestrogen, testosterone and TBARS and catalase activity compared with control group (p < 0.05). However, GPx activity was reduced by WTS exposure (p < 0.05). There appeared to be a trend of increased LH and prolactin levels with prenatal WTS exposure; however, it was not statistically significant compared with control group (p > 0.05). The activity of SOD was not affected by prenatal WTS exposure (p > 0.05). In conclusion, prenatal WTS exposure altered reproductive hormones as well as oxidative stress biomarkers in adult male offspring rats.     

Association between leptin,obesity, hormonal interplay and male infertility

Male infertility is a major health problem worldwide. We investigated a possible association between leptin, obesity, hormonal interplay and male infertility. This cross‐sectional study of 313 males (178 infertile and 135 fertile) was carried out in 2017. The subjects were categorised by body mass index (BMI) and body fat percentage (BF%) into normal weight, overweight and obese. Significantly higher levels of BMI and BF% (p‐value < 0.001) and lower levels of FSH, LH, testosterone, and SHBG (p‐value < 0.001) were found in infertile males. However, no significant difference was observed in leptin levels (p‐value = 0.35). Leptin levels were significantly higher, and all the sex hormones were significantly lower (p‐value < 0.001) in obese subjects, whereas according to BF% only leptin, FSH and SHBG were significantly different. Leptin showed a significant positive correlation with BMI and BF% (p < 0.001). A strong positive link to serum testosterone was found with age, FSH, and LH (p < 0.001) and a negative one with BMI and BF% (p < 0.001). In mutivariable anlaysis, after adjusting for the other covariates, a significant association between FSH and testosterone (p‐value <0.001) was found. Serum leptin levels did not differ significantly in fertile and infertile groups, and no association was found with infertility. Furthermore, male obesity was found to be associated with infertility with the decrease in levels of sex hormones.     

Antioxidant activity of seminal plasma in fertile and infertile men

This study was conducted to evaluate and compare the total antioxidant capacity among fertile and infertile men. Thirty infertile patients and 20 fertility-proven healthy donors with normal sperm analysis were included in the study. Total antioxidant capacity, zinc and fructose levels of seminal plasma, and various sperm parameters were compared among fertile controls and idiopathic infertility patients prospectively. The mean antioxidant capacity of fertile controls (2.02 +/- 0.16 mmol/L) was significantly higher than that of the infertile patients group (1.78 +/- 0.23 mmol/L) (p < .01). Furthermore, asthenozoospermic and asthenoteratozoospermic groups had significantly lower mean antioxidant values (1.73 +/- 0.11 and 1.64 +/- 0.13, respectively) when compared to fertile control group (p < .01). The mean fructose level was significantly lower in the fertile control group and mean zinc level was significantly lower in the entire infertile group. On the other hand, antioxidant capacity is positively correlated to sperm motility (p = .001). Decreased antioxidant capacity was associated with impaired sperm function as a result of either increased ROS production or insufficient antioxidant capacity.     

Effects of lead,cadmium, copper and zinc levels on the male reproductive function

This study aimed to investigate the effects of heavy metals on measures of male fertility. One hundred and two infertile men with occupational exposure and thirty fertile men were included in this study. Blood and urinary levels of lead, cadmium, zinc and copper were measured by atomic absorption spectrophotometry. Semen parameters and a motile sperm organelle morphology examination were also performed. Measures of hormonal levels, oxidation–reduction potential, DNA fragmentation index and chromatin condensation were assessed for all participants. Heavy metals levels, oxidative stress and DNA quality were significantly higher in the infertile group compared to controls. FSH and testosterone levels were lower in the infertile group. A urinary cadmium level was positively associated with abnormal sperm morphology (r = .225, p < .05). Normal morphology was inversely correlated with the duration of the exposure (r = −.227, p = .022). The blood lead level was positively related to the level of testosterone (r = .223, p = .031). Cadmium and lead blood levels were positively correlated with the level of chromatin decondensation (r = .528, p < .001; r = .280, p = .017). Our study showed that occupational exposure to heavy metals is very harmful to reproductive health. DNA quality and oxidative stress investigations must be recommended for reprotoxic exposed patients prior to in vitro fertilisation treatment.     

Hypoxia pathway has more impact than inflammation pathway on etiology of infertile men with varicocele

This study aimed to compare main molecular markers of hypoxia (HIF1‐α and P53) and inflammation (TLR‐2, TLR‐4 and TNF‐α) pathways between infertile men with varicocele and fertile individuals. Sperm parameters such as sperm concentration, motility and morphology were assessed according to World Health Organization (Laboratory manual for the examination and processing of human semen. Geneva, Switzerland, 2010) guideline in 20 infertile men with grade II or III varicocele, and 20 fertile men candidate of family balancing. In addition, sperm DNA fragmentation and molecular markers involved in hypoxia and inflammation pathways were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and real‐time PCR respectively. Mean of sperm parameters (concentration, motility and morphology) and DNA integrity were significantly lower in infertile men with varicocele compared to fertile individuals. Unlike markers involved in inflammation pathway, mean expression of markers of hypoxia pathway (HIF1‐α and P53) was significantly higher in infertile men with varicocele compared to fertile individuals (p < 0.05), and also a significant correlation was observed between expression of HIF1‐α and P53 (r = 0.461; p = 0.003). Overall, the result of this study suggests higher likelihood of involvement of hypoxia pathway, in comparison with inflammation pathway, in pathogenesis varicocele associated with male infertility.     

Inflammatory and anti‐inflammatory cytokines in the seminal plasma of infertile men suffering from varicocele

Varicocele is one of causes of the declined sperm quality and low sperm production, which can lead to infertility in males. There are several experimental and epidemiological findings which support the idea that inflammatory mechanisms play an essential role in varicocele pathogenesis. Besides, in this pathological state, interleukin‐37 (IL‐37) as an anti‐inflammatory cytokine is able to bind interleukin‐18‐binding protein (IL‐18BP), and subsequently binds IL‐18 receptor β, inhibiting the pro‐inflammatory activity of IL‐18. To explore the interaction between IL‐37 and IL‐18 in infertility, we measured the amount of these cytokines in the seminal fluid of infertile men affected by varicocele. The seminal plasma levels of IL‐37 and IL‐18 were measured in 75 infertile men with varicocele and 75 healthy fertile controls (age range, 30–48 years) using enzyme‐linked immunosorbent assay. The seminal levels of IL‐37 and IL‐18 were significantly increased in infertile men with varicocele when compared to fertile controls (p < .0001). Because of the essential role(s) of cytokines in inflammatory response of cell systems, it could be possible that sperm motility is reduced following increased IL‐18, activated neutrophils and reactive oxygen species in semen of infertile patients with varicocele. Moreover, the results of this study indicated that interaction between IL‐37 and IL‐18Rβ can lead to reduced inflammatory responses. It seems that IL‐37 might be a potential biomarker and therapeutic target for male infertility.     

Seminal cell-free DNA and sperm characteristic’s: An added biomarker for male infertility investigation

Cell-free DNA (Cf-DNA) fragments may constitute an easy-to-measure molecular tool for guiding the choice of care provided to infertile couples who benefit assisted reproductive technology (ART) programmes. Data on Cf-DNA levels in the seminal plasma of men with sperm alterations are scarce. The objective of the present study was to quantify the presence of Cf-DNA in semen by using a quantitative real-time PCR. We compared men with abnormal sperm characteristics (n = 21) with normospermic controls (n = 21). The PCR assay evidenced significantly higher mean Cf-DNA levels in patients with sperm abnormalities than in controls (2.09 versus 1.18 µg/ml, respectively; p = .0003). The Cf-DNA levels were notably higher in men with azoospermia (3.65 µg/ml, versus 1.34 µg/ml in matched controls; p = .03) and men with teratozoospermia (1.80 µg/ml, versus 1.29 µg/ml in matched controls; p = .008). Our data report a significant association between elevated Cf-DNA levels and sperm abnormalities. These results may open up new diagnostic and prognostic perspectives in male infertility.     

Assessment of seminal granulysin in infertile men with varicocele

Varicocele has a common association with male infertility, but its exact role is still debated. Apoptosis has been suggested as one of the mechanisms of varicocele‐associated infertility. Granulysin is a molecule that plays a role in apoptosis with no previous study about its role in male infertility. This case‐controlled study aimed to assess seminal plasma granulysin level in infertile patients with varicocele. This study involved 90 men that were allocated into fertile normozoospermic men (n = 20), infertile men without varicocele (n = 30) and infertile men with varicocele (n = 40). These men were subjected to history taking, clinical examination, semen analysis and estimation of seminal granulysin. In general, seminal granulysin level was significantly elevated in infertile men compared with fertile men. Infertile men with varicocele showed significantly higher seminal granulysin compared with infertile men without varicocele, in bilateral varicocele cases and in grade III varicocele. Seminal granulysin level was negatively correlated with sperm concentration, sperm motility, sperm normal forms percentage and testicular volumes. It is concluded that increased seminal granulysin has a negative impact on spermatogenesis in infertile men in general and in infertile men associated with varicocele in particular.     

Antioxidant activity in the semen of fertile and infertile men

OBJECTIVES: To evaluate catalase- and superoxide dismutase (SOD)-like activities in the seminal plasma of fertile and infertile men. METHODS: Semen samples were obtained from consecutive men presenting for vasectomy (n = 12) and infertility evaluation (n = 105) at our institution. Catalase-like activity was measured by the decrease in hydrogen peroxide after incubation with seminal plasma. SOD-like activity was measured as the inhibition of nitroblue tetrazolium reduction due to superoxide anion generation by xanthine plus xanthine oxidase. RESULTS: Mean seminal catalase-like activity (+/-SEM) in fertile men was not significantly different from that of infertile men (369 +/- 49 versus 326 +/- 17 U/mL, respectively). Mean SOD-like activity in the semen of infertile men was significantly greater than in the semen of fertile controls (46.7 +/- 1.5 versus 37.0 +/- 2.8 U/mL, respectively, P <0.05). CONCLUSIONS: Our data show that infertile men do not have deficient seminal plasma SOD- and/or catalase-like activity (two key antioxidants). These findings suggest that the high semen ROS levels in some infertile men are likely due to excessive generation of ROS rather than deficient ROS scavenging activity in semen.     

Oxidative stress-related miRNAs in spermatozoa may reveal the severity of damage in grade III varicocele

Varicocele is associated with excessive production of reactive oxygen species (ROS). Although the harmful effects of ROS on sperm DNA, proteins and lipids are well documented, its impact on the expression of miRNAs in spermatozoa has not been fully understood. In this study, the expression patterns of microRNAs (miRNAs), miR-21, miR-34a and miR-122a as well as the level of ROS in the fertile control (FC; proven fertility without varicocele, n = 15) and grade III varicocele patients with normal (VN; n = 15) and abnormal (VA; n = 15) spermogram were investigated. The real-time PCR was performed to analyse the expression of the miRNAs, while oxidative stress was evaluated by measuring the concentrations of MDA. Our results showed that the expression levels of miR-21 (p = .001), miR-34a, (p = .007) and miR-122a (p < .001) were significantly decreased in spermatozoa of VN and VA patients in comparison with the fertile group. Also, increased levels of oxidative stress were detected in semen samples of varicocele patients compared with the fertile control (p < .0001). Overall, these findings demonstrate oxidative stress changes the expression pattern of some miRNAs, and these alterations could be a valuable diagnostic marker for the diagnosis and prognosis of varicocele-induced oxidative stress to retain the male fertility during the spermatogenesis process.     

Single nucleotide polymorphisms in Renalase and KCNQ1 genes and female infertility: A cross‐sectional study in Pakistan

A global increase in the incidence of subfertility is observed, and research suggests strong genetic influences that might restrict fertility directly or indirectly. It therefore becomes important to rule out the existence of genetic causes and counsel infertile couples before offering “Advanced Infertility Treatment Techniques.” This cross‐sectional study aimed to explore the association of KCNQ1 (rs2237895) and Renalase (rs2576178 and rs10887800) single nucleotide polymorphisms with different causes of infertility by analysing 508 fertile and 164 infertile women. Gene variant (AC/CC) of KCNQ1 rs2237895 showed a slight difference in the endometriosis group compared to the fertile group (p = .049), with the C allele showing a significant association with infertility overall (OR = 1.42 [1.100–1.833]; p < .0069). The variant AG/GG of Renalase rs2576178 was significantly associated with overall infertility (OR = 2.266; p < .001), with a strong G allele association with unexplained infertility OR = 2.796 (p = .002) that remained significant after adjusting for age and body mass index. Similarly, Renalase rs10887800 AG/GG and G allele showed significant association with both infertility due to polycystic ovarian syndrome and unexplained infertility. Expression of single nucleotide polymorphism rs2237895 and rs2576178 in both KCNQ1 and Renalase genes might be responsible for altering reproductive potential, hence leading to infertility in women.