Sub-clinical hypothyroidism in infertile Nigerian women with hyperprolactinaemia

Studies on the impact of subclinical hypothyroidism in infertility are scarce and this seeks to determine the proportion of infertile Nigerian women with hyperprolactinaemia that had subclinical hypothyroidism. Serum prolactin and thyroid stimulating hormone were determined using ELECSYS 1010 auto analyzer. Two hundred infertile women were evaluated and 67(33.7%) had hyperprolactinaemia. Subclinical hypothyroidism was observed in 14.9% of women with hyperprolactinaemia, 4.5% and 10.5% of women with primary and secondary infertility, while hyperprolactinaemia was observed in 29.9% and 70.1% in primary and secondary infertility respectively. Mean levels of thyroid stimulating hormone and prolactin were higher in secondary infertility than primary infertility. Subclinical hypothyroidism and hyperprolactinaemia were higher in secondary infertility than primary infertility. The ratio of proportions between hypothyroidism and hyperprolactinaemia was 1:7. Keywords: Sub clinical hypothyroidism, Hyperprolactinaemia, Primary infertility, Secondary infertility.     

Chromosomal aberrations, Yq microdeletion, and sperm DNA fragmentation in infertile men opting for assisted reproduction

Male infertility is a multi‐factorial disorder, and identification of its etiology in an individual is critical for treatment. Systematically elucidating the underlying genetic causes (chromosomal and Yq microdeletion) and factors, such as reactive oxygen species (ROS) levels and total antioxidant capacity (TAC), which contribute to sperm DNA damage, may help to reduce the number of men with idiopathic infertility and provide them with the most suitable therapeutics and counseling. This study was done to comprehensively investigate genetic and oxidative stress factors that might be the etiology of a large percentage of men with idiopathic infertility. One hundred twelve infertile men and 76 fertile controls were screened for chromosomal aberrations and Yq microdeletions. ROS, TAC, and sperm DNA damage were assessed in cytogenetically normal, non‐azoospermic men with intact Y chromosome (n = 93). ROS was assessed in neat and washed semen by chemiluminescence; seminal TAC with a commercially available kit; and sperm DNA damage by the comet assay. Two men had cytogenetic abnormalities and seven men harbored Yq microdeletions. ROS levels in neat and washed semen of infertile men were significantly higher (P < 0.01) than controls. Infertile men had significantly lower (P < 0.01) TAC levels (1.79 mM), whereas sperm DNA fragmentation in infertile men was significantly higher (P < 0.01) than controls. Genetic factors and oxidative stress cumulatively account for large number of idiopathic infertile cases. Unlike, genetic causes, which cannot be cured, timely identification and management of oxidative stress may help to reverse/reduce the effects on induced DNA damage, and improve the outcomes for infertile males. Mol. Reprod. Dev. 79: 637–650, 2012. © 2012 Wiley Periodicals, Inc.     

No association between the G196A and C270T polymorphism of the brain-derived neurotrophic factor gene and male infertility

Brain-derived neurotrophic factor (BDNF) plays important roles in neuronal development and reproductive action. Abnormal expression of BDNF gene has been detected in human sperm and seminal serum. In the present study, we investigated the possible association of G196A and C270T polymorphism of BDNF gene with male infertility. The genotypes of the G196A and C270T polymorphisms were in Hardy-Weinberg equilibrium both in fertile and infertile group. The genotype distribution frequencies were similar between infertile and fertile group. The results showed that the G196A and C270T polymorphism of the BDNF gene is unrelated to the male infertility, at least in a Chinese population.     

The role of endothelial nitric oxide synthase (eNOS) T‐786C,G894T,and 4a/b gene polymorphisms in the risk of idiopathic male infertility

A considerable number of infertile men have no known mechanism for their infertility. This study aims to examine if there is an association between endothelial nitric oxide synthase (eNOS) T‐786C, G894T, and 4a/b gene polymorphisms and idiopathic male infertility. Three hundred fifty‐two men with idiopathic infertility (mean age 32.4 ± 11.4 years) and 356 healthy controls (mean age 33.2 ± 11.6 years) with documented fertility were recruited in this study. Genotypes for T‐786C, G894T, and 4a/b gene polymorphisms were identified by the polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) analysis. The eNOS ?786CC genotype (0.310 vs. 0.081; odds ratio (OR), 3.64; 95% confidence interval (CI), 2.28–4.46; P = 0.001), 894TT genotype (0.131 vs. 0.006; OR, 3.62; 95% CI, 2.68–4.87; P = 0.001) and 4aa genotype (0.128 vs. 0.009; OR, 2.82; 95% CI, 1.88–3.89; P = 0.004) were significantly more frequent in infertile subjects. Furthermore, there was a significant difference between the group of infertile patients with azoospermia and oligoasthenoteratozoospermia (OAT) when compared by genotype distribution (?786CC vs. 786TT, 894TT vs. 894GG, and 4aa vs. 4bb) (all P < 0.01). We also found an association between the eNOS “?786C,” “894T,” and “a” alleles and an increased risk of poor semen parameters. Our data revealed a significant relationship between eNOS genotypes and the phenotype of infertility. Mol. Reprod. Dev. 77: 720–727, 2010. © 2010 Wiley‐Liss, Inc.     

Hereditary haemochromatosis gene (HFE) H63D mutation shows an association with abnormal sperm motility

The aim of this study was to screen infertile men for HFE H63D mutation in correlation with clinical characteristics of infertile men (sperm concentration, sperm motility, morphology, testicular volume, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and total Testosterone levels) and find out if the HFE H63D mutation has an effect on male infertility. After excluding hormonal treatment, any scrotal pathology, having any systemic diseases such as diabetes mellitus, sickle cell anemia and microdeletions of the Y chromosome, a total of 148 infertile men with age range between 17 and 52-years-old (average age 29.6 ± 7.2) were enrolled into the study. Our analysis indicates that the mean FSH levels are significantly higher (6.3 ± 4.6 mIU/ml, P = 0.03), whereas sperm motility is significantly lower (36.6 ± 28.1%, P = 0.01) in the infertile men with the HFE H63D mutation compared with subjects lacking this mutation. Comparison of allele frequencies of the infertile men with Ts < 50% versus the infertile men with Ts > 50% revealed a significant difference as expected (P = 0.001, OR = 0.14, %95 CI = 0.04–0.44). Comparison of allele frequencies of infertile men with abnormal sperm motility versus infertile men with normal sperm motility revealed a highly significant difference (P = 0.005, OR = 3.11, %95 CI = 1.41–6.86). Thus, the HFE H63D mutation seems to be an important risk factor for impaired sperm motility and is clinically associated with male infertility.     

Anticardiolipin antibodies in women with unexplained infertility

Concept of autoimmune basis of infertility is still controversial, particularly regarding the presence of non-organ specific autoantibodies. Non-organ specific anticardiolipin (aCL) and antithyroglobulin (TgAt) antibodies were detected in infertile women. Both partners were evaluated according to the criteria of The American Society for Reproductive Medicine. All the results were normal in cases of unexplained infertility. Antisperm antibodies (ASA) were determined by a mixed antiglobulin reaction (MAR) and the Kibrick agglutination assay, aCL by commercial ELISA, TgAt by commercial RIA. Fertile women had children. Subjects were grouped in fertile (n=27), infertile (n=65), and cases of unexplained infertility (n=42). In fertile women, aCL was below the negative cut-off value (100 %), while women with unexplained infertility were positive in 23.8 %. Anticardiolipin (aCL) antibodies were detected in 21.5 % of infertile patients, most of them with unexplained infertility (15.4 %). Other positive women had partners with ASA (4.6 %), or exhibited a negative postcoital test (1.5 %). In this study aCL were not detected in women with ASA. TgAt incidence was increased in infertile (20 %) and unexplained infertility group (21.4 %) compared to the fertile controls (18.5 %). Increased incidence of aCL and TgAt in infertile women supports the contention that these autoantibodies contribute to the infertility     

Association of the human aryl hydrocarbon receptor repressor (AhRR)-c.565C>G transversion with male infertility: A case-control study from Iran

Dioxins (eg, 2,3,7,8-tetrachlorodibenzo-p-dioxin/TCDD), as environmental endocrine disruptors and toxic carcinogens, can affect male reproductive health. The influence of dioxins is mediated via the aryl hydrocarbon receptor (AhR) pathway and its repressor (AhRR). In this study, we investigated the association of AhRR-c.565C>G transversion polymorphism with male infertility. In a hospital-based case-control study, 221 semen samples (111 infertile and 110 healthy controls) based on World Health Organization guidelines were collected from in vitro fertilization centers of Babol, Iran. The AhRR-c.565C>G (rs2292596) polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism analysis. The difference in the allele frequency of AhRR-c.565C>G transversion polymorphism did not reach a significant level. The genotype frequency was statistically significantly different between fertile and infertile men. We found that polymorphism rs2292596 (Pro185Ala) was statistically s ignificantly associated with the risk of male infertility. In addition, the statistical difference became more significant when the frequency was compared between the Pro/Pro genotype and the Pro/Ala plus Ala/Ala genotype. The 185 Pro wild-type alleles of AhRR may be associated with the risk of male infertility. The proallele also may diminish inhibition of AhR-mediated signaling of exposure to environmental pollutants.     

The SLC19A1 80G>A polymorphism is not associated with male infertility

Previous studies have revealed that genetic factors may be involved in regulating folate turnover, e.g. methylenetetrahydrofolate reductase polymorphism in the development of male infertility. Folate transporter, encoded by the SLC19A1 gene, commonly referred to as reduced folate carrier (RFC) is a transmembrane protein, which transfers hydrophilic folates across the cell membrane. It was hypothesized that common polymorphism within the SLC19A1 gene (rs1051266:G>A, 80G>A) may alter RFC function. The aim of this study was to investigate a potential association between the SLC19A1 80G>A polymorphism and male infertility in a case–control study. The SLC19A1 80G>A polymorphism was determined by means of a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay in 213 infertile Caucasian men and 226 ethnically matched controls. The distribution of SLC19A1 genotypes in the infertile men was as follows: GG 26.8%, GA 51.2%, AA 22.1% and in fertile men: GG 24.8%, GA 50.4%, AA 24.8%, and was comparable in the both the evaluated groups. Odds ratios (95% confidence interval, CI): 0.90 (0.59–1.38) and 0.88 (0.56–1.36) for dominant and recessive models remained non-significant, also after adjustment for age: 0.89 (0.57–1.37) and 0.80 (0.51–1.25), respectively. Our study demonstrated that polymorphism 80G>A of the SLC19A1 gene is not associated with male infertility.     

Y chromosome—a tool in infertility studies of Latvian population

Human Y chromosome is used as a tool in male infertility and population genetic studies. The aims of this research were to analyse the prevalence of Y chromosome microdeletions among infertile Latvian men, and to identify possible lineages of Y chromosome that may be at increased risk of developing infertility. A study encompassed 105 infertile men with different spermatogenic disturbances. Deletions on Y chromosome were detected in 5 out of 105 (∼5%) cases analysed in this study. Three of them carried deletion in AZFc region and two individuals had AZFa+b+c deletion. Study of Y chromosome haplogroups showed that N3a1 and R1a1 lineages were found less frequently in the infertile male group compared to ethnic Latvian group, however K* cluster was predominantly found in infertile male Y chromosomes. Conclusions: (1) Our study advocates running Y chromosome microdeletion analyses only in cases of severe form of infertility; (2) Ychromosome haplogroup analysis showed statistically significant tendencies that some haplogroups are more common in ethnic male group, but others are more common in infertile males.     

Association between the JC Polyomavirus Infection and Male Infertility

In recent years the incidence of male infertility has increased. Many risk factors have been taken into consideration, including viral infections. Investigations into viral agents and male infertility have mainly been focused on human papillomaviruses, while no reports have been published on polyomaviruses and male infertility. The aim of this study was to verify whether JC virus and BK virus are associated with male infertility. Matched semen and urine samples from 106 infertile males and 100 fertile males, as controls, were analyzed. Specific PCR analyses were carried out to detect and quantify large T (Tag) coding sequences of JCV and BKV. DNA sequencing, carried out in Tag JCV-positive samples, was addressed to viral protein 1 (VP1) coding sequences. The prevalence of JCV Tag sequences in semen and urine samples from infertile males was 34% (72/212), whereas the BKV prevalence was 0.94% (2/212). Specifically, JCV Tag sequences were detected in 24.5% (26/106) of semen and 43.4% (46/106) of urine samples from infertile men. In semen and urine samples from controls the prevalence was 11% and 28%, respectively. A statistically significant difference (p<0.05) in JCV prevalence was disclosed in semen and urine samples of cases vs. controls. A higher JC viral DNA load was detected in samples from infertile males than in controls. In samples from infertile males the JC virus type 2 strain, subtype 2b, was more prevalent than ubiquitous type 1. JCV type 2 strain infection has been found to be associated with male infertility. These data suggest that the JC virus should be taken into consideration as an infectious agent which is responsible for male infertility.     

LOSS OF SEX IN CLONAL POPULATIONS OF A FLOWERING PLANT,DECODON VERTICILLATUS (LYTHRACEAE)

The loss of traits that no longer increase fitness is a pervasive feature of evolution, although detailed studies of the genetic, developmental, and evolutionary factors involved are few. Most perennial plants practice both sexual and clonal reproduction, and it has been hypothesized that populations with little sexual recruitment may lose the capacity for sexual reproduction by fixing mutations that disable one or more of the many processes involved in sex. The clonal, tristylous aquatic plant, Decodon verticillatus, exhibits marked geographical variation in sexual recruitment. Populations at the northern limit of the range are usually monomorphic for style length consist of single genotypes, and produce almost no seed, due, in part, to environmental conditions that inhibit pollination, fertilization, and seed maturation. Controlled crosses in a greenhouse provided evidence for greatly reduced sexual capacity in an exclusively clonal, monomorphic population. Plants from this infertile population produced only 3–18% as many seeds per pollination as fertile populations. Observations of pollen tube growth indicated that infertility is due to severe reductions in pollen tube numbers both early after pollination and later when pollen tubes were traversing the ovary, due primarily to the inability of pistils to support normal tube growth. A three-year greenhouse experiment comparing fertility, survival, and growth of F1 progenies produced from reciprocal crosses between plants from the infertile population and those from nearby fertile populations suggested that the genetic basis for infertility is simple and may involve a single recessive mutation. In addition, the results did not reveal any association between infertility and other aspects of survival and vegetative vigor. The infertile genotype was likely fixed in the population through founder effect rather than indirect selection resulting from antagonistic pleiotropy or direct selection of advantages associated with reduced investment in sexual reproduction. A broader comparison of sexual fertility in 15 clonal, monomorphic populations and five genotypically diverse, trimorphic populations under greenhouse conditions revealed substantial infertility in all but one monomorphic population. Populations varied somewhat in the stage at which infertility was expressed, however, pollen tube growth was impaired in all populations. These results provide strong support for the hypothesis that complex traits like sex are degraded by mutation when they no longer increase fitness.     

Fat distribution patterns in young amenorrheic females

The present study analyzes body fat distribution, a well-known and important indicator of reproductive capability, in young women between 18 and 28 years of age (mean=23.3 years) suffering from secondary amenorrhea and therefore temporary infertility resulting from self-starvation. Body composition parameters estimated by means of dual energy x-ray absorptiometry and the fat distribution index, indicating body shape, were compared with those of healthy controls. Although members of the infertile, amenorrheic group exhibited dramatically low body weight and total amount of body fat, and therefore a marked negative energy balance in comparison with the healthy controls, the sex-specific fat distribution patterns did not differ between infertile and fertile young women. In contrast, the lower the weight and total fat amount, the more gynoid the fat distribution, even in infertile women. This observation may be interpreted in an evolutionary sense: Our ancestors had to cope with frequent food shortages, even starvation, and therefore lengthy periods of negative energy balance. In addition to pregnancy and lactation, temporary infertility as a result of long-term negative energy balance was not an uncommon phenomenon in female life histories. Nevertheless, after a time of plenty, reproductive function recovered, and therefore the gynoid fat distribution patterns in temporarily infertile young women may be interpreted as signal of reproductive capability, which resumes after a time of surplus.     

A novel mutation in PCD-associated gene DNAAF3 causes male infertility due to asthenozoospermia

Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive disease manifested with recurrent infections of respiratory tract and infertility. DNAAF3 is identified as a novel gene associated with PCD and different mutations in DNAAF3 results in different clinical features of PCD patients, such as situs inversus, sinusitis and bronchiectasis. However, the sperm phenotypic characteristics of PCD males are generally poorly investigated. Our reproductive medicine centre received a case of PCD patient with infertility, who presented with sinusitis, recurrent infections of the lower airway and severe asthenozoospermia; However, no situs inversus was found in the patient. A novel homozygous mutation in DNAAF3(c.551T>A; p.V184E) was identified in the PCD patient by whole-exome sequencing. Subsequent Sanger sequencing further confirmed that the DNAAF3 had a homozygous missense variant in the fifth exon. Transmission electron microscopy and immunostaining analysis of the sperms from the patient showed a complete absence of outer dynein arms and partial absence of inner dynein arms, which resulted in the reduction in sperm motility. However, this infertility was overcome by intracytoplasmic sperm injections, as his wife achieved successful pregnancy. These findings showed that the PCD-associated pathogenic mutation within DNAAF3 also causes severe asthenozoospermia and male infertility ultimately due to sperm flagella axoneme defect in humans. Our study not only contributes to understand the sperm phenotypic characteristics of patients with DNAAF3 mutations but also expands the spectrum of DNAAF3 mutations and may contribute to the genetic diagnosis and therapy for infertile patient with PCD.     

Association of the leukemia inhibitory factor gene mutation and the antiphospholipid antibodies in the peripheral blood of infertile women

To characterize the impact of the potentially functional mutation--the G to A transition at the position 3400 of the leukemia inhibitory factor (LIF; a pluripotent cytokine that plays a central role in the control of the embryo implantation) gene that leads to the exchange of valine with methionine at codon 64 we evaluated the association of the LIF gene mutation and the levels of antiphospolipid antibodies (aPLs) in the peripheral blood of infertile women (the aPLs examination was part of our routine immunological test during the infertility check-up). Eight infertile mutation-positive women were diagnosed with idiopathic infertility (n=5) and endometriosis (n=3) and their levels of aPLs in serum were compared with 115 infertile women without any LIF gene mutation. Enzyme-linked immunosorbent assay was used for the detection of seven antiphospholipid antibodies; the results were statistically assessed by the Fisher's 2 by 2 exact test to evaluate the association of the LIF gene mutations and aPLs in serum of infertile patients. The presence of aPLs was significantly higher in our study group (100%) than in 30% of aPLs-positives in control infertile patients (p = 0.0035) which indicates that the aPLs are elevated in women with LIF gene mutations.     

Methylation loss at H19 imprinted gene correlates withmethylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples from infertile males

Aberrant methylation at the H19 paternal imprinted gene has been identified in different cohorts of infertile males. The causes of H19 methylation errors are poorly understood. In this study, we investigated the methylation status of the H19 gene in semen DNA samples from infertile males affected by MTHFR gene promoter hypermethylation. DNA from normal and abnormal semen samples harbouring MTHFR gene promoter hypermethylated, hmMTHFR-nor and hmMTHFR-abn, and without MTHFR methylation, MTHFR-nor and MTHFR-abn, were investigated for methylation status in the H19 locus using bisulfite-treated DNA PCR, followed by cloning and sequencing. The prevalence of H19 hypomethylated clones was 20% in hmMTHFR-nor and 0% in MTHFR-nor semen samples (p < 0.05), and 28% in hmMTHFR-abn compared with 16% in MTHFR-abn semen samples (p > 0.05). These results underscore the association between H19 methylation defects and hypermethylation of the MTHFR gene promoter in normal semen samples and suggest that aberrant methylation at H19 may occur in the normal sperm of infertile males affected by MTHFR gene dysfunction. These findings provide new insights into the mechanisms causing abnormal methylation in imprinted genes and, in turn, male infertility.     

Beneficial effects of varicocele embolization on semen parameters

The suffering caused by infertility in a man can have multiple aspects. It can display a narcissistic dimension, an objectal dimension (object-libido) turned toward others or/and an identity dimension. Two clinical case reports were used here to (i) illustrate all these aspects of infertility suffering, (ii) to evidence the difficulty for infertile men to speak about their infertility and (iii) underlie the importance for professional of medical assisted reproduction to be attentive to this suffering that many men keep silent. An empathetic attention to infertile men may give a way to express this suffering and thus allow the beginning of a psychoanalytic approach which is necessary in infertility and especially for infertile men who do not easily express their suffering.     

雄性不育大鼠近交系MIJ的建立及其遗传特征观察

以发现的雄性不育大鼠的正常表型同胞鼠为种鼠,通过全同胞近亲交配方式,采用选优法成功培育出自发雄性不育大鼠近交系MIJ.同系异体皮肤移植验证其遗传纯合度,观察其表型特征,并通过遗传测交试验测定雄性不育性状的遗传方式.结果表明.MIJ种群符合近交系标准;雄性不育大鼠呈睾丸下降延迟、睾丸及附睾发育迟缓、精子数量少及精子生成障碍;近交系内其他个体表型正常.不育性状呈隐性遗传方式,由常染色体上单一隐性基因控制.该雄性不育大鼠可作为人类男性不育研究的动物模型.     

The testis‐specific gene 1700102P08Rik is essential for male fertility

Male infertility is a rising problem around the world. Often the cause of male infertility is unclear, and this hampers diagnosis and treatment. Spermatogenesis is a complex process under sophisticated regulation by many testis‐specific genes. Here, we report the testis‐specific gene 1700102P08Rik is conserved in both the human and mouse and highly expressed in spermatocytes. To investigate the role of 1700102P08Rik in male fertility, knockout mice were generated by CRISPR‐Cas9. 1700102P08Rik knockout male mice were infertile with smaller testis and epididymis, but female knockout mice retained normal fertility. Spermatogenesis in the 1700102P08Rik knockout male mouse was arrested at the spermatocyte stage, and no sperm were found in the epididymis. The deletion of 1700102P08Rik causes apoptosis in the testis but did not affect the serum concentration of testosterone, luteinizing hormone, and follicle‐stimulating hormone or the synapsis and recombination of homologous chromosomes. We also found that 1700102P08Rik is downregulated in spermatocyte arrest in men. Together, these results indicate that the 1700102P08Rik gene is essential for spermatogenesis and its dysfunction leads to male infertility.     

Y chromosome--a tool in infertility studies of Latvian population

Human Y chromosome is used as a tool in male infertility and population genetic studies. The aims of this research were to analyse the prevalence of Y chromosome microdeletions among infertile Latvian men, and to identify possible lineages of Y chromosome that may be at increased risk of developing infertility. A study encompassed 105 infertile men with different spermatogenic disturbances. Deletions on Y chromosome were detected in 5 out of 105 (approximately 5%) cases analysed in this study. Three of them carried deletion in AZFc region and two individuals had AZFa + b + c deletion. Study of Y chromosome haplogroups showed that N3a1 and R1a1 lineages were found less frequently in the infertile male group compared to ethnic Latvian group, however K* cluster was predominantly found in infertile male Y chromosomes. Conclusions: 1) Our study advocates running Y chromosome microdeletion analyses only in cases of severe form of infertility; 2) Y chromosome haplogroup analysis showed statistically significant tendencies that some haplogroups are more common in ethnic male group, but others are more common in infertile males.     

Role of 677C→T polymorphism a single substitution in methylenetetrahydrofolate reductase (MTHFR) gene in North Indian infertile men

Failure or severe difficulty in conceiving a child is surprisingly common, worldwide problem. Half of these cases are due to male factors with defects in sperm (1 in 15 men) being the single most common cause. Also about 60–75 % of male infertility cases are idiopathic, since the molecular mechanisms underlying the defects remain unknown. DNA methylation is crucial for spermatogenesis and high methylenetetrahydrofolate reductase (MTHFR) activity in adult testis than other organs in mouse, signifies its critical role in spermatogenesis. According to recent findings there is a correlation of epigenetic regulation of several imprinted genes with disturbed spermatogenesis and fertility. Consequently any change in the MTHFR gene sequence can modify the spermatogenesis including transmission of infertility to the carriers. The aim of the study is to analyze the distribution of the single nucleotide polymorphism C677T in the MTHFR gene in 637 North Indian infertile patients and 364 fertile North Indian men as controls by using PCR–RFLP technique and Chi Square test for statistical analysis. The average MTHFR 677CC, 677CT, 677TT genotype frequencies of total infertile men were 70.17, 24.17, 5.65 % in infertile men and 75.27, 21.7, 2.74 % in controls, respectively. The average frequency of the MTHFR 677T allele was 17.73 % in infertile men as compared to 13.59 % in controls. The statistical difference was significant. Disease risk was found 2.27-folds increased in patients who were carrying T allele. We found an association of C677T polymorphism with male infertility and that it may be a genetic risk factor for male infertility in North Indian population.