Examining the causal relationship between sex hormone-binding globulin (SHBG) and infertility: A Mendelian randomization study.

BACKGROUND: The causal relationship between sex hormone-binding globulin (SHBG) and infertility has remained unclear. Thus, we used Mendelian randomization (MR) to investigate this relationship. METHODS: Risk factors for SHBG were extracted from European individuals within the UK Biobank using single-nucleotide polymorphism (SNP) data. Summary-level data for infertility outcomes were obtained from the FinnGen dataset. The causal relationship between SHBG and infertility was examined using inverse variance weighted, weighted model, weighted median, and MR-Egger regression analyses. Additionally, Cochran's Q test and Egger intercept tests were used to confirm the heterogeneity and pleiotropy of identified instrumental variables (IVs). RESULTS: Our findings revealed a significant negative association between sex hormone-binding globulin (SHBG) levels and infertility, particularly with anovulation, a specific form of female infertility. However, SHBG did not exert a causal impact on male infertility or on female infertility of tubal origin. CONCLUSIONS: SHBG expression offers protection against the development of certain types of female infertility, suggesting it is a potential therapeutic target for infertility.

Exploring correlations: Human seminal plasma and blood serum biochemistry in relation to semen quality.

Male infertility is a pressing global issue, prompting the need for biomarkers correlating with seminal parameters for diagnosis. Our study investigated 10 biochemical and energetic parameters in the seminal plasma and blood sera of fertile (25 subjects) and infertile (88 subjects) Polish men, correlations between their levels in seminal plasma and semen quality, and correlations between blood sera and seminal plasma levels of examined parameters. Infertile men displayed elevated seminal plasma glucose and fructose but reduced HDL levels compared to fertile men. We observed also weak negative correlations between seminal plasma triglycerides and sperm concentration in both groups. Moreover, infertile men exhibited positive correlations between seminal plasma HDL/LDL concentrations and sperm concentration. Fertile men showed moderate negative correlations between glucose/triglycerides concentrations and sperm count and between seminal plasma triglycerides levels and sperm vitality. Semen volume correlated with triglycerides (negative) and fructose (positive) concentrations in infertile men. Sperm motility correlated negatively with total cholesterol, LDL, and triglycerides concentrations in fertile men, and weakly with AMP-activated protein kinase in infertile men. Weak negative correlations between seminal plasma fructose/AMP-activated protein kinase concentrations and sperm progressive motility were observed in infertile men, whereas in fertile men seminal plasma AMP-activated protein kinase levels were positively correlated with progressive motility. Correlation analysis between blood serum and seminal plasma parameters revealed intriguing connections, notably regarding LDL, AMP-activated protein kinase, and carnitine, suggesting systemic influences on seminal plasma composition. These findings emphasize the complex interplay between metabolic factors and sperm parameters, offering promising directions for future research in male infertility diagnostics and therapeutics.

Detection of AZF microdeletions and analysis of reproductive hormonal profiles in Hainan men undergoing assisted reproductive technology.

BACKGROUND: Male infertility has become a global health problem, and genetic factors are one of the essential causes. Y chromosome microdeletion is the leading genetic factor cause of male infertility. The objective of this study is to investigate the correlation between male infertility and Y chromosome microdeletions in Hainan, the sole tropical island province of China. METHODS: We analyzed the semen of 897 infertile men from Hainan in this study. Semen analysis was measured according to WHO criteria by professionals at the Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, where samples were collected. Y chromosome AZF microdeletions were confirmed by detecting six STS markers using multiple polymerase chain reactions on peripheral blood DNA. The levels of reproductive hormones, including FSH, LH, PRL, T, and E2, were quantified using the enzyme-linked immunosorbent assay (ELISA). RESULTS: The incidence of Y chromosome microdeletion in Hainan infertile men was 7.13%. The occurrence rate of Y chromosome microdeletion was 6.69% (34/508) in the oligozoospermia group and 7.71% (30/389) in the azoospermia group. The deletion of various types in the AZF subregion was observed in the group with azoospermia, whereas no AZFb deletion was detected in the oligozoospermia group. Among all patients with microdeletions, the deletion rate of the AZFc region was the higher at 68.75% (44 out of 64), followed by a deletion rate of 6.25% (4 out of 64) for the AZFa region and a deletion rate of 4.69% (3 out of 64) for the AZFb region. The deletion rate of the AZFa region was significantly higher in patients with azoospermia than in patients with oligozoospermia (0.51% vs. 0.39%, p < 0.001). In comparison, the deletion rate of the AZFc region was significantly higher in patients with oligozoospermia (3.08% vs. 6.30%, p < 0.001). Additionally, the AZFb + c subregion association deletion was observed in the highest proportion among all patients (0.89%, 8/897), followed by AZFa + b + c deletion (0.56%, 5/897), and exclusively occurred in patients with azoospermia. Hormone analysis revealed FSH (21.63 ± 2.01 U/L vs. 10.15 ± 0.96 U/L, p = 0.001), LH (8.96 ± 0.90 U/L vs. 4.58 ± 0.42 U/L, p < 0.001) and PRL (263.45 ± 21.84 mIU/L vs. 170.76 ± 17.10 mIU/L, p = 0.002) were significantly increased in azoospermia patients with microdeletions. Still, P and E2 levels were not significantly different between the two groups. CONCLUSIONS: The incidence of AZF microdeletion can reach 7.13% in infertile men in Hainan province, and the deletion of the AZFc subregion is the highest. Although the Y chromosome microdeletion rate is distinct in different regions or populations, the regions mentioned above of the Y chromosome may serve an indispensable role in regulating spermatogenesis. The analysis of Y chromosome microdeletion plays a crucial role in the clinical assessment and diagnosis of male infertility.

[Tumor necrosis factor in the ejaculate as an indicator of reduced fertility].

INTRODUCTION: Pro-inflammatory cytokine - tumor necrosis factor-alpha (TNF) is one of the components of the seminal plasma proteome; its meaning has not been definitively revealed. A comparative analysis of the concentration of this protein in the blood serum and in the ejaculate and changes in its level in the semen of men with infertility is f scientific interest. THE PURPOSE OF THE STUDY: determination of TNF- level in the blood serum and seminal plasma of healthy men and patients with reduced fertility. MATERIALS AND METHODS: 70 men of reproductive age with azoospermia (main group, n=18), with oligoastenozoospermia (comparison group, n=18) and with normal spermogram parameters (control group, n=34) were examined. The ejaculate was examined using an SQA-V semen analyzer (MES, Israel). In seminal plasma samples, the concentration of TNF was determined using the alpha-TNF-ELISA-BEST test system (A-8756, Vector-Best LL, Russia). RESULTS: The concentration of TNF- in blood serum had a significant variation (CV=85.31%) and amounted to 2.75+/-2.18 pg/ml, which is 2.55 times lower than the same indicator in seminal plasma (7.01+/-5.98 pg/ml, CV=126.15%, p<0.00001). When comparing the content of TNF- in seminal plasma, significant differences were found in the examined patients (Kruskal-Wallis test H=24.75991; p<0.00001). Pairwise comparison revealed a statistically significant difference in the level of TNF- in seminal plasma between the comparison and control groups (p2-3=0.000023), as well as between the main group and the comparison group (p1-2=0.000043); there were no significant differences between the main and control groups (p>0.05). When determining the content of TNF- in the blood serum, there was no statistically significant difference between the groups (p>0.05). There were no correlations between the concentration of TNF- in blood serum and in seminal plasma (R=0.295374), and the total number of spermatozoa in the ejaculate (R=-0.027945); and the concentration of spermatozoa in the ejaculate (R=-0.042902). DISCUSSION: It is unlikely that TNF crosses into seminal plasma from serum against a concentration gradient. It is most likely that TNF is produced locally in the organs of the reproductive system by resident immune cells or cells involved in spermatogenesis. An increased content of TNF- in seminal plasma in patients of the comparison group may indicate the presence of an inflammatory process in the reproductive system and a reduced fertility of the ejaculate. CONCLUSION: The physiological role of TNF in sperm, its sources in the organs of the male reproductive system, and the pathogenetic mechanisms of the participation of the TNF in pathological processes in male reproductive system still remain unclear. All this justifies the need for further study of the TNF level in seminal plasma in normal conditions and in diseases of the urogenital tract in men.

Effects of the Neuropeptides Pituitary Adenylate Cyclase Activating Polypeptide and Vasoactive Intestinal Peptide in Male Fertility.

Background and Objectives: The neuroendocrine system plays a crucial role in regulating various bodily functions, including reproduction, with evidence suggesting its significant involvement in male fertility and sperm development. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are expressed in both male and female reproductive tissues, influencing penile erection and regulating steroidogenesis in males. Therefore, our study aimed to compare the protein levels of VIP and PACAP in seminal plasma between healthy controls and sub-fertile patients. Additionally, we sought to correlate the levels of these biomarkers with clinical, functional, and laboratory findings in the participants. Materials and Methods: The study included a total of 163 male participants for analysis. The participants were further stratified into subgroups of fertile and sub-fertile men of four subgroups according to the 2021 WHO guidelines. Seminal plasma concentrations of the neuropeptides VIP and PACAP were measured using human enzyme-linked immunosorbent assay technique. Results: The findings showed statistically significant differences in total sperm count, sperm concentration, total motility, and vitality (p < 0.001) between the fertile group and the sub-fertile group. Specifically, significant differences found between healthy males and oligoasthenospermic patients (p = 0.002), and between asthenospermic and oligoasthenospermic patients (p = 0.039). An ROC analysis showed associated sensitivity and specificity values of 62.2% and 55.6%, respectively, to PACAP seminal levels differentiated between sub-fertile patients from fertile males (p = 0.028). No significant difference in seminal levels of VIP was found between the sub-fertile and fertile groups. Conclusions: Previous research leads to the point of PACAP active involvement in spermatogenesis. In accordance to our study, in human semen samples, we have seen a significance change in PACAP levels amongst patients with low sperm count or with both low sperm count and low motility, hinting at its contribution and acting as a possible factor in this complex process. Thus, alterations in the levels or actions of these neuropeptides have been associated with certain reproductive disorders in males.

Distribution and Positive Predictive Value of Follicle Stimulating Hormone Among Nonazoospermic Men.

PURPOSE: Our goal was to characterize the distribution of follicle stimulating hormone (FSH) in fertile and subfertile nonazoospermic men, and to determine the ability of various FSH thresholds to predict fertility status. MATERIALS AND METHODS: We performed a retrospective cohort study of 1389 nonazoospermic men who presented for fertility evaluation. Men with at least 2 semen analyses and 1 FSH level were included. Men were dichotomized into fertile and subfertile groups based on total motile sperm count. FSH was evaluated within a multivariable model, and positive predictive values (PPVs) for subfertility were used to assess the clinical utility of various FSH thresholds. RESULTS: One thousand fifteen (80%) men were classified as fertile and 274 (20%) as subfertile. Age, presence of varicocele, and testosterone levels were not statistically different between the groups. Median FSH was 4.0 vs 6.0 (P < .001) among fertile vs subfertile men. Multiple FSH thresholds ranging from 2.9 to 9.3 performed similarly in predicting fertility status (PPV 0.49-0.59). Only FSH thresholds above the 95th percentile (12.1) had PPVs greater than 0.7. The highest PPV (0.84) was seen at an FSH of 20.8 (99th percentile). CONCLUSIONS: While there were significant differences in FSH levels among fertile and subfertile nonazoospermic men, multiple FSH cutoffs between 2.2 and 9.3 performed poorly for prediction of fertility status as determined by total motile sperm count. It was not until the 95th percentile FSH value that a clinically useful level of predictability for subfertility was reached, indicating that FSH should not be used as a standalone test of fertility status. Nonetheless, FSH testing remains clinically useful and may be most informative in the setting of extreme values or discordant FSH and semen analysis results.

Exposure to potentially toxic elements (PTEs) and the risk of male infertility- A Systematic review and meta-analysis.

BACKGROUND: Infertility has been defined as a failure to conceive for at least 12 months of regular unprotected sexual intercourse. The male factors are responsible for about 50 % of cases. Various factors such as endocrine, immunological, genetic, exposure to toxicants, and idiopathic factors are involved in male infertility. Recently, the role of PTEs in reproductive performance has been explored by various studies. OBJECTIVES: Current systematic review and meta-analysis have been carried out to compile and statistically analyze the findings of relevant studies and reach some conclusion. METHODOLOGY: A literature search was done according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines in three scientific literature databases; PubMed, Google Scholar, and Science Direct. Meta-analysis was performed using Review Manager 5.4 software. The study's protocol was registered in PROSPERO (CRD42023465776). RESULTS: Meta-analysis of lead in the blood of infertile cases and healthy controls indicated a significant association with male infertility, observed standard mean difference (SMD) was 0.67 at 95 % confidence interval (CI) (0.07, 1.28), and p = 0.03. In the case of lead analysis in semen, the values are as follows: SMD = 1.19 at 95 % CI (0.42, 1.96) with p = 0.002. Significant association appears for cadmium in semen with SMD 0.92 at 95 % CI (0.54, 1.29) and p < 0.00001. No significant association was observed for arsenic, barium, and mercury in blood. CONCLUSION: Most of the studies focus on the detection of PTE in semen samples followed by blood as sample type. Lead and cadmium exposure is significantly associated with male infertility. However, non-significant results for arsenic, barium, and mercury are observed.

Associations between cytokines and the risk of female and male infertility: A two-sample Mendelian randomization analysis.

PURPOSE: Observational studies have linked cytokines to the occurrence of female and male infertility. However, it is not clear how biomarkers of inflammation are causally related to infertility. To explore whether genetic variants in circulating cytokines are associated with the pathogenesis of infertility, we performed two-sample Mendelian randomization (MR) analysis. METHODS: A total of 31,112 individuals of European ancestry were included in a genome-wide association study (GWAS) of 47 circulating cytokines as instrumental variables (IVs). Outcome data were female infertility, including four different subtypes, and male infertility, from the FinnGen consortium. Five MR methods, including inverse-variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were employed to examine the genetic association between cytokines and the risk of female infertility and male infertility. The false discovery rate (FDR) was controlled using the Benjamini-Hochberg method. RESULTS: After FDR correction, cis-protein quantitative trait locus (cis-pQTL) instruments showed that the cytokines GROa and MCSF were positively associated with female infertility. In analyses of subtypes of female infertility, eotaxin and sICAM were inversely associated with ovulation-related infertility; MCP3 alone was positively associated with uterus-related infertility; GROa and MCSF were positively correlated with infertility of cervical, vaginal, and other or unspecified origin; and MIP1a was negatively correlated with tubal origin infertility. The cytokines HGF, IL-2ra, and RANTES were positively correlated with male infertility. Similar findings were obtained in sensitivity analyses. There was no evidence of pleiotropy or heterogeneity in the results. CONCLUSION: These findings contribute to current understanding of the role of cytokine biomarkers in the etiology of female and male infertility. Furthermore clinical experimental validation is required to evaluate the potential of these cytokines as biomarkers.

Single and multi-dose pharmacology of recombinant and urinary human chorionic gonadotrophin in men.

OBJECTIVE: Human choriogonadotrophin (hCG) treatment of gonadotrophin-deficient infertile men uses hCG of urinary (uhCG) or recombinant (rhCG) origin, but these treatments have not been compared nor are there studies defining rhCG dosing in men. DESIGN: hCG products were studied in randomized cross-over single-dose studies of standard (Study 1, 1500 IU and 62.5 µg, respectively) or high (Study 2, 5000 IU and 250 µg) dose and a multi-dose population pharmacology study of hCG use. PARTICIPANTS: Eight (Study 1) and seven (Study 2) volunteers in cross-over and 52 gonadotrophin-deficient men in the multi-dose study MEASUREMENTS: In cross-over studies, serum testosterone (T), dihydrotestosterone (DHT) and estradiol by liquid chromatography-mass spectrometry (LCMS) and serum hCG, LH, FSH, SHBG and T (observational study) by immunoassays. RESULTS: After standard and high-dose injection, serum hCG and testosterone responses had similar timing and peak concentrations except for a mildly lower early (<48 h) serum testosterone with uhCG. In the multi-dosing study, both hCGs had similar pharmacokinetics (pooled half-life 5.8 days, p < .001), while serum testosterone concentrations were stable after injection and did not differ between hCG products. Bench testing verified that 20% of pens from 4/10 individuals were used inappropriately. CONCLUSIONS: Although hCG pharmacokinetics are not formally bioequivalent, the similar pharmacodynamic effects on serum testosterone indicate that at the doses tested both hCGs provide comparable clinical effects. The starting dose of rhCG for treating gonadotrophin-deficient men should be 62.5 µg (6 clicks) of the rhCG pen.

Are they functional hypogonadal men? Testosterone serum levels unravel male idiopathic infertility subgroups.

PURPOSE: To evaluate total testosterone distribution in male idiopathic infertility. METHODS: A retrospective, real-world case-control clinical study was conducted. Cases consisted of men evaluated for couple infertility, specifically those with alterations in semen parameters and normal gonadotropin levels, and after excluding all known causes of male infertility. Controls were male subjects who underwent semen analysis for screening purposes, without any abnormality detected. The total testosterone distribution was evaluated in cases and controls. Further analyses were performed subgrouping cases according to total testosterone reference threshold suggested by scientific societies (i.e., 3.5 ng/mL). RESULTS: Cases included 214 idiopathic infertile men (mean age 38.2 ± 6.2 years) and controls 224 subjects with normozoospermia (mean age 33.7 ± 7.5 years). Total testosterone was not-normally distributed in both cases and controls, with positive asymmetric distribution slightly shifted on the left in cases. The rate of subjects with testosterone lower than 3.5 ng/mL was higher in cases (23.8%) than controls (4.5%) (p < 0.001). In cases with testosterone lower than 3.5 ng/mL, a significant direct correlation between testosterone and the percentage of normal morphology sperms was highlighted, also applying multivariate stepwise linear regression analysis (R = 0.430, standard error = 0.3, p = 0.020). CONCLUSION: Although idiopathic infertile men show by definition altered semen analysis and gonadotropins within reference ranges, testosterone serum levels are widely variable in this population. Approximately a quarter of these patients present some sort of functional hypogonadism. Our data support the need to better classify idiopathic male infertility and total testosterone serum levels could be a supportive parameter in tracing the patient's therapeutic profile.

The Association of ICSI Outcomes with Semen and Blood Bisphenol A Concentrations of the Male Partner.

This study investigated the association of blood and semen Bisphenol A (BPA) levels of the male partner on the reproductive outcome in intracytoplasmic sperm injection (ICSI) treatment cycles. For this prospective study (ClinicalTrials.gov identifier: NCT02703584), blood and semen samples of the male partner of the 75 women who had ICSI were analyzed. The study group consisted of men who had ICSI for male factor infertility other than azoospermia, while men with normal spermiogram whose partners underwent ICSI due to tubal factor infertility were taken as the study group. Habitual consumption of drinking water from plastic carboys/bottles (PBW) at home was also questioned in both groups as it was considered as chronic BPA exposure. The association of ICSI outcome with blood BPA (bBPA) and semen BPA (sBPA) levels was analyzed in both groups. No significant correlation was found between sperm parameters and bBPA levels in both groups. A negative correlation was found between sBPA levels and total sperm count and progressive sperm motility in men who consumed PBW. Embryo development arrest was found to be significantly higher in patients who have high sBPA levels. Although sBPA levels were not different in PBW consumers, bBPA levels were found to be significantly lower in those who consumed tap water (TW) than those who used PBW. Elevated bBPA were associated with a significant decrease in clinical pregnancy rate. Considering the widespread human exposure to BPA, the effect of BPA on the male reproductive system needs to be further examined.

The Association Between Lipid Serum and Semen Parameters: a Systematic Review.

Increased lipid levels sometimes not only affect sexual function but also are considered to harm semen quality. It is often a suspicion that elevated lipids are a factor in infertility. We conduct a systematic review. Articles that met the criteria were identified according to The Preferred Reporting Items for Systematic Review and Meta-analysis of recommendations in the PubMed, ProQuest, EBSCO, Web of Science Wiley Online, Springer Link, Scopus, and Science Direct databases with no time restriction for publication. Seven studies are eligible for qualitative analysis from nine studies that have the potential to be assessed. These studies measure the correlation of serum lipids (VLDL, HDL, LDL, triglycerides, total cholesterol, free cholesterol, phospholipids, free fatty acids) with semen parameters (concentration, motility, morphology, DNA fragmentation index). Although not all studies consistently report that lipids impact semen quality, this review suspects that lipids have a significant impact on sperm quality. This study implies that it is necessary to maintain lipid levels to maintain sperm quality and quality of life. However, further investigation with an observational cohort study design needs to be carried out to assess the effect of lipids on semen quality more precisely for the promotion of reproductive health care.

Ceiling effect of clomiphene citrate on the testosterone to estradiol ratio in eugonadal infertile men.

INTRODUCTION: The testosterone to estradiol ratio (T/E2 ratio) reportedly exerts a stronger effect on semen quality and sexual desire than does testosterone alone. Clomiphene citrate is a selective estrogen receptor modulator that has long been used as an empirical treatment option in the management of idiopathic oligozoospermia. Clomiphene may change the hypothalamus-pituitary-gonad axis and result in the alteration of the T/E2 ratio. No reliable data are available regarding the change in the T/E2 ratio after clomiphene use in eugonadism. METHODS: This study included 24 male patients who were diagnosed with idiopathic infertility with eugonadism. They all received clomiphene citrate (25 mg/day) as empirical treatment. Blood tests for serum testosterone, estradiol, prolactin, luteinizing hormone, and follicle stimulating hormone were performed before and after 4 weeks of clomiphene use. Paired t-tests were used to evaluate the significance of the hormone level change. RESULTS: Overall, the patients' T/E2 ratio did not increase significantly after clomiphene use. In the subgroup analysis, the T/E2 ratio of patients with a baseline ratio of <200 increased significantly after clomiphene use. CONCLUSIONS: Clomiphene citrate may significantly increase the T/E2 ratio in eugonadal men under the premise of its ceiling effect (T/E2 ratio < 200), providing practitioners with guidance on the use of clomiphene in this demographic.

Prevalence of Hyperprolactinemia and Clinically Apparent Prolactinomas in Men Undergoing Fertility Evaluation.

OBJECTIVE: To determine prevalence of hyperprolactinemia and prolactinoma among men presenting for initial fertility evaluation. METHODS: We performed a retrospective review of men presenting for initial fertility evaluation at a tertiary care, academic health system between 1999 and 2018. Men with measured prolactin levels were analyzed to determine prevalence of hyperprolactinemia and prolactinoma. We compared clinical characteristics of men with and without hyperprolactinemia. Univariable and multivariable analysis were used to determine factors associated with hyperprolactinemia. We assessed effects of hyperprolactinemia and prolactinoma on testosterone levels, semen parameters and pregnancy outcomes after treatment. RESULTS: A total of 3101 men had serum prolactin level measured. 65 (2.1%) had hyperprolactinemia. Patients with hyperprolactinemia had lower testosterone (median 280 ng/dL vs 313 ng/dL, P = 0.038) and lower total motile sperm count (median 7.0 million vs 34.7 million, P = 0.001) compared to men without hyperprolactinemia. 43.1% of men with hyperprolactinemia had oligospermia vs 21.5% of men without hyperprolactinemia (P<0.001). Univariable analysis demonstrated that men with elevated luteinizing hormone (LH) (OR 1.077, P = 0.001) and follicle-stimulating hormone (FSH) (OR 1.032, P = 0.002) were more likely to have hyperprolactinemia. Men with oligospermia were more likely to have hyperprolactinemia (OR 2.334, P = 0.004). On multivariable analysis, neither hormone parameters nor oligospermia were associated with elevated prolactin (P>0.05). Of the 65 men with hyperprolactinemia, 11 (17%) were diagnosed with a prolactinoma, resulting in an overall prevalence of 11 in 3101 (0.35%). CONCLUSION: The overall prevalence of prolactinoma in our cohort of men undergoing fertility evaluation was 35-fold higher than the prevalence in the general male population.

Vitamin D Supplementation Improves Fasting Insulin Levels and HDL Cholesterol in Infertile Men.

CONTEXT: Vitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator. OBJECTIVE: This work aimed to determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men. METHODS: A single-center, double-blinded, randomized clinical trial (NCT01304927) was conducted. A total of 307 infertile men were randomly assigned (1:1) to a single dose of 300 000 IU cholecalciferol followed by 1400 IU cholecalciferol + 500 mg of calcium daily (n = 151) or placebo (n = 156) for 150 days. Reported metabolic parameters including fasting plasma glucose, glycated hemoglobin A1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols, and triglycerides were secondary end points. The primary end point semen quality has previously been reported. RESULTS: Men receiving vitamin D supplementation improved their vitamin D status, whereas vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone. At the end of the trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs 74 pmol/L, P = .018) and 19% lower HOMA-IR (2.2 vs 2.7, P = .025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs 1.32 mmol/L, P = .008) compared with the placebo group. CONCLUSION: High-dose vitamin D supplementation has beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men.

Association Between Serum Vitamin D Concentration with Spermiogram Parameters and Reproductive Hormones Among Infertile Iranian Males: a Cross-sectional Study.

Infertility is a health concern affecting more than 186 million people globally, and male factors play a role in almost half of cases. Recently, the possible impact of vitamin D on male reproduction has become the center of attention. Our study intended to assess the correlation between serum vitamin D concentrations with sperm parameters and sex hormones in infertile Iranian men compared to fertile men. This cross-sectional study was performed among the 114 couples who were referred to the Urology Clinic of Imam Reza hospital in Mashhad, Iran. According to the inclusion criteria, 57 patients were entered into the infertility group, and 57 cases entered into the fertile group. Semen quality assessment was performed based on WHO guidelines, and the serum was analyzed for 25-hydroxy vitamin D, LH (luteinizing hormone), FSH (follicle-stimulating hormone), and testosterone by ELISA method. Vitamin D level was significantly higher in the fertile group compared with infertile males (p < 0.001). Moreover, vitamin D level was positively correlated with some fertility indicators assessed by spermiogram test including sperm motility (p < 0.001, r = 0.483) and sperm count (p = 0.019, r = 0.216). Additionally, vitamin D was positively associated with testosterone level (p = 0.025, r = 0.210). There was no significant correlation between vitamin D concentrations with sperms morphology, LH, and FSH level. Our study showed a significantly lower vitamin D level in infertile males compared to the fertile group. In conclusion, our study results showed a positive correlation between serum vitamin D with sperm motility, sperm count, and serum testosterone level in fertile males compared to infertile men and suggest the beneficial effects of vitamin D on male reproduction.