Where do obesity and male infertility collide?

The parallel rise in obesity and male infertility in modern societies necessitates the identification of susceptibility genes underlying these interconnected health issues. In our study, we conducted a comprehensive search in the OMIM database to identify genes commonly associated with male infertility and obesity. Subsequently, we performed an insilico analysis using the REVEL algorithm to detect pathogenic single nucleotide polymorphisms (SNPs) in the coding region of these candidate genes. To validate our findings in vivo, we conducted a comprehensive analysis of SNPs and gene expression of candidate genes in 200 obese infertile subjects and 240 obese fertile individuals using ARMS-PCR. Additionally, we analyzed 20 fertile and 22 infertile obese individuals using Realtime-qPCR. By removing duplicated queries, we obtained 197 obesity-related genes and 102 male infertility-related genes from the OMIM database. Interestingly, the APOB gene was found in common between the two datasets. REVEL identified the rs13306194 variant as potentially pathogenic with a calculated score of 0.524. The study identified a significant association between the AA (P value = 0.001) genotype and A allele (P value = 0.003) of the APOB rs13306194 variant and infertility in obese men. APOB expression levels were significantly lower in obese infertile men compared to obese fertile controls (p < 0.01). Moreover, the AA genotype of rs13306194 APOB was associated with a significant decrease in APOB gene expression in obese infertile men (p = 0.05). There is a significant association between the Waist-to-Hip Ratio (WHR) and LH with infertility in the obese infertile group. These results are likely to contribute to a better understanding of the causes of male infertility and its association with obesity.

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study.

Introduction: Studies have shown that the gut microbiota is associated with male infertility (MI). However, their causal relationship and potential mediators need more evidence to prove. We aimed to investigate the causal relationship between the gut microbiome and MI and the potential mediating role of inflammatory cytokines from a genetic perspective through a Mendelian randomization approach. Methods: This study used data from genome-wide association studies of gut microbes (Mibiogen, n = 18, 340), inflammatory cytokines (NFBC1966, FYPCRS, FINRISK 1997 and 2002, n=13, 365), and male infertility (Finngen, n=120, 706) to perform two-way Mendelian randomization (MR), mediated MR, and multivariate MR(MVMR) analyses. In this study, the inverse variance weighting method was used as the primary analysis method, and other methods were used as supplementary analysis methods. Results: In the present study, two gut microbes and two inflammatory cytokines were found to have a potential causal relationship with MI. Of the two gut microorganisms causally associated with male infertility, Anaerotruncus increased the risk of male infertility (odds ratio = 1.81, 95% confidence interval = 1.18-2.77, P = 0.0062), and Bacteroides decreased the risk of male infertility (odds ratio = 0.57, 95% confidence interval = 0.33-0.96, P = 0.0363). In addition, of the two inflammatory cytokines identified, hepatocyte growth factor(HGF) reduced the risk of male infertility (odds ratio = 0.50, 95% confidence interval = 0.35-0.71, P = 0.0001), Monocyte chemotactic protein 3 (MCP-3) increased the risk of male infertility (odds ratio = 1.28, 95% confidence interval = 1.03-1.61, P = 0.0039). Mediated MR analysis showed that HGF mediated the causal effect of Bacteroides on MI (mediated percentage 38.9%). Multivariate MR analyses suggest that HGF may be one of the pathways through which Bacteroides affects MI, with other unexplored pathways. Conclusion: The present study suggests a causal relationship between specific gut microbiota, inflammatory cytokines, and MI. In addition, HGF may mediate the relationship between Bacteroides and MI.

Decreased embryo developmental potential and lower cumulative pregnancy rate in men with multiple morphological abnormalities of the sperm flagella.

Objective: Multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by abnormal flagellar phenotypes, which is a particular kind of asthenoteratozoospermia. Previous studies have reported a comparable intracytoplasmic sperm injection (ICSI) outcome in terms of fertilization rate and clinical pregnancy rate in patients with MMAF compared with those with no MMAF; however, others have conflicting opinions. Assisted reproductive technology (ART) outcomes in individuals with MMAF are still controversial and open to debate. Methods: A total of 38 patients with MMAF treated at an academic reproductive center between January 2014 and July 2022 were evaluated in the current retrospective cohort study and followed up until January 2023. Propensity score matching was used to adjust for the baseline clinical characteristics of the patients and to create a comparable control group. The genetic pathogenesis of MMAF was confirmed by whole exome sequencing. The main outcomes were the embryo developmental potential, the cumulative pregnancy rate (CLPR), and the cumulative live birth rate (CLBR). Results: Pathogenic variants in known genes of DNAH1, DNAH11, CFAP43, FSIP2, and SPEF2 were identified in patients with MMAF. Laboratory outcomes, including the fertilization rate, 2PN cleavage rate, blastocyst formation rate, and available blastocyst rate, followed a trend of decline in the MMAF group (p < 0.05). Moreover, according to the embryo transfer times and complete cycles, the CLPR in the cohort of MMAF was lower compared with the oligoasthenospermia pool (p = 0.033 and p = 0.020, respectively), while no statistical differences were observed in the neonatal outcomes. Conclusion: The current study presented decreased embryo developmental potential and compromised clinical outcomes in the MMAF cohort. These findings may provide clinicians with evidence to support genetic counseling and clinical guidance in specific patients with MMAF.

Mendelian randomization reveals the impact of diet on infertility in men and women.

Background: Although studies on the effects of diet on fertility has progressed, some cumulative evidence has piled against popular hypotheses. The aim of our study was to investigate the effects of 31 diets including 23 individual dietary intakes and 8 dietary habits on infertility in men and women. Methods: The datas of diets and infertility were collected from genome-wide association studies (GWAS). Mendelian randomization (MR) methods were used to analyze causal relationships. Multivariate MR (MVMR) adjusted for the effects of other exposures on causality. And MR-Egger, Cochran's Q, radial MR, and MR-PRESSO tests were employed to assess heterogeneity and horizontal pleiotropy. Results: Our study found that coffee intake (OR, 3.6967; 95% CI, 1.0348 - 13.2065; P = 0.0442) and cooked vegetable intakes (OR, 54.7865; 95% CI, 2.9011 - 1030.5500; P = 0.0076) increased the risk of male infertility. For women, beer was a risk factor for infertility (OR, 4.0932; 95% CI, 1.8728 - 8.9461; P = 0.0004); but processed meat was negatively associated with infertility (OR, 0.5148; 95% CI, 0.2730 - 0.9705; P = 0.0401). MVMR demonstrated selenium as a protective factor against female infertility (OR, 7.4474e-12; 95% CI, 5.4780e-22 - 1.0125e-01; P = 0.0314). Conclusion: We found the causal relationships between four diets and infertility. We look forward to more high-quality epidemiologic studies to prove our conclusions.

Phase angle at bioelectric impedance analysis is associated with detrimental sperm quality in idiopathic male infertility: a preliminary clinical study.

Background: In 2020, 38% of adults were affected by obesity, while infertility globally affected 1 in 6 people at some stage of their lives.Body mass index (BMI) provides an easy but occasionally inaccurate estimation of body composition. To achieve a more precise assessment, bioelectric impedance analysis serves as a validated tool that administers electrical energy through surface electrodes. Phase angle as a function of the relationship between tissues resistance and reactance, is a trustworthy predictor of body composition and cell membrane integrity. Objectives: We aim to assess whether there is an association between phase angle and seminal parameters, as well as sperm DNA fragmentation percentage. Design: Semen samples of 520 idiopathic infertile patients were analyzed according to 2021 World Health Organization guidelines and evaluated for sperm DNA fragmentation rate. Each participants underwent bioelectric impedance analysis. Results: Median age was 40 years old, median BMI was 26.3 kg/m2, median phase angle was 6.2°. In the logistic regression analysis adjusted for age and total intracorporeal water, phase angle (continuous) was significantly associated with oligozoospermia (odds ratio [OR]:0.4; p<0.01) and sperm morphology (OR: 0.65; p=0.05) and slightly with sperm DNA fragmentation (OR: 0.98; p=0.07). In subgroup analysis, the logistic regression analysis adjusted for the mentioned parameters showed that a phase angle between 6.2 and 7 (°) (OR: 0.63; p=0.02) and >7 (°) (OR: 0.12; p<0.01) were associated with a reduced risk of oligozoospermia compared to values <6.2 (°). Similarly, a phase angle between 6.2 and 7 (°) (OR: 0.57; p< 0.01 and OR: 0.58; p= 0.01) and PA > 7 (°) (OR: 0.12; p= 0.03 and OR: 0.21; p< 0.01) were associated with a reduced risk of lower sperm concentration and lower total sperm count, respectively, compared to a phase angle < 6.2 (°). Conclusion: Our study suggests a negative association between phase angle and detrimental sperm parameters in male idiopathic infertility.

Infertility and Impaired Fecundity in Women and Men in the United States, 2015-2019.

Objectives-Using National Survey of Family Growth data from 2015-2019, this report presents updated national estimates of infertility in U.S. women and men and estimates of impaired fecundity (physical ability to have children) in U.S. women. Detailed demographic breakdowns are also presented, and overall estimates for 2015-2019 are compared with those for 2011-2015. Methods-Data for this report come primarily from the 2015-2019 National Survey of Family Growth, which consisted of 21,441 interviews with men and women ages 15-49, conducted from September 2015 through September 2019. The response rate was 65.9% for women and 62.4% for men. Results-The percentage of women ages 15-44 who had impaired fecundity did not change between 2011-2015 and 2015-2019. The percentage of married women with impaired fecundity also remained stable over this time period. Among all women, 13.4% of women ages 15-49 and 15.4% of women ages 25-49 had impaired fecundity in 2015-2019. The percentage of married women ages 15-44 who were infertile rose from 2011-2015 (6.7%) to 2015-2019 (8.7%). Among married and cohabiting women ages 15-49 in 2015-2019, 7.8% had infertility. Both infertility and impaired fecundity were associated with age for nulliparous (never had a live birth) women after adjusting for other factors. Some form of infertility (either subfertility or nonsurgical sterility) was seen in 11.4% of men ages 15-49 and 12.8% of men ages 25-49 in 2015-2019. . Conclusion-Although these findings are not nationally representative, this report illustrates how linked NHCS-HUD data may provide insight into maternal health outcomes of patients who received housing assistance compared with those who did not.

A comprehensive analysis of spermatozoal RNA elements in idiopathic infertile males undergoing fertility treatment.

Current approaches to diagnosing male infertility inadequately assess the complexity of the male gamete. Beyond the paternal haploid genome, spermatozoa also deliver coding and non-coding RNAs to the oocyte. While sperm-borne RNAs have demonstrated potential involvement in embryo development, the underlying mechanisms remain unclear. In this study, 47 sperm samples from normozoospermic males undergoing fertility treatment using donor oocytes were sequenced and analyzed to evaluate associations between sperm RNA elements (exon-sized sequences) and blastocyst progression. A total of 366 RNA elements (REs) were significantly associated with blastocyst rate (padj < 0.05), some of which were linked to genes related to critical developmental processes, including mitotic spindle formation and both ectoderm and mesoderm specification. Of note, 27 RE-associated RNAs are predicted targets of our previously reported list of developmentally significant miRNAs. Inverse RE-miRNA expression patterns were consistent with miRNA-mediated down-regulation. This study provides a comprehensive set of REs which differ by the patient's ability to produce blastocysts. This knowledge can be leveraged to improve clinical screening of male infertility and ultimately reduce time to pregnancy.

Reactive oxygen species and their role in the andrological factor of couple fertility.

Reactive oxygen species play a significant role in male fertility and infertility. They are essential for physiological processes, but when their concentration becomes excessive, they can be a cause of various sperm pathologies. Seminal leukocytes and pathologically abnormal sperm are the primary sources of oxygen radicals in ejaculate. They negatively affect sperm quality, including DNA fragmentation and sperm motility impairment. Addressing increased concentrations of reactive oxygen species involves various appropriate lifestyle modifications and measures, including the use of antioxidants, treatment of urogenital infections, management of varicocele, weight reduction, and others. In many cases, these interventions can lead to adjustments in the condition and improvement in sperm quality. Such improvements can subsequently lead to enhanced outcomes in assisted reproduction or even an increased likelihood of natural conception. In some instances, the need for donor sperm may be eliminated. However, a key factor is adhering to a sufficiently prolonged treatment, which requires patience on the part of both, the physician and the patient.

The quality of life of men experiencing infertility: a systematic review.

BACKGROUND: Men experiencing infertility encounter numerous problems at the individual, family, and social levels as well as quality of life (QOL). This study was designed to investigate the QOL of men experiencing infertility through a systematic review. MATERIALS AND METHODS: This systematic review was conducted without any time limitation (Retrieval date: July 1, 2023) in international databases such as Scopus, Web of Science, PubMed, and Google Scholar. The search was performed by two reviewers separately using keywords such as QOL, infertility, and men. Studies were selected based on inclusion and exclusion criteria. The quality of the articles were evaluated based on the Newcastle-Ottawa Scale. In the initial search, 308 studies were reviewed, and after removing duplicates and checking the title and abstract, the full text of 87 studies were evaluated. RESULTS: Finally, 24 studies were included in the final review based on the research objectives. Based on the results, men's QOL scores in different studies varied from 55.15 ± 13.52 to 91.45 ± 13.66%. Of the total reviewed articles, the lowest and highest scores were related to mental health problems and physical dimensions, respectively. CONCLUSION: The reported findings vary across various studies conducted in different countries. Analysis of the factors affecting these differences is necessary, and it is recommended to design a standard tool for assessing the quality of life of infertile men. Given the importance of the QOL in men experiencing infertility, it is crucial to consider it in the health system. Moreover, a plan should be designed, implemented and evaluated according to each country's contex to improve the quality of life of infertile men.

Non-invasive biomarkers for sperm retrieval in non-obstructive patients: a comprehensive review.

Recent advancements in reproductive medicine have guided novel strategies for addressing male infertility, particularly in cases of non-obstructive azoospermia (NOA). Two prominent invasive interventions, namely testicular sperm extraction (TESE) and microdissection TESE (micro-TESE), have emerged as key techniques to retrieve gametes for assisted reproduction technologies (ART). Both heterogeneity and complexity of NOA pose a multifaceted challenge to clinicians, as the invasiveness of these procedures and their unpredictable success underscore the need for more precise guidance. Seminal plasma can be aptly regarded as a liquid biopsy of the male reproductive tract, encompassing secretions from the testes, epididymides, seminal vesicles, bulbourethral glands, and prostate. This fluid harbors a variety of cell-free nucleic acids, microvesicles, proteins, and metabolites intricately linked to gonadal activity. However, despite numerous investigations exploring potential biomarkers from seminal fluid, their widespread inclusion into the clinical practice remains limited. This could be partially due to the complex interplay of diverse clinical and genetic factors inherent to NOA that likely contributes to the absence of definitive biomarkers for residual spermatogenesis. It is conceivable that the integration of clinical data with biomarkers could increase the potential in predicting surgical procedure outcomes and their choice in NOA cases. This comprehensive review addresses the challenge of sperm retrieval in NOA through non-invasive biomarkers. Moreover, we delve into promising perspectives, elucidating innovative approaches grounded in multi-omics methodologies, including genomics, transcriptomics and proteomics. These cutting-edge techniques, combined with the clinical and genetics features of patients, could improve the use of biomarkers in personalized medical approaches, patient counseling, and the decision-making continuum. Finally, Artificial intelligence (AI) holds significant potential in the realm of combining biomarkers and clinical data, also in the context of identifying non-invasive biomarkers for sperm retrieval.

Gonadal dysfunction in a man with Noonan syndrome from the LZTR1 variant: case report and review of literature.

Noonan syndrome (NS) is a genetic disorder characterized by multiple congenital defects caused by mutations in the RAS/mitogen-activated protein kinase pathway. Male fertility has been reported to be impaired in NS, but only a few studies have focused on fertility status in NS patients and underlying mechanisms are still incompletely understood. We describe the case of a 35-year-old man who underwent an andrological evaluation due to erectile dysfunction and severe oligospermia. A syndromic facial appearance and reduced testis size were present on clinical examination. Hormonal evaluation showed normal total testosterone level, high FSH level, and low-normal AMH and inhibin B, compatible with primary Sertoli cell dysfunction. Genetic analysis demonstrated the pathogenetic heterozygous variant c.742G>A, p.(Gly248Arg) of the LZTR1 gene (NM_006767.3). This case report provides increased knowledge on primary gonadal dysfunction in men with NS and enriches the clinical spectrum of NS from a rare variant in the novel gene LZTR1.

Loss of PBX1 function in Leydig cells causes testicular dysgenesis and male sterility.

Leydig cells are essential components of testicular interstitial tissue and serve as a primary source of androgen in males. A functional deficiency in Leydig cells often causes severe reproductive disorders; however, the transcriptional programs underlying the fate decisions and steroidogenesis of these cells have not been fully defined. In this study, we report that the homeodomain transcription factor PBX1 is a master regulator of Leydig cell differentiation and testosterone production in mice. PBX1 was highly expressed in Leydig cells and peritubular myoid cells in the adult testis. Conditional deletion of Pbx1 in Leydig cells caused spermatogenic defects and complete sterility. Histological examinations revealed that Pbx1 deletion impaired testicular structure and led to disorganization of the seminiferous tubules. Single-cell RNA-seq analysis revealed that loss of Pbx1 function affected the fate decisions of progenitor Leydig cells and altered the transcription of genes associated with testosterone synthesis in the adult testis. Pbx1 directly regulates the transcription of genes that play important roles in steroidogenesis (Prlr, Nr2f2 and Nedd4). Further analysis demonstrated that deletion of Pbx1 leads to a significant decrease in testosterone levels, accompanied by increases in pregnenolone, androstenedione and luteinizing hormone. Collectively, our data revealed that PBX1 is indispensable for maintaining Leydig cell function. These findings provide insights into testicular dysgenesis and the regulation of hormone secretion in Leydig cells.

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.

Use of empirical medical therapies for idiopathic male infertility in Australia and New Zealand.

OBJECTIVE: Idiopathic male infertility is common, yet there is no approved treatment. This study aimed to understand practice patterns towards empirical medical therapy (EMT) for idiopathic male infertility in Australia and New Zealand (NZ). DESIGN: Clinical members of the Endocrine Society of Australia, Fertility Society of Australia & NZ, and Urological Society of Australia & NZ were invited to complete a survey. Questions included demographics, EMT practice habits, and thoughts regarding infertility case scenarios. Unadjusted group differences between specialists, those with and without additional training in male infertility, and frequency of managing it were evaluated. RESULTS: Overall, 147 of 2340 members participated (6.3%); majority were endocrinologists and gynaecologists. Participants were experienced; 35% had completed additional training in male infertility and 36.2% reported they frequently manage male infertility. Gynaecologists were more likely to manage male infertility and attend education courses than endocrinologists and urologists. Beliefs about the effect of EMT on sperm concentration and pregnancy did not differ between speciality types. Many respondents considered all patient scenarios suitable for EMT. Of medications, hCG and clomiphene were selected most. Two respondents indicated they would use testosterone to treat male infertility. CONCLUSIONS: This study demonstrates common use of EMT in Australia and NZ for idiopathic male infertility. The breadth of responses reflects a lack of consensus within the current literature, highlighting the need for further research to clarify their role in the management of idiopathic male infertility.

Age-related increase in live-birth rates of first frozen thaw embryo versus first fresh transfer in initial assisted reproductive technology cycles without PGT.

BACKGROUND: The landscape of assisted reproductive technology (ART) has seen a significant shift towards frozen-thawed embryo transfers (FET) over fresh transfers, driven by technological advancements and clinical considerations. This study aimed to compare live birth outcomes between primary FET and fresh transfers, focusing on cycles without preimplantation genetic testing (PGT), using United States national data from the SART CORS database spanning from 2014 to 2020. METHODS: We performed a retrospective cohort study of autologous first ART cycles without PGT comparing primary embryo transfer (frozen thaw vs. fresh) success rates from the 2014-2020 SARTCORS database. Live-birth rates (LBR) and cumulative live-birth rates (CLBR) were compared between first FET versus first fresh embryo transfer from an index retrieval. Multivariate logistic regression (MLR) determined association between live birth outcomes and method of transfer. In a subsequent sub-analysis, we compared these two embryo transfer methods among patients with either diminished ovarian reserve (DOR) or male factor infertility. RESULTS: 228,171 first ART cycles resulted in primary embryo transfer. 62,100 initial FETs and 166,071 fresh transfers were compared. Initial FETs demonstrated higher LBR and CLBR compared to fresh transfers (LBR 48.3% vs. 39.8%, p < 0.001; CLBR 74.0% vs. 60.0%, p < 0.0001). MLR indicated greater chances of live birth with FET across all age groups, with adjusted odds ratio (aOR) of live-birth incrementally increasing with advancing age groups. For DOR cycles, LBR and CLBR were significantly higher for FET compared to fresh (33.9% vs. 26.0%, p < 0.001, 44.5% vs. 37.6%, p < 0.0001), respectively. MF cycles also demonstrated higher LBR and CLBR with FET (52.3% vs. 44.2%, p < 0.001, 81.2% vs. 68.9%, p < 0.0001), respectively. MLR demonstrated that in DOR cycles, initial FET was associated with greater chance of live birth in age groups ≥ 35yo (p < 0.01), with aOR of live birth increasingly considerably for those > 42yo (aOR 2.63, p < 0.0001). CONCLUSIONS: Overall LBR and CLBR were greater for first FET than fresh transfers with incremental increases in odds of live birth with advancing age, suggesting the presence of a more favorable age-related change in endometrial receptivity present in frozen-thawed cycles. For both DOR and MF cycles, LBR and CLBR after primary transfer were greater for first FET than fresh. However, this was particularly evident in older ages for DOR cycles. This suggests that supraphysiologic stimulation in older DOR cycles may be detrimental to endometrial receptivity, which is in part corrected for in FET cycles.

Sperm Chromatin Dispersion Test Detects Sperm DNA Fragmentation Mainly Associated with Unviable Spermatozoa and Underestimates the Values with Respect to TUNEL Assay.

Several clinical laboratories assess sperm DNA fragmentation (sDF) in addition to semen analysis in male infertility diagnosis. Among tests evaluating sDF, TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) and SCD (Sperm Chromatin Dispersion) are widely used. Our lab developed a modified version of TUNEL (TUNEL/PI) able to distinguish two sperm populations (PI Brighter and PI Dimmer) differently associated with sperm viability and reproductive outcomes. The aim of this study was to compare sDF levels detected by SCD and TUNEL/PI in the semen samples from 71 male subjects attending our Andrology Laboratory. Our results demonstrate that SCD is less sensitive in determining sDF compared to TUNEL/PI. The statistically significant positive correlation found between sDF evaluated by SCD and PI Dimmer (consisting of all dead spermatozoa) suggests that SCD mainly detects sDF in unviable spermatozoa. We confirmed that most spermatozoa detected by SCD are unviable by performing SCD after incubation in hypo-osmotic medium to discriminate viable and unviable cells in 52 samples. Such results might explain the lower ability of this test in discriminating couples having successful ART outcomes demonstrated in published metanalyses. Overall, our results indicate that SCD is less sensitive in evaluating sDF for diagnostic purposes.

[Clinical guidelines for male infertility: controversial issues and the need to reach interdisciplinary consensus].

A review of controversial issues about the terminology on male infertility and reproductive function, which is currently used, as well as proposals for updating clinical guidelines for the diagnosis and treatment of male infertility and men in infertile couples are presented in the article. An algorithm is described, the elements of which ensure referral of patients based on the possibility and timing of restoration of reproductive function, taking into account the reproductive health of a woman, as well as increasing the likelihood of successful treatment aimed at the birth of a healthy child.

Radiation and male reproductive system: Damage and protection.

Male fertility has been declining in recent decades, and a growing body of research points to environmental and lifestyle factors as the cause. The widespread use of radiation technology may result in more people affected by male infertility, as it is well established that radiation can cause reproductive impairment in men. This article provides a review of radiation-induced damage to male reproduction, and the effects of damage mechanisms and pharmacotherapy. It is hoped that this review will contribute to the understanding of the effects of radiation on male reproduction, and provide information for research into drugs that can protect the reproductive health of males.

Correlación entre el polimorfismo de los genes LHCGR y NR5A1y el riesgo de infertilidad masculina / Correlation between LHCGR and NR5A1 genes polymorphism and male infertility risk

Introducción La infertilidad constituye un problema de salud que afecta gravemente la reproducción humana. En el caso de la infertilidad masculina, la mayoría de los casos se deben a factores genéticos. En este estudio nos propusimos realizar un análisis de correlación entre la infertilidad masculina idiopática y el polimorfismo de un solo nucleótido (SNP, por Single Nucleotide Polymorphism) de los genes LHCGR (rs2293275) y NR5A1 (rs1057517779) en la población azerí de Irán. Métodos En este estudio de casos y controles participaron 100 varones infértiles y 100 varones sanos procedentes de la población azerí iraní. La genotipificación se realizó mediante el aislamiento del ADN genómico a partir de muestras de sangre total con el sistema de amplificación por reacción en cadena de la polimerasa refractario a mutaciones Tetra-primer (Tetra-ARMS-PCR). El análisis de los datos se llevó a cabo mediante la prueba de Chi-cuadrado (χ2) y la prueba exacta de Fisher. Resultados Según el análisis de genotipificación del polimorfismo LHCGR (rs2293275), la frecuencia del alelo C en el grupo de casos era significativamente mayor que en el grupo de control (p<0,05). El análisis del polimorfismo NR5A1 (rs1057517779) indicó que la frecuencia del alelo A y del genotipo heterocigoto GA en el grupo de casos era significativamente superior a la del grupo de control (p<0,05). Conclusión Nuestro estudio demostró que los SNP de los genes LHCGR (rs2293275) y NR5A1 (rs1057517779) pueden desempeñar un papel crucial en la infertilidad masculina de la población azerí en Irán. Sin embargo, se requieren más estudios realizados en otros orígenes étnicos con muestras de mayor tamaño para obtener resultados más precisos. Además, podrían ser necesarios experimentos funcionales para comprender el papel de estos polimorfismos en las vías moleculares implicadas en la fertilidad masculina. (AU)

Introduction Infertility is one of the important phenomena in human reproduction. Genetic factors are the most important cause of male infertility. Here, we aimed to investigate the correlation between idiopathic male infertility and SNPs of the LHCGR (rs2293275) and NR5A1 (rs1057517779) genes in the Iranian-Azeri population. Methods This case-control study consisted of 100 males with infertility and 100 healthy males from the Iranian Azeri population. Genomic DNA isolation from whole blood samples and Tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS-PCR) method was used for genotyping. The data analysis was performed by Chi-square (χ2) and Fisher's exact tests. Results Genotyping analysis for LHCGR (rs2293275) polymorphism indicated that the frequency of C in the case group was significantly higher than in the control group (P<.05). Moreover, genotyping analysis for NR5A1 (rs1057517779) polymorphism indicated that the frequencies of the A allele and heterozygote GA genotype in the case group were significantly higher than those in the control group (P<.05). Conclusion Our study demonstrated that the SNPs of LHCGR (rs2293275) and NR5A1 (rs1057517779) genes may play a critical role in male infertility in the Iranian Azeri population. However, further studies on other ethnic origins with larger sample sizes are essential for accessing more accurate results. Moreover, functional experiments might be needed to understand the role of these polymorphisms in the molecular pathways involved in male fertility. (AU)