Male infertility.

Aims: The potential mechanisms underlying unexplained infertility, which is a condition in which couples experience infertility without an identifiable cause in both man and woman, have not yet been clarified. The present study aimed to investigate the role of Sirtuin 1 (SIRT1) gene in male infertility and unexplained infertility. Methods: A total of 50 couples who applied for infertility evaluation and treatment were included in the study. The couples' medical histories were taken and their fertility status was evaluated. Semen analysis results evaluated according to World Health Organization (WHO, 2010) criteria were divided into low and normal semen parameter groups in terms of sperm count and motility parameters. Couples were further categorized into three groups according to their fertility status; Non-infertility group (n=13): Couples without clinical infertility (no female and male factor (normal semen variables)). Male infertility group (n=19): Couples with clinical infertility (no female factor, with male factor (abnormal semen variables)). Unexplained infertility group (n=18): Couples with clinical infertility without an identifiable cause in male (normal semen variables) and female. Changes in SIRT1 gene expression between the groups were investigated using qPCR. Results: SIRT1 gene expression was not associated with sperm count and motility parameters. However, SIRT1 expression was observed to be significantly decreased in male infertility and, more importantly, in unexplained infertility groups, compared to the non-infertility group. Conclusions: Our study suggests that decreased SIRT1 may play a role in fertilization potential by affecting possibly different functions of sperm rather than count and motility parameters and may be one of the possible mechanisms underlying unexplained infertility.

Male infertility as a window to health

Significance of sperm characteristics in the evaluation of male infertility

It has been reported that fatherhood status may be a risk factor for prostate cancer. In the current study, the authors examined the subsequent occurrence of prostate cancer in a cohort of men evaluated for infertility to determine whether male infertility is a risk factor for prostate cancer. A total of 22,562 men who were evaluated for infertility from 1967 to 1998 were identified from 15 California infertility centers and linked to the California Cancer Registry. The incidence of prostate cancer was compared with the incidence in an age-matched and geography-matched sample of men from the general population. The risk of prostate cancer in men with and those without male factor infertility was modeled using a Cox proportional hazards regression model. A total of 168 cases of prostate cancer that developed after infertility were identified. Men evaluated for infertility but not necessarily with male factors were not found to have an increased risk of cancer compared with the general population (standardized incidence ratio [SIR], 0.9; 95% confidence interval [95% CI], 0.8-1.1). This risk was found to be highest for men with male factor infertility who developed high-grade prostate cancer (SIR, 2.0; 95% CI, 1.2-3.0). On multivariate analyses, men with male factor infertility were found to be 2.6 times more likely to be diagnosed with high-grade prostate cancer (hazard ratio, 2.6; 95% CI, 1.4-4.8). Men with male factor infertility were found to have an increased risk of subsequently developing high-grade prostate cancer. Male infertility may be an early and identifiable risk factor for the development of clinically significant prostate cancer.

Study question Can next generation sequencing (NGS) contribute to diagnoses male idiopathic infertility? Summary answer A male factor gene panel identifies pathogenic variants associated to spermatogenic failure in oligozoospermia and cryptozoospermia patients. What is known already In 50% of cases, infertility is due to a male factor problem. Although the causes of male infertility are heterogeneous, genetic causes account for approximately 30% of cases. Some phenotypes have been associated with specific genetic disorders such as chromosomal abnormalities and chromosome Y microdeletions. However, current genetic studies explain only 4% of cases, whilst most cases of male factor infertility remain without a clear diagnosis. Therefore, new techniques that explain the cause of male infertility are needed. Advances in NGS allowed us to study a large number of genes involved in spermatogenesis process in patients with idiopathic infertility. Study design, size, duration A retrospective study was performed from July 2020 until May 2021. A total of 30 patients with abnormal seminal count parameters (oligozoospermic and cryptozoospermic) were included in the male factor gene panel study. Patients carrying Y-chromosome microdeletions or abnormal karyotype were excluded. The control group included 20 normozoospermic healthy donors selected on the basis of normal semen parameters according to the WHO criteria (2010). Participants/materials, setting, methods Genomic DNA extraction from blood-EDTA of the patients was performed using the commercial MagMax DNA MultiSample Ultra kit and the King-Fisher automated extractor (ThermoFisher®). Next Generation Sequencing (NGS) was done using a panel with 426 genes involved in the spermatogenesis process. Panel sequencing for identification of genetic variants was performed using Nextera Enrichment technology (Illumina®). FASTAQ data were processed using BWA and GATK algorithms. VCF files were analyzed using Variant Interpreter software. Main results and the role of chance After data analysis, we observed that eight of the thirty patients studied were carriers of mutations in least one of the genes included in the panel (8/30, 26.7%). We identified the following pathogenic variants: a missense mutation (Phe1052Val) and a deletion (Phe508del) of CFTR gene (2/30, 6.6%), two frameshifts (Asp128GlufsTer34 and Lys1299Ter) of CEP290 (2/30, 6.6%), a missense mutation (Tyr284Cys) of GNRHR gene (1/30, 3.3%), a missense mutation (Tyr416Cys) of SCN5A gene (1/30, 3.3%), a deletion (Ser83del) of NANOS1 gene (1/30, 3.3%), a stop gained in splice region Arg341Ter of TEX14 gene (1/30, 3.3%), a splicing donor c.362 + 2T>C of ESR2 gene (1/30, 3.3%) and a missense mutation (Ser321Leu) of DNAH5 gene (1/30, 3.3%), which are related to spermatogenesis failure. Additionally, some variants classified as benign have been identified, which are not associated with pathogenicity. All the variants identified are related with male infertility, affecting spermatogenesis process, such as congenital bilateral absence of the vas deferens (CFTR), reproductive system syndrome (CEP190), endocrine disorder (GNRHR, hypogonadotropic hypogonadism), testis expressed (SCN5A), spermatogenic failure (NANOS1, TEX14 and ESR2) and syndromic infertility (DNAH5). Nevertheless, no pathogenic mutations associated to spermatogenic failure were observed in the control group. Limitations, reasons for caution The main limitation of this study is the small number of patients included. Further studies including a higher number of males with idiopathic infertility are warranted to confidently link the genetic variants included in our gene panel to spermatogenic failure. Wider implications of the findings The gene list included in our panel represents a step-forward in the diagnosis screening of males with altered sperm parameters. Our results may add in the knowledge of male factor infertility in order to provide etiologic factors towards a personalized treatment and adequate genetic counselling. Trial registration number Not applicable

The male factor is considered a major contributory factor to infertility. Apart from the conventional causes for male infertility such as varicocoele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma and tumours, a new and important cause has been identified as being responsible for the so-called idiopathic male infertility: oxidative stress. Oxidative Stress (OS) is a condition that occurs when the production of Reactive Oxygen Species (ROS) overwhelms the antioxidant defense produced against them. In male reproductive pathological conditions, the OS significantly impairs spermatogenesis and sperm function, which may lead to male infertility. Reactive Oxygen Species (ROS) known as free radicals are oxidizing agents generated as a result of metabolism of oxygen and have at least one unpaired electron that make them very reactive species. Spermatozoa generate Reactive Oxygen Species (ROS) in physiological amounts, which play a role in sperm functions during sperm capacitation, Acrosome Reaction (AR) and oocyte fusion, but they need to be controlled and their concentrations maintained at a level that is not deleterious to the cells. Administration of antioxidants in patients with 'male factor' infertility has begun to attract considerable interest. The main difficulty of such an approach is our incomplete understanding of the role of free radicals in normal and abnormal sperm function leading to male infertility. The purpose of the present review is to address the relationship between ROS and idiopathic male factor infertility.

To analyze the reproductive outcome in infertile couples which underwent intraperitoneal insemination (IPI). We analyzed a series of 216 couples who underwent IPI. Indications for treatment were unexplained infertility in 51 couples and male factor in 165. The 51 couples with unexplained infertility underwent a total of 71 cycles (20 couples underwent a second IPI cycle). The 165 couples with male factor underwent 243 cycles (165 first cycles and 78 second cycles). Out of the 314 cycles performed, a total of 41 clinical pregnancies were observed, with a corresponding conception rate of 13.1%. The values of conception rates for unexplained and male factor infertility were 21.1 (based on 15 pregnancies) and 10.7% (based on 26 pregnancies), respectively. Out of the 41 pregnant women, 26 gave birth to a child, thus the overall livebirth rate was 8.3% (12.7 and 7.0%, respectively, for unexplained infertility and male factor diagnostic subgroups). Considering the couples with unexplained infertility, the conception rates were 9.0, 30.8 and 20.0% for strata of < 5, 5-10 and > or = 10 millions of inseminated spermatozoa. The corresponding values were 6.8, 12.5 and 18.5%, respectively, in couples with male factor infertility (chi(2)1 trend p < 0.05). In conclusion, this series provides quantitative estimates of pregnancy rates after IPI in Italian couples with unexplained infertility or male infertility and suggested that the number of motile sperm inseminated is a determinant of pregnancy with this technique.

Infertility is a significant global health issue, affecting 8–12% of couples of reproductive age, with male factor infertility contributing to 30–50% of cases. Despite advances in assisted reproductive technologies, particularly intra-cytoplasmic sperm injection, male infertility remains understudied compared to female infertility. This review aims to explore the genetic underpinnings of male factor infertility, including identified genetic mutations, chromosomal abnormalities, and epigenetic factors, and to investigate the broader health implications for affected men. The emerging data suggest that male infertility is not only a reproductive issue but also a potential predictor of chronic diseases, including autoimmune disorders, cancer, and premature death. Additionally, the inheritance of male factor infertility and its potential effects on offspring health remains indeterminate. Studies have shown conflicting results regarding the impact of parental infertility and fertility treatments on the semen quality and reproductive health of offspring. This review summarizes the current understanding of the genetic causes of male infertility, highlights the impact of chromosomal disorders, reviews the spectrum of sperm quality and hormonal profiles, and discourses on the need for further research to clarify the relationships between parental subfertility, male infertility, and offspring health. By investigating these complex interrelationships, future research can help shape more effective diagnostic and treatment strategies for male infertility and its broader implications for men’s health and future generations.

The field of male infertility remains a niche specialty within urology. Although a male factor is implicated in at least 50% of all cases of infertility, and male infertility is thought to be associated with overall male health and longevity, this subspecialty comprises a relatively small proportion of urologic training. There remains a large knowledge gap with regards to prevalence of male factor infertility, as well as the need for health services for the diagnosis and treatment of male infertility. Health services research is a multidisciplinary approach that combines both qualitative and quantitative methodologies to improve patient care and outcomes pertaining to male infertility. This review summarizes the current literature pertaining to health services for male infertility and identifies opportunities for future research to improve access to and outcomes of male infertility care, including improvements in costs of care, patient education, and health policy.

Introduction: The prevalence of infertility has increased worldwide. The etiological factors are also changing in trend and prominence. Male infertility is driving the epidemic in many regions of the world. Therefore, the aim of this study was to explore male factor infertility in the Gambia. Methodology: The design was a longitudinal descriptive study of subfertile couples at a specialist tertiary hospital in Banjul, the Gambia, from August 2022 to May 2023. Data were extracted from patients folders and entered into a computer database. Descriptive statistics were used to analyze the data and results expressed in tables, graphs, and percentages. Results: Total number of subfertile couples analyzed was 152: male factor 69 (45.4%), ovulation disorder 34 (22.4%), tubal factor 20 (13.2%), uterine factor 8 (5.3%), and unexplained 21 (13.8%). The median age of male folk was 50 years, with an age range of 31 to 64 years. The rates of asthenoteratozospermia, oligospermia, and azospermia were 37.8%, 36.2%, and 26%, respectively. In azoospermic males, over 75% had elevated FSH (12–44 miu/mL). Conclusions: The prevalence of male infertility is at 45.4%, which is 3-fold and 2-fold higher than tubal and ovarian factors, respectively. Male infertility is a problem with obvious implications. The predominant types of male infertility we observed in this study will almost always require multidisciplinary care and ICSI.

The aim of this study was to characterise the clinical and laboratory parameters in young in vitro fertilisation(IVF) patients with high order recurrent implantation failure (RIF). The first 3 cycles (n = 141 cycles) of 47 consecutive (age <35 years) couples with RIF (> or =6 IVF cycles) were compared with 252 consecutive cycles of 152 couples,treated during the same period, who conceived within the first 3 IVF cycles. The incidence of male factor infertility or of combined male and female factors was significantly higher in the study group than the control group (male factor: 78.7 versus 42.5%, p= 0.002, OR = 3.2 (95% CI: 1.56.8)). Lower fertilisation rates were noted for the intracytoplasmic sperm injection (ICSI)-treated oocytes of the study group compared with the control group. The availability of high quality embryos for transfer was significantly lower in the RIF group. On multivariate logistic regression analysis, the significantly different variables between the groups were cause of infertility (male factor or combined male and female factors) (p = 0.03),fertilisation rate (p = 0.038), and semen concentration (p = 0.05). CONCLUSIONS; Young IVF patients with high order RIF are characterised by male factor infertility, lower fertilisation rate with ICSI, and fewer high quality embryos available for transfer.

Background and Objectives: Male infertility has emerged as a growing global health concern, contributing to 20-30% of all infertility cases. It is a multifactorial condition, arising from genetic, endocrine, structural, environmental and lifestyle factors. This narrative review synthesizes current evidence on epidemiology, diagnostic advances and therapeutic strategies while highlighting emerging trends and research priorities. Materials and Methods: This review adheres to SANRA guidelines. Literature was sourced from PubMed, Saudi Digital Library, Google Scholar, and PsycINFO using MeSH terms including "Male Infertility," "Diagnosis," "Treatment," and "Epidemiology." Results: Diagnostic evaluation of male infertility includes clinical assessment, advanced semen analysis, imaging techniques, hormonal assays and molecular testing. Despite significant advances in the evaluation of male infertility, idiopathic causes (30-40%) remain challenging. Management strategies include lifestyle modifications, medical therapies including hormones and drugs, surgical interventions, and assisted reproductive technologies (ARTs). However, outcomes remain suboptimal in idiopathic and severe cases, particularly regarding sperm DNA fragmentation and environmental exposures. Conclusions: Substantial knowledge gaps exist in male infertility, particularly in idiopathic cases, molecular mechanisms of environmental pollutants, and long-term ART offspring outcomes. Future research priorities include: (1) molecular and epigenetic biomarkers for improved diagnosis and prognosis; (2) environmental exposure assessment and mitigation strategies; (3) metabolomics-guided personalized therapies; (4) regenerative medicine approaches including spermatogonial stem cell therapy; and (5) multidisciplinary integrative care models. Addressing these gaps through coordinated research and clinical innovation is essential for improving male reproductive health globally.

Background: Infertility affects about 10-15% of reproductive age couples. The main causes of infertility include male factor, ovulatory disorders, tubal factor and endometriosis. This study was conducted to determine the role of Diagnostic hystero-laparoscopy (DHL) in the evaluation of female infertility.Methods: This study was a prospective study done in a tertiary care centre over a period of 1 year on all infertile couples. The exclusion criteria: male factor infertility, hypothyroidism, hyperprolactinemia, acute pelvic inflammatory disease. Diagnostic hysterolaparoscopy was performed in all study patients in pre ovulatory phase, under general anaesthesia. The findings were then documented and analysed.Results: A total number of 90 patients were recruited for the study. The mean age of the patients was 28±3 years. The mean BMI of the study patients was 25±4 kg/m2. The mean duration of infertility was 5.4 years. On laparoscopy, 28 patients had polycystic ovaries (31.1%), 4 patients had pelvic adhesions (4.4%), 2 patients had endometriosis (2.2%) and tubal block was identified in 10 patients (11.11%). 10 patients had abnormal findings on hysteroscopy.Conclusions: Hystero laparoscopy is an effective diagnostic tool in the evaluation of infertility and has to be included in basic diagnostic workup.

New insights to guide patient care: the bidirectional relationship between male infertility and male health

Infertility is a devastating experience for both partners as they try to conceive. Historically, when a couple could not conceive, the woman has carried the stigma of infertility; however, men and women are just as likely to contribute to the couple’s infertility. With the development of assisted reproductive technology (ART), the treatment burden for male and unexplained infertility has fallen mainly on women. Equalizing this burden requires reviving research on male infertility to both improve treatment options and enable natural conception. Despite many scientific efforts, infertility in men due to sperm dysfunction is mainly diagnosed by a semen analysis. The semen analysis is limited as it only examines general sperm properties such as concentration, motility, and morphology. A diagnosis of male infertility rarely includes an assessment of internal sperm components such as DNA, which is well documented to have an impact on infertility, or other components such as RNA and centrioles, which are beginning to be adopted. Assessment of these components is not typically included in current diagnostic testing because available treatments are limited. Recent research has expanded our understanding of sperm biology and suggests that these components may also contribute to the failure to achieve pregnancy. Understanding the sperm’s internal components, and how they contribute to male infertility, would provide avenues for new therapies that are based on treating men directly for male infertility, which may enable less invasive treatments and even natural conception.