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Translational Andrology and Urology Feb 2024Basic semen analysis is the first step in the evaluation of male infertility. It includes an assessment of sperm morphology which is believed to reflect on overall... (Review)
Review
BACKGROUND AND OBJECTIVE
Basic semen analysis is the first step in the evaluation of male infertility. It includes an assessment of sperm morphology which is believed to reflect on overall spermatogenesis and sperm function. Teratozoospermia, defined as abnormal sperm morphology, is frequently present in association with severe oligoasthenozoospermia, but isolated teratozoospermia (in the presence of normal counts and motility) is a poorly understood clinical entity with conflicting implications in terms of fertility potential and treatment strategies. The following paper aims to: (I) discuss the classification of sperm morphology, causes, and molecular mechanism of teratozoospermia; (II) analyze the clinical significance and potential treatment options of isolated teratozoospermia as a cause of male infertility and a predictor of fertility outcome; and (III) provide a SWOT (strengths, weaknesses, opportunities, and threats) analysis based on the existing literature on this topic.
METHODS
A comprehensive search from database inception to 25 April 2023 was conducted in PubMed for relevant papers relating to isolated teratozoospermia in male infertility. Finally, seven systematic reviews/reviews/meta-analyses and 81 original articles were synthesized into the current narrative review.
KEY CONTENT AND FINDINGS
Classification of sperm morphology has evolved significantly since the first edition of the World Health Organization (WHO) Manual of Human Semen Analysis. Kruger's strict criteria are the most used classification and have been shown to correlate with fertility outcomes. There are many causes of teratozoospermia including genetic and environmental factors and physical conditions like varicocele. Teratozoospermia correlates with sperm DNA damage, elevated oxidative stress, low antioxidant function, and apoptotic alterations, which can result in impaired spermatozoa function and lower pregnancy rates. However, the clinical correlation between teratozoospermia and assisted reproductive technology (ART) outcome shows conflicting data with recent meta-analyses suggesting that isolated teratozoospermia was not associated with poor fertility outcomes from ART and that intrauterine insemination (IUI) can be an effective option even in the presence of teratozoospermia. There is very limited data on effective therapeutic options to treat idiopathic isolated teratozoospermia. The opportunity for future research is huge to fill the gap in the medical literature on this topic.
CONCLUSIONS
Contemporary literature on isolated teratozoospermia shows conflicting results in terms of its actual clinical implication in male infertility and the utility of available treatment options. Further research is warranted on this clinical entity to improve sperm function and future paternity.
PubMed: 38481866
DOI: 10.21037/tau-23-397 -
Frontiers in Endocrinology 2024Infertility affects approximately 10-15% of couples worldwide who are attempting to conceive, with male infertility accounting for 50% of infertility cases. Male... (Review)
Review
Infertility affects approximately 10-15% of couples worldwide who are attempting to conceive, with male infertility accounting for 50% of infertility cases. Male infertility is related to various factors such as hormone imbalance, urogenital diseases, environmental factors, and genetic factors. Owing to its relationship with genetic factors, male infertility cannot be diagnosed through routine examination in most cases, and is clinically called 'idiopathic male infertility.' Recent studies have provided evidence that microRNAs (miRNAs) are expressed in a cell-or stage-specific manner during spermatogenesis. This review focuses on the role of miRNAs in male infertility and spermatogenesis. Data were collected from published studies that investigated the effects of miRNAs on spermatogenesis, sperm quality and quantity, fertilization, embryo development, and assisted reproductive technology (ART) outcomes. Based on the findings of these studies, we summarize the targets of miRNAs and the resulting functional effects that occur due to changes in miRNA expression at various stages of spermatogenesis, including undifferentiated and differentiating spermatogonia, spermatocytes, spermatids, and Sertoli cells (SCs). In addition, we discuss potential markers for diagnosing male infertility and predicting the varicocele grade, surgical outcomes, ART outcomes, and sperm retrieval rates in patients with non-obstructive azoospermia (NOA).
Topics: Humans; Male; MicroRNAs; Semen; Infertility, Male; Spermatogenesis; Phenotype; Biomarkers
PubMed: 38449855
DOI: 10.3389/fendo.2024.1293368 -
The World Journal of Men's Health Jul 2024Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s)...
PURPOSE
Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele.
MATERIALS AND METHODS
A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×10), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist.
RESULTS
Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high.
CONCLUSIONS
This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage.
PubMed: 38449451
DOI: 10.5534/wjmh.230260 -
JBRA Assisted Reproduction Mar 2024Sperm Associated Antigen 11A (SPAG11A) protein is a family of the epididymis-specific secretory proteins implicated in sperm maturation and function. Varicocele might...
OBJECTIVE
Sperm Associated Antigen 11A (SPAG11A) protein is a family of the epididymis-specific secretory proteins implicated in sperm maturation and function. Varicocele might cause pathophysiological difficulties in the testis and epididymis, with a harmful effect on the environment for spermatogenesis and sperm maturation. The aim of this study was to evaluate the expression level of the SPAG11A gene and sperm parameters in infertile men with grade 1 and 2 varicocele before and after treatment.
METHODS
Semen specimens were collected from 20 infertile men with varicocele pre-and post-treatment and 10 healthy volunteers. Semen analysis was conducted according to world health organization guidelines. Real time PCR (qRT-PCR) reaction was applied for determination of SPAG11A mRNA expression.
RESULTS
The results showed that there was a significant difference between the concentration and normal morphology between pre- and post-treatment groups and the controls. There were significant differences between pre-treatment and control groups in terms of progressive and non-progressive mobility. SPAG11A mRNA levels were significantly lower in the pre-treatment group than in healthy control subjects (p=0.007). There was no statistically significant difference in the expression of SPAG11A as well as semen parameters in the post-treatment group compared to the pre-treatment group.
CONCLUSIONS
SPAG11A gene expression and semen parameters may be affected by varicocele. Whether varicocele treatment is an effective approach to reduce the adverse effect of this disease on SPAG11A expression and semen parameters needs further investigation.
PubMed: 38446746
DOI: 10.5935/1518-0557.20220060 -
F1000Research 2023Azoospermia is the most severe type of male infertility. This study aimed to identify useful clinical parameters to predict sperm retrieval success. This could assist...
BACKGROUND
Azoospermia is the most severe type of male infertility. This study aimed to identify useful clinical parameters to predict sperm retrieval success. This could assist clinicians in accurately diagnosing and treating patients based on the individual clinical parameters of patients.
METHODS
A retrospective cohort study was performed involving 517 patients with azoospermia who underwent sperm retrieval in Jakarta, Indonesia, between January 2010 and April 2023. Clinical evaluation and scrotal ultrasound, serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were evaluated before surgery. Multivariate analyses were conducted to determine clinical parameters that could predict overall sperm retrieval success. Further subgroup analysis was performed to determine the factors that the diagnosis of non-obstructive azoospermia (NOA) diagnosis and sperm retrieval success among patients with NOA.
RESULTS
A total of 2,987 infertile men attended our clinic. Men with azoospermia (n=517) who met the inclusion criteria and did not fulfil any exclusion criteria were included in the study. The overall sperm retrieval success was 47.58%. Logistic regression revealed that FSH 7.76 mIU/mL (sensitivity: 60.1%, specificity: 63.3%, p<0.001); longest testicular axis length 3.89 cm (sensitivity: 33.6%, specificity: 41.6%); and varicocele (p<0.001) were independent factors for overall sperm retrieval. The FSH cutoff of 7.45 mIU/mL (sensitivity: 31.3%, specificity: 37.7%, p<0,001); longest testicular axis length 3.85 cm (sensitivity: 76.7%, specificity: 65.4%, p<0.001); and varicocele (p<0.001) were independent factors for NOA diagnosis. Varicocele was the only clinical parameter that significantly predicted the success of sperm retrieval in patients with NOA.
CONCLUSIONS
FSH, LH, longest testicular axis, and varicocele are among the clinical parameters that are useful for predicting overall sperm retrieval success and NOA diagnosis. However, varicocele is the only clinical parameter that significantly predicts sperm retrieval success in patients with NOA. High-quality studies are required to assess the other predictors of sperm retrieval success.
Topics: Humans; Male; Azoospermia; Indonesia; Retrospective Studies; Sperm Retrieval; Varicocele; Semen; Follicle Stimulating Hormone
PubMed: 38434641
DOI: 10.12688/f1000research.141969.1 -
Urology Annals 2024Varicocele is a reversible cause of male infertility. However, there are conflicting data available concerning the benefit of varicocele repair for patients with...
BACKGROUND
Varicocele is a reversible cause of male infertility. However, there are conflicting data available concerning the benefit of varicocele repair for patients with nonobstructive azoospermia (NOA) and severe oligoasthenoteratozoospermia (OAT).
OBJECTIVE
To address the benefit of varicocelectomy in patients with severe OAT and NOA with regard to their semen parameters and surgical sperm retrieval rate in those who underwent testicular sperm extraction (TESE) or testicular sperm aspiration (TESA).
MATERIALS AND METHODS
This retrospective cohort study was conducted on a sample of 13 patients diagnosed with NOA and severe OAT who underwent varicocelectomy for infertility treatment with no prespecified exclusion criteria.
RESULTS
Thirteen patients were enrolled. Five patients were diagnosed with NOA; eight were diagnosed with severe OAT. For improvements in the semen parameters postoperatively, the semen concentration of all patients was significantly increased compared to the preoperative concentration (3.59 ± 10.0.8 vs. 0.25 ± 0.31, = 0.02) and the remaining parameters were unchanged. Regarding sperm retrieval, three patients underwent TESE and two patients underwent TESA, in which all had positive results.
CONCLUSION
Varicocele repair was found to improve the semen parameters in patients with NOA and severe OAT and produced a successful surgical sperm retrieval rate in all patients who underwent TESA or TESE.
PubMed: 38415238
DOI: 10.4103/ua.ua_24_23 -
Biology Jan 2024Male-factor infertility is implicated in over half of the millions of cases of infertility worldwide, and varicoceles are the most common correctable cause of... (Review)
Review
Male-factor infertility is implicated in over half of the millions of cases of infertility worldwide, and varicoceles are the most common correctable cause of male-factor infertility. The pathophysiologic mechanism for varicoceles is complex and next-generation technologies offer promising insights into the molecular underpinnings of this condition. In this narrative review, we highlight historical and contemporary paradigms associated with varicoceles, with an emphasis on the biological underpinnings of this disease. Specifically, we review the literature describing the underlying causes of varicoceles, discuss the molecular and cellular mechanisms causing pathological changes in some (but not all) men, and highlight key articles regarding the next-generation analyses (e.g., transcriptome, epigenome, proteome, and microbiome) being applied to better understand the condition and its treatment. These data demonstrate an ongoing evolution of the knowledge of varicoceles and the potential for improved personalized care in the future for men with this condition.
PubMed: 38392299
DOI: 10.3390/biology13020080 -
Canadian Urological Association Journal... Feb 2024Chronic epididymitis imposes significant physical and psychosocial distress on affected patients. Despite being a commonly encountered urologic condition, there remains...
INTRODUCTION
Chronic epididymitis imposes significant physical and psychosocial distress on affected patients. Despite being a commonly encountered urologic condition, there remains a paucity of understanding and literature surrounding the management and natural history of isolated epididymal pain. Typically, patients who do not respond to conservative management undergo an epididymectomy.; however, the literature on its efficacy is also scarce, with success rates varying widely from 10-90% in existing studies. Our goal was to better describe the etiology, and natural history of isolated epididymal pain. Furthermore, we aimed to describe the rates of success associated with epididymectomy.
METHODS
A retrospective case-control study was conducted at the Manitoba Men's Health Clinic, with the approval of the University of Manitoba Research Ethics Board. All patients presenting with chronic epididymitis, defined as discomfort or pain localized to the epididymis for at least three months, were identified. Information regarding patient demographics, past medical and surgical history, duration of pain, localization of pain, findings on previous ultrasounds, prior conservative therapies trialed and response rates, as well as response rates to surgical therapy were collected.
RESULTS
From April 2022 to 2023, a total of 275 patients with chronic orchialgia were identified, and among them, 74 patients specifically presented with chronic isolated epididymal pain. The average duration of symptoms was as follows: 22.9% of patients experienced symptoms for 3-6 months, 10% for 6-12 months, and 67.1% for over 12 months; 13.5% (n=10) had associated ejaculatory pain, 8.1% (n=6) had lower urinary tract symptoms, and 4.1% (n=3) had erectile dysfunction. Ultrasound findings were observed in 68.9% of patients, with 31.1% having an epididymal cyst, 27.1% having a varicocele, 5.4% having a spermatocele, and 4.1% having a hydrocele. Among those who underwent conservative therapy, only 36.2% of patients reported a positive response. Surgical intervention was performed on 23 patients, including 16 who underwent an epididymectomy, three who underwent cord denervation, and two who underwent vasovasostomy and spermatocelectomy each. Most (81.3%, n=13) patients who underwent an epididymectomy had a positive response to the surgical intervention, defined as no pain on followup, while all patients undergoing other surgical interventions experienced a positive response.
CONCLUSIONS
Chronic epididymal pain is a condition with limited data surrounding its management. Prior to referral, a large proportion of patients did not undergo any conservative treatment, and of those that did, there was limited response. For those who underwent surgical intervention, all were pain-free on followup, except three patients who underwent epididymectomy.
PubMed: 38381926
DOI: 10.5489/cuaj.8701 -
International Journal of Fertility &... Feb 2024Varicocele is one of the most common treatable causes of male infertility, and its treatment may be beneficial for fertility. This study aimed to evaluate fertility rate...
BACKGROUND
Varicocele is one of the most common treatable causes of male infertility, and its treatment may be beneficial for fertility. This study aimed to evaluate fertility rate and DNA fragmentation index (DFI) following varicocelectomy in primary infertile men with clinical varicocele.
MATERIALS AND METHODS
This prospective longitudinal study was conducted on primary infertility men, in a tertiary center from December 2018 to December 2019 with one-year follow-up. Data of the semen parameters, DFI (%), and fertility rate were gathered before, as well as 4 and 12 months after undergoing varicocelectomy. For data analysis, SPSS software and analytical test were used.
RESULTS
Out of 76 patients who were analyzed, 22 (29%) became fertile and 54 (71%) remained infertile. Semen parameters and DFI (%) were improved significantly following varicocelectomy (P<0.001). Smoking history, occupational heated exposure, body mass index (BMI), and infertility duration were determined as predictors associated with fertility status (P<0.05).
CONCLUSION
Although varicocele repair improved the DFI, the fertility rate was achieved in less than one-third of patients; it seems that the other parameters, such as the history of smoking, occupational heated exposure, overweight, and duration of infertility should be considered as predictors of fertility status, in primary infertile men who are a candidate for varicocelectomy.
PubMed: 38368521
DOI: 10.22074/ijfs.2023.1990486.1441 -
Archivio Italiano Di Urologia,... Feb 2024Varicocele is the most common treatable cause of male infertility. The study aimed to compare varicocelectomy efficacy in men with primary (PI) and secondary infertility...
INTRODUCTION AND OBJECTIVES
Varicocele is the most common treatable cause of male infertility. The study aimed to compare varicocelectomy efficacy in men with primary (PI) and secondary infertility (SI).
PATIENTS AND METHODS
Medical records of 100 men suffering from PI and SI and having varicocelectomy at the Republican Specialized Scientific-Practical Medical Center of Urology were retrospectively selected and analyzed. Patients were divided into 2 groups. Group I included 58 men with PI and Group II 42 men with SI. Preoperative clinical characteristics and semen parameters before and after varicocelectomy were analyzed and compared between groups.
RESULTS
Analysis revealed that the mean age of patients of group I was significantly lower (p<0.001) and the duration of infertility was accurately shorter (p<0.01) than those of group II. Main semen parameters increased significantly in group I (e.g., sperm concentration increased by 50%, from 62.2 ± 8.7 to 93.5 ± 10.0 M/ml, and total motile sperm count increased by 113%, from 76.7±17.1 to 163.4±27.8 M p<0.05), while in group II only rate of progressive motile sperm increased significantly (by 107%, from 13.5± .6 to 28.0±5.2% p<0.05). We identified a significant difference in varicocelectomy efficacy between group I and group II in change of total motile sperm count (by 113% vs 74% respectively, p<0.01). We also revealed a discrepancy between groups in correlation ratio (r) between initial and post-surgical percent of progressive motile sperm.
CONCLUSIONS
Patients with SI were older and had longer infertility period. Varicocelectomy resulted in significant semen parameters improvement in patients with PI. In patients with SI, only a percent of progressively motile sperm improved significantly. It indicates that advanced male age and long infertility duration may have a negative impact on varicocelectomy success.
Topics: Humans; Male; Retrospective Studies; Semen; Infertility, Male; Sperm Count; Semen Analysis; Varicocele; Sperm Motility; Microsurgery
PubMed: 38363232
DOI: 10.4081/aiua.2024.12082