جستجوی مقالات مرتبط با کلیدواژه « azoospermia » در نشریات گروه « پزشکی »

Spermatogenic maturation arrest is thought to be caused by epigenetic defects, specifically in chromatin remodeling and histone modification. This study evaluated the status of chromatin remodeling chromodomain helicase DNA binding protein 5 (CHD5) and histone modifications histone 4 lys-12 acetylation (H4K12ac) and histone 3 lys-9 trimethylation (H3K9me3) in human testicular biopsies, based on maturation arrest type.

The cross-sectional study utilized 18 Bouin-fixed paraffin-embedded (BFPE) specimens prepared from residual tissue from routine laboratory tests of infertile patients. The expression of CHD5, H4K12ac, and H3K9me3 was examined through immunohistochemistry (IHC). The intensity was measured using ImageJ with IHC Profiler and StarDist plugins. Statistical analysis was performed using Python with Scipy.Stats module. The data were tested with Shapiro– Wilk for normality and Levene test for homogeneity. The differences in the intensity of spermatogenic cells were assessed using Kruskal-Wallis and Mann-Whitney tests. A difference was considered statistically significant if P<0.05.

We found three types of maturation arrest, including Sertoli cell only (n=5), spermatocyte arrest (n=4), and spermatid arrest (n=9). CHD5 was positive in spermatogonia and round spermatids but absent in spermatocytes. The mean grey value (MGV) of CHD5 in spermatogonia was generally weak in spermatocyte arrest (157.4 ± 16.6) and spermatid arrest (155.3 ± 16.8), and there was no significant difference between them [P=0.49, 95% confidence interval (CI): (-4.3, 6), effect size (r): 0.02]. Although there was a significant difference in the expression of H3K9me3 and H4K12ac (P<0.001), both histone modifications were found in all observed spermatogenic cells.

The expressions of CHD5, H3K9me3, and H4K12ac in different spermatogenic cell types produce similar results, indicating that they cannot be used as markers to determine the type of spermatogenic maturation arrest in humans. The significant finding in this research is the expression of CHD5 in human spermatogonia cells, which requires further study for elaboration.

From a diagnostic standpoint, certain approaches to genetic screening in clinical practice remain ambiguous in the era of assisted reproduction. Even the most current guidelines do not provide definite guidance on testing protocols, leaving clinicians to carefully determine which tests best serve patients struggling with infertility. The lack of uniformity in the current practice of male fertility evaluation can prove to be quite costly, thus necessitating healthcare practitioners to carefully appraise the necessity and weigh the advantages against potential economic and psychological detriments. The objective of this review is to map the existing literature on the general topic of the clinical indications of routine karyotyping and/or AZF screening in infertile men, identify key concepts, determine where the gaps are, and lastly, provide an overview of the conclusions drawn from a body of knowledge that varies widely in terms of methodologies or disciplines.

A thorough search was conducted for the published findings up until July 2023, utilizing PubMed (MEDLINE). This comprehensive search involved the use of specific search keywords, either individually or in combination. The search terms employed were as follows: “Karyotype”, "Klinefelter" or "KS" or "47,XXY", "AZF" or "Azoospermi*" and/or "microdeletion*" in the title or abstract. Once the titles and abstracts of selected articles were obtained, the complete texts of linked papers were meticulously scrutinized.

A total of 191 records were identified from PubMed. During screening, 161 records (84.3%) were eliminated. Finally, 30 papers were included in this scoping review, which was conducted in 18 countries. The number of sequence tag sites (STSs) used in the studies varied from 5 to 59. The rate of AZF deletions among patients with NOA ranged from 1.3% to 53%. The mean frequency was estimated to be 5.6%. The rate of YCM among patients with XXY karyotype was nil in 19 out of 30 studies (63%), whilst, in the remaining studies, the rate varied from 0.8% to 67%.

This review provides insights into managing male infertility. The presence of spermatozoa in ejaculation and successful surgical retrieval cannot be excluded for individuals with AZFb/AZFbc microdeletions. Screening for Y chromosome microdeletions is not needed for mosaic or classic KS. Only 1% of individuals with sperm concentration exceeding 1×106 sperm/mL and less than 5×106 sperm/mL exhibit AZF microdeletions; therefore, testing referral for such populations may need reassessment. Individuals with mosaic monosomy X karyotype and certain chromosomal anomalies should be referred for AZF deletion screening. These findings have implications for male infertility management and future research.

Infertility is a common clinical condition and about half of the major causes are due to male-related infertility. Pathogenesis of this abnormality is generally undefined; so establishing a proper treatment option is relatively uncertain. In recent years, several evidences demonstrated that mesenchymal stem cells (MSCs) can be a hope for innovative and efficient treatment of male infertility. This study reviews possible applications of MSCs in the restoration of spermatogenesis in male infertility of both humans and animals to suggest new avenues for future clinical practices. Articles published in “PubMed” and “Google Scholar” from January 1, 2000, to August 1, 2023, were investigated by searching items of “mesenchymal stem cells”, “cell therapy”, “cell transplantation”, and, “regenerative medicine” keywords, in addition to the “urology”, “andrology”, “reproductive medicine”, “male infertility”, “azoospermia”, and “spermatogenesis”. The results obtained from the transplantation of MSCs in the treatment of male infertility seemed encouraging and they revealed the safety and efficacy of these cells to recover spermatogenesis; eventhough further stem cell research is still required before recruiting clinical application of MSCs in the treatment of human male infertility. Undertaking more well-defined, standardized, and reproducible protocols and enrolling larger sample sizes during a longer follow-up period can benefit the relevance of MSC transplantation in the restoration of spermatogenesis and treatment of male infertility. It seems that developing and utilizing stem cell transplantations, exosomes, scaffold delivery systems, and three dimensional (3D) culture methods may open a new window to getting more benefits from cell therapy in the treatment of men infertility.

The purpose of the current study was to report a case with 45,X/ 46,XY/46,X,idic(Yp) mosaicism showing the male phenotype with mixed gonadal dysgenesis.

A 27 year-old individual, phenotypically male, presented with azoospermia and a micropenis. Both testes were not visualized in the scrotal sac. Due to the presence of a small-sized uterus, the individual was referred to the KSHEMA Center for Genetic Services for chromosomal analysis. Karyotyping revealed a mosaic karyotype of 45,X[44]/46,XY[5]/46,X,idic(Yp)[1]. This finding was further confirmed through fluorescent in situ hybridization (FISH) analysis. The individual's mosaic karyotype consisted of three cell lines, with a higher proportion of the 45,X cell line and lower proportions of the idic(Yp) and 46,XY cell lines. It is worth noting that this mosaic condition in postnatal peripheral blood has not been reported in the literature thus far.

The case report demonstrated the importance of performing karyotype and FISH analysis in understanding genetic defects including mosaicism and other chromosomal aberrations, which can influence not only growth and puberty but also sexual development and maturation. Hence, performing cytogenetic and molecular cytogenetic analysis will help clinicians to take a further step in understanding and managing the condition.

Genetic factors play a major role in the development of male idiopathic infertility. Because of the multi-genetic base of this disease, not all genetic factors have been investigated. PIWI genes have been reported to be involved in the regulation of piRNAs in spermatogenesis. Our study assessed the association between HIWI3 rs11703684 (C>T) gene polymorphism with the risk of male idiopathic azoospermia/oligozoospermia in the Kurdish population of Kermanshah.

In this case-control investigation, we included two hundred individuals consisting of 100 men with idiopathic azoospermia/oligozoospermia and 100 fertile men as the control group. To determine genotypes of HIWI3 C>T polymorphism, we used the Tetra Arms-PCR technique and significant values were considered as p<0.05.

Our findings did not show a statistically significant difference in the genotype frequency of the recessive model (P = 0.118; OR = 0.158; CI, 0.019–1.339), dominant (P = 0.169; OR = 0.625; CI, 0.341–1.144) and co-dominant (P = 0.527; OR = 0.778; CI, 0.417–1.450). In addition, the results described a negative difference in allelic frequency of HIWI3 (rs11703684 C>T) in men with idiopathic azoospermia/oligozoospermia and control group (P = 0.288; OR = 0.749; CI, 0.463–1.212).

The current study does not indicate the probability effect of HIWI3 rs11703684 (C>T) gene polymorphism on the male idiopathic azoospermia/oligozoospermia in the Kurdish population of Kermanshah. The critical role of PIWI genes in spermatogenesis and as a candidate risk factor for male infertility remained unknown.

 Clomiphene citrate (CC) has been suggested to increase the chance of sperm retrieval with microdissection testicular sperm extraction (micro-TESE).

 This study aimed to evaluate the effect of CC on micro-TESE results, due to the great controversy in this regard.

 112 participants were included in this cross-sectional study and were divided into a case (n = 54) and a control group (n = 58) diagnosed with non-abstractive azoospermia. The case group received 25 mg of CC daily for 3 months, while the control group did not receive anything. All participants underwent micro-TESE by an andrologist, and at the end, the results were compared between groups. Hormone tests, including follicle-stimulating hormone, luteinizing hormone, testosterone, and prolactin were analyzed.

 The mean age of participants was the same in the case and the control groups, and no significant relationship was observed between the 2 groups (p = 0.16). 25.9% of sperm and 31.0% of sperm were observed and extracted in the CC-treated and the control group, respectively.

 Our findings showed that after receiving CC, the number of sperm extraction did not increase but it rather decreased. However, the initial level of hormones such as testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin, and the men's age, testicle size, smoking, and opium addiction, underlying diseases had no significant relationship in the 2 groups and did not affect the results.

In this phase I clinical trial, our primary objective was to develop an innovative therapeutic approachutilizing autologous bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) for the treatment of nonobstructiveazoospermia (NOA). Additionally, we aimed to assess the feasibility and safety of this approach. We recruited 80 participants in this non-randomized, open-label clinical trial, including patientsundergoing NOA treatment using autologous BM-MSCs (n=40) and those receiving hormone therapy as a control group(n=40). Detailed participant characteristics, such as age, baseline hormonal profiles, etiology of NOA, and medical history,were thoroughly documented. Autotransplantation of BM-MSCs into the testicular network was achieved using microsurgicaltesticular sperm extraction (microTESE). Semen analysis and hormonal assessments were performed both before andsix months after treatment. Additionally, we conducted an in-silico analysis to explore potential protein-protein interactionsbetween exosomes secreted from BM-MSCs and receptors present in human seminiferous tubule cells. Our results revealed significant improvements following treatment, including increased testosterone and inhibin Blevels, elevated sperm concentration, and reduced levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), andprolactin. Notably, in nine patients (22.5%) previously diagnosed with secondary infertility and exhibiting azoospermia beforetreatment, the proposed approach yielded successful outcomes, as indicated by hormonal profile changes over six months.Importantly, these improvements were achieved without complications. Additionally, our in-silico analysis identified potentialbinding interactions between the protein content of BM-MSC-derived exosomes and receptors integral to spermatogenesis. Autotransplantation of BM-MSCs into the testicular network using microTESE in NOA patients led to the regenerationof seminiferous tubules and the regulation of hormonal profiles governing spermatogenesis. Our findings supportthe safety and effectiveness of autologous BM-MSCs as a promising treatment modality for NOA, with a particular focus onthe achieved outcomes in patients with secondary infertility (registration number: IRCT20190519043634N1).

In recent years, a partial relationship has been discovered between thyroid hormones and the formation of germ cells and the process of spermatogenesis. The current study aimed to assess thyroid hormone levels and the relationship between those levels and semen quality.

Forty-seven infertile males, as the treatment group, and 25 healthy individuals, as the control group, were enrolled in this study. Thyroid-stimulating hormone (TSH), triiodothyronine (T3) hormone, and tetraiodothyronine (T4) hormone were calculated, and the parameters of seminal fluid (count, motility, and morphology) were assessed for semen quality.

The results demonstrated that sperm counts, sperm motility%, and normal morphology% were significantly lower in the infertile male group compared with the healthy group. The results further represented a highly significant level of TSH and total T3, while the total T4 was negligible in the infertile male group in comparison with the healthy group. The infertile male group was divided into subgroups based on sperm abnormalities, including asthenozoospermia, oligozoospermia, and azoospermia. Based on the findings, there was a significant reduction in TSH, T3, and T4 levels in oligozoospermia compared with the other groups. However, the levels of TSH, T3, and T4 were significantly higher in asthenozoospermia compared with the other groups, demonstrating the existence of a relationship between thyroid indicators and Asthenozoospermia.

Overall, the mean serum levels of TSH, T3, and T4 were significantly lower in the infertile male group compared with the healthy group. Thus, they were negatively associated with sperm counts, motility%, and normal morphology%. Hence, these negative impacts on thyroid hormones were associated with different sperm abnormalities and semen quality in the infertile males group.

Ring chromosomes are the result of breakage and re-union of distal ends of chromosomal arms. They have a generalfrequency of 1 in 50,000 and 1 in 58,000 for chromosome 13. Ring chromosome 13 is usually presented as a syndromicsituation stigmatized by particular features, including developmental delay, mental retardation and CNS, skeletalor organ anomalies. As an experimental study, here we report a 31 years old male with no major phenotypic manifestationwho was evaluated for azoospermia, while his karyotype revealed presence of a mosaic ring chromosome 13. Hehad a history of bilateral varicocelectomy and no other major finding in his routine infertility work up was determined.Genetic counseling did not provide any clue for mental disability or dysmorphic features. Pathology examination ofthe testicular tissue revealed very scarce number of spermatid/spermatozoa within the tubules in conjunction withdegrees of maturation arrest mostly in spermatocyte stage. In our knowledge, this is the first report of a ring chromosome13, manifested by an isolated male infertility.

Azoospermia is a risk factor for infertility affecting approximately 1% of the male population. Genetic factors are associated with non-obstructive azoospermia (NOA). Pygo2 and PRDM9 genes are involved in the spermatogenesis process. The present study aimed to assess the association of single nucleotide polymorphism (SNP) in the Pygo2 (rs61758740 and rs61758741) and PRDM9 (rs2973631 and rs1874165) genes with idiopathic azoospermia (IA). A cross-sectional study was conducted from October 2018 to August 2019 at Rooya Infertility Centre (Qom, Iran). A total of 100 infertile patients with NOA and 100 men with normal fertility were enrolled in the study. Tetra-primer amplification refractory mutation system-PCR method was used to detect SNPs rs61758740, rs61758741, and rs2973631. The restriction fragment length polymorphism method was used for SNP rs1874165. In addition, luteinizing, follicle-stimulating, and testosterone hormone levels were measured.  The results showed a significant increase in luteinizing and follicle-stimulating hormone levels in the patient group (P<0.001), but a non-significant difference in testosterone levels in both groups. SNP rs61758740 (T>C) was associated with the increased risk of azoospermia (OR: 2.359, 95% Cl: 1.192-4.666, P=0.012). SNP rs2973631 showed a significant difference in genotype frequency between the patient and control groups in the dominant, recessive, and codominant models. However, in the case of SNP rs1874165, the difference was significant in the dominant, codominant, and overdominant models.  There is an association between azoospermia and SNPs in Pygo2 and PRDM9 genes in Iranian infertile male patients with IA. SNPs can be considered a risk factor for male infertility. It should be noted that this article was published in preprint form on the website of europepmc (https://europepmc.org/article/ppr/ppr416800).

The objective of this study was to evaluate treatment outcomes and assess predictors of clinical pregnancy in obstructive azoospermia cases treated with testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in Ghana.

This study was a retrospective study conducted on 67 men seeking treatment for obstructive azoospermia at two study sites in Ghana from January 2018 to December 2019. First, archived data were reviewed and treatment outcomes of cases of obstructive azoospermia from the hospital records were evaluated. Infertile men who met the inclusion criteria were recruited. Descriptive data were expressed in the form of frequencies and percentages. The dependent and independent variables were analyzed using multiple logistic regression and reported as odds ratios (ORs). The confidence interval (CI) was set at 95% and a p-value <0.05 was considered significant.

The mean age of male participants was 42.43±9.11 years (mean±SD) while the mean age of their partners was 32.89±5.73 years (mean±SD). The average duration of infertility before intervention was 5.01±3.60 years (mean±SD). Successful pregnancy was observed in 52.2% (35/67) of the participants. After adjusting for confounders, the rate of a successful clinical pregnancy was 0.07 lower for every additional year increase in the male’s age [AOR=0.93 (95%CI=0.87-0.99), p=0.02].

Overall the rate of clinical pregnancy following TESE/ICSI from our study was 52.2%. A man’s age was a strong predictor of successful clinical pregnancy among couples treated with TESE-ICSI for obstructive azoospermia in Ghana.

Approximately 1 in 1000 men have a 47,XYY karyotype. Previous publications have presented cases of infertile XYY men and have suggested that the additional Y chromosome may cause disrupted meiosis leading to sperm apoptosis. The purpose of the current study was to determine whether XYY men are overrepresented in infertility cohorts.

In this paper, an ongoing infertility cohort was evaluated for Y chromosome microdeletions using the MLPA technique and the data from the first 2000 referrals were recorded. Moreover, the MLPA technique detected 47,XYY karyotypes.

Four XYY individuals were identified within the cohort. One of the four XYY men was shown to have an apparent gr/gr partial AZFc deletion on both Y chromosomes while Sertoli cell only syndrome was detected in another case. The other two cases (out of 2000) might, therefore, represent an incidental finding.

The gr/gr deletion is not detectable by the multiplex PCR method; there-fore, there might be additional explanations for the fertility problems of infertile XYY men reported in previously published articles. It seems that among other cases, their XYY karyotype may be coincidental, rather than causative of their fertility issues

Epigenetic and genetic changes have important roles in stem cell achievements. Accordingly, the aim of thisstudy is the evaluation of the epigenetic and genetic alterations of different culture systems, considering their efficacy inpropagating human spermatogonial stem cells isolated by magnetic-activated cell sorting (MACS). In this experimental study, obstructive azoospermia (OA) patient-derived spermatogonial cells were divided into two groups. The MACS enriched and non-enriched spermatogonial stem cells (SSCs) were cultured in the control and treated groups; co-culture of SSCs with Sertoli cells of men with OA, co-culture of SSCs with healthy Sertoli cells of fertile men, the culture of SSCs on PLA nanofiber and culture of testicular cell suspension. Gene-specific methylation by MSP, expression of pluripotency (NANOG, C-MYC and OCT-4), and germ cells specific genes (Integrin α6, Integrin β1, PLZF) evaluated. Cultured SSCs from the optimized group were transplanted into the recipient azoospermic mouse. The use of MACS for the purification of human stem cells was effective at about 69% with the culture of the testicular suspension, being the best culture system. Upon purification, the germ-specific gene expression was significantly higher in testicular cell suspension and treated groups (P≤0.05). During the culture time, gene-specific methylation patterns of the examined genes did not show any changes. Our data from transplantation indicated the homing of the donor-derived cells and the presence of human functional sperm. Our in vivo and in vitro results confirmed that culture of testicular cell suspension and selection ofspermatogonial cells could be effective ways for purification and enrichment of the functional human spermatogonial cells. The epigenetic patterns showed that the specific methylation of the evaluated genes at this stage remained constant with no alteration throughout the entire culture systems over time.

We aim to determine the prevalence of renal anomalies in patients with congenital vas deferens agenesisreferred for infertility assessment. This cross-sectional study was carried out on eligible infertile men from 2016 to 2019.Infertile men who were suspected of obstructive azoospermia were referred to the Ultrasound ward and they wereexamined by abdominal ultrasound for detecting the genital and kidney anomalies. An informed consent form wasfilled out by patients. Data was entered into SPSS software 21. Patients were divided into two groups in termsof congenital bilateral absence of vas deferens (CBAVD) or congenital unilateral absence of the vas deferens(CUAVD). Using the Chi-square test kidney anomalies between groups were compared. The P<0.05 was consideredsignificant. The mean age of participants was 33.05 ± 6.35. The frequency of CBAVD was 66 and the frequency of leftside VD and right side VD were 23 and 21, respectively. The percentage of other comorbidities was calculated. Outof 110 cases, 12 (11%) men had coexistence of vas deferens and kidney agenesis. Other studies are in agreement withour findings. Although the percentage of CBAVD and CUAVD were 9.1% and 1.8% respectively, the difference wasnot significant (P=0.07). Considering the fact that kidney agenesis is a remarkable congenital anomaly that coexists with themajority of vas deferens agenesis cases and could not be detected by routine laboratory tests or transrectal ultrasoundexamination, it should be ruled out with transabdominal ultrasound examination after detection of vas deferensagenesis.

Infertility is a common disease that affects 15 to 20% of couples at some point in their lives. Among infertile couples, male factor accounts for 50% of infertile cases. Assisted reproductive techniques are the gold standard approach in case of failure in medical or surgical treatments. Moreover, the role of the urologist in these approach- es is to provide appropriate sperm on the day of oocyte pick-up. However, sperm re- trieval procedure is quite different in azoospermic and non-azoospermic men. Alt- hough most cases of infertile patients are not azoospermic, their ejaculation disorder prevents obtaining sperm for assisted reproductive techniques. This review article explains common problems of sperm retrieval in non-azoospermic patients with per- sistent ejaculatory dysfunction and introduces some management strategies. In fact, it is possible to design a classic approach for managing such patients, which definite- ly reduces the problems faced by clinicians as well.

Some previous human and animal studies have supported the idea that KDM3A down-regulation might be the main cause of male infertility, especially in non-obstructive azoospermia (NOA). The regulatory role of micro-RNAs (miRNA) has been investigated in the development of male infertility.

The expression level of hsa-miR-30a-5p in azoospermia was evaluated to reveal its possible association with the etiology of male infertility.

In this case-control study, 30 men with azoospermia (19 of whom had NOA) were selected as the case individuals, and 11 men with obstructive azoospermia (OA) were selected as control individuals. The best miRNA with the strongest ability to target the KDM3A gene was detected via comprehensive bioinformatics analysis. Reverse transcriptase quantitative polymerase chain reaction was used to assess the expression level of hsa-miR-30a-5p. After analyzing the data, the expression level of hsa-miR-30a-5p was compared between men with NOA and men with OA.

The findings supported the idea that hsa-miR-30a-5p is the miRNA with the best ability to target the KDM3A transcript. The expression analysis of hsa-miR-30a-5p indicated a significant overexpression (p = 0.04) in men with NOA compared to in men with OA.

Hsa-miR-30a-5p was overexpressed in men with NOA compared to in control individuals. Hsa-miR-30a-5p could target the KDM3A transcript and may suppress its expression.

Chemotherapeutic agents such as cyclophosphamide and busulfan have been shown to have a negative impact on the spermatogenesis process. Based on this fact, the objective of this study was to investigate the effects of edaravone on spermato- genesis in busulfan-induced mice.

Forty adult male mice were equally divided into the four groups: 1) control, 2) edaravone, 3) busulfan, and 4) busulfan + edaravone. Then, the sperm parameters, histo- pathological examinations, and serum levels of testosterone, follicle-stimulating hor- mone (FSH), and luteinizing hormone (LH) were also assessed. Caspase-3, Beclin-1, and ATG-7 mRNA levels were also determined using real-time PCR.

Our results revealed that treatment of mice with edaravone in busulfan-induced azoospermia significantly improves sperm parameters, including total count, morpholo- gy, and viability (p<0.05). Furthermore, edaravone administration led to a significant in- crease in serum testosterone (p<0.0001) and FSH (p<0.001) levels, as well as testis weight (p<0.05) and volume (p<0.01). Edaravone also prevented a decrease in the num- ber of testicular cells including spermatogonia (p<0.0001), primary spermatocytes (p< 0.001), round spermatids (p<0.0001), Sertoli (p<0.01), and Leydig cells (p<0.0001) in busulfan-treated mice. Additionally, in busulfan-induced azoospermia, edaravone signif- icantly reduced the percentage of sperm with immature chromatin (p<0.0001). Following treatment with edaravone, a decrease in reactive oxygen species (ROS) and an increase in glutathione (GSH) production were noted compared to busulfan-treated mice. Further- more, caspase-3 (p<0.05), Beclin-1, and ATG-7 (p<0.001) genes expression decreased significantly in treatment groups compared to busulfan-induced azoospermia.

According to our findings, edaravone can improve spermatogenesis in busulfan-induced azoospermia through free radical scavenging and autophagy modula- tion in testicular tissue.