Purpose: In this systematic review and meta-analysis, we investigated assisted reproductive technology (ART) success in infertile men with clinical varicocele and abnormal semen parameters who underwent varicocele repair (VR) before the ART procedure as compared to those who did not. Materials and Methods: A comprehensive search of the Scopus, PubMed, Embase, and Cochrane Library databases was conducted using a specific query string to identify studies examining the impact of VR on ART outcomes, including fertilization rate, clinical pregnancy, pregnancy loss, and live-birth rate, until October 2023. Outcomes were analyzed based on the type of ART. Studies on VR in infertile men with non-obstructive azoospermia and those who underwent ART only due to female factor infertility were excluded from the study. Results: Out of 1,554 articles reviewed, only 9 met the inclusion criteria for the study. All the included articles were observational studies. The variability in study quality in the included literature resulted in a moderate overall risk of bias. Data analysis showed that for intrauterine insemination, there was no difference in the clinical pregnancy rate (odds ratio [OR] 1.01, 95% confidence interval [CI]: 0.42, 2.45; p=0.97). However, for intracytoplasmic sperm injection (ICSI), men with VR showed a significant improvement in fertilization rate (mean difference 10.9, 95% CI: 5.94, 15.89; p<0.01), clinical pregnancy rate (OR 1.38, 95% CI: 1.07, 1.78; p=0.01) and live-birth rate (OR 2.07, 95% CI: 1.45, 2.97; p<0.01), compared to men who did not undergo VR. Conclusions The findings of this systematic review and meta-analysis suggest that VR has a positive impact on pregnancy and live birth rates after ICSI. However, biases like small sample sizes and heterogeneous populations highlight the need for larger, well-designed prospective studies to validate these findings.

Purpose: In this systematic review and meta-analysis, we investigated assisted reproductive technology (ART) success in infertile men with clinical varicocele and abnormal semen parameters who underwent varicocele repair (VR) before the ART procedure as compared to those who did not. Materials and Methods: A comprehensive search of the Scopus, PubMed, Embase, and Cochrane Library databases was conducted using a specific query string to identify studies examining the impact of VR on ART outcomes, including fertilization rate, clinical pregnancy, pregnancy loss, and live-birth rate, until October 2023. Outcomes were analyzed based on the type of ART. Studies on VR in infertile men with non-obstructive azoospermia and those who underwent ART only due to female factor infertility were excluded from the study. Results: Out of 1,554 articles reviewed, only 9 met the inclusion criteria for the study. All the included articles were observational studies. The variability in study quality in the included literature resulted in a moderate overall risk of bias. Data analysis showed that for intrauterine insemination, there was no difference in the clinical pregnancy rate (odds ratio [OR] 1.01, 95% confidence interval [CI]: 0.42, 2.45; p=0.97). However, for intracytoplasmic sperm injection (ICSI), men with VR showed a significant improvement in fertilization rate (mean difference 10.9, 95% CI: 5.94, 15.89; p<0.01), clinical pregnancy rate (OR 1.38, 95% CI: 1.07, 1.78; p=0.01) and live-birth rate (OR 2.07, 95% CI: 1.45, 2.97; p<0.01), compared to men who did not undergo VR. Conclusions The findings of this systematic review and meta-analysis suggest that VR has a positive impact on pregnancy and live birth rates after ICSI. However, biases like small sample sizes and heterogeneous populations highlight the need for larger, well-designed prospective studies to validate these findings.

Purpose: In this systematic review and meta-analysis, we investigated assisted reproductive technology (ART) success in infertile men with clinical varicocele and abnormal semen parameters who underwent varicocele repair (VR) before the ART procedure as compared to those who did not. Materials and Methods: A comprehensive search of the Scopus, PubMed, Embase, and Cochrane Library databases was conducted using a specific query string to identify studies examining the impact of VR on ART outcomes, including fertilization rate, clinical pregnancy, pregnancy loss, and live-birth rate, until October 2023. Outcomes were analyzed based on the type of ART. Studies on VR in infertile men with non-obstructive azoospermia and those who underwent ART only due to female factor infertility were excluded from the study. Results: Out of 1,554 articles reviewed, only 9 met the inclusion criteria for the study. All the included articles were observational studies. The variability in study quality in the included literature resulted in a moderate overall risk of bias. Data analysis showed that for intrauterine insemination, there was no difference in the clinical pregnancy rate (odds ratio [OR] 1.01, 95% confidence interval [CI]: 0.42, 2.45; p=0.97). However, for intracytoplasmic sperm injection (ICSI), men with VR showed a significant improvement in fertilization rate (mean difference 10.9, 95% CI: 5.94, 15.89; p<0.01), clinical pregnancy rate (OR 1.38, 95% CI: 1.07, 1.78; p=0.01) and live-birth rate (OR 2.07, 95% CI: 1.45, 2.97; p<0.01), compared to men who did not undergo VR. Conclusions The findings of this systematic review and meta-analysis suggest that VR has a positive impact on pregnancy and live birth rates after ICSI. However, biases like small sample sizes and heterogeneous populations highlight the need for larger, well-designed prospective studies to validate these findings.

Purpose: In this systematic review and meta-analysis, we investigated assisted reproductive technology (ART) success in infertile men with clinical varicocele and abnormal semen parameters who underwent varicocele repair (VR) before the ART procedure as compared to those who did not. Materials and Methods: A comprehensive search of the Scopus, PubMed, Embase, and Cochrane Library databases was conducted using a specific query string to identify studies examining the impact of VR on ART outcomes, including fertilization rate, clinical pregnancy, pregnancy loss, and live-birth rate, until October 2023. Outcomes were analyzed based on the type of ART. Studies on VR in infertile men with non-obstructive azoospermia and those who underwent ART only due to female factor infertility were excluded from the study. Results: Out of 1,554 articles reviewed, only 9 met the inclusion criteria for the study. All the included articles were observational studies. The variability in study quality in the included literature resulted in a moderate overall risk of bias. Data analysis showed that for intrauterine insemination, there was no difference in the clinical pregnancy rate (odds ratio [OR] 1.01, 95% confidence interval [CI]: 0.42, 2.45; p=0.97). However, for intracytoplasmic sperm injection (ICSI), men with VR showed a significant improvement in fertilization rate (mean difference 10.9, 95% CI: 5.94, 15.89; p<0.01), clinical pregnancy rate (OR 1.38, 95% CI: 1.07, 1.78; p=0.01) and live-birth rate (OR 2.07, 95% CI: 1.45, 2.97; p<0.01), compared to men who did not undergo VR. Conclusions The findings of this systematic review and meta-analysis suggest that VR has a positive impact on pregnancy and live birth rates after ICSI. However, biases like small sample sizes and heterogeneous populations highlight the need for larger, well-designed prospective studies to validate these findings.

Purpose: In this systematic review and meta-analysis, we investigated assisted reproductive technology (ART) success in infertile men with clinical varicocele and abnormal semen parameters who underwent varicocele repair (VR) before the ART procedure as compared to those who did not. Materials and Methods: A comprehensive search of the Scopus, PubMed, Embase, and Cochrane Library databases was conducted using a specific query string to identify studies examining the impact of VR on ART outcomes, including fertilization rate, clinical pregnancy, pregnancy loss, and live-birth rate, until October 2023. Outcomes were analyzed based on the type of ART. Studies on VR in infertile men with non-obstructive azoospermia and those who underwent ART only due to female factor infertility were excluded from the study. Results: Out of 1,554 articles reviewed, only 9 met the inclusion criteria for the study. All the included articles were observational studies. The variability in study quality in the included literature resulted in a moderate overall risk of bias. Data analysis showed that for intrauterine insemination, there was no difference in the clinical pregnancy rate (odds ratio [OR] 1.01, 95% confidence interval [CI]: 0.42, 2.45; p=0.97). However, for intracytoplasmic sperm injection (ICSI), men with VR showed a significant improvement in fertilization rate (mean difference 10.9, 95% CI: 5.94, 15.89; p<0.01), clinical pregnancy rate (OR 1.38, 95% CI: 1.07, 1.78; p=0.01) and live-birth rate (OR 2.07, 95% CI: 1.45, 2.97; p<0.01), compared to men who did not undergo VR. Conclusions The findings of this systematic review and meta-analysis suggest that VR has a positive impact on pregnancy and live birth rates after ICSI. However, biases like small sample sizes and heterogeneous populations highlight the need for larger, well-designed prospective studies to validate these findings.

Varicocele is a prevalent condition in the infertile male population. However, to date, which patients may benefit most from varicocele repair is still a matter of debate. The purpose of this study was to evaluate whether certain preintervention sperm parameters are predictive of successful varicocele repair, defined as an improvement in total motile sperm count (TMSC). We performed a retrospective study on 111 patients with varicocele who had undergone varicocele repair, collected from the Department of Endocrinology, Metabolic Diseases and Nutrition, University of Catania (Catania, Italy), and the Unit of Urology at the Selcuk University School of Medicine (Konya, Türkiye). The predictive analysis was conducted through the use of the Brain Project, an innovative tool that allows a complete and totally unbiased search of mathematical expressions that relate the object of study to the various parameters available. Varicocele repair was considered successful when TMSC increased by at least 50% of the preintervention value. For patients with preintervention TMSC below 5 × 10 6 , improvement was considered clinically relevant when the increase exceeded 50% and the absolute TMSC value was >5 × 10 6 . From the preintervention TMSC alone, we found a model that predicts patients who appear to benefit little from varicocele repair with a sensitivity of 50.0% and a specificity of 81.8%. Varicocele grade and serum follicle-stimulating hormone (FSH) levels did not play a predictive role, but it should be noted that all patients enrolled in this study were selected with intermediate- or high-grade varicocele and normal FSH levels. In conclusion, preintervention TMSC is predictive of the success of varicocele repair in terms of TMSC improvement in patients with intermediate- or high-grade varicoceles and normal FSH levels.
Humans ; Varicocele/complications* ; Male ; Retrospective Studies ; Machine Learning ; Adult ; Treatment Outcome ; Sperm Count ; Infertility, Male/etiology* ; Sperm Motility ; Follicle Stimulating Hormone/blood* ; Young Adult

Purpose: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA). Materials and Methods: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD). Results: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD −1.125, 95% confidence interval [CI] −1.410, −0.840; p<0.0001) with high inter-study heterogeneity (I2=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD −1.014, 95% CI −1.263, −0.765; p<0.0001, and SMD −1.495, 95% CI −2.116, −0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD −2.197, 95% CI −3.187, −1.207; p<0.0001), sperm chromatin structure assay (SMD −0.857, 95% CI −1.156, −0.559; p<0.0001) or TUNEL (SMD −1.599, 95% CI −2.478, −0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD −2.450, 95% CI −3.903 to −0.997, p=0.001) with high inter-study heterogeneity (I2=93.7%). Conclusions Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

Purpose: The mesoderm specific transcription (MEST) gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on MEST methylation pattern in spermatozoa of infertile patients found higher methylation in spermatozoa from infertile patients than fertile controls. To provide an updated and comprehensive systematic review and meta-analysis on the MEST gene methylation pattern in patients with abnormal sperm parameters compared to men with normal parameters. Materials and Methods: This meta-analysis was registered in PROSPERO (CRD42023397056) and performed following the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating MEST gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included. Results: Of 354 abstracts evaluated for eligibility, only 6 studies were included in the quantitative synthesis, involving a total of 301 patients and 163 controls. Our analysis showed significantly higher levels of MEST gene methylation in patients compared with controls (standard mean difference [SMD] 2.150, 95% confidence interval [CI] 0.377, 3.922; p=0.017), although there was significant heterogeneity between studies (Q-value=239.90, p<0.001; I2=97.91%). No significant evidence of publication bias was found, although one study was sensitive enough to skew the results, leading to a loss of significance (SMD 1.543, 95% CI –0.300, 3.387; p=0.101). In meta-regression analysis, we found that the results were independent of both ages (p=0.6519) and sperm concentration (p=0.2360). Conclusions Sperm DNA methylation may be associated with epigenetic risk in assisted reproductive techniques (ART). The MEST gene could be included in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART.

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 (×106), 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.