2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T98a,To evaluate novel preoperative hormonal predictors of sperm retrieval success in men with idiopathic non-obstructive azoospermia (NOA) undergoing microsurgical testicular sperm extraction (mTESE). Multi-institutional retrospective cohort study conducted between 2014 and 2024. 60 men with strictly defined idiopathic NOA from multiple sites participating in the MOBYUS Male Infertility Research Consortium were included, comprising a prediction cohort (n=30) and an independent multi-institutional validation cohort (n=30). Idiopathic NOA was defined by azoospermia on two separate semen analyses without prior paternity, evidence of obstruction, prior genitourinary surgery, documented genetic abnormalities, or use of empirical medical therapy within one year prior to surgery. Sensitivity analyses were performed by excluding men with FSH <7.6 IU/L and men with hypospermatogenesis on pathology. Preoperative serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone (T) levels measured within one year prior to mTESE. Hormone-derived ratios, including T/FSH, T/LH, and LH/FSH, were subsequently derived for analysis. Successful sperm retrieval at mTESE served as the primary outcome. Predictive performance was evaluated using logistic regression to assess hormonal predictors, area under the receiver operating characteristic curve (AUC), and partition analysis to identify optimal clinical thresholds for sperm retrieval prediction. Men with successful sperm retrieval had significantly lower gonadotropin levels and a higher T/FSH ratio (43.0 vs. 20.9, p=0.004). Among all hormonal metrics, T/FSH demonstrated the strongest discriminative ability (AUC=0.81). The significance remained after excluding men with hypospermatogenesis noted on testicular pathology. In external validation, T/FSH was the only variable that maintained statistical significance (p=0.03; AUC=0.74). Partition analysis further revealed a two-step model (T/FSH>20 and LH<10) that achieved 93% sensitivity and 81% specificity for predicting sperm retrieval success. This multi-institutional study demonstrates that the T/FSH ratio is a reproducible and clinically meaningful predictor of sperm retrieval success in men with idiopathic NOA. Across two independent and diverse cohorts, this ratio consistently outperformed single-hormone predictors and remained the only externally validated preoperative predictor of mTESE success.31:T6e9,Prolonged stress adversely affects male reproductive health, with infertility affecting millions of couples worldwide due to lifestyle and mental health factors. Chronic unpredictable stress (CUS) has been shown to induce testicular dysfunction via blood-testis barrier (BTB) disruption. The BTB, maintained by ectoplasmic specialisations (ES), is regulated by β1-integrin and phosphorylated focal adhesion kinase (FAK)-associated proteins. Still, the impact of prolonged stress on these regulators has not been fully explored. This study investigated CUS-induced testicular damage over extended durations. Sprague-Dawley rats were exposed to CUS for 8, 14, or 18 weeks, with respective controls (n = 6/group). Depressive behaviour was confirmed by increased anhedonia, anxiety-like behaviour, and corticosterone levels, alongside decreased exploratory activity. Sperm count, motility, morphology, and chromatin integrity were significantly reduced, particularly in the 14- and 18-week CUS groups. FSH, LH, and testosterone levels were also decreased in all CUS-exposed groups. Western blot analysis revealed marked reductions in BTB markers, 11β-HSD, and irisin, with increased testicular apoptosis. Disruption of pFAK (Tyr397) signaling destabilized the apical ES, while reduced pFAK (Tyr407) expression and decreased levels of p-Akt, p-mTOR, and phospho-p70S6 kinase loosened tight junctions. Overall, prolonged CUS exerted cumulative adverse effects on male reproductive function, with both the magnitude and duration of stress critically influencing severity. These findings elucidate the mechanism by which chronic stress compromises BTB integrity and impairs spermatogenesis, highlighting the progressive nature of stress-induced reproductive dysfunction.32:T76a,To systematically investigate the genetic architecture of severe male infertility in Indian men, with a specific focus on chromosomal abnormalities and the contribution of de novo variants. We recruited 247 infertile males between 2021 and 2024 presenting with severe quantitative and qualitative sperm defects. All patients underwent karyotyping and Y chromosome microdeletion STS-PCR. A single molecule molecular inversion probe-based targeted sequencing assay covering 39 male infertility genes was performed in 120 patients, while whole exome sequencing (WES) was conducted in 48 patients using a duo/trio-based approach to enable segregation and de novo variant detection. Gonosomal aneuploidies were observed in 3/247 patients (1.2%, 95% CI 0.3-3.5%) and causal AZF microdeletions in 8/247 (3.2%, 95% CI 1.4-6.3%). Targeted sequencing identified pathogenic/likely pathogenic (P/LP) variants in 4/120 patients (3.3%, 95% CI 0.9-8.3%), with additional CFTR variants in 3 patients where parental DNA was unavailable for phasing. WES yielded P/LP variants in 4/48 patients (8.3%, 95% CI 2.3-19.9%) affecting PMFBP1, DNAH1, and AR genes, confirmed via segregation analysis. No de novo or copy number variants were confirmed as causative, though several candidate genes were prioritised. Sequencing-based approaches provided an additional ~ 6-8% diagnostic yield, with the overall diagnostic rate reaching 7.7% (19/247; 95% CI 4.7-11.8%). Sequencing-based strategies, particularly family-based trio WES, significantly enhance diagnostic yield beyond current guideline-recommended tests, with data supporting their adoption as first-tier investigations for severe male infertility. This represents India's largest cohort-based genomic study on male infertility to date. Larger family-based cohorts will be essential to delineate the contribution of de novo variants to male infertility genetics.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Male Infertility: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Male Infertility (condition). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/condition/Male%20Infertility\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Conditions\",\"item\":\"https://www.reachrx.ai/hub/tag/condition\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Male Infertility\",\"item\":\"https://www.reachrx.ai/hub/tag/condition/Male%20Infertility\"}]}}"}}]],["$","$L2f",null,{"title":"Male Infertility: Research & Clinical Takeaways","description":"Discover peer-reviewed research on Male Infertility with concise clinician summaries and next-step guidance.","papers":[{"doi":"10.1093/humrep/deag130","pmid":"42671480","title":"A Western-style diet exacerbates male infertility in\n M1ap\n knockout mice","journal_title":"Human Reproduction","journal_issn":"0268-1161","published_at":"2026-08-31T00:00:00.000Z","url":"https://doi.org/10.1093/humrep/deag130","source_score":68,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-04T06:22:18.380Z","updated_at":"2026-09-04T06:22:18.380Z","tags":[{"paper_doi":"10.1093/humrep/deag130","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"condition","value":"Male Infertility","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"condition","value":"Spermatogenic Failure","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"condition","value":"Subfertility","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"modality","value":"Dietary Intervention","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"modality","value":"Genetic Knockout Model","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"study_design","value":"Animal Experimental Study","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"warning","value":"No exact sample sizes (number of mice per group) are reported in the abstract; the sample_size tag was omitted.","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"warning","value":"The abstract does not report absolute numeric effect sizes (e.g., pups per litter, % motility), limiting quantitative summary.","value_numeric":null},{"paper_doi":"10.1093/humrep/deag130","tag_type":"warning","value":"The study design is a controlled animal experiment, not a clinical trial — the 'practice_changing' impact flag reflects the clinical framing in the abstract but should be interpreted cautiously pending human validation.","value_numeric":null}],"summaries":{"what_studied":"This mouse study examined the individual and combined effects of *M1ap* knockout (loss of M1AP function, a known genetic cause of male infertility) and a Western (high-fat, high-sugar) diet on male fertility, spermatogenesis, and sperm quality in C57BL/6J mice at young (10–12 weeks) and aged (26–28 weeks) timepoints.","key_result":"The combined *M1ap*-/- plus Western diet group had more abnormal and sloughed germ cells, fewer pups per litter, and more significantly compromised sperm motility and morphology than either the gene deletion or Western diet alone — demonstrating an additive or synergistic worsening of subfertility.","limitations":"- Mouse model only; findings require validation in human cohorts with *M1AP* variants.\n- Study does not quantify the magnitude of individual vs. combined effects with precise statistics in the abstract.\n- Limited to a single inbred strain (C57BL/6J), which may not generalize to other genetic backgrounds.","practice_takeaway":"Men with known or suspected *M1AP* loss-of-function variants presenting at infertility clinics may be particularly vulnerable to diet-related worsening of sperm parameters — advising against a Western-style diet before assisted reproduction seems prudent. This study supports routinely discussing dietary and lifestyle factors alongside genetic workup in male infertility consultations."}},{"doi":"10.1007/s10815-026-04002-0","pmid":"42629513","title":"Gut microbiota signatures associated with spermatogenic capacity and sperm retrieval outcomes in non-obstructive azoospermia","journal_title":"Journal of Assisted Reproduction and Genetics","journal_issn":"1058-0468","published_at":"2026-08-22T00:00:00.000Z","url":"https://doi.org/10.1007/s10815-026-04002-0","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-01T06:21:04.307Z","updated_at":"2026-09-01T06:21:04.307Z","tags":[{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"condition","value":"Male Infertility","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"condition","value":"Non-Obstructive Azoospermia","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"condition","value":"Obstructive Azoospermia","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"modality","value":"Gut Microbiome Profiling","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"modality","value":"Microdissection Testicular Sperm Extraction","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"sample_size","value":"n=39","value_numeric":39},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"warning","value":"All participants were recruited from a single center in Taiwan; findings may not generalize to other ethnicities or dietary backgrounds.","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"warning","value":"Observational design with single-timepoint sampling cannot establish whether microbiota differences cause, result from, or merely accompany the underlying testicular phenotype.","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"warning","value":"The role of Finegoldia magna in spermatogenesis is entirely novel and biologically uncharacterized; no causal mechanism has been established.","value_numeric":null},{"paper_doi":"10.1007/s10815-026-04002-0","tag_type":"warning","value":"The study is exploratory and underpowered (n=25 NOA); all ROC cutoffs should be considered hypothesis-generating only. Wide confidence intervals (e.g., AUC 95% CI 0.544–0.934 for F/B ratio) reflect this uncertainty.","value_numeric":null}],"summaries":{"what_studied":"This prospective cohort study profiled gut microbiota (full-length 16S rRNA, PacBio) in 39 azoospermic men (OA n=14, NOA n=25) and evaluated whether microbial signatures were associated with successful sperm retrieval after microdissection testicular sperm extraction (mTESE).","key_result":"NOA patients had reduced Bacteroidota (23.5% vs 28.5%, p<0.001) and elevated Proteobacteria (9.7% vs 3.8%, p<0.001) vs OA. Within NOA, successful retrieval (52%, 13/25) was linked to a higher Firmicutes-to-Bacteroidota ratio (AUC 0.76; 76.9% sensitivity, 75.0% specificity at cutoff ≥2.20) and enrichment of *Finegoldia magna* (AUC 0.756; 100% specificity at abundance ≥8.7%, though sensitivity was only 46.2%).","limitations":"- Small sample (n=39 total; n=25 NOA) limits statistical power and generalizability.\n- Single timepoint 16S rRNA sequencing cannot assess functional capacity (no metagenomics or metabolomics) or temporal stability of microbiota.\n- Single Taiwanese tertiary center cohort; ROC cutoffs are hypothesis-generating only, with no external validation.","practice_takeaway":"Gut microbiota profiling is not ready for clinical use in NOA counseling, but these exploratory findings suggest the Firmicutes-to-Bacteroidota ratio and *Finegoldia magna* abundance warrant further study as non-invasive correlates of mTESE success. Clinicians should await validation in larger, multicenter cohorts before applying any microbiota-based thresholds."}},{"doi":"10.1093/humrep/deag104","pmid":"42526509","title":"Body fat percentage in relation to semen characteristics, testicular volume, and reproductive hormones: a cross-sectional study","journal_title":"Human Reproduction","journal_issn":"0268-1161","published_at":"2026-07-29T00:00:00.000Z","url":"https://doi.org/10.1093/humrep/deag104","source_score":89,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-05T13:22:55.631Z","updated_at":"2026-08-05T13:22:55.631Z","tags":[{"paper_doi":"10.1093/humrep/deag104","tag_type":"age_group","value":"adolescent","value_numeric":null},{"paper_doi":"10.1093/humrep/deag104","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1093/humrep/deag104","tag_type":"condition","value":"Male Infertility","value_numeric":null},{"paper_doi":"10.1093/humrep/deag104","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1093/humrep/deag104","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1093/humrep/deag104","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1093/humrep/deag104","tag_type":"modality","value":"Bioelectrical Impedance Analysis","value_numeric":null},{"paper_doi":"10.1093/humrep/deag104","tag_type":"sample_size","value":"n=1058","value_numeric":1058},{"paper_doi":"10.1093/humrep/deag104","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1093/humrep/deag104","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1093/humrep/deag104","tag_type":"warning","value":"One author (K.S.H.) disclosed holding stocks in Eli Lilly and Novo Nordisk, which may be relevant given the study's focus on obesity-related outcomes.","value_numeric":null},{"paper_doi":"10.1093/humrep/deag104","tag_type":"warning","value":"The 'adolescent' age group tag reflects the cohort age of ~18 years and 9 months — participants are on the cusp of adolescent/adult classification.","value_numeric":null},{"paper_doi":"10.1093/humrep/deag104","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously: findings are cross-sectional, and the authors explicitly note causality is not established.","value_numeric":null}],"summaries":{"what_studied":"This cross-sectional study examined whether body fat percentage (measured by bioelectrical impedance) is associated with semen characteristics, testicular volume, and reproductive hormone levels in 1,058 Danish men (~18.75 years old) from the FEPOS cohort (2017–2019), comparing it against BMI and waist-to-height ratio as adiposity measures.","key_result":"High body fat (20–24%) was associated with a **23% lower total sperm count** vs. normal (8–19%); very high body fat (≥25%) showed a 15% lower total sperm count (not statistically significant). Higher body fat was also linked to lower SHBG and testosterone, and higher free androgen index, LH, and estradiol. Body fat percentage predicted sperm count and concentration better than BMI or waist-to-height ratio, and the association with total sperm count and morphology persisted even in normal-weight men (BMI 18.5–24.9).","limitations":"- Low participation rate (19%) introduces potential selection bias, partially addressed with selection weights.\n- Cross-sectional design raises reverse causation risk, though a sensitivity analysis using BMI at age 11 suggested minimal concern.\n- Bioelectrical impedance, while better than BMI, can still misclassify body fat percentage.","practice_takeaway":"Body fat percentage may be a more sensitive marker of impaired semen quality and hormonal disruption than BMI alone — even normal-weight young men with high body fat showed worse sperm parameters. Clinicians evaluating male fertility should consider body composition assessment beyond standard BMI."}},{"doi":"10.1038/s41443-026-01279-8","pmid":"42477174","title":"The effect of stress on testosterone and sexual function","journal_title":"International Journal of Impotence Research","journal_issn":"0955-9930","published_at":"2026-07-20T00:00:00.000Z","url":"https://doi.org/10.1038/s41443-026-01279-8","source_score":35,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-04T18:17:56.292Z","updated_at":"2026-08-04T18:17:56.292Z","tags":[{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"condition","value":"Erectile Dysfunction","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"condition","value":"Male Hypogonadism","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"condition","value":"Male Infertility","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"condition","value":"Sexual Dysfunction","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"warning","value":"No specific patient numbers, effect sizes, or quantitative outcomes are reported — this is a narrative review without meta-analytic data. Findings are mechanistic and observational in nature.","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"warning","value":"The distinction between 'acute physiological' and 'chronic psychological' stress may oversimplify a continuum — the review itself notes these categories have distinct but potentially overlapping mechanisms.","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01279-8","tag_type":"warning","value":"The review focuses exclusively on males; applicability to other sexes or gender identities is not addressed.","value_numeric":null}],"summaries":{"what_studied":"This narrative review examined how acute physiological stress and chronic psychological stress affect testosterone levels and sexual function in males, exploring mechanisms including HPA axis activation, sympathetic nervous system engagement, allostatic load, and metabolic dysregulation.","key_result":"Acute physiological stress causes transient testosterone reductions and temporary sexual dysfunction via sympathetic activation and HPA axis engagement; chronic psychological stress leads to sustained endocrine dysregulation, including testosterone suppression, erectile dysfunction, diminished sperm quality, and reduced sexual desire—largely mediated through metabolic dysregulation.","limitations":"As a narrative review, it is subject to selection bias and does not pool quantitative data; no specific effect sizes or absolute numbers are reported. The review does not address female populations or non-binary individuals.","practice_takeaway":"Clinicians evaluating men with low testosterone or sexual dysfunction should screen for both acute and chronic stress, as each requires distinct management approaches. Chronic stress with high allostatic load warrants attention to metabolic health as a key mediator of testosterone suppression."}},{"doi":"10.1093/humrep/deag083.203","pmid":null,"title":"L26/O-205 Exposure to air pollution mixtures during spermatogenesis and sperm DNA methylation in men seeking infertility treatment","journal_title":"Human Reproduction","journal_issn":"0268-1161","published_at":"2026-07-08T00:00:00.000Z","url":"https://doi.org/10.1093/humrep/deag083.203","source_score":14,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-07-22T13:37:36.970Z","updated_at":"2026-07-22T13:37:36.970Z","tags":[{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"condition","value":"Air Pollution Exposure","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"condition","value":"Male Infertility","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"generic","value":"folic acid","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"generic","value":"zinc","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"modality","value":"Environmental Exposure Assessment","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"sample_size","value":"n=1220","value_numeric":1220},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"study_design","value":"Ancillary Study of Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"warning","value":"Geographic restriction to Salt Lake City, Utah may limit generalizability to regions with different air pollution profiles.","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"warning","value":"The p-value thresholds used (p < 0.0001 and p < 0.0005) are not genome-wide significance thresholds for an 850K-CpG array; type I error risk is substantial and authors acknowledge replication is needed.","value_numeric":null},{"paper_doi":"10.1093/humrep/deag083.203","tag_type":"warning","value":"This is an ancillary observational study nested within an RCT; the RCT intervention (folic acid/zinc) is not the focus here, but randomization assignment was adjusted for in models.","value_numeric":null}],"summaries":{"what_studied":"This ancillary study of the FAZST RCT (2013–2017, Salt Lake City, Utah) examined whether exposure to air pollution mixtures (O3, NO2, SO2, PM2.5 constituents) during spermatogenesis was associated with differential sperm DNA methylation in 1,220 men seeking infertility treatment.","key_result":"Air pollution mixtures were associated with differential methylation at 9 CpGs (p < 0.0001, annotated to 8 genes, 7 hypermethylated) and 30 additional CpGs (p < 0.0005, annotated to 26 genes), implicating pathways in spermatogonial stem cell maintenance, chromosomal organization, RNA/protein processing, and the endosomal-lysosomal system; O3 and NO2 were the top contributors. Notably, the paternally imprinted gene *GNAS*—linked to semen quality and embryonic development—was hypermethylated.","limitations":"- Testing ~850K CpGs raises substantial type I error risk; findings at p < 0.0005 need replication.\n- Study participants were drawn from a single geographic region (Utah), limiting generalizability given regional variation in pollution mixtures.\n- Observational ancillary design; causal inference is limited.","practice_takeaway":"Men's exposure to common air pollutants—especially ozone and NO2—during the ~74-day spermatogenesis window may alter sperm epigenetic marks at genes critical for fertility and offspring development. Clinicians counseling men before infertility treatment may consider discussing air pollution exposure as a modifiable environmental factor, though replication is needed before firm clinical guidance."}},{"doi":"10.1007/s10815-026-03939-6","pmid":"42337201","title":"AI-enabled precision reproductive medicine: a comprehensive review of clinical applications, decision frameworks, and evidence-based implementation","journal_title":"Journal of Assisted Reproduction and Genetics","journal_issn":"1058-0468","published_at":"2026-06-24T00:00:00.000Z","url":"https://doi.org/10.1007/s10815-026-03939-6","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-05T13:38:31.728Z","updated_at":"2026-07-05T13:38:31.728Z","tags":[{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"condition","value":"Infertility","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"condition","value":"Male Infertility","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"condition","value":"Non-Obstructive Azoospermia","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"condition","value":"Polycystic Ovary Syndrome","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"condition","value":"Recurrent Implantation Failure","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"modality","value":"Artificial Intelligence / Machine Learning","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"modality","value":"Computer-Assisted Semen Analysis","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"modality","value":"Deep Learning","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"modality","value":"Large Language Model","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"modality","value":"Time-Lapse Embryo Imaging","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"warning","value":"Full text was not accessible; summary is based on the abstract and reference list only, which may omit nuanced findings from the body of the review.","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously — while one cited RCT (Illingworth et al., Nat Med 2024) supports AI embryo selection, the broader review itself does not generate new clinical data.","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03939-6","tag_type":"warning","value":"This is a narrative review without systematic search methodology or meta-analysis; conclusions reflect author synthesis, not pooled evidence.","value_numeric":null}],"summaries":{"what_studied":"This comprehensive review synthesizes AI applications across the full ART continuum — including sperm/oocyte evaluation, embryo selection, pregnancy prediction, ovarian reserve assessment, and AI-powered patient communication — drawing on studies published up to 2026.","key_result":"AI tools demonstrated value across multiple ART domains: deep learning improved blastocyst selection (one RCT showed noninferiority vs. manual morphology), AI-assisted microfluidic sperm recovery enabled a first clinical pregnancy in non-obstructive azoospermia, and large language models showed potential to enhance patient health literacy and engagement in reproductive care.","limitations":"As a narrative review, it does not perform meta-analysis or quantify pooled effect sizes. Most cited AI models face challenges with data privacy, limited external validation, and poor generalizability across clinic settings and imaging systems.","practice_takeaway":"AI-based embryo selection tools (e.g., deep learning ranking systems) are now supported by RCT-level evidence for noninferiority and can be considered as adjuncts to standard morphology grading. Clinicians should remain cautious about deploying AI models outside the populations and imaging systems on which they were trained."}},{"doi":"10.1093/humrep/deag086","pmid":"42249589","title":"Novel variants in\n YTHDC2\n cause non-obstructive azoospermia by disrupting the mitotic-to-meiotic transition in humans and mice","journal_title":"Human Reproduction","journal_issn":"0268-1161","published_at":"2026-06-05T00:00:00.000Z","url":"https://doi.org/10.1093/humrep/deag086","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-17T13:29:54.682Z","updated_at":"2026-06-17T13:29:54.682Z","tags":[{"paper_doi":"10.1093/humrep/deag086","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"condition","value":"Male Infertility","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"condition","value":"Non-Obstructive Azoospermia","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"condition","value":"Severe Oligozoospermia","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"modality","value":"Genetic Screening","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"modality","value":"Whole-Exome Sequencing","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"sample_size","value":"n=145","value_numeric":145},{"paper_doi":"10.1093/humrep/deag086","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"study_design","value":"Genetic Cohort Study with In Vivo Functional Validation","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"warning","value":"Functional validation covers only one of four identified variants (MT1/p.E1164V); clinical pathogenicity of MT2, MT3, and MT4 relies on bioinformatic and co-segregation data only.","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"warning","value":"Only 5 patients carried YTHDC2 variants; the small sample limits generalizability and frequency estimates.","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"warning","value":"Sample size tag (n=145) reflects the total screened cohort (56 families + 89 sporadic men); only 5 had YTHDC2 variants.","value_numeric":null},{"paper_doi":"10.1093/humrep/deag086","tag_type":"warning","value":"The study design is a cohort genetic screen plus animal model — not an RCT; level of evidence reflects this observational/functional design.","value_numeric":null}],"summaries":{"what_studied":"This study screened a cohort of 56 consanguineous families and 89 sporadic infertile men with non-obstructive azoospermia (NOA) or severe oligozoospermia for pathogenic variants in *YTHDC2*, then validated the top candidate variant (p.E1164V) using a CRISPR/Cas9 knock-in mouse model to define the mechanism of spermatogenic failure.","key_result":"Five infertile men from three unrelated families carried biallelic pathogenic missense variants in *YTHDC2*; all showed meiotic prophase arrest. The knock-in mouse model recapitulated the human phenotype and revealed that these variants reduce MEIOC and RBM46 levels while aberrantly upregulating mitotic regulators (CCNA2, CCND1, WEE1) in meiosis-entry cells, indicating failure to silence the mitotic program.","limitations":"Only five patients with *YTHDC2* variants were identified (small sample size); in vivo functional validation was performed for only one variant (MT1/p.E1164V), leaving the pathogenic mechanisms of the other three variants unconfirmed.","practice_takeaway":"Consider adding *YTHDC2* to genetic panels for men with unexplained NOA or severe oligozoospermia, especially in consanguineous families. Biallelic missense variants in this gene are a newly established, mechanistically validated cause of male meiotic arrest."}},{"doi":"10.1007/s10815-026-03911-4","pmid":"42174372","title":"TEX43, a testis-enriched microtubule-associated gene, exerts minimal impact on spermatogenesis and fertility in mice and humans","journal_title":"Journal of Assisted Reproduction and Genetics","journal_issn":"1058-0468","published_at":"2026-05-23T00:00:00.000Z","url":"https://doi.org/10.21203/rs.3.rs-8181104/v1","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-02T13:27:21.930Z","updated_at":"2026-06-02T13:27:21.930Z","tags":[{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"condition","value":"Asthenoteratozoospermia","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"condition","value":"Male Infertility","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"generic","value":"TEX43 gene variant","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"modality","value":"Intracytoplasmic Sperm Injection","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"modality","value":"Whole-Exome Sequencing","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"sample_size","value":"n=146","value_numeric":146},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"study_design","value":"Controlled Laboratory Study with Human Genetic Cohort","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"warning","value":"Intronic variants (carried by 8 of 9 patients) have unknown functional significance; no splicing assays were performed.","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"warning","value":"Mouse and human data are conflated throughout; the KO mouse findings may not directly translate to human TEX43 variant pathophysiology.","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"warning","value":"Study design is mixed (mouse KO model + small human cohort); the level of evidence reflects the human cohort component, which is observational and underpowered.","value_numeric":null},{"paper_doi":"10.1007/s10815-026-03911-4","tag_type":"warning","value":"The abstract and full text report slightly different numbers of patients with TEX43 variants (abstract states 5 with exonic variants achieving live births; full text table lists 5 patients total with 4 live births and 1 biochemical pregnancy) — the table data appear most detailed and were used here.","value_numeric":null}],"summaries":{"what_studied":"This study characterized TEX43 expression and function in spermatogenesis using a CRISPR/Cas9 Tex43 knockout (KO) mouse model, plus whole-exome sequencing (WES) of 146 infertile men with asthenoteratozoospermia to identify TEX43 variants and their clinical outcomes.","key_result":"Tex43-KO mice had modestly reduced sperm density (28.6 vs. 41.2 ×10⁶/ml; P<0.01) and increased flagellar end-piece microtubule disorganization (~30% vs. ~5%; P<0.01), but preserved motility, normal litter size (6.8 vs. 7.2 pups; P>0.05), and fertility. WES found 9 men with TEX43 variants; 4 of 5 who underwent ICSI achieved live births, including 1 with the p.R37Q missense variant predicted to weaken microtubule binding.","limitations":"- Human cohort is small (9 variant carriers), limiting generalizability.\n- Intronic variants lack functional splicing validation (no minigene assays performed).\n- No family segregation data to confirm variant inheritance in most cases.","practice_takeaway":"TEX43 variants in infertile men do not preclude ICSI success—4 of 5 patients with exonic variants achieved live births. Clinicians can counsel couples that TEX43 variants are likely subtle fertility modifiers, not absolute barriers to reproduction with ART."}},{"doi":"10.1093/humupd/dmag013","pmid":"42172631","title":"Sperm mitochondrial DNA copy number: a marker of male fertility and reproductive success","journal_title":"Human Reproduction Update","journal_issn":"1355-4786","published_at":"2026-05-22T00:00:00.000Z","url":"https://doi.org/10.1093/humupd/dmag013","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-28T13:24:23.343Z","updated_at":"2026-05-28T13:24:23.343Z","tags":[{"paper_doi":"10.1093/humupd/dmag013","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"condition","value":"Male Infertility","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"condition","value":"Semen Quality Impairment","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"generic","value":"mitochondrial transcription factor A (TFAM)","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"modality","value":"Antioxidant Therapy","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"modality","value":"Biomarker Assessment","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"modality","value":"Mitochondria-Directed Pharmacotherapy","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"sample_size","value":"n=21","value_numeric":21},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"study_design","value":"Systematic Review","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"warning","value":"Associations with couple-level reproductive outcomes were described as 'inconsistent,' so clinical impact flag is conservative (limited_evidence).","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"warning","value":"Level of evidence set to 2 (systematic review of observational/clinical cohort studies); no meta-analysis was performed, which may lower effective evidence quality.","value_numeric":null},{"paper_doi":"10.1093/humupd/dmag013","tag_type":"warning","value":"The sample_size tag reflects the number of included studies (n=21), not individual participants — total participant count was not reported in the abstract.","value_numeric":null}],"summaries":{"what_studied":"This systematic review evaluated sperm mitochondrial DNA copy number (mtDNAcn) as a biomarker of male fertility, synthesizing 21 epidemiologic, experimental, and clinical studies examining its associations with semen quality, couple fecundity, ART outcomes, embryo development, and sperm epigenetics (literature up to April 1, 2026).","key_result":"Across 21 studies, elevated sperm mtDNAcn was consistently linked to lower sperm concentration, total count, motility, and normal morphology, higher DNA fragmentation and chromatin abnormalities, and — less consistently — reduced likelihood of pregnancy and poorer embryo quality in ART; emerging data also connect mtDNAcn to altered sperm nuclear DNA methylation patterns.","limitations":"- Inconsistent associations with couple-level reproductive outcomes limit definitive clinical conclusions.\n- No standardized measurement protocols across sperm fractions or laboratory platforms, hampering cross-study comparability.\n- Only English-language articles were included, introducing potential language bias.","practice_takeaway":"Sperm mtDNAcn may serve as an adjunctive marker alongside standard semen analysis to better characterize male reproductive health, particularly in cases of unexplained infertility. Routine clinical use awaits standardized quantification methods and prospective validation of clinically meaningful thresholds."}},{"doi":"10.1038/s41443-026-01289-6","pmid":"42162188","title":"Attention-deficit/hyperactivity disorder stimulant use is associated with reduced semen volume in reproductive-age men: a multi-center analysis","journal_title":"International Journal of Impotence Research","journal_issn":"0955-9930","published_at":"2026-05-20T00:00:00.000Z","url":"https://doi.org/10.1038/s41443-026-01289-6","source_score":15,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-08T13:46:35.786Z","updated_at":"2026-06-08T13:46:35.786Z","tags":[{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"brand","value":"Ritalin","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"brand","value":"Vyvanse","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"condition","value":"Attention-Deficit/Hyperactivity Disorder","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"condition","value":"Male Infertility","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"generic","value":"amphetamine","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"generic","value":"dextroamphetamine","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"generic","value":"lisdexamfetamine","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"generic","value":"methylphenidate","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"modality","value":"CNS Stimulant","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"sample_size","value":"n=1164","value_numeric":1164},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"study_design","value":"Retrospective Matched Cohort Study","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"warning","value":"Brand name tags (Vyvanse, Ritalin) are illustrative representatives of the drug classes studied; the paper does not name specific brands.","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"warning","value":"Methamphetamine was included in the exposure definition but is an illicit/controlled substance in most contexts; prescription use may reflect rare clinical scenarios (e.g., obesity treatment). No subgroup data for methamphetamine were reported separately.","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"warning","value":"One author (SDL) disclosed a paid consulting relationship with Tolmar Pharmaceuticals, though no funding conflict with this study was declared.","value_numeric":null},{"paper_doi":"10.1038/s41443-026-01289-6","tag_type":"warning","value":"Sample size tag reflects the final matched analytic cohort (388 exposed + 776 controls = 1,164), not the full screened population of 2,039. The screened total is larger but many were excluded.","value_numeric":null}],"summaries":{"what_studied":"Multi-center retrospective matched cohort study evaluating whether recent ADHD stimulant use (methylphenidate, amphetamines) within 90 days of semen testing affected semen parameters in 388 exposed men vs. 776 age-matched unexposed controls, all aged 18–40 with ADHD, across two tertiary care centers (1995–2025).","key_result":"Stimulant exposure was linked to a modest but significant reduction in semen volume (median 2.70 mL vs. 2.95 mL in controls; p = 0.02), corresponding to an 8.4% lower volume on multivariable regression (95% CI: −14.4% to −1.8%; p = 0.01). No significant differences were found in sperm concentration, motility, total sperm count, or total motile sperm count. Amphetamine users drove the volume difference; methylphenidate users showed no significant difference vs. controls.","limitations":"- No data on dose, frequency, or adherence; dose-response relationships cannot be assessed.\n- Single semen sample per patient, despite known intra-individual variability.\n- Cohort drawn from men already undergoing semen analysis, introducing potential selection bias toward fertility-evaluated individuals.","practice_takeaway":"Reassure reproductive-age men with ADHD that stimulant use causes only a small, likely clinically insignificant drop in semen volume and does not impair sperm count, motility, or concentration. Routine fertility counseling and clinical decision-making for these patients need not change based on stimulant use alone."}},{"doi":"10.1016/j.fertnstert.2026.04.023","pmid":"42082073","title":"Testosterone-to-Follicle Stimulating Hormone Ratio Predicts Sperm Retrieval Success in Men with Idiopathic Non-Obstructive Azoospermia","journal_title":"Fertility and Sterility","journal_issn":"0015-0282","published_at":"2026-05-05T00:00:00.000Z","url":"https://doi.org/10.1016/j.fertnstert.2026.04.023","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-06","doi":"10.1016/j.fertnstert.2026.04.023","days":"14","issn":"0015-0282","rank":"4","field":"Clinical Medicine","score":"7","category":"Obstetrics & Gynecology","categories":["Obstetrics & Gynecology"],"_categories":["Obstetrics & Gynecology"]},"pubmed":{"doi":"10.1016/j.fertnstert.2026.04.023","title":"Testosterone-to-Follicle Stimulating Hormone Ratio Predicts Sperm Retrieval Success in Men with Idiopathic Non-Obstructive Azoospermia.","journal":"Fertility and sterility","methods":"","results":"Men with successful sperm retrieval had significantly lower gonadotropin levels and a higher T/FSH ratio (43.0 vs. 20.9, p=0.004). Among all hormonal metrics, T/FSH demonstrated the strongest discriminative ability (AUC=0.81). The significance remained after excluding men with hypospermatogenesis noted on testicular pathology. In external validation, T/FSH was the only variable that maintained statistical significance (p=0.03; AUC=0.74). Partition analysis further revealed a two-step model (T/FSH>20 and LH<10) that achieved 93% sensitivity and 81% specificity for predicting sperm retrieval success.","abstract":"$30","keywords":["Hormonal Predictors","Male Infertility","Microsurgical testicular sperm extraction","Non-obstructive azoospermia","Sperm retrieval success"],"pubmed_id":"42082073","conclusions":"This multi-institutional study demonstrates that the T/FSH ratio is a reproducible and clinically meaningful predictor of sperm retrieval success in men with idiopathic NOA. Across two independent and diverse cohorts, this ratio consistently outperformed single-hormone predictors and remained the only externally validated preoperative predictor of mTESE success.","publication_date":"2026-05-05T00:00:00"},"crossref":{"DOI":"10.1016/j.fertnstert.2026.04.023","URL":"https://doi.org/10.1016/j.fertnstert.2026.04.023","ISSN":["0015-0282"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S0015028226002657?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S0015028226002657?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Testosterone-to-Follicle Stimulating Hormone Ratio Predicts Sperm Retrieval Success in Men with Idiopathic Non-Obstructive 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Azoospermia","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.04.023","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.04.023","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.04.023","tag_type":"modality","value":"Hormonal Biomarker","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.04.023","tag_type":"modality","value":"Surgical Sperm Retrieval","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.04.023","tag_type":"sample_size","value":"n=60","value_numeric":60},{"paper_doi":"10.1016/j.fertnstert.2026.04.023","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.04.023","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.04.023","tag_type":"warning","value":"Small cohort (n=60 total; 30 per sub-cohort) — the 'practice_changing' flag reflects the novelty and external validation of the T/FSH ratio, but findings should be interpreted cautiously until replicated in larger prospective studies.","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.04.023","tag_type":"warning","value":"Testosterone units are not explicitly stated in the abstract; T/FSH ratio thresholds (e.g., >20) may vary depending on assay and unit conventions used at individual institutions.","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.04.023","tag_type":"warning","value":"The study excludes men with genetic abnormalities, prior genitourinary surgery, or empirical medical therapy, so results may not generalize to all NOA presentations.","value_numeric":null}],"summaries":{"what_studied":"Preoperative hormonal predictors — FSH, LH, testosterone (T), and derived ratios (T/FSH, T/LH, LH/FSH) — were evaluated for their ability to predict successful sperm retrieval in 60 men with idiopathic non-obstructive azoospermia (NOA) undergoing mTESE (2014–2024), using a split prediction (n=30) and external validation cohort (n=30).","key_result":"T/FSH was the strongest predictor of mTESE success (AUC=0.81 in prediction cohort; AUC=0.74 in validation cohort), with successful retrieval associated with a higher T/FSH ratio (43.0 vs. 20.9, p=0.004). A two-step model (T/FSH >20 **and** LH <10) achieved 93% sensitivity and 81% specificity.","limitations":"- Small total sample size (n=60) limits statistical power and generalizability.\n- Retrospective design introduces selection bias.\n- Strict idiopathic NOA definition (excluding genetic causes, prior surgery, empirical therapy) may limit applicability to broader NOA populations.","practice_takeaway":"Before mTESE, calculate the T/FSH ratio: a value >20 combined with LH <10 predicts sperm retrieval with 93% sensitivity and 81% specificity in idiopathic NOA. This simple blood-test-derived ratio may help counsel patients on likelihood of success before surgery."}},{"doi":"10.1016/j.fertnstert.2026.01.019","pmid":"41611115","title":"Micromanagement: how the male reproductive microbiome shapes male fertility","journal_title":"Fertility and Sterility","journal_issn":"0015-0282","published_at":"2026-01-28T00:00:00.000Z","url":"https://doi.org/10.1016/j.fertnstert.2026.01.019","source_score":13,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T22:49:51.956Z","updated_at":"2026-05-07T22:49:51.956Z","tags":[{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"condition","value":"Gut Dysbiosis","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"condition","value":"Male Infertility","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"condition","value":"Sperm DNA Fragmentation","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"modality","value":"Antibiotic","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"modality","value":"Probiotic","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"study_design","value":"Narrative Systematic Review","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"warning","value":"Level of evidence set to 3 (narrative systematic review without meta-analysis) due to stated methodological heterogeneity precluding quantitative synthesis.","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"warning","value":"Most supporting mechanistic data come from animal studies; direct human causality is not established.","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"warning","value":"No sample size is reported in this review; it synthesizes heterogeneous cohorts without pooled N.","value_numeric":null},{"paper_doi":"10.1016/j.fertnstert.2026.01.019","tag_type":"warning","value":"Published date is 2026-01-28; today is 2026-05-07 — this is a very recent publication and downstream clinical guidelines have not yet incorporated these findings.","value_numeric":null}],"summaries":{"what_studied":"A narrative systematic review evaluating the male reproductive microbiome's role in sperm function and fertility, focusing on seminal microbial profiles, semen parameters, oxidative stress, sperm DNA fragmentation, and assisted reproduction outcomes in human studies, with supporting mechanistic animal data.","key_result":"Anaerobe-rich seminal profiles (often *Prevotella* or *Atopobium*) are more frequently linked to higher oxidative stress, greater sperm DNA fragmentation, and lower motility; *Lactobacillus*-rich profiles more often correlate with better redox status and DNA integrity. Rapid partner microbiome exchange can shift semen quality over short periods. Small antibiotic/probiotic trials show variable benefits with limited durability.","limitations":"- Predominantly small, cross-sectional studies prevent causal inference.\n- Significant methodological heterogeneity in design and lab methods precluded meta-analysis.\n- Antibiotic and probiotic trials lack reproductive endpoint data and long-term follow-up.","practice_takeaway":"Clinicians evaluating male infertility should be aware that seminal microbial profiles may influence sperm DNA integrity and motility, and that couple-level microbiome exchange is real and rapid. Routine microbiome-targeted interventions are not yet supported by adequately powered trials, but this remains an active area to watch."}},{"doi":"10.1007/s43032-025-02025-z","pmid":"41504834","title":"Chronic Stress Destabilizes Ectoplasmic Specialization Dynamics in the Rat Testis via Downregulating the Focal Adhesion Kinase-Associated Protein Complex","journal_title":"Reproductive Sciences","journal_issn":"1933-7191","published_at":"2026-01-08T00:00:00.000Z","url":"https://doi.org/10.1007/s43032-025-02025-z","source_score":15,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-10","doi":"10.1007/s43032-025-02025-z","days":"7","issn":"1933-7191","rank":"4","field":"Clinical Medicine","score":"15","category":"Obstetrics & Gynecology","categories":["Obstetrics & Gynecology"],"_categories":["Obstetrics & Gynecology"]},"pubmed":{"doi":"10.1007/s43032-025-02025-z","title":"Chronic Stress Destabilizes Ectoplasmic Specialization Dynamics in the Rat Testis via 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No de novo or copy‑number variants were confirmed as causative.","limitations":"WES was performed in only 48 patients, limiting power for rare and de novo variant detection. Three CFTR findings lacked parental phasing. No causative de novo or CNVs were confirmed despite candidate genes being prioritized.","practice_takeaway":"Family‑based trio WES added yield beyond karyotype and Y‑microdeletion testing and supports early use in severe male infertility where available. Expect about a 6–8% added diagnostic return over guideline tests in this setting."}}],"initialOffset":14,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Male Infertility"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Male Infertility"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Male Infertility"}}}]]

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