RESUMO
Testicular sperm retrieval (TSR) techniques are valuable in the context of severe idiopathic male factor infertility; however, there are few studies in the literature examining the long-term impact of TSR on testicular function. The objective was to determine whether testicular sperm aspiration (TESA) or microdissection testicular sperm extraction (micro-TESE) worsens the pre-existing spermatogenesis deficiency in men with either cryptozoospermia or severe oligozoospermia. The study population consisted of 145 men with either cryptozoospermia or severe oligozoospermia that underwent TESA or micro-TESE and had long-term post-operative semen analyses (SA). Patients with SA prior to and following TSR were included (n = 24). Amongst them, 16 men underwent TESA and 8 underwent micro-TESE. The follow-up SA was obtained at a mean of 3.0 ± 2.0 years following TSR (range: 0.3-8.3 years) amongst all participants. The post-operative semen parameters in the TESA group were similar to the pre-intervention parameters (p > 0.1). Similarly, the micro-TESE cohort did not demonstrate significant alterations in semen parameters post-intervention (p > 0.05). None of the men in the study became azoospermic following the TSR. Our study indicates TESA or micro-TESE do not appear to worsen the pre-existing spermatogenesis deficiencies in cryptozoospermic and oligozoospermic men over a long-term period. Larger studies are required to corroborate these findings.
Assuntos
Azoospermia , Infertilidade Masculina , Oligospermia , Azoospermia/etiologia , Azoospermia/cirurgia , Humanos , Masculino , Microdissecção/métodos , Oligospermia/etiologia , Estudos Retrospectivos , Recuperação Espermática , Espermatogênese , Testículo/cirurgiaRESUMO
PURPOSE: The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.
Assuntos
Infertilidade Masculina/diagnóstico , Medicina Reprodutiva/normas , Urologia/normas , Aconselhamento/normas , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/normas , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/terapia , Estilo de Vida , Masculino , Medicina Reprodutiva/métodos , Escroto/diagnóstico por imagem , Análise do Sêmen , Sociedades Médicas/normas , Ultrassonografia , Estados Unidos , Urologia/métodosRESUMO
PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.
Assuntos
Infertilidade Masculina/terapia , Medicina Reprodutiva/normas , Urologia/normas , Varicocele/terapia , Aconselhamento/normas , Suplementos Nutricionais , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/normas , Fertilização in vitro/métodos , Fertilização in vitro/normas , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/etiologia , Masculino , Medicina Reprodutiva/métodos , Escroto/diagnóstico por imagem , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Análise do Sêmen , Sociedades Médicas/normas , Recuperação Espermática/normas , Resultado do Tratamento , Estados Unidos , Urologia/métodos , Varicocele/complicações , Varicocele/diagnósticoRESUMO
OBJECTIVES: Men with nonobstructive azoospermia (NOA), cryptozoospermia and severe oligozoospermia are candidates for microdissection testicular sperm extraction (micro-TESE) and intracytoplasmic sperm injection (ICSI). We sought to evaluate micro-TESE outcomes and the need for bilateral testicular exploration in the three groups of men. METHODS: We conducted a retrospective study of 233 consecutive micro-TESEs in men with nonobstructive azoospermia (n = 173), cryptozoospermia (n = 43) and severe oligozoospermia (n = 17). The decision to terminate the micro-TESE after a unilateral or bilateral testicular exploration was determined at the time of surgery and was based on the presence or absence of mature spermatozoa in the harvested micro-biopsies. Final assessment of sperm recovery, on the day of ICSI, was reported as successful (available spermatozoon for ICSI) or unsuccessful (no spermatozoon for ICSI). RESULTS: Unilateral testicular exploration resulted in successful sperm retrieval in 43% (75/173), 79% (34/43) and 100% (17/17) of men with NOA, cryptozoospermia and severe oligozoospermia respectively. Therefore, 57%, 21% and none of the men with NOA, cryptozoospermia and severe oligozoospermia, respectively, required a bilateral micro-TESE. Overall, micro-TESE resulted in successful sperm retrieval in 52% (90/173), 91% (39/43) and 100% (17/17) of men with NOA, cryptozoospermia and severe oligozoospermia respectively. CONCLUSION: Our data indicate that men with severe oligozoospermia are unlikely to require a bilateral testicular exploration at micro-TESE. Moreover, most cryptozoospermic men will have a successful sperm retrieval by micro-TESE with the majority of these patients requiring a unilateral exploration. In contrast, over 50% of the men with nonobstructive azoospermia will require a bilateral micro-TESE.
Assuntos
Azoospermia , Oligospermia , Azoospermia/cirurgia , Humanos , Masculino , Microdissecção , Oligospermia/terapia , Estudos Retrospectivos , Recuperação Espermática , Espermatozoides , Testículo/cirurgiaRESUMO
We herein summarise the evidence concerning the impact of sperm DNA fragmentation in various clinical infertility scenarios and the advances on sperm DNA fragmentation tests. The collected evidence was used to formulate 41 recommendations. Of these, 13 recommendations concern technical aspects of sperm DNA fragmentation testing, including pre-analytical information, clinical thresholds and interpretation of results. The remaining 28 recommendations relate to indications for sperm DNA fragmentation testing and clinical management. Clinical scenarios like varicocele, unexplained infertility, idiopathic infertility, recurrent pregnancy loss, intrauterine insemination, in vitro fertilisation/intracytoplasmic sperm injection, fertility counselling for men with infertility risk factors and sperm cryopreservation have been contemplated. The bulk evidence supporting the recommendations has increased in recent years, but it is still of moderate to low quality. This guideline provides clinicians with advice on best practices in sperm DNA fragmentation testing. Also, recommendations are provided on possible management strategies to overcome infertility related to sperm DNA fragmentation, based on the best available evidence. Lastly, we identified gaps in knowledge and opportunities for research and elaborated a list of recommendations to stimulate further investigation.
Assuntos
Infertilidade Masculina , Varicocele , Fragmentação do DNA , Feminino , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Infertilidade Masculina/terapia , Masculino , Gravidez , Injeções de Esperma Intracitoplásmicas , EspermatozoidesRESUMO
Dietary folate is a major source of methyl groups required for DNA methylation, an epigenetic modification that is actively maintained and remodeled during spermatogenesis. While high-dose folic acid supplementation (up to 10 times the daily recommended dose) has been shown to improve sperm parameters in infertile men, the effects of supplementation on the sperm epigenome are unknown. To assess the impact of 6 months of high-dose folic acid supplementation on the sperm epigenome, we studied 30 men with idiopathic infertility. Blood folate concentrations increased significantly after supplementation with no significant improvements in sperm parameters. Methylation levels of the differentially methylated regions of several imprinted loci (H19, DLK1/GTL2, MEST, SNRPN, PLAGL1, KCNQ1OT1) were normal both before and after supplementation. Reduced representation bisulfite sequencing (RRBS) revealed a significant global loss of methylation across different regions of the sperm genome. The most marked loss of DNA methylation was found in sperm from patients homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, a common polymorphism in a key enzyme required for folate metabolism. RRBS analysis also showed that most of the differentially methylated tiles were located in DNA repeats, low CpG-density and intergenic regions. Ingenuity Pathway Analysis revealed that methylation of promoter regions was altered in several genes involved in cancer and neurobehavioral disorders including CBFA2T3, PTPN6, COL18A1, ALDH2, UBE4B, ERBB2, GABRB3, CNTNAP4 and NIPA1. Our data reveal alterations of the human sperm epigenome associated with high-dose folic acid supplementation, effects that were exacerbated by a common polymorphism in MTHFR.
Assuntos
Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Adulto , DNA/genética , DNA/metabolismo , Metilação de DNA , Epigênese Genética/efeitos dos fármacos , Ácido Fólico/efeitos adversos , Ácido Fólico/sangue , Genes Reguladores , Genótipo , Humanos , Masculino , Polimorfismo Genético , Espermatozoides/enzimologia , Proteínas Centrais de snRNP/genéticaRESUMO
In 1992 and subsequently, several reports indicated that ICSI was a successful technique to achieve clinical pregnancy and live birth using spermatozoa with severely impaired characteristics. The initial optimism over the ability of ICSI to overcome significant sperm abnormalities was later tempered by the findings of more recent publications suggesting that some sperm deficits may not be as effectively treated with ICSI. In search for effective treatment for couples with severe male factor, a number of small retrospective and prospective studies have reported high pregnancy and live birth rates using testicular sperm for men with necrozoospermia, cryptozoospermia and oligozoospermia with or without elevated sperm DNA damage. Although the data suggest that there may be some benefit in performing testicular sperm retrieval (TSR)-ICSI in select groups of non-azoospermic infertile men, there are potential risks involved with TSR. Clinicians should balance these risks prior to the recommendation of TSR-ICSI on the result of a semen analysis or sperm DNA test alone. Careful evaluation and management of male factor infertility is important. The use of TSR-ICSI in the absence of specific sperm DNA defects is still experimental.
Assuntos
Oligospermia/genética , Injeções de Esperma Intracitoplásmicas , Recuperação Espermática , Coeficiente de Natalidade , Dano ao DNA , Feminino , Humanos , Nascido Vivo , Masculino , Gravidez , Taxa de Gravidez , Resultado do TratamentoRESUMO
BACKGROUND: More than 70 million couples worldwide are affected by infertility, with male-factor infertility accounting for about half of the cases. Semen analysis is critical for determining male fertility potential, but conventional testing is costly and complex. Here, we demonstrate a paper-based microfluidic approach to quantify male fertility potential, simultaneously measuring 3 critical semen parameters in 10 min: live and motile sperm concentrations and sperm motility. METHODS: The device measures the colorimetric change of yellow tetrazolium dye to purple formazan by the diaphorase flavoprotein enzyme present in metabolically active human sperm to quantify live and motile sperm concentration. Sperm motility was determined as the ratio of motile to live sperm. We assessed the performance of the device by use of clinical semen samples, in parallel with standard clinical approaches. RESULTS: Detection limits of 8.46 and 15.18 million/mL were achieved for live and motile sperm concentrations, respectively. The live and motile sperm concentrations and motility values from our device correlated with those of the standard clinical approaches (R(2) ≥ 0.84). In all cases, our device provided 100% agreement in terms of clinical outcome. The device was also robust and could tolerate conditions of high absolute humidity (22.8 g/m(3)) up to 16 weeks when packaged with desiccant. CONCLUSIONS: Our device outperforms existing commercial paper-based assays by quantitatively measuring live and motile sperm concentrations and motility, in only 10 min. This approach is applicable to current clinical practices as well as self-diagnostic applications.
Assuntos
Colorimetria , Infertilidade Masculina , Dispositivos Lab-On-A-Chip , Análise do Sêmen/métodos , Humanos , Limite de Detecção , Masculino , PapelRESUMO
DNA analysis is essential for diagnosis and monitoring of many diseases. Conventional DNA testing is generally limited to the laboratory. Increasing access to relevant technologies can improve patient care and outcomes in both developed and developing regions. Here, we demonstrate direct DNA analysis in paper-based devices, uniquely enabled by ion concentration polarization at the interface of patterned nanoporous membranes in paper (paper-based ICP). Hepatitis B virus DNA targets in human serum are simultaneously preconcentrated, separated, and detected in a single 10 min operation. A limit of detection of 150 copies/mL is achieved without prior viral load amplification, sufficient for early diagnosis of hepatitis B. We clinically assess the DNA integrity of sperm cells in raw human semen samples. The percent DNA fragmentation results from the paper-based ICP devices strongly correlate (R(2) = 0.98) with the sperm chromatin structure assay. In all cases, agreement was 100% with respect to the clinical decision. Paper-based ICP can provide inexpensive and accessible advanced molecular diagnostics.
Assuntos
DNA/sangue , Vírus da Hepatite B/isolamento & purificação , Papel , Espermatozoides/metabolismo , DNA Viral/sangue , Hepatite B/diagnóstico , Hepatite B/virologia , Vírus da Hepatite B/genética , Humanos , Masculino , Nanoestruturas/química , Tamanho da Partícula , Porosidade , Sêmen/citologia , Propriedades de SuperfícieRESUMO
Subfertile men and women are usually cared for by different clinicians, namely urologists and gynaecologists. While these doctors share each other's goals, they may not always appreciate the content or implications of their opposite number's clinical decisions; to some degree they may practice in "silos." We address this problem by reviewing the effectiveness of medical treatments for male factor subfertility in the context of female factors. The effectiveness of treatments for couples with male factor subfertility, other than IVF with ICSI, appears modest. However, data from randomized controlled trials suggest benefits from some treatments: clomiphene and tamoxifen for the male (common odds ratio for pregnancy [COR] 2.42; 95% CI 1.47 to 3.94), antioxidants (COR 4.18; 95% CI 2.65 to 6.59) and surgical management of a clinical varicocele (COR 2.39; 95% CI 1.56 to 3.66). Nevertheless, close attention to female age and the duration of subfertility help to avoid lost opportunity through delays in treatment when IVF with ICSI is indicated. Making treatment decisions squarely in the context of the couple's overall prognosis is key for optimal outcomes. Future trials of male fertility treatments should focus on pregnancy as the primary outcome, rather than less important surrogates such as sperm quality.
Les hommes et les femmes hypofertiles obtiennent habituellement leurs soins auprès de cliniciens distincts, soit des urologues et des gynécologues, respectivement. Bien que ces professionnels de la santé aient des objectifs communs, il est possible qu'ils ne comprennent pas toujours le contenu ou les implications des décisions cliniques de leurs homologues; on pourrait même en venir à affirmer qu'ils agissent de façon cloisonnée. Nous traitons de ce problème en analysant l'efficacité des traitements médicaux visant l'hypofertilité masculine dans le contexte des facteurs féminins. À l'exception de l'utilisation concomitante de la FIV et de l'IICS, l'efficacité des traitements offerts aux couples qui font face à une hypofertilité attribuable à des causes imputables à l'homme semble modeste. Toutefois, des données issues d'essais comparatifs randomisés semblent indiquer que certains traitements offrent des avantages : clomiphène et tamoxifène administrés à l'homme (rapport de cotes commun pour ce qui est de la grossesse [RCC], 2,42; IC à 95 %, 1,47 - 3,94), antioxydants (RCC, 4,18; IC à 95 %, 2,65 - 6,59) et prise en charge chirurgicale d'une varicocèle clinique (RCC, 2,39; IC à 95 %, 1,56 - 3,66). Quoi qu'il en soit, le fait de bien porter attention à l'âge de la femme et à la durée de l'hypofertilité aide à éviter les occasions manquées en raison de délais dans la mise en Åuvre du traitement, dans les cas où l'utilisation concomitante de la FIV et de l'IICS s'avère indiquée. Le fait de prendre des décisions en s'assurant de tenir absolument compte du pronostic global du couple est d'une importance capitale pour l'obtention d'issues optimales. L'obtention d'une grossesse (et non des critères auxiliaires moins importants, tels que la qualité des spermatozoïdes) devrait constituer le critère d'évaluation principal des futurs essais visant les traitements contre l'infertilité masculine.
Assuntos
Ginecologia , Infertilidade Masculina/terapia , Urologia , Adulto , Fatores Etários , Antioxidantes/administração & dosagem , Clomifeno/uso terapêutico , Prestação Integrada de Cuidados de Saúde/métodos , Antagonistas de Estrogênios , Feminino , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/fisiopatologia , Masculino , Pessoa de Meia-Idade , Gravidez , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamoxifeno/uso terapêutico , Resultado do Tratamento , Varicocele/complicações , Varicocele/cirurgiaRESUMO
BACKGROUND: Sperm DNA damage is common in infertile men and is associated with poor semen parameters but the impact of an isolated sperm abnormality on sperm DNA damage has not been studied. OBJECTIVE: To evaluate sperm DNA damage in a large cohort of infertile men with isolated sperm defects. DESIGN, SETTING AND PARTICIPANTS: Retrospective study of 1084 consecutive, non-azoospermic infertile men with an isolated sperm defect: isolated oligozoospermia (iOligo), isolated asthenozoospermia (iAstheno) or isolated teratozoospermia (iTerato). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We examined and compared clinical parameters, conventional semen parameters and %sperm DNA fragmentation (%SDF, assessed by flow cytometry-based Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling assay) in the three groups of men. RESULTS AND LIMITATIONS: The mean (±SD) %SDF was significantly higher in the iAstheno compared to the iOligo and iTerato groups (25.0 ± 14.0 vs. 19.2 ± 11.6 and 20.7 ± 12.1 %, respectively, P < 0.0001). Similarly, the proportion of men with high %SDF (>30 %) was significantly higher in the iAstheno compared to the iOligo and iTerato groups (31 % vs. 18 % and 19 %, respectively, P < 0.0001). In the group of 713 men with iAstheno, %SDF was positively correlated with paternal age (r = 0.20, P < 0.0001) and inversely correlated with %progressive motility (r = -0.18, P < 0.0001). In the subset of 218 men with iTerato, %SDF was also positively correlated with paternal age (r = 0.15, P = 0.018) and inversely correlated with %progressive motility (r = -0.26, P = 0.0001). CONCLUSIONS: In this large cohort of infertile men with isolated sperm abnormalities, we have found that the sperm DNA fragmentation level is highest in the men with sperm motility defects and that 31 % of these men have high levels of sperm DNA fragmentation. The data indicate that poor motility is the sperm parameter abnormality most closely related to sperm DNA damage.
Assuntos
Dano ao DNA , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Motilidade dos Espermatozoides/genética , Espermatozoides/patologia , Adulto , Astenozoospermia/genética , Astenozoospermia/patologia , Fragmentação do DNA , Humanos , Masculino , Pessoa de Meia-Idade , Oligospermia/genética , Oligospermia/patologia , Idade Paterna , Estudos Retrospectivos , Espermatozoides/fisiologiaRESUMO
The objective of the study was to investigate the relationship between advanced paternal age and sperm DNA fragmentation (SDF) levels, specifically identifying the age at which a significant increase in SDF occurs. This is a retrospective cohort study involving 4250 consecutive semen samples from patients presenting for infertility evaluation. Patients were stratified into seven age groups: < 26 (n = 36; 0.8 %), 26-30 (n = 500; 11.8 %), 31-35 (n = 1269; 29.9 %), 36-40 (n = 1268; 29.8 %), 41-45 (n = 732; 17.2 %), 46-50 (n = 304; 7.2 %), > 50 (n = 141; 3.3 %). The main outcome measures included comparing mean SDF levels throughout different age groups and assessing the prevalence of normal, intermediate, and high SDF among the age groups. A positive correlation was observed between paternal age and SDF (r = 0.17, p < 0.001). SDF remained relatively constant until the age of 35 but increased significantly beyond age 35. Mean SDF levels in the older age groups (36-40, 41-45, 46-50, and >50 years) were significantly higher than in the younger age groups (<26, 26-30, and 31-35 years) (p < 0.001). The prevalence of normal SDF was highest among the younger age groups, whereas the prevalence of high SDF was highest among the older age groups. Interestingly, the prevalence of intermediate SDF was relatively constant throughout the age groups (ranging between 29.8 % to 37.2 %). The increase in SDF after the age of 35 highlights the importance of considering male age in infertility evaluations. Assessing SDF in men over the age of 35 is crucial in couples seeking to conceive.
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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.
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PURPOSE: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. MATERIALS AND METHODS: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). RESULTS: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864. CONCLUSIONS: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.
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PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.
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PURPOSE: This study aimed to examine current global practices in regenerative therapy (RT) for erectile dysfunction (ED) and to establish expert recommendations for its use, addressing the current lack of solid evidence and standardized guidelines. MATERIALS AND METHODS: A 39-question survey was developed by senior Global Andrology Forum (GAF) experts to comprehensively cover clinical aspects of RT. This was distributed globally via a secure online Google Form to ED specialists through the GAF website, international professional societies, and social media, the responses were analyzed and presented for frequencies as percentages. Consensus on expert recommendations for RT use was achieved using the Delphi method. RESULTS: Out of 479 respondents from 62 countries, a third reported using RT for ED. The most popular treatment was low-intensity shock wave therapy (54.6%), followed by platelet-rich plasma (24.5%) and their combination (14.7%), with stem cell therapy being the least used (3.7%). The primary indication for RT was the refractory or adverse effects of PDE5 inhibitors, with the best effectiveness reported in middle-aged and mild-to-moderate ED patients. Respondents were confident about its overall safety, with a significant number expressing interest in RT's future use, despite pending guidelines support. CONCLUSIONS: This inaugural global survey reveals a growing use of RT in ED treatment, showcasing its diverse clinical applications and potential for future widespread adoption. However, the lack of comprehensive evidence and clear guidelines requires further research to standardize RT practices in ED treatment.
RESUMO
BACKGROUND: Sperm DNA damage is associated with male infertility, lower pregnancy rates and pregnancy loss. OBJECTIVE: The primary aim of our study was to evaluate the prevalence of sperm DNA damage in younger and older men with normozoospermia. DESIGN, SETTING AND PARTICIPANTS: We obtained semen from 277 consecutive non-azoospermic men presenting for sperm DNA testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main outcome measures included sperm % DNA fragmentation index (%DFI, using sperm chromatin structure assay), sperm concentration, motility and morphology, and, paternal age. RESULTS AND LIMITATIONS: Sperm % DFI was positively correlated with paternal age (r = 0.20, P < 0.001) and inversely correlated % progressive motility (r = -0.16, P = 0.01). Sperm %DFI was significantly higher in older (≥40 years) compared to younger (<40 years) normozoospermic men (17 ± 13 vs. 12 ± 8, respectively P = 0.008), whereas, sperm concentration, progressive motility and morphology were not significantly different in these two groups. Moreover, the prevalence of high levels of sperm DNA damage (>30 % DFI) was significantly higher in older compared to younger normozoospermic men (17 % vs. 3 %, respectively, P < 0.001). CONCLUSION: The data indicate that a conventional semen analysis can often fail to detect a defect in spermatogenesis (high %DFI) in older men and suggest that infertile couples with advanced paternal age, including those with normal semen parameters, should consider sperm DNA testing as part of the couple evaluation.
Assuntos
Dano ao DNA/genética , Infertilidade Masculina/genética , Idade Paterna , Espermatogênese/genética , Espermatozoides/patologia , Adulto , Fragmentação do DNA , Feminino , Humanos , Infertilidade Masculina/patologia , Masculino , Pessoa de Meia-Idade , Ploidias , Gravidez , Análise do Sêmen , Contagem de EspermatozoidesRESUMO
BACKGROUND: Sperm DNA damage is associated with male infertility but whether normozoospermic infertile men also have DNA damage is unknown. OBJECTIVE: To evaluate sperm DNA and chromatin integrity in men with mild male factor infertility. DESIGN, SETTING AND PARTICIPANTS: Prospective study of 102 consecutive men (78 normozoospermic, 15 asthenozoospermic, 9 oligozoospermic) enrolled for intrauterine insemination (IUI) and 15 fertile controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standard semen parameters and sperm chromatin and DNA integrity were assessed and compared between groups. Sperm chromatin quality was assessed by (1) aniline blue staining (AB is specific to histone lysines), (2) iodoacetamide fluorescein fluorescence (IAF targets free protamine sulfhydryl groups) and (3) sperm chromatin structure assay (SCSA) with the results expressed as % DNA fragmentation index (%DFI). RESULTS AND LIMITATIONS: The mean (±SD) percentage of spermatozoa with positive IAF fluorescence was significantly higher in the IUI population compared to fertile controls (17 % ± 10 % vs. 8 % ± 6 %, P = 0.0011) and also in the normozoospermic subset (n = 78) compared to controls (16 % ± 9 % vs. 8 % ± 6 %, P < 0.0001, ANOVA). We also observed a trend toward lower %progressive motility, and higher %AB staining and %DFI in the IUI group compared to controls. We observed significant relationships between sperm %DFI and progressive motility (r = -0.40, P < 0.0001) and between positive AB staining and IAF fluorescence (r = 0.58, P < 0.0001). CONCLUSIONS: The data indicate that sperm chromatin integrity may be abnormal in men enrolled in IUI treatment cycles, despite the fact that most of these men are normozoospermic.