RESUMO
OBJECTIVE: To evaluate the effect of varicocelectomy on sperm deoxyribonucleic acid fragmentation (SDF) rates in infertile men with clinical varicocele. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile men with clinical varicocele subjected to varicocelectomy. INTERVENTION(S): Systematic search using PubMed/Medline, EMBASE, Cochrane's central database, Scielo, and Google Scholar to identify relevant studies published from inception until January 2021. We included studies comparing SDF rates before and after varicocelectomy in infertile men with clinical varicocele. MAIN OUTCOME MEASURE(S): The primary outcome was the difference between the SDF rates before and after varicocelectomy. A meta-analysis of weighted data using random-effects models was performed. Results were reported as weighted mean differences (WMD) with 95% confidence intervals (CIs). Subgroup analyses were performed on the basis of the SDF assay, varicocelectomy technique, preoperative SDF levels, varicocele grade, follow-up time, and study design. RESULT(S): Nineteen studies involving 1,070 patients provided SDF data. Varicocelectomy was associated with reduced postoperative SDF rates (WMD -7.23%; 95% CI: -8.86 to -5.59; I2 = 91%). The treatment effect size was moderate (Cohen's d = 0.68; 95% CI: 0.77 to 0.60). The pooled results were consistent for studies using sperm chromatin structure assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, sperm chromatin dispersion test, and microsurgical varicocele repair. Subgroup analyses showed that the treatment effect was more pronounced in men with elevated vs. normal preoperative SDF levels, but the impact of varicocele grade remained equivocal. Meta-regression analysis demonstrated that SDF decreased after varicocelectomy as a function of preoperative SDF levels (coefficient: 0.23; 95% CI: 0.07 to 0.39). CONCLUSION(S): We concluded that pooled results from studies including infertile men with clinical varicocele indicated that varicocelectomy reduced the SDF rates. The treatment effect was greater in men with elevated (vs. normal) preoperative SDF levels. Further research is required to determine the full clinical implications of SDF reduction for these men.
Assuntos
Fragmentação do DNA , Fertilidade , Infertilidade Masculina/cirurgia , Espermatozoides/patologia , Procedimentos Cirúrgicos Urológicos Masculinos , Varicocele/cirurgia , Adulto , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Masculino , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Varicocele/complicações , Varicocele/patologia , Varicocele/fisiopatologiaRESUMO
Given the nature of the multiple causes of male infertility, some of them are «reversible¼ and can be managed with a surgical procedure to recover, in some cases, the fertilizing capacity of the male reproductive tract. With appropriate use of diagnostic tools and clinical judgement, the physician can identify the ideal candidates for these procedures. Together with the expertise and experience of the surgeon, these treatments can manage to resolve the barrier, and men may become fertile again. In this chapter, we will review some of the most commonly used surgical procedures for the treatment of male infertility and make a brief description of their technical details.
Assuntos
Infertilidade Masculina/cirurgia , Humanos , Masculino , Procedimentos Cirúrgicos Urológicos Masculinos/métodosRESUMO
The couple from this clinical case consisted of a 55 years old male with an obstructive interval of 25 years post vasectomy, and a 38 years old female partner. Both partners had normal results in infertility workup. Five mature oocytes were injected with motile spermatozoa showing morphological alterations, obtained by percutaneous epididymal sperm aspiration. Four oocytes fertilized, and three embryos were transferred with assisted hatching on day three of development, of which one was a high-quality embryo. A clinical pregnancy was confirmed by the detection of two gestational sacs with foetal heartbeats. Pregnancy was ongoing during the submission of this manuscript. The use of ICSI with PESA/TESA should be considered as a feasible alternative when vasectomy reversal fails in vasectomized men wishing to father again. Case reports like this may inspire the counseling of couples that have suffered from a previous vasectomy reversal failure and support the recommendation of ICSI with PESA treatment, which could allow those couples to have their own children, even in the presence of advanced parental age.
Assuntos
Gravidez de Gêmeos , Injeções de Esperma Intracitoplásmicas/métodos , Recuperação Espermática , Vasectomia , Adulto , Azoospermia/cirurgia , Feminino , Humanos , Infertilidade Masculina/cirurgia , Masculino , GravidezRESUMO
BACKGROUND: Cysteine-rich secretory protein (CRISP-3), a protein involved in inflammatory response, is highly increased in seminal plasma of adolescents with varicocoele and altered semen analysis, but not in adolescents with varicocoele and normal semen. It is not known, however, whether this increased seminal concentration occurs as an acute marker during the initial stages of varicocoele or whether this persists as an altered protein pathway. OBJECTIVE: The purpose of this study, thus, was to test the hypothesis that this inflammatory state persists through adulthood and the correction of varicocoele could correct this state, by identifying the levels of CRISP-3 in seminal plasma. MATERIALS AND METHODS: This study was carried out in two substudies: (i) to verify the effect of varicocoele and (ii) to verify the effect of varicocelectomy on seminal plasma CRISP-3 levels. Seminal plasma CRISP-3 levels (29 and 31 kDa isoforms) were assessed for each provided sample using standard Western blotting. RESULTS: The varicocoele group presented higher seminal levels of CRISP-3 when compared to controls, with a 67.5-fold increase in the unglycosylated isoform (29 kDa) and a 5.2-fold increase in the glycosylated isoform (31 kDa). In contrast, CRISP-3 levels decreased following varicocelectomy, both in the unglycosylated (5.6-fold decrease) and in the glycosylated (4.3-fold decrease) isoforms. DISCUSSION: CRISP-3, a protein involved in inflammation, is increased in seminal plasma of men with varicocoele and this is partially reversed by varicocelectomy. Monitoring its seminal levels may be useful for assessing inflammation-related alterations to fertility in men with varicocoele. CONCLUSION: We conclude that, in the presence of varicocoele, there is a marked increase in seminal CRISP-3 levels. Surgical intervention (varicocelectomy) decreases CRISP-3 levels and improves semen quality.
Assuntos
Proteínas e Peptídeos Salivares/metabolismo , Sêmen/metabolismo , Proteínas de Plasma Seminal/metabolismo , Varicocele/patologia , Varicocele/cirurgia , Humanos , Infertilidade Masculina/patologia , Infertilidade Masculina/cirurgia , Inflamação/patologia , Masculino , Proteínas e Peptídeos Salivares/genética , Análise do Sêmen , Proteínas de Plasma Seminal/genética , Varicocele/imunologiaRESUMO
Varicocele, the leading cause of male infertility, can impair sperm quality and fertility via various oxidative stress mechanisms. An imbalance between excessive reactive oxygen species production and antioxidant protection causes alterations in nuclear and mitochondrial sperm DNA, thus rendering a subset of varicocele men less fertile. In particular, sperm DNA fragmentation is usually elevated in men with clinical varicocele in both abnormal and normal semen parameters by the current World Health Organization criteria. In this review, we discuss the evidence concerning the association between varicocele, oxidative stress, and SDF, and the possible mechanisms involved in infertility. Furthermore, we summarize the role of varicocele repair as a means of alleviating SDF and improving fertility. Lastly, we critically appraise the evidence-based algorithm recently issued by the Society for Translational Medicine aimed at guiding urologists on the use of SDF testing in men with varicocele seeking fertility. Current evidence based on careful review of published studies confirms the effectiveness of varicocelectomy as a means of both reducing oxidatively induced sperm DNA damage and potentially improving fertility. Varicocele repair should be offered as part of treatment option for male partners of infertile couples presenting with palpable varicoceles.
Assuntos
Fragmentação do DNA , Infertilidade Masculina/genética , Estresse Oxidativo , Espermatozoides , Varicocele/complicações , Varicocele/cirurgia , Humanos , Infertilidade Masculina/cirurgia , Masculino , Guias de Prática Clínica como AssuntoRESUMO
Introducción: Durante años, el varicocele se ha propugnado como la causa más común de infertilidad, siendo esta patología la de mayor incidencia en los varones como factor causal (19 - 41%). Material y Métodos: Se evaluaron 228 pacientes, sexo masculino (18 y 39 años) con subfertilidad primaria con o sin varicocele. Se realizó historia clínica, examen físico, laboratorio y espermograma por duplicado. Se dividieron un grupo de 120 pacientes con subfertilidad primaria, varicocele izquierdo y por lo menos un parámetro seminal alterado en dos muestras sometidos a varicocelectomía y control seminal 6 y 9 meses post-operatorio y otro grupo 108 pacientes de iguales características pero sin varicocele. Se utilizaron criterios OMS en concentración, motilidad y morfología espermática. Estudio de casos y controles. Resultados: La mejoría en la concentración de espermatozoides tras el tratamiento quirúrgico fue de 20,06% (p 0,0001) a los 6 meses y 26,31% (p 0,0001) a los 9 meses. La motilidad aumentó 21,32% (p 0,001) a los 6 meses y 28,28% (p 0,0001) a los 9 meses y la morfología mejoró un 26,8% (p 0,0001) a los 6 meses y 57,38% (p 0,0001) a los 9 meses. Todas las variables resultaron estadísticamente significativas tras el tratamiento quirúrgico. No hubo diferencia estadísticamente significativa en ninguna de las variables entre el grupo pre-quirúrgico y el grupo control, y si las hubo en todas las variables estudiadas entre el grupo control comparado con el post- quirúrgico, a favor de este último. Los porcentajes de mejoras entre el grupo post-quirúrgico a los 6 meses y 9 meses de la cirugía, a favor de este último fueron 7,5% (p 0,0001) en la concentración, 5,28 % (p 0.0001) en la motilidad y 25,32% (p 0.0001) en la morfología... Conclusiones: Los parámetros seminales evidenciaron cambios positivos luego de la varicocelectomia y más aún con el transcurrir del tiempo.
Introduction: Varicocele has been proposed for years as the most common cause of infertility, and this condition is the prevalent incidence as causal factor. (19-41%) Material and methods: 228 male patients (between 18 and 39 years old) were evaluated with primary sub fertility with or without varicocele. The records included history, physical examination and two spermogram for patient. The population was divided in two groups. The first one of 120 patients with primary subfertility, left varicocele and at least one abnormal seminal parameter in two samples, with surgical resection of varicocele and final seminal post-surgical evaluation at 6 and 9 months. The other group included 108 patients with similar characteristics but without varicocele. The WHO criteria for spermatic concentration, motility and morphology were applied. Evaluation of cases and controls. Results: The improvement in spermatozoa concentration after treatment was of 20.06% (p<0,0001). The motility improved 21,32% at 6 months (p<0,0001) and 28,28% at 9 months (p<0,0001).The morphology improved 26,8% at 6 months (p<0,0001) and 57,38% at 9 months (p<0,0001)All the parameters were statistically significant after surgery. While there were no significant differences in any parameter between the pre-surgical group and the control group, there were differences in all the parameters evaluated between the control group and the post-surgical group, with best results in the latter.The percentages of improvement in the post-surgical group were 7,5%(p < 0,0001) in concentration, 5,28% in motility and 25,32% in morphology...Conclusions: The seminal parameters showed positive changes after varicocelectomy, especially over time.
Assuntos
Humanos , Masculino , Doenças dos Genitais Masculinos , Infertilidade Masculina , Infertilidade Masculina/cirurgia , Doenças Urogenitais Masculinas/cirurgia , Varicocele , Andrologia , Padrões de Referência/análiseRESUMO
Preoperative and postoperative sperm parameter values from infertile men with varicocele were analyzed by computer-aided sperm analysis (CASA) to assess if sperm characteristics improved after varicocelectomy. Semen samples of men with proven fertility (n = 38) and men with varicocele-related infertility (n = 61) were also analyzed. Conventional semen analysis was performed according to WHO (2010) criteria and a CASA system was employed to assess kinetic parameters and sperm concentration. Seminal parameters values in the fertile group were very far above from those of the patients, either before or after surgery. No significant improvement in the percentage normal sperm morphology (P = 0.10), sperm concentration (P = 0.52), total sperm count (P = 0.76), subjective motility (%) (P = 0.97) nor kinematics (P = 0.30) was observed after varicocelectomy when all groups were compared. Neither was significant improvement found in percentage normal sperm morphology (P = 0.91), sperm concentration (P = 0.10), total sperm count (P = 0.89) or percentage motility (P = 0.77) after varicocelectomy in paired comparisons of preoperative and postoperative data. Analysis of paired samples revealed that the total sperm count (P = 0.01) and most sperm kinetic parameters: curvilinear velocity (P = 0.002), straight-line velocity (P = 0.0004), average path velocity (P = 0.0005), linearity (P = 0.02), and wobble (P = 0.006) improved after surgery. CASA offers the potential for accurate quantitative assessment of each patient's response to varicocelectomy.
Assuntos
Espermatozoides/fisiologia , Espermatozoides/ultraestrutura , Varicocele/cirurgia , Adolescente , Adulto , Diagnóstico por Computador , Voluntários Saudáveis , Humanos , Infertilidade Masculina/cirurgia , Masculino , Microcirurgia , Período Pós-Operatório , Análise do Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Varicocele/diagnóstico por imagem , Adulto JovemRESUMO
STUDY HYPOTHESIS: We hypothesize that fertility disorders in patients with aberrant expression of Cysteine-RIch Secretory Protein 2 (CRISP2) could be linked to the proposed functional role of this protein in fertilization. STUDY FINDING: Our in vivo and in vitro observations reveal that Crisp2-knockout mice exhibit significant defects in fertility-associated parameters under demanding conditions, as well as deficiencies in sperm fertilizing ability, hyperactivation development and intracellular Ca(2+) regulation. WHAT IS KNOWN ALREADY: Testicular CRISP2 is present in mature sperm and has been proposed to participate in gamete fusion in both humans and rodents. Interestingly, evidence in humans shows that aberrant expression of CRISP2 is associated with male infertility. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: A mouse line carrying a deletion in the sixth exon of the Crisp2 gene was generated. The analyses of the reproductive phenotype of Crisp2(-/-) adult males included the evaluation of their fertility before and after being subjected to unilateral vasectomy, in vivo fertilization rates obtained after mating with either estrus or superovulated females, in vitro sperm fertilizing ability and different sperm functional parameters associated with capacitation such as tyrosine phosphorylation (by western blot), acrosome reaction (by Coomassie Blue staining), hyperactivation (by computer-assisted sperm analysis) and intracellular Ca(2+) levels (by flow cytometry). MAIN RESULTS AND THE ROLE OF CHANCE: Crisp2(-/-) males presented normal fertility and in vivo fertilization rates when mated with estrus females. However, the mutant mice showed clear defects in those reproductive parameters compared with controls under more demanding conditions, i.e. when subjected to unilateral vasectomy to reduce the number of ejaculated sperm (n = 5; P< 0.05), or when mated with hormone-treated females containing a high number of eggs in the ampulla (n ≥ 5; P< 0.01). In vitro fertilization studies revealed that Crisp2(-/-) sperm exhibited deficiencies to penetrate the egg vestments (i.e. cumulus oophorus and zona pellucida) and to fuse with the egg (n ≥ 6; P< 0.01). Consistent with this, Crisp2-null sperm showed lower levels of hyperactivation (n = 7; P< 0.05), a vigorous motility required for penetration of the egg coats, as well as a dysregulation in intracellular Ca(2+) levels associated with capacitation (n = 5; P< 0.001). LIMITATIONS, REASONS FOR CAUTION: The analysis of the possible mechanisms involved in fertility disorders in men with abnormal expression of CRISP2 was carried out in Crisp2 knockout mice due to the ethical and technical problems inherent to the use of human gametes for fertilization studies. WIDER IMPLICATIONS OF THE FINDINGS: Our findings in mice showing that Crisp2(-/-) males exhibit fertility and fertilization defects under demanding conditions support fertilization defects in sperm as a mechanism underlying infertility in men with aberrant expression of CRISP2. Moreover, our observations in mice resemble the situation in humans where fertility disorders can or cannot be detected depending on the accumulation of own individual defects or the fertility status of the partner. Finally, the fact that reproductive defects in mice are masked by conventional mating highlights the need of using different experimental approaches to analyze male fertility. STUDY FUNDING AND COMPETING INTERESTS: This study was supported by the World Health Organization (H9/TSA/037), the National Research Council of Argentina (PIP 2009-290), the National Agency for Scientific and Technological Promotion of Argentina (PICT 2011, 2023) and the Rene Baron Foundation to P.S.C. and by the MEXT of Japan to M.I. The authors declare that there are no conflicts of interest.
Assuntos
Sequência de Bases , Glicoproteínas/genética , Infertilidade Masculina/genética , Deleção de Sequência , Interações Espermatozoide-Óvulo/genética , Espermatozoides/metabolismo , Adulto , Animais , Cálcio/metabolismo , Moléculas de Adesão Celular , Estro/genética , Éxons , Feminino , Expressão Gênica , Glicoproteínas/deficiência , Humanos , Infertilidade Masculina/fisiopatologia , Infertilidade Masculina/cirurgia , Tamanho da Ninhada de Vivíparos , Masculino , Proteínas de Membrana , Camundongos , Camundongos Knockout , Capacitação Espermática/genética , Espermatozoides/patologia , Vasectomia , Zona Pelúcida/metabolismoAssuntos
Infertilidade Masculina/etiologia , Varicocele/complicações , Humanos , Infertilidade Masculina/metabolismo , Infertilidade Masculina/fisiopatologia , Infertilidade Masculina/cirurgia , Infertilidade Masculina/terapia , Masculino , Técnicas de Reprodução Assistida , Varicocele/metabolismo , Varicocele/fisiopatologia , Varicocele/cirurgia , Varicocele/terapiaRESUMO
Varicocele affects approximately 35%-40% of men presenting for an infertility evaluation. There is fair evidence indicating that surgical repair of clinical varicocele improves semen parameters, decreases seminal oxidative stress and sperm DNA fragmentation, and increases the chances of natural conception. However, it is unclear whether performing varicocelectomy in men with clinical varicocele prior to assisted reproductive technology (ART) improve treatment outcomes. The objective of this study was to evaluate the role of varicocelectomy on ART pregnancy outcomes in nonazoospermic infertile men with clinical varicocele. An electronic search was performed to collect all evidence that fitted our eligibility criteria using the MEDLINE and EMBASE databases until April 2015. Four retrospective studies were included, all of which involved intracytoplasmic sperm injection (ICSI), and accounted for 870 cycles (438 subjected to ICSI with prior varicocelectomy, and 432 without prior varicocelectomy). There was a significant increase in the clinical pregnancy rates (OR = 1.59, 95% CI: 1.19-2.12, Iâ 2 = 25%) and live birth rates (OR = 2.17, 95% CI: 1.55-3.06, Iâ 2 = 0%) in the varicocelectomy group compared to the group subjected to ICSI without previous varicocelectomy. Our results indicate that performing varicocelectomy in patients with clinical varicocele prior to ICSI is associated with improved pregnancy outcomes.