RESUMEN
Semen analysis (SA) poorly predicts male fertility, because it does not assess sperm fertilizing ability. The percentage of capacitated sperm determined by GM1 localization ("Cap-Score™"), differs between cohorts of fertile and potentially infertile men, and retrospectively, between men conceiving or failing to conceive by intrauterine insemination (IUI). Here, we prospectively tested whether Cap-Score can predict male fertility with the outcome being clinical pregnancy within ≤3 IUI cycles. Cap-Score and SA were performed (n = 208) with outcomes initially available for 91 men. Men were predicted to have either low (n = 47) or high (n = 44) chance of generating pregnancy using previously-defined Cap-Score reference ranges. Absolute and cumulative pregnancy rates were reduced in men predicted to have low pregnancy rates versus high ([absolute: 10.6% vs. 29.5%; p = 0.04]; [cumulative: 4.3% vs. 18.2%, 9.9% vs. 29.1%, and 14.0% vs. 32.8% for cycles 1-3; n = 91, 64, and 41; p = 0.02]). Only Cap-Score, not male/female age or SA results, differed significantly between outcome groups. Logistic regression evaluated Cap-Score and SA results relative to the probability of generating pregnancy (PGP) for men who were successful in, or completed, three IUI cycles (n = 57). Cap-Score was significantly related to PGP (p = 0.01). The model fit was then tested with 67 additional patients (n = 124; five clinics); the equation changed minimally, but fit improved (p < 0.001; margin of error: 4%). The Akaike Information Criterion found the best model used Cap-Score as the only predictor. These data show that Cap-Score provides a practical, predictive assessment of male fertility, with applications in assisted reproduction and treatment of male infertility.
Asunto(s)
Infertilidad Masculina/diagnóstico , Embarazo , Probabilidad , Análisis de Semen/métodos , Capacitación Espermática , Adulto , Estudios de Factibilidad , Femenino , Fertilidad , Fertilización/fisiología , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Resultado del Embarazo , Índice de Embarazo , Estudios Prospectivos , Motilidad Espermática/fisiologíaRESUMEN
Background and Objective: Conventional semen analysis (SA) remains an essential tool in the initial male fertility evaluation and subsequent follow-up. However, it neither provides information about the functional status of spermatozoa nor addresses disorders such as idiopathic or unexplained infertility (UI). Recently, assessment of sperm DNA fragmentation (SDF) has been proposed as an extended sperm test that may help overcome these inherent limitations of basic SA. In this review, we aim to: (I) discuss the pathophysiological aspects of SDF, including natural repair mechanisms, causes, and impact on reproductive outcomes; (II) explain different assessment tools of SDF, and describe potential therapeutic options to manage infertile men with high SDF; and (III) analyse the strengths, weaknesses, opportunities and threats (SWOT) of current research on the topic. Methods: This review was constructed from original studies, systematic reviews and meta-analyses that were published over the years up until August 2021, related to the various aspects of SDF. Key Content and Findings: Different mechanisms lead to high SDF, including defective chromatin packaging, apoptosis, and seminal oxidative stress. The relevance of sperm DNA integrity to male fertility/infertility has been supported by the frequent observation of high levels of SDF in infertile men, and in association with risk factors for infertility. Additionally, high SDF levels have been inversely correlated with the outcomes of natural pregnancy and assisted reproduction. Terminal deoxynucleotidyl transferase dUTP nick end labelling, sperm chromatin structure assay, sperm chromatin dispersion, and Comet assay are four commonly used assays for measurement of SDF. Addressing lifestyle risks and underlying conditions, antioxidants, hormonal therapy, and advanced sperm selection techniques have all been proposed as potential therapeutic options to lower SDF. Conclusions: The sum of literature provides evidence of detrimental effects of high SDF on both natural and assisted fertility outcomes. Standardization of the techniques used for assessment of SDF and their incorporation into the work up of infertile couples may have significant implications on the future management of a selected category of infertile men with high SDF.
RESUMEN
INTRODUCTION: Semen analysis (SA) plays a key role in guiding treatments of male reproductive diseases and infertility due to male factors; however, it remains challenging to conduct an accurate SA due to lack of standardization, highly subjective assessments, and problems with automated procedures. Therefore, quality assurance (QA) and teaching courses are essential for making the laboratory results more consistent. MATERIALS AND METHODS: The external quality assurance (EQA) scheme was organized by national human sperm bank technology training bases in Guangdong province in China between 2009 and 2020. Until 2020, 124 laboratories from China participated in the EQA program. The EQA scheme per year has been organized involving two semen aliquots for sperm concentration, two video recordings for motility, and two smears for sperm morphology. All samples used in the EQA scheme were obtained from different healthy donors or patients. RESULTS: We estimated that the median coefficient of variation (CV) of sperm concentration, ignoring the method used, was 26.6%. Using a 100 µm deep counting chamber led to a decreasing CV of 13.6%. For sperm motility, the median CV of nonprogressive motility was high (50.8%), but the CV of progressive motility (13.2%), immotile sperm (14.3%), and total motility (11.8%) were acceptable. The morphology assessment revealed large variability (44.4%) irrespective of the classification criteria. DISCUSSION: The reduction of interlaboratory variability is still a challenge during SA in China. Therefore, it is critical to increase awareness of joining EQA schemes and establish standardized training centers to follow WHO-recommended procedures toward Chinese standards.