Relation between Traditional Semen Parameters, Sperm DNA Fragmentation, and Unexplained Recurrent Miscarriage: A Systematic Review and Meta-analysis

Author(s):  
Yanpeng Dai ◽  
Junjie Liu ◽  
Enwu Yuan ◽  
Ying Shi ◽  
Linlin Zhang

Abstract Background: Several studies have explored the relation between traditional semen parameters, sperm DNA fragmentation (SDF), and unexplained recurrent miscarriage (RM), but these findings remain controversial. Hence, we conducted this meta-analysis to explore the relation between traditional semen parameters, SDF, and unexplained RM. Methods: Multiple databases including PubMed, Google Scholar, MEDLINE, EMBASE, Cochrane Library, Web of Science databases, and China National Knowledge Infrastructure (CNKI) were searched to identify relevant publications. From the eligible publications, data were extracted independently by two researchers. The heterogeneity between publications was calculated using the I2 statistics and Cochran’s Q test. Statistical analyses were conducted using Stata/SE 12.0 (StataCorp, College Station, Texas, USA). Based on heterogeneity assessment, random- or fixed-effects models were selected to calculate the weighted mean differences (WMDs) and their corresponding 95% confidence intervals (CIs). To estimate the stability of the pooled results, a sensitivity analysis was conducted by excluding each study. To estimate the possible publication bias, Egger’s regression test and Begg’s funnel plot were used. Results: A total of 280 publications were produced using the search strategy. According to the inclusion/exclusion criteria, 19 publications were eligible. A total of 1182 couples with unexplained RM and 1231 couples without RM were included in this meta-analysis to assess the relation between traditional semen parameters, SDF, and unexplained RM. Our results showed that couples with unexplained RM had significantly increased levels of SDF (WMD=8.77, 95% CI=4.03 to 13.51, P<0.001) and significantly decreased levels of progressive motility (WMD=-4.75, 95% CI=-8.35 to -1.15, P<0.05) and total motility (WMD=-10.30, 95% CI=-15.03 to -5.57, P<0.05) than those of couples without RM, but not significantly different in volume (WMD=-0.12, 95% CI=-0.32 to 0.08, P>0.05), sperm concentration (WMD=-2.28, 95% CI=-4.58 to 0.02, P>0.05) and total sperm count (WMD=-10.73, 95% CI=-22.11 to 0.66, P>0.05) between couples with and without RM.Conclusion: Couples with unexplained RM had significantly increased levels of SDF and significantly decreased levels of progressive motility and total motility than those of couples without RM. SDF assay may be considered as part of the evaluation of couples with unexplained RM.

2022 ◽  
Vol 12 ◽  
Author(s):  
Yanpeng Dai ◽  
Junjie Liu ◽  
Enwu Yuan ◽  
Yushan Li ◽  
Ying Shi ◽  
...  

Several studies have explored the relationship among traditional semen parameters, sperm DNA fragmentation (SDF), and unexplained recurrent miscarriage (RM); however, the findings remain controversial. Hence, we conducted a meta-analysis to explore the relationship among traditional semen parameters, SDF, and unexplained RM. Multiple databases, including PubMed, Google Scholar, MEDLINE, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI), were searched to identify relevant publications. From the eligible publications, data were extracted independently by two researchers. A total of 280 publications were identified using the search strategy. According to the inclusion/exclusion criteria, 19 publications were eligible. A total of 1182 couples with unexplained RM and 1231 couples without RM were included in this meta-analysis to assess the relationship among traditional semen parameters, SDF, and unexplained RM. Our results showed that couples with unexplained RM had significantly increased levels of SDF and significantly decreased levels of total motility and progressive motility compared with couples without RM, although significant differences were not observed in the semen volume, sperm concentration, and total sperm count between couples with and without RM. The SDF assay may be considered for inclusion in evaluations of couples with unexplained RM.


Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 236 ◽  
Author(s):  
Sheryl Homa ◽  
Anna Vassiliou ◽  
Jesse Stone ◽  
Aideen Killeen ◽  
Andrew Dawkins ◽  
...  

Oxidative stress (OS) is a significant cause of DNA fragmentation and is associated with poor embryo development and recurrent miscarriage. The aim of this study was to compare two different methods for assessing seminal OS and their ability to predict sperm DNA fragmentation and abnormal semen parameters. Semen samples were collected from 520 men attending for routine diagnostic testing following informed consent. Oxidative stress was assessed using either a chemiluminescence assay to measure reactive oxygen species (ROS) or an electrochemical assay to measure oxidation reduction potential (sORP). Sperm DNA fragmentation (DFI) and sperm with immature chromatin (HDS) were assessed using sperm chromatin structure assay (SCSA). Semen analysis was performed according to WHO 2010 guidelines. Reactive oxygen species sORP and DFI are negatively correlated with sperm motility (p = 0.0012, 0.0002, <0.0001 respectively) and vitality (p < 0.0001, 0.019, <0.0001 respectively). The correlation was stronger for sORP than ROS. Reactive oxygen species (p < 0.0001), sORP (p < 0.0001), DFI (p < 0.0089) and HDS (p < 0.0001) were significantly elevated in samples with abnormal semen parameters, compared to those with normal parameters. Samples with polymorphonuclear leukocytes (PMN) have excessive ROS levels compared to those without (p < 0.0001), but sORP and DFI in this group are not significantly increased. DNA fragmentation was significantly elevated in samples with OS measured by ROS (p = 0.0052) or sORP (p = 0.004). The results demonstrate the multi-dimensional nature of oxidative stress and that neither assay can be used alone in the diagnosis of OS, especially in cases of leukocytospermia.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Akira Komiya ◽  
Tomonori Kato ◽  
Yoko Kawauchi ◽  
Akihiko Watanabe ◽  
Hideki Fuse

Objective. The clinical factors associated with sperm DNA fragmentation (SDF) were investigated in male patients with infertility.Materials and Methods. Fifty-four ejaculates from infertile Japanese males were used. Thirty-three and twenty-one were from the patients with varicoceles and idiopathic causes of infertility, respectively. We performed blood tests, including the serum sex hormone levels, and conventional and computer-assisted semen analyses. The sperm nuclear vacuolization (SNV) was evaluated using a high-magnification microscope. The SDF was evaluated using the sperm chromatin dispersion test (SCDt) to determine the SDF index (SDFI). The SDFI was compared with semen parameters and other clinical variables, including lifestyle factors.Results. The SDFI was 41.3 ± 22.2% (mean ± standard deviation) and did not depend on the cause of infertility. Chronic alcohol use increased the SDFI to 49.6 ± 23.3% compared with 33.9 ± 18.0% in nondrinkers. The SDFI was related to adverse conventional semen parameters and sperm motion characteristics and correlated with the serum FSH level. The SNV showed a tendency to increase with the SDFI. The multivariate analysis revealed that the sperm progressive motility and chronic alcohol use were significant predictors of the SDF.Conclusion. The SCDt should be offered to chronic alcohol users and those with decreased sperm progressive motility.


Author(s):  
G.U.S. Wijesekara ◽  
D.M.S. Fernando ◽  
S. Wijeratne

AbstractBackgroundLead (Pb) is one of the metals most prevalent in the environment and is known to cause infertility and deoxyribonucleic acid (DNA) fragmentation. This study aimed to determine the association between seminal plasma Pb and sperm DNA fragmentation in men investigated for infertility.MethodsMale partners (n = 300) of couples investigated for infertility were recruited after informed consent was obtained. Sperm parameters were assessed according to the World Health Organization (WHO) guidelines. Seminal plasma Pb was estimated by atomic absorption spectrophotometry after digestion with nitric acid.ResultsIn Pb-positive and -negative groups the sperm parameters and sperm DNA fragmentation were compared using independent sample t-test and the Mann-Whitney U-test, respectively. The mean [standard deviation (SD)] age and duration of infertility were 34.8 (5.34) years and 45.7 (35.09) months, respectively, and the mean Pb concentration was 15.7 μg/dL. In Pb positives compared to Pb negatives the means (SD) of sperm count, progressive motility viability and normal morphology were lower (p > 0.05) but the DNA fragmentation was significantly higher 39.80% (25.08) than Pb negatives 22.65% (11.30). Seminal plasma Pb concentration and sperm DNA fragmentation had a positive correlation (r = 0.38, p = 0.03). A negative correlation was observed between sperm DNA fragmentation and sperm concentration, progressive motility, total motility and viability. When the DNA fragmentation was ≥30% sperm concentration and viability decreased (p < 0.05).ConclusionsPb in seminal plasma had a significant effect on sperm DNA fragmentation but not with other sperm parameters.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Tenori. Lir. Neto ◽  
M Roque ◽  
S Esteves

Abstract Study question Does varicocelectomy improve sperm DNA quality in men with infertility and clinically detected varicoceles? Summary answer Varicocelectomy reduces sperm DNA fragmentation (SDF) rates in infertile men with clinical varicocele. What is known already Varicocele has been linked to male infertility through various non-mutually exclusive mechanisms, including an increase in reactive oxygen species (ROS) production that may lead to sperm DNA damage. Damage to sperm DNA may result in longer time-to-pregnancy, unexplained infertility, recurrent pregnancy loss, and failed intrauterine insemination or in vitro fertilization/intracytoplasmic sperm injection. Therefore, interventions aimed at decreasing SDF rates, including varicocele repair, have been explored to improve fertility and pregnancy outcomes potentially, either by natural conception or using medically assisted reproduction. Study design, size, duration Systematic review and meta-analysis Participants/materials, setting, methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our systematic search included PubMed/Medline, EMBASE, Scielo, and Google Scholar to identify all relevant studies written in English and published from inception until October 2020. Inclusion criteria were studies comparing SDF rates before and after varicocelectomy in infertile men with clinical varicocele. Articles were included if the following SDF assays were utilized: SCSA, TUNEL, SCD test, or alkaline Comet. Main results and the role of chance Thirteen studies fulfilled the inclusion criteria and were selected for the analysis. The estimated weighted mean difference of SDF rates after varicocelectomy was –6.58% (13 studies, 95% CI –8.33%, –4.84%; I2=90% p &lt; 0.0001). Subgroup analysis revealed a significant decrease in SDF rates using SCSA (eight studies, WMD –6.80%, 95% CI –9.31%, –4.28%; I2=89%, p &lt; 0.0001), and TUNEL (three studies, WMD –4.86%, 95% CI –7.38%, –2.34%; I2=89%, p &lt; 0.0001). The test for subgroup difference revealed that pooled results were conservative using the above SDF assays. Comet and SCD tests were used in only one study each; thus, a meta-analysis was not applicable. The studies were further categorized by the surgical technique (microsurgical versus non-microsurgical). This subgroup analysis showed a significant decrease in SDF rates using microsurgical technique (10 studies, WMD –6.70%, 95% CI –9.04%, –4.37%; I2=91%, p &lt; 0.0001). After varicocelectomy, SDF rates were also decreased when non-microsurgical approaches were used, albeit the effect was not statistically significant (2 studies, WMD –6.84%, 95% CI –10.05%, 1.38%; I2=86%) (Figure 3). The heterogeneity was not materially affected by performing analyses by the above subgroups, suggesting that the SDF assay and surgical technique do not explain the inconsistency in the treatment effect across primary studies. Limitations, reasons for caution There were no randomized controlled trials comparing varicocelectomy to placebo for alleviating SDF levels. Heterogeneity was high, which may be explained by the low number of included studies. Pregnancy data are not available in most studies, thus the impact of reduced SDF after varicocelectomy on pregnancy rates unclear. Wider implications of the findings: Our study indicates a positive association between varicocelectomy and reduced postoperative SDF rates in men with clinical varicocele and infertility, independentetly of the assays used to measure SDF. These findings may help counsel and manage infertile men with varicocele and high SDF levels. Trial registration number Not applicable


2020 ◽  
Vol 9 (5) ◽  
pp. 1341
Author(s):  
Monica Muratori ◽  
Giulia Pellegrino ◽  
Giusi Mangone ◽  
Chiara Azzari ◽  
Francesco Lotti ◽  
...  

Sperm DNA fragmentation (sDF) negatively affects reproduction and is traditionally detected in total sperm population including viable and non-viable spermatozoa. Here, we aimed at exploring the ability of DNA fragmentation to discriminate fertile and subfertile men when detected in viable (viable sDF), non-viable (non-viable sDF), and total spermatozoa (total sDF). We revealed sDF in 91 male partners of infertile couples and 71 fertile men (max 1 year from natural conception) with LiveTUNEL coupled to flow cytometry, able to reveal simultaneously DNA fragmentation and cell viability. We found that the three sDF parameters discriminated fertile and subfertile men with similar accuracy and independently from age and basal semen parameters: AUCs (area under the curves) (95% CI) were: 0.696 (0.615–0.776), p < 0.001 for total sDF; 0.718 (0.640–0.797), p < 0.001 for viable sDF; 0.760 (0.685–0.835), p < 0.001 for non-viable sDF. We also found that total and non-viable but not viable sDF significantly correlated to age and semen quality. In conclusion, the three sDF parameters similarly discriminated fertile and subfertile men. Viable spermatozoa with DNA fragmentation are likely cells able to fertilize the oocyte but failing to properly support subsequent embryo development. Non-viable sDF could be a sign of a subtler damage extended beyond the non-viable cells.


2010 ◽  
Vol 22 (1) ◽  
pp. 312 ◽  
Author(s):  
M. Hidalgo ◽  
M. R. Murabito ◽  
M. J. Gálvez ◽  
S. Demyda ◽  
L. J. De Luca ◽  
...  

Recently, a new procedure for the analysis of sperm DNA fragmentation has been developed for humans and different mammalian species, using a commercial kit based on the sperm chromatin dispersion (SCD) test; however, a descriptive study in canine semen has not been performed. The aim of this work was to assess the sperm DNA fragmentation in canine ejaculates using the SCD test and 2 different staining techniques. For this purpose, ejaculates were collectedby digital manipulation from4 healthy dogs of different breeds (1 German Pointer, 2 Spanish Greyhounds, and 1 Crossbreed). After collection, the sperm-rich fraction of the ejaculates from 3 dogs were pooled each time (n = 4) and then extended in Dulbecco’s phosphate buffered saline. All the pooled semen samples presented physiological values concerning routine semen parameters (motility, morphology, and sperm concentration). The sperm DNA fragmentation was assessed using the Sperm-Halomax® commercial kit specifically developed for canine semen (Halotech DNA SL, Madrid, Spain). Two semen aliquots of the diluted pooled semen samples were processed on each pre-treated slide provided in the kit following the manufacturer’s instructions. The last step was the staining technique. We stained each slide with 2 different staining procedures. The first half of the slide was stained with propidium iodide (Sigma-Aldrich, St. Louis, MO, USA) mixed in a proportion 1 : 1 with an antifading solution. The second half of the slide was stained for 15 min in Wright solution (1.01383.0500, Merck, Whitehouse Station, NJ, USA) 1 :1 in Phosphate Buffer pH 6.88 (1.07294.1000, Merck). The stained slides were observed using fluorescence and light microscopy, respectively. Five hundred sperm per slide were counted. Spermatozoa with fragmented DNA showed a large and spotty halo of chromatin dispersion. Unfragmented sperm only showed a small and compact halo. Statistical analyses were performed using the Statistical Package for Social Science version 12.0 (SPSS Inc., Chicago, IL, USA). The sperm DNA fragmentation index was compared between Wright and fluorescence staining methods by ANOVA. Results were expressed as mean ± standard error of the mean. The first report of the sperm DNA fragmentation index in canine ejaculates was 2.26 ± 0.53% for Wright staining and 1.99 ± 0.10% for fluorescence technique. No differences were found between staining procedures. In conclusion, it was possible to assess the sperm DNA fragmentation of canine ejaculates using 2 different staining procedures, expecting that continuous research could be useful in defining the role of DNA fragmentation SCD test in canine semen evaluation and cryopreservation.


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