Measuring Sperm DNA Fragmentation and Clinical Outcomes of Medically Assisted Reproduction: A Systematic Review and Meta-Analysis

Abstract

Sperm DNA fragmentation has been associated with reduced fertilization rates, embryo quality, pregnancy rates and increased miscarriage rates. Various methods exist to test sperm DNA fragmentation such as the sperm chromatin structure assay (SCSA), the sperm chromatin dispersion (SCD) test, the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay and the single cell gel electrophoresis (Comet) assay. We performed a systematic review and meta-analysis to assess the value of measuring sperm DNA fragmentation in predicting chance of ongoing pregnancy with IVF or ICSI. Out of 658 unique studies, 30 had extractable data and were thus included in the meta-analysis. Overall, the sperm DNA fragmentation tests had a reasonable to good sensitivity. A wide variety of other factors may also affect the IVF/ICSI outcome, reflected by limited to very low specificity. The constructed hierarchical summary receiver operating characteristic (HSROC) curve indicated a fair discriminatory capacity of the TUNEL assay (area under the curve (AUC) of 0.71; 95% CI 0.66 to 0.74) and Comet assay (AUC of 0.73; 95% CI 0.19 to 0.97). The SCSA and the SCD test had poor predictive capacity. Importantly, for the TUNEL assay, SCD test and Comet assay, meta-regression showed no differences in predictive value between IVF and ICSI. For the SCSA meta-regression indicated the predictive values for IVF and ICSI were different. The present review suggests that current sperm DNA fragmentation tests have limited capacity to predict the chance of pregnancy in the context of MAR. Furthermore, sperm DNA fragmentation tests have little or no difference in predictive value between IVF and ICSI. At this moment, there is insufficient evidence to recommend the routine use of sperm DNA fragmentation tests in couples undergoing MAR both for the prediction of pregnancy and for the choice of treatment. Given the significant limitations of the evidence and the methodological weakness and design of the included studies, we do urge for further research on the predictive value of sperm DNA fragmentation for the chance of pregnancy after MAR, also in comparison with other predictors of pregnancy after MAR.

High sperm DNA fragmentation delays human embryo kinetics when oocytes from young and healthy donors are microinjected

“…One recent meta-analysis (Cissen et al, 2016) concluded that there was insufficient evidence to recommend the routine use of sperm DNA fragmentation tests in couples undergoing ART for either the prediction of pregnancy or the choice of treatment. One recent meta-analysis (Cissen et al, 2016) concluded that there was insufficient evidence to recommend the routine use of sperm DNA fragmentation tests in couples undergoing ART for either the prediction of pregnancy or the choice of treatment.…”

“…Many studies have assessed the association between sDNAf test results and pregnancy probability in IVF and ICSI cycles (Evenson & Wixon, 2006) (Li et al, 2006) (Cissen et al, 2016) (Collins et al, 2008) (Zhao et al, 2014) .…”

Effect of different oxidative stress degrees generated by hydrogen peroxide on motility and DNA fragmentation of zebrafish (Danio rerio) spermatozoa

“…In the recent past, a systematic review of humans indicated that predictive value of SDF tests is not evident (Cissen et al, ). It is possible that a more objective evaluation, such as a quantitative evaluation of SDF, could reduce the variability of results.…”

“…However, despite this packaging, nuclear and mitochondrial DNA are substrates that are sensitive to ROS. Reinardy et al (2013) In the recent past, a systematic review of humans indicated that predictive value of SDF tests is not evident (Cissen et al, 2016). It is possible that a more objective evaluation, such as a quantitative evaluation of SDF, could reduce the variability of results.…”

Abnormal Chromatin Condensation in Spermatozoa and Dna Fragmentation in Spermatozoa: Is There a Correlation?

“…Попытки метаанализа данных о значении измерения ФДС в репродукции показывают, что од-нозначного ответа дать нельзя, результаты весьма про-тиворечивы: нет данных о предиктивности теста, не подтверждаются данные о преимуществе ИКСИ перед ЭКО при повышенной фрагментации ДНК [84,[93][94][95][96]. Авторы отмечают низкое качество рандомизированных исследований и считают, что рекомендовать тест для универсального использования рано: есть работы, в ко-торых не найдено различий исхода ВРТ и беременно-сти при различиях в содержании ФДС, исследованы небольшие гетерогенные популяции, исследования про-водятся разными методами и различаются по дизайну экспериментов.…”