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.
Highlights
The diagnosis of male subfertility is based upon the analysis of semen volume and sperm concentration, motility and morphology
We found 21 studies reported on the structure assay (SCSA) [103,110–112,114,117,118,123–136], 18 studies on the sperm chromatin dispersion (SCD) test [97,98,101,102,106–109,113,115,116,120,122,137–141], 18 studies reported on the TUNEL assay [92–95,96,99,100,104,119,134,142–149] and seven studies reported on the alkaline Comet assay [95,105,121,134,150–152]
In the meta-analysis of Evenson and Wixon there was a non-significant trend towards the occurrence of pregnancy (odds ratio (OR) 1.6; 95% confidence interval (CI) 0.92 to 2.94) when infertile couples were treated with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and the DNA fragmentation index (DFI), determined by the SCSA, was below 30% [153]
Summary
The diagnosis of male subfertility is based upon the analysis of semen volume and sperm concentration, motility and morphology. There is a direct relationship between semen quality and pregnancy rates both in natural conception and after medically assisted reproduction (MAR), there is no definite predictive threshold for success for conventional semen parameters [1–4]. Conventional semen analysis does not assess all aspects of the function of testis and sperm quality. New tests for predicting the chance of pregnancy would be clinically useful. There have been attempts to propose sperm DNA fragmentation as such a new test for male reproductive capability [5]. The integrity of our genome is continuously challenged by endogenous metabolic by-products and exogenous factors. Toxic effects of drugs, cigarette smoking, pollution, and factors as xenobiotics, high testicular temperature (fever, varicocele) and advanced age have been associated with increased sperm DNA damage [24–28]
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