Measuring Sperm DNA Fragmentation and Clinical Outcomes of Medically Assisted Reproduction: A Systematic Review and Meta-Analysis.
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.
Department of Obstetrics & Gynaecology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.
Maartje
M
Cissen
Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Madelon van
MV
Wely
Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Irma
I
Scholten
Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
Steven
S
Mansell
Department of Obstetrics & Gynaecology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.
Jan Peter de
JP
Bruin
The Robinson Institute/School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia.
Ben Willem
BW
Mol
Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.
Didi
D
Braat
Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Sjoerd
S
Repping
Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Geert
G
Hamer
D000022:Abortion, Spontaneous / Q000453:epidemiology; D002843:Chromatin / Q000235:genetics; D020552:Comet Assay; D053938:DNA Fragmentation; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D011247:Pregnancy; D018873:Pregnancy Rate; D055101:Semen Analysis; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*
D002843:Chromatin