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      A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome

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          Abstract

          Sperm DNA damage is prevalent among infertile men and is known to influence natural reproduction. However, the impact of sperm DNA damage on assisted reproduction outcomes remains controversial. Here, we conducted a meta-analysis of studies on sperm DNA damage (assessed by SCSA, TUNEL, SCD, or Comet assay) and clinical pregnancy after IVF and/or ICSI treatment from MEDLINE, EMBASE, and PUBMED database searches for this analysis. We identified 41 articles (with a total of 56 studies) including 16 IVF studies, 24 ICSI studies, and 16 mixed (IVF + ICSI) studies. These studies measured DNA damage (by one of four assays: 23 SCSA, 18 TUNEL, 8 SCD, and 7 Comet) and included a total of 8068 treatment cycles (3734 IVF, 2282 ICSI, and 2052 mixed IVF + ICSI). The combined OR of 1.68 (95% CI: 1.49–1.89; P < 0.0001) indicates that sperm DNA damage affects clinical pregnancy following IVF and/or ICSI treatment. In addition, the combined OR estimates of IVF (16 estimates, OR = 1.65; 95% CI: 1.34–2.04; P < 0.0001), ICSI (24 estimates, OR = 1.31; 95% CI: 1.08–1.59; P = 0.0068), and mixed IVF + ICSI studies (16 estimates, OR = 2.37; 95% CI: 1.89–2.97; P < 0.0001) were also statistically significant. There is sufficient evidence in the existing literature suggesting that sperm DNA damage has a negative effect on clinical pregnancy following IVF and/or ICSI treatment.

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          Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome.

          The sperm chromatin structure assay (SCSA) has been suggested as a predictor of fertility in vivo as well as in vitro. The available data however, have been based on limited numbers of treatments. We aimed to define the clinical role of SCSA in assisted reproduction. A total of 998 cycles [387 intrauterine insemination (IUI), 388 IVF and 223 ICSI] from 637 couples were included. SCSA results were expressed as DNA fragmentation index (DFI) and high DNA stainable (HDS) cell fractions. Outcome parameters were biochemical pregnancy (BP), clinical pregnancy (CP) and delivery (D). For IUI, the odds ratios (ORs) for BP, CP and D were significantly lower for couples with DFI >30% as compared with those with DFI 30% group, the results of ICSI were significantly better than those of IVF. DFI can be used as an independent predictor of fertility in couples undergoing IUI. As a result, we propose that all infertile men should be tested with SCSA as a supplement to the standard semen analysis. When DFI exceeds 30%, ICSI should be the method of choice.
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            Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis.

            Sperm DNA damage is common amongst infertile men and may adversely impact natural reproduction, IUI-assisted reproduction and to a lesser degree IVF pregnancy. The aim of this study was to examine the influence of sperm DNA damage on the risk of spontaneous pregnancy loss after IVF and ICSI. We conducted a systematic review and meta-analysis of studies on sperm DNA damage and pregnancy loss after an IVF and/or ICSI pregnancy. Two by two tables were constructed and odds ratios (ORs) were derived from 11 estimates of pregnancy loss (five IVF and six ICSI studies from seven reports). These 11 studies involved 1549 cycles of treatment (808 IVF and 741 ICSI cycles) with 640 pregnancies (345 IVF and 295 ICSI) and 122 pregnancy losses. The combined OR of 2.48 (95% CI 1.52, 4.04, P < 0.0001) indicates that sperm DNA damage is predictive of pregnancy loss after IVF and ICSI. In conclusion, sperm DNA damage is associated with a significantly increased risk of pregnancy loss after IVF and ICSI. These data provide a clinical indication for the evaluation of sperm DNA damage prior to IVF or ICSI and a rationale for further investigating the association between sperm DNA damage and pregnancy loss.
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              Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic.

              The sperm chromatin structure assay (SCSA) was used to measure over 500 human semen samples from two independent studies: Study I, 402 samples from 165 presumably fertile couples wishing to achieve pregnancy over 12 menstrual cycles; Study II, samples from 115 patients seeking fertility counselling. The SCSA measures susceptibility to DNA denaturation in situ in spermatozoa exposed to acid for 30 s, followed by acridine orange staining. SCSA data from the male partners of 73 couples (group 1) achieving pregnancy during months 1-3 of Study I were used as the standard of 'sperm chromatin compatible with high fertility' and were significantly different from those of 40 couples (group 3) achieving pregnancy in months 4-12 (P or = 30% COMP alpha t, a threshold level considered not compatible with good fertility. Using selected cut-off values for chromatin integrity, the SCSA data predicted seven of 18 miscarriages (39%).
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                Author and article information

                Journal
                Asian J Androl
                Asian J. Androl
                AJA
                Asian Journal of Andrology
                Medknow Publications & Media Pvt Ltd (India )
                1008-682X
                1745-7262
                Jan-Feb 2017
                24 June 2016
                : 19
                : 1
                : 80-90
                Affiliations
                [1 ]Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City, UT, USA
                [2 ]Division of Urology, Department of Surgery, St. Mary's Hospital Center, St. Mary's Hospital, 3830 Lacombe Avenue, Montreal, Quebec H3T 1M5, Canada
                [3 ]Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA
                [4 ]Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT, USA
                Author notes
                Correspondence: Dr. DT Carrell ( douglas.carrell@ 123456hsc.utah.edu )
                [*]

                These authors contributed equally to this work.

                Article
                AJA-19-80
                10.4103/1008-682X.182822
                5227680
                27345006
                806fc8f2-ee68-45f0-96bc-d2e66e9a78b1
                Copyright: © 2017 AJA, SIMM & SJTU

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 13 January 2016
                : 25 February 2016
                : 20 May 2016
                Categories
                Original Article

                assisted reproductive technology outcomes,clinical pregnancy,meta-analysis,sperm dna damage,systematic review

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