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      Male age: negative impact on sperm DNA fragmentation

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          Abstract

          The main goal of semen processing in Assisted Reproductive Techniques (ART) is to select sperm with good viability and, at the same time, remove Reactive Oxygen Species (ROS) sources (such as leukocytes) and reduce the percentage of morphologically abnormal sperm for fertility treatment. We performed a comparative analysis on sperm DNA fragmentation after Density Gradient Centrifugation (DGC) using products sold by two competing companies. Our results showed comparable DNA Fragmentation Index (DFI) after treatment with both DGC products. However, in both cases, a comparable number of samples do not benefit from the treatment. Interestingly, increasing evidences indicated that male age has a negative impact on sperm DNA fragmentation, but the mechanisms underlying age-dependent patterns of sperm decline have not yet been fully understood. Thus, we performed a comparative analysis of DFI before and after treatment with DGC products in age-stratified sample populations. Our results showed a worsening of the baseline DFI in the eldest group and the benefits of DGC on sperm DNA were compromised. In conclusion, our work consolidates the current evidences suggesting that both paternal and maternal aging, critically affects reproductive success.

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          The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis.

          Sheena EM Lewis, M Rajkhowa, Jackson Kirkman-Brown … (2012)
          Is there an association between high levels of sperm DNA damage and miscarriage? Miscarriage rates are positively correlated with sperm DNA damage levels. Most ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates. A systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012. We used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment. We identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P < 0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P < 0.00001). There is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss. The use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy. None.
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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.

            Antonio Ciampi, J Boman, Armand Zini … (2008)
            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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              Consistent age-dependent declines in human semen quality: a systematic review and meta-analysis.

              Sheri L. Johnson, Jessica Dunleavy, Neil J. Gemmell … (2015)
              Reduced fertility typically occurs among women in their late 30s, but increasing evidence indicates that advanced paternal age is associated with changes in reproduction as well. Numerous studies have investigated age-based declines in semen traits, but the impact of paternal age on semen parameter values remains inconclusive. Using data from 90 studies (93,839 subjects), we conducted a systematic review and meta-analysis to quantify the effect of male age on seven ejaculate traits (semen volume, sperm concentration, total sperm count, morphology, total motility, progressive motility and DNA fragmentation). Age-associated declines in semen volume, percentage motility, progressive motility, normal morphology and unfragmented cells were statistically significant and results generally seemed to be robust against confounding factors. Unexpectedly, sperm concentration did not decline with increasing male age, even though we found that sperm concentration declined over time. Our findings indicate that male age needs more recognition as a potential contributor to the negative pregnancy outcomes and reduced offspring health associated with delayed first reproduction. We suggest that greater focus on collection of DNA fragmentation and progressive motility in a clinical setting may lead to better patient outcomes during fertility treatments of aging couples.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Aging (Albany NY)
                Journal ID (iso-abbrev): Aging (Albany NY)
                Journal ID (publisher-id): Aging
                Title: Aging (Albany NY)
                Publisher: Impact Journals
                ISSN (Electronic): 1945-4589
                Publication date Collection: 15 May 2019
                Publication date (Electronic): 14 May 2019
                Volume: 11
                Issue: 9
                Pages: 2749-2761
                Affiliations
                [1 ]Division of Gynecology and Reproductive Medicine, Department of Gynecology, Humanitas Fertility Center, Humanitas Research Hospital, 20089 Rozzano (Milan), Italy
                [2 ]Humanitas Clinical and Research Center, 20089 Rozzano (Milan), Italy
                [3 ]Department of Medical Biotechnology and Translational Medicine, University of Milan, 20090 Segrate (Milan), Italy
                [* ]Equal contribution
                Author notes
                Correspondence to: Elena M. Borroni; email: elena.borroni@ 123456humanitasresearch.it
                Article
                Publisher ID: 101946
                DOI: 10.18632/aging.101946
                PMC ID: 6535069
                PubMed ID: 31085803
                SO-VID: 8c14da5e-e0c6-4e72-9145-cbd1dcb7b11a
                Copyright © Copyright © 2019 Albani et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 26 February 2019
                Date accepted : 29 April 2019
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Cell biology
                Keywords: male age,sperm,sperm dna fragmentation (sdf),fertility,dna fragmentation index (dfi),density gradient centrifugation (dgc),assisted reproductive techniques (art)
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: male age, sperm, sperm dna fragmentation (sdf), fertility, dna fragmentation index (dfi), density gradient centrifugation (dgc), assisted reproductive techniques (art)

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