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INVITED COMMENTARY
Year : 2016  |  Volume : 18  |  Issue : 3  |  Page : 434

Use of testicular sperm to combat the negative effects of DNA fragmentation


1 Men's Health Center, 8240 Naab Road, Suite 220, Indianapolis, Indiana 46260, USA
2 Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA

Date of Web Publication05-Apr-2016

Correspondence Address:
Dr. Jason R Kovac
Men's Health Center, 8240 Naab Road, Suite 220, Indianapolis, Indiana 46260
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1008-682X.179158

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How to cite this article:
Kovac JR, Lipshultz LI. Use of testicular sperm to combat the negative effects of DNA fragmentation. Asian J Androl 2016;18:434

How to cite this URL:
Kovac JR, Lipshultz LI. Use of testicular sperm to combat the negative effects of DNA fragmentation. Asian J Androl [serial online] 2016 [cited 2020 Nov 24];18:434. Available from: https://www.ajandrology.com/text.asp?2016/18/3/434/179158 - DOI: 10.4103/1008-682X.179158

Numerous approaches to the detection of novel biomarkers for male fertility have been proposed. As reviewed in the manuscript by Bieniek et al. [1] analysis of seminal plasma has yielded numerous possible candidate biomarkers. Since semen analysis is a critical component in the initial workup for infertile males, seminal fluid biomarkers inherently have several distinct advantages. For most individuals, the sample is relatively easy to produce and, given an appropriate volume, can be separated into multiple aliquots for separate tests. Disadvantages include the fact that seminal fluid is a composition of excretions from multiple glands, including the seminal vesicles and prostate.

DNA fragmentation has been investigated for a decade with regards to not only its potential as a biomarker, but also as a measurable value by which to postulate fertility outcomes and record spermatogenic damage from reactive oxygen species (ROS). [2],[3] Simply put, DNA fragmentation is a measure of DNA integrity assessed through different methods such as the Comet and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) tests. [4]

ROS-induced DNA damage, manifested as increased DNA fragmentation, occurs primarily during posttesticular transport of spermatozoa through the epididymis. As such, a strong relationship between ROS and DNA fragmentation has been established. [5],[6] Indeed, DNA damage can be evoked in vitro by exposing mature sperm to high levels of ROS. [7],[8] Highly abnormal (>30%) DNA fragmentation rates have also been identified in ~8% of infertile men with a normal semen analysis; [9] these data highlight the potential importance of this seminal biomarker.

A role for testicular sperm retrieval as treatment for DNA fragmentation was hypothesized in a study that followed four couples with multiple in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) cycle failures using ejaculated sperm. Pregnancy was subsequently achieved using testicular sperm aspiration. [2] While the authors did not directly examine DNA fragmentation, the theorized relationship was provocative.

When considering natural pregnancies, high seminal DNA fragmentation rates treated with multivitamins and anti-oxidants have failed to show significant improvements in fertility. Conversely, work by Greco et al. examined and compared the characteristics and outcomes of ejaculated and testicular spermatozoa from 18 men undergoing IVF/ICSI. [3] The authors found that DNA fragmentation (via TUNEL) was lower in testicular sperm compared to that of ejaculated sperm. [2] Moreover, IVF/ICSI with testicular sperm yielded improved outcomes in men with high rates of DNA fragmentation. [3] Following these results, it was recommended that in men with previous IVF/ICSI failures using ejaculated sperm containing high levels of DNA fragmentation, testicular samples should be considered to improve outcomes. [3],[10]

Another point to remember is that varicoceles, known contributors to male factor subfertility, can increase ROS and DNA fragmentation rates. Microsurgical repair of the varicocele can obviate these negative semen analysis/seminal biomarker characteristics. [11] It is thus tempting to speculate that in men with prior IVF/ICSI failures and concurrent varicoceles, repair followed by a testicular sperm harvest at least 3 months following the surgical procedure could yield the most successful outcomes. Trials are encouraged and would no doubt lead to interesting results.

 
  References Top

1.
Bieniek JM, Drabovich AP, Lo KC. Seminal biomarkers for the evaluation of male infertility. Asian J Androl 2016; 18: 426-33. [Doi: 10.4103/1008-682X.175781]. [Epub ahead of print].  Back to cited text no. 1
    
2.
Weissman A, Horowitz E, Ravhon A, Nahum H, Golan A, et al. Pregnancies and live births following ICSI with testicular spermatozoa after repeated implantation failure using ejaculated spermatozoa. Reprod Biomed Online 2008; 17: 605-9.  Back to cited text no. 2
    
3.
Greco E, Scarselli F, Iacobelli M, Rienzi L, Ubaldi F, et al. Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa. Hum Reprod 2005; 20: 226-30.  Back to cited text no. 3
    
4.
Sakkas D, Alvarez JG. Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertil Steril 2010; 93: 1027-36.  Back to cited text no. 4
    
5.
Ollero M, Gil-Guzman E, Lopez MC, Sharma RK, Agarwal A, et al. Characterization of subsets of human spermatozoa at different stages of maturation: implications in the diagnosis and treatment of male infertility. Hum Reprod 2001; 16: 1912-21.  Back to cited text no. 5
    
6.
Gil-Guzman E, Ollero M, Lopez MC, Sharma RK, Alvarez JG, et al. Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation. Hum Reprod 2001; 16: 1922-30.  Back to cited text no. 6
    
7.
Aitken RJ, Gordon E, Harkiss D, Twigg JP, Milne P, et al. Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod 1998; 59: 1037-46.  Back to cited text no. 7
    
8.
Lopes S, Jurisicova A, Sun JG, Casper RF. Reactive oxygen species: potential cause for DNA fragmentation in human spermatozoa. Hum Reprod 1998; 13: 896-900.  Back to cited text no. 8
    
9.
Zini A, Bielecki R, Phang D, Zenzes MT. Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men. Fertil Steril 2001; 75: 674-7.  Back to cited text no. 9
    
10.
Alvarez JG. 'Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular sperm'. Hum Reprod 2005; 20: 2031-2.  Back to cited text no. 10
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11.
Smit M, Romijn JC, Wildhagen MF, Veldhoven JL, Weber RF, et al. Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate. J Urol 2010; 183: 270-4.  Back to cited text no. 11
    



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1 Recent advances in understanding & managing male infertility
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