Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa

Greco, Ermanno; Scarselli, Filomena; Iacobelli, Marcello; Rienzi, Laura; Ubaldi, Filippo; Ferrero, S.; Franco, Giorgio; Anniballo, Nazareno; Mendoza, Carmen; Tesařík, Jan

doi:10.1093/humrep/deh590

Cited by 370 publications

(266 citation statements)

References 38 publications

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“…The disadvantage of TUNEL assay is that since it does not include the lysis step, the accessibility of TdT to all the 3′OH ends in tightly packed sperm genome is limited [111]. As a result of which the suggested clinical thresholds is lower (18%) in different studies [85,[112][113][114] as compared with the established threshold of 27-30%. A recent study by Mitchell LA et al 2010 [115], has suggested an improvised TUNEL assay which provides solution to increase the accessibility of TdT and also incorporates the assessment of the vitality in the same flow cytometry assay.…”

Section: Research Laboratory Aspects and Relevance Of Dna Integrity Tmentioning

confidence: 99%

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

Shamsi

Imam

Dada

2011

J Assist Reprod Genet

130

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Sperm is not a simple carrier of paternal genetic information but its role extends clearly beyond fertilization. Integrity of sperm genome is an essential pre-requisite for birth of healthy offspring and evaluation of sperm should entail DNA integrity analysis. DNA integrity analysis is a better diagnostic and prognostic marker of sperm reproductive potential. Conventional semen analysis emphasizes on sperm concentration, viability, motility and morphology and has been proven to be a poor indicator of reproductive potential and pregnancy outcome. To overcome the drawbacks associated with conventional semen analysis more useful fertility tests and molecular biomarkers have been explored. Among the different tests which have evolved for assessing the sperm reproductive potential, tests for sperm DNA quality are most promising. Sperm DNA damage has been closely associated with numerous indicators of reproductive health including fertilization, embryo quality, implantation, spontaneous abortion, congenital malformations and childhood diseases. It therefore has great potential as a prognostic test for both in vitro and in vivo conception. This review presents an updated account of tests that have better diagnostic and prognostic implications in the evaluation of sperm DNA damage. The basic principles, outline of methodology, advantage, disadvantage, clinical significance of each technique and implications of these tests have been discussed. The logistics of each test with respect to available resources and equipment in an andrology laboratory, the feasibility of performing these tests in routine diagnostic workup of infertile men and the opportunities and challenges provided by DNA testing in male fertility determination are also presented.

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Section: Research Laboratory Aspects and Relevance Of Dna Integrity Tmentioning

confidence: 99%

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

Shamsi

Imam

Dada

2011

J Assist Reprod Genet

130

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“…In addition, physiological intracytoplasmic sperm injection (PICSI) or intracytoplasmic morphologically selected sperm injection (IMSI) are common laboratory interventions and have been shown to be effective in selecting spermatozoa with reduced levels of SDF (Huszar et al, 2007;Parmegiani et al, 2010;Gos alvez et al, 2013;Garolla et al, 2014), although their effect on clinical outcomes is yet to be reported. Surgically extracted testicular sperm has also been shown to have lower levels of SDF compared to that of the ejaculate and its use in patients with high SDF has been shown to have a positive effect on pregnancy outcomes (Greco et al, 2005;Esteves et al, 2015). Additionally, a less invasive procedure that is sometimes recommended for patients with high SDF is frequent ejaculation, as longer periods of abstinence has been associated with higher SDF (Gosalvez et al, 2011;Pons et al, 2013;Sanchez-Martin et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Intervention improves assisted conception intracytoplasmic sperm injection outcomes for patients with high levels of sperm DNA fragmentation: a retrospective analysis

Bradley¹,

McArthur²,

Gee³

et al. 2016

Andrology

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SUMMARYSperm DNA fragmentation (SDF) is used in assisted reproductive technology (ART) programs as an indicator for sperm quality, although there is still a lack of consensus as to its clinical utility. In this retrospective study, we examined intracytoplasmic sperm injection (ICSI) outcomes of 1924 infertile patients who underwent SDF analysis using the sperm chromatin integrity test. ART patients were classified as having low [DNA fragmentation index (DFI) <29%] or high SDF (DFI ≥29%) and by whether or not an intervention [physiological intracytoplasmic sperm injection (PICSI), intracytoplasmic morphologically selected sperm injection (IMSI), testicular sperm extraction (TESE)/testicular sperm aspiration (TESA), frequent ejaculation] was performed. High SDF patients who did not have an intervention had a lower fertilization rate and poorer clinical outcomes from blastocyst transfers as compared with low SDF patients; the fertilization rate was 66.0% vs. 70.2% (p = 0.042), single embryo transfer (SET) fetal heart pregnancy rate was 28.5% vs. 45.2% (p = 0.042), and SET live birth rate was 24.9% vs. 40.6% (p = 0.060), respectively. Furthermore, high SDF patients who had an intervention had significantly improved blastocyst transfer outcomes, similar to those of low SDF patients; the SET live birth rate for high SDF intervention patients was 43.8% as compared with 24.9% for high SDF no intervention patients (p = 0.037) and 40.6% for low SDF patients (p = 0.446). Analysis of the three main intervention subgroups for high SDF patients revealed that TESE/TESA patients had the highest SET live birth rate; in comparison with 24.2% for high SDF patients who did not have an intervention, PICSI patients had 38.3% (p = 0.151), IMSI patients had 28.7% (p = 0.680), and TESE/TESA patients had 49.8% (p = 0.020). Our data suggest that SDF results indicate ICSI outcomes and that patients who have high SDF benefit from an intervention.

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“…That is, testicular sperm had no disulfide bonds within chromatin. Although we were apprehensive that DNA fragmentation might occur easily without disulfide bonds, DNA fragmentation was revealed to be less than 5% even in human testes [34]. It was suggested that testicular spermatozoa, which had no disulfide bonds and less DNA fragmentation in their chromatin, could improve embryonic development.…”

Section: Discussionmentioning

confidence: 94%

“…Assessment of sperm chromatin and DNA fragmentation should help to determine whether repeated ICSI or testicular sperm extraction (TESE)-ICSI is more appropriate [34]. Additional evidence will be needed to establish a practical assessment of human sperm quality to improve ICSI outcome.…”

Section: Discussionmentioning

confidence: 99%

Embryo development after intracytoplasmic sperm injection can be predicted by assessment of sperm nuclear chromatin

Takayama

Katayose

Sato

2009

Reprod Medicine & Biology

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Purpose To assess the influence of structural differences in sperm nuclei on embryo development in intracytoplasmic sperm injection (ICSI). Methods Semen obtained from forty-four infertile patients who underwent ICSI was examined. In assessing blastocyst development, only those patients who had successfully obtained over five fertilized eggs were included to exclude any oocyte factors (n = 22). Spermatozoa were assessed using excitation fluorescence flow cytometry with acridine orange and the sperm chromatin dispersion (SCD) test. Results There was a significant positive correlation between the COMP values obtained from flow cytometry and blastocyst formation. (r = 0.477, p = 0.025). There was a significant negative correlation between the SCD values representing DNA fragmentation and blastocyst formation. (r = 0.796, p \ 0.001). COMP values and SCD values were independent parameters to assess sperm nuclear quality regarding embryo development in vitro (r = 0.224, p = 0.080). Conclusion Results suggest that injection of spermatozoa with fewer disulfide bonds and less nuclear DNA fragmentation could achieve better blastocyst formation in human ICSI. Assessment of sperm chromatin should help to predict embryo development after ICSI.

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Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa

Abstract: These data show that ICSI with testicular spermatozoa provides the first efficient assisted reproduction treatment option for men with high levels of sperm DNA damage.

Cited by 370 publications

References 38 publications

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

Intervention improves assisted conception intracytoplasmic sperm injection outcomes for patients with high levels of sperm DNA fragmentation: a retrospective analysis

Embryo development after intracytoplasmic sperm injection can be predicted by assessment of sperm nuclear chromatin

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