Impact Of DNA Fragmentation Research Articles

Sperm DNA Fragmentation: Unraveling Its Imperative Impact on Male Infertility Based on Recent Evidence.

Male factors may be present in up to 50-70% of infertile couples and the prevalence of male infertility accounts for 20-30% of infertility cases. Understanding the mechanisms and causes behind male infertility remains a challenge, but new diagnostic tools such as DNA fragmentation might aid in cases where the routine semen analysis is insufficient. DNA fragmentation, which refers to damages or breaks of the genetic material of the spermatozoa, is considered one of the main causes of male infertility due to impaired functional capability of sperm. The aim of the present narrative review is to investigate and enlighten the potential correlation between DNA fragmentation and male infertility parameters such as the seminal profile and the reproductive outcomes. Comprehensive research in PubMed/Medline and Scopus databases was conducted and 28 studies were included in the present review. Fourteen studies provided data regarding the impact of DNA fragmentation and seminal parameters and showed a correlation of significantly lower sperm count, lower concentration, motility, and abnormal morphology with an increased DNA fragmentation index (DFI). Similarly, 15 studies provided data regarding the impact of DFI on reproductive outcomes. Two studies showed higher aneuploidy rates with higher DFI values, and seven studies showed significantly lower pregnancy rates and live birth rates with higher DFI values. Ultimately, the studies included in this review highlight, collectively, the importance of measuring sperm DFI in the assessment of male infertility. Further studies are needed to explore the effectiveness of interventions aiming to reduce DFI levels.

O-299 Sperm DNA fragmentation by TUNEL influences live birth in egg recipients after euploid embryo transfer

Abstract Study question Does sperm DNA fragmentation (SDF) by TUNEL affect reproductive success measured as live birth rate (LBR) in egg recipients after euploid embryo transfer? Summary answer SDF increases miscarriage rates in egg recipients with PGT-A. Therefore, live birth rates depends on sperm DNA damage in egg recipients after euploid embryo transfer. What is known already Sperm DNA integrity is important for optimal fertilisation, implantation and pregnancy. Although controversial, several studies have shown that sperm DNA fragmentation correlates with adverse pregnancy outcomes in infertile men. Ooplasmic sperm DNA fragmentation repair mechanisms may occur in female gametes, mainly in young women. However, research on the impact of DNA fragmentation on LBR are limited. Also, chromosomally normal embryos analysed by PGT-A offers opportunity to isolate female factor and study male factor. The aim of this study is to assess whether high level of semen DNA damage has an impact on reproductive outcomes in terms of live birth rate. Study design, size, duration This is a retrospective study of 467 PGT-A cycles in egg recipients. The study population consists of infertile couples for euploid embryo transfer (February 2017-November 2022). Semen samples were obtained to measure DNA damage from 447 men. PGT-A was performed in 1831 blastocysts. Trophectoderm biopsies (d5/d6 blastocysts) were analysed by NGS (Veriseq Illumina). Embryos were frozen and 568 blastocysts transferred in the subsequent cycle. Conventional hormone replacement was used for endometrial preparation in recipient patients. Participants/materials, setting, methods Cohort study with 447 infertile couples attending to private fertility clinic undergoing ART with their autologous semen, donated oocytes and PGT-A. SDF was measured by Terminal-deoxyribonucleotidyl-ARTSferase-mediated dUTP Nodule End Labelling (TUNEL) assay using the FITC-labelled-dUTP in situ cell death detection kit (Roche). The cohort was divided into two groups according the DNA fragmentation index (DFI): high SDF group (DFI>20%) and normal SDF group (DFI≤20%). To evaluate reproductive outcomes Chi-square and Linear regression tests were used. Main results and the role of chance Of the 447 couples included (average paternal age 41.29 + 7.32 years), 66.5% of male partners had normal semen parameters. We reported high sperm DNA fragmentation in 8% of patients. Overall, the embryo aneuploidy rate was 31.7%. For the further statistical analysis confounding factors such as, female and male age, embryo quality, day of embryo biopsy were included. PGT-A analysis showed an aneuploidy rate of 32.1% in the high DNA fragmentation group and 30.3% in the normal DNA fragmentation group (p = 0.453). Regarding clinical data, the overall implantation rate was 34.9%. There was no significant difference between elevate DNA fragmentation and normal DNA fragmentation with respect to biochemical miscarriage rate (4.3% vs 7.6%, p = 0.799). Although not significant differences between groups, a lower implantation rate near to reach significance was found in the high SDF group (20.0% vs 34.4%, p = 0.050). Pregnancy and clinical pregnancy rates were significantly lower in the high DNA fragmentation group (26.1% vs 44.9%, p = 0.042; 21.7% vs 31.3%, p = 0.044;), respectively. Also, miscarriage rate was significantly higher in the high SDF group (40% vs 12.5%, p = 0.014). Therefore, the live birth rate was significantly lower in the high SDF group (13.0% vs 32.6%, p = 0.024). Limitations, reasons for caution Larger studies including a higher number of samples are needed to confirm the correlation observed between LBR in eggs recipients with semen DNA fragmentation. Those patients with a DFI higher than control values should be treated with antioxidants. The pregnancy outcomes should be analyzed after treatment of DNA fragmentation. Wider implications of the findings Our findings suggest that autologous semen DNA fragmentation influence in live birth rate in egg recipients. Our data show that live birth rates decreased in patients with a high DFI after PGT-A. This study confirms published studies in the literature showing that ART outcomes are affected by sperm DNA fragmentation. Trial registration number Not Applicable

Male fertility: summary overview of the publications October – December 2021

The article presents an overview of the most significant publications on the topic of male infertility. The main selection criteria were the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank. As a result, a list of 10 articles published in the IV quarter (October — December) of 2021 was compiled. The review includes articles on the following topics: genetic causes of male infertility, the effectiveness of antioxidants, the use of testicular spermatozoa in Intra Cytoplasmic Sperm Injection, the impact of DNA fragmentation of spermatozoa on the results of assisted reproductive technology, the relationship of male fertility with physical activity, the consumption of sweetened beverages and vitamin D intake, as well as the prognostic value of blood anti-Mullerian hormone levels before testicular biopsy.

Sperm DNA fragmentation increases with age but not chromatin decondensation

OBJECTIVE: The impact of Sperm DNA damages and chromatin structure (DNA packaging) on reproductive outcome is no longer a matter for debates. The relationship between paternal age and sperm DNA fragmentation is now of common knowledge. We have tried to define here if the chromatin structure follows the same type of variations.DESIGN: We have tested in a retrospective study including 633 patients consulting for hypofertility DNA fragmentation index % (DFI), and DNA decondensation %(SDI).MATERIALS AND METHODS: Sperm DNA fragmentation has been studied by TUNEL assay either coupled with flow cytometry or on slides when sperm concentration was too low (<1 million sperm per ml). The correlation between our 2 techniques has been controlled. DNA decondensation (SDI) was tested using aniline blue. The effect of age and abstinence was analysed using variance covariance analysis (Table 1).Table 1DFI and SDI according to paternal agepaternal ageNfragmentation index % (DFI)decondensation index % (SDI)≥ 3418022,2 ± 9,118,0 ± 9,935-3924523,9 ± 10,217,6 ± 11,140-4916425,8 ± 12,317,5 ± 7,9≥ 504435,1 ± 14,115,0 ± 4,2statistical significancyp<0.001p<0.01 Open table in a new tab CONCLUSIONS: Sperm DNA fragmentation and chromatin structure are not correlated. Increase of DFI with age can be interpreted as a weaker resistance to reactive oxygen species with age. This increase in reactive oxygen species (ROS) in sperm surrounding has a rather positive effect on chromatin structure: DNA packaging needs oxidation of the protamine cystein moieties to cystin in order to lock the DNA. If the impact of DNA fragmentation on ART is rather well documented, poor chromatin structure leads to chromosomal anomalies which are a classical feature in IVF/ICSI embryos. DFI and SDI are independent but complementary: they have a mandatory place in the realisation of a complete male fertility check up especially in relation with paternal age. OBJECTIVE: The impact of Sperm DNA damages and chromatin structure (DNA packaging) on reproductive outcome is no longer a matter for debates. The relationship between paternal age and sperm DNA fragmentation is now of common knowledge. We have tried to define here if the chromatin structure follows the same type of variations. DESIGN: We have tested in a retrospective study including 633 patients consulting for hypofertility DNA fragmentation index % (DFI), and DNA decondensation %(SDI). MATERIALS AND METHODS: Sperm DNA fragmentation has been studied by TUNEL assay either coupled with flow cytometry or on slides when sperm concentration was too low (<1 million sperm per ml). The correlation between our 2 techniques has been controlled. DNA decondensation (SDI) was tested using aniline blue. The effect of age and abstinence was analysed using variance covariance analysis (Table 1). CONCLUSIONS: Sperm DNA fragmentation and chromatin structure are not correlated. Increase of DFI with age can be interpreted as a weaker resistance to reactive oxygen species with age. This increase in reactive oxygen species (ROS) in sperm surrounding has a rather positive effect on chromatin structure: DNA packaging needs oxidation of the protamine cystein moieties to cystin in order to lock the DNA. If the impact of DNA fragmentation on ART is rather well documented, poor chromatin structure leads to chromosomal anomalies which are a classical feature in IVF/ICSI embryos. DFI and SDI are independent but complementary: they have a mandatory place in the realisation of a complete male fertility check up especially in relation with paternal age.