Sperm DNA fragmentation index influences assisted reproductive technology outcome: A systematic review and meta‐analysis combined with a retrospective cohort study

Abstract

Studies have explored the influence of DNA damage in assisted reproductive technology (ART), but the outcome remains controversial. To determine whether sperm DNA fragmentation index (DFI) has any effect on ART outcomes, we collected detailed data regarding 1,333 IVF cycles performed at our centre, and the data of our retrospective cohort study were extracted for this meta‐analysis. We searched PubMed, Web of Science, EMBASE and Google Scholar and performed a systemic review and meta‐analysis. Primary meta‐analysis of 10 studies comprising 1,785 couples showed that live birth rate was no significantly different between low‐DFI group and high‐DFI group (p > 0.05). Secondary meta‐analysis of 25 studies comprising 3,992 couples showed a higher miscarriage rate in high‐DFI group than in low‐DFI group (RR=1.57 [1.18, 2.09], p < 0.01). Meta‐analysis of eight studies comprising 17,879 embryos revealed a lower good‐quality embryo rate (RR=0.65 [0.62, 0.68], p < 0.01). Meta‐analysis of 23 studies comprising 6,771 cycles showed that the high‐DFI group had a lower clinical pregnancy rate than low‐DFI group (RR=0.85 [0.75, 0.96], p < 0.01). Heterogeneity of included studies weakened our conclusions. Our study showed that DFI has adverse effects on ART outcome. More well‐designed studies exploring the association between DFI and ART outcome are desired.

DNA fragmentation index (DFI) as a measure of sperm quality and fertility in mice

“…This observation is consistent with the perception that sperm nuclear DNA integrity is essential to embryo development [25][26][27] . Our findings in mice are consistent with results obtained in humans in which sperm with a high proportion of DNA fragmentation were found to be associated with impaired embryo development and increased miscarriage rates 8,10,11,[41][42][43][44] . Figure 7.…”

“…Numerous studies have attempted to assess the association between outcomes of assisted reproductive technologies (ART) and sperm DNA fragmentation (SDF) which has a negative effect on sperm quality and fertility [4][5][6][7][8] . However, due to variation between SDF assays and protocols, differences in study populations, lack of test standardization, systematic reviews and meta-analyses have been unable to make robust conclusions regarding the full impact of DNA fragmentation on sperm quality and fertility [9][10][11][12][13][14][15][16][17][18][19] . Therefore, today male fertility status is based on an assessment of conventional sperm parameters (count, motility and morphology) despite the inability to differentiate between infertile and fertile males 9,20,21 .…”

Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility

“…Indeed, although the oocyte is able to repair the sperm DNA damage that occurs during their passage in both the male and female genital tracts, an excessive degree of damage that exceeds the repairing ability of the oocyte will result in an adverse pregnancy outcome [27]. The negative impact of sperm DNA fragmentation on the pregnancy outcome (including recurrent pregnancy loss) has already been confirmed by three different meta-analyses [27][28][29]. In line with this evidence, abnormal sperm protamination (e.g., altered P1/P2 ratio) is associated with poor sperm and embryo quality, as well as with low fertilization and pregnancy rates [30].…”

Predictive value of oxidative stress testing in semen for sperm DNA fragmentation assessed by sperm chromatin dispersion test

“…19,29,30 Furthermore, SDF negatively affects sperm fertility potential and embryo development in natural conception and assisted reproductive techniques (ART). [31][32][33] In addition, evidence suggests that the assessment of oxidative stress could be important for infertile patients, who could take advantage of antioxidants supplementation or modification of the lifestyle (eg, smoking, exposure to pollutants, varicocoele, high BMI). 34 In light of these considerations, there is a need to better understand the association between seminal oxidative stress and SDF, and for the development of new predictive and diagnostic methods.…”