O-209 The impact of sperm DNA fragmentation on pregnancy outcomes depends on oocyte dimorphisms

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
D Braga ◽  
A Setti ◽  
R Provenza ◽  
P Guilherme ◽  
A Iaconelli ◽  
...  

Abstract Study question Does the impact of sperm DNA fragmentation (SDF) on Intracytoplasmic sperm injection (ICSI) outcomes depend on the presence of oocyte dimorphisms? Summary answer There is a significant influence of oocyte quality on the impact of SDF on pregnancy outcomes. What is known already Sperm DNA fragmentation has been associated with ICSI outcomes. DNA damage is commonly encountered in human spermatozoa and it has been widely accepted that the oocyte assumes responsibility for the repair and remodelling of both the maternal and paternal genomes during the oocyte-embryo transition. Indeed, spermatozoa with DNA damage can fertilise oocytes and still lead to embryo development due to the oocyte DNA repair capacity. Considering the vital role played by the oocyte in the developmental process, it could be hypostatised that the oocyte quality, translated as oocyte morphology, would influence the machinery responsible for sperm DNA repair after fertilization. Study design, size, duration This cohort study included 3,035 oocytes from 525 patients undergoing ICSI cycles in a university-affiliated IVF-center, between June/2016 and July/2019. Oocytes were split into groups according to the SDF index of the sample used for ICSI: low-fragmentation (<30% SDF, n = 2,277) and high-fragmentation (≥30% SDF, n = 758). Oocytes were evaluated before sperm injection and the dimorphisms were recorded. The influence of SDF index on ICSI outcomes, depending on the presence of oocytes dimorphisms was evaluated. Participants/materials, setting, methods Data was evaluated using generalized linear models (GZLM) followed by Bonferroni post hoc. The results are expressed as mean ± standard error for continuous variables or percentages for dichotomous variables, and p-values. The sample size calculation suggested that a sample of at least 504 subjects had 95% power to detect a 20% effect with a significance level of 5% (α). The study was performed in a private university–affiliated in vitro fertilization (IVF) center. Main results and the role of chance The association of both factors: the presence of oocyte dimorphisms (dark cytoplasm, vacuoles in the ooplasm, and resistant membrane) and high SDF index resulted in the lowest fertilization rate among groups, while oocytes free of these dimorphisms injected with samples with <30% SDF had the highest fertilization rate (p = 0.05, p < 0.01 and p < 0.01 for dark cytoplasm, vacuoles in the ooplasm and resistant membrane respectively). The impact of SDF index on high quality embryos rate on cleavage stage was also influence by the presence smooth endoplasmic reticulum clusters and resistant membrane oocytes (p = 0.013 and p = 0.018). As for the clinical outcomes, the impact of SDF index on the implantation rate was influenced by the presence of vacuoles in the ooplasm (p < 0.01), smooth endoplasmic reticulum clusters (p < 0.01), large perivitelline space (p < 0.01), resistant membrane (p < 0.01), and non-resistant membrane (p < 0.01), while the influence of SDF index on the pregnancy rate was influenced by the presence large perivitelline space (p < 0.01), resistant membrane (p = 0.018) and non-resistant membrane (p < 0.01). The effect of SDF on the miscarriage rate was also increased in the presence of large perivitelline space (p = 0.045), non-resistant membrane (0.037) and centrally located cytoplasmic granular area (p = 0.025). Limitations, reasons for caution The retrospective nature is a limitation. It could be argued that using samples with high SDF index does not necessarily mean that a sperm cell with a fragmented DNA was injected, however, the higher the SDF index, the higher the chance of selecting one with fragmented DNA. Wider implications of the findings The findings presented here highlight the crucial role of male and female factors when facing assisted reproduction. The association of low oocyte quality and high SDF index may lead to impaired results. As the oocyte defect cannot be modified, in vivo upgrading of spermatozoa before the treatment should be encouraged. Trial registration number Not applicable

Zygote ◽  
2021 ◽  
pp. 1-8
Author(s):  
Shikai Wang ◽  
Weihong Tan ◽  
Yueyue Huang ◽  
Xianbao Mao ◽  
Zhengda Li ◽  
...  

Summary To determine the effects of sperm DNA fragmentation (SDF) on embryo morphokinetic parameters, cleavage patterns and embryo quality, this retrospective study analyzed 151 intracytoplasmic sperm injection (ICSI) cycles (1152 embryos collected) between November 2016 and June 2019. SDF was assessed using sperm chromatin dispersion. The cycles were divided into two groups based on the SDF rate: SDF < 15% (n = 114) and SDF ≥ 15% (n = 37). The embryo morphokinetic parameters, cleavage patterns, and embryo quality were compared between the two groups. The morphokinetic parameters tPNf, t2, t3, t4, t5, t6, and t8 were achieved significantly earlier in the SDF < 15% group compared with in the SDF ≥ 15% group. The fertilization and 2PN rates seemed to be significantly higher in the SDF < 15% group compared with in the SDF ≥ 15% group, while the abnormal cleavage rates were similar. However, a significantly higher rate of chaotic cleavage (CC) was observed in the SDF ≥ 15% group. The D3 high-quality embryo and available embryo rates were similar between the two groups. The blastocyst formation, high-quality blastocyst, and available blastocyst rates in the SDF < 15% group were significantly higher than those in the SDF ≥ 15% group. With an increase in SDF level, the chemical pregnancy, clinical pregnancy and implantation rates tended to decrease, while the miscarriage rate increased. This study demonstrated that SDF ≥ 15% reduces the fertilization rate of ICSI cycles and affects certain morphokinetic parameters. A higher SDF level can also induce a higher rate of CC, with subsequent decreases in the blastocyst formation rate and blastocyst quality.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Tenori. Lir. Neto ◽  
M Roque ◽  
S Esteves

Abstract Study question Does varicocelectomy improve sperm DNA quality in men with infertility and clinically detected varicoceles? Summary answer Varicocelectomy reduces sperm DNA fragmentation (SDF) rates in infertile men with clinical varicocele. What is known already Varicocele has been linked to male infertility through various non-mutually exclusive mechanisms, including an increase in reactive oxygen species (ROS) production that may lead to sperm DNA damage. Damage to sperm DNA may result in longer time-to-pregnancy, unexplained infertility, recurrent pregnancy loss, and failed intrauterine insemination or in vitro fertilization/intracytoplasmic sperm injection. Therefore, interventions aimed at decreasing SDF rates, including varicocele repair, have been explored to improve fertility and pregnancy outcomes potentially, either by natural conception or using medically assisted reproduction. Study design, size, duration Systematic review and meta-analysis Participants/materials, setting, methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our systematic search included PubMed/Medline, EMBASE, Scielo, and Google Scholar to identify all relevant studies written in English and published from inception until October 2020. Inclusion criteria were studies comparing SDF rates before and after varicocelectomy in infertile men with clinical varicocele. Articles were included if the following SDF assays were utilized: SCSA, TUNEL, SCD test, or alkaline Comet. Main results and the role of chance Thirteen studies fulfilled the inclusion criteria and were selected for the analysis. The estimated weighted mean difference of SDF rates after varicocelectomy was –6.58% (13 studies, 95% CI –8.33%, –4.84%; I2=90% p &lt; 0.0001). Subgroup analysis revealed a significant decrease in SDF rates using SCSA (eight studies, WMD –6.80%, 95% CI –9.31%, –4.28%; I2=89%, p &lt; 0.0001), and TUNEL (three studies, WMD –4.86%, 95% CI –7.38%, –2.34%; I2=89%, p &lt; 0.0001). The test for subgroup difference revealed that pooled results were conservative using the above SDF assays. Comet and SCD tests were used in only one study each; thus, a meta-analysis was not applicable. The studies were further categorized by the surgical technique (microsurgical versus non-microsurgical). This subgroup analysis showed a significant decrease in SDF rates using microsurgical technique (10 studies, WMD –6.70%, 95% CI –9.04%, –4.37%; I2=91%, p &lt; 0.0001). After varicocelectomy, SDF rates were also decreased when non-microsurgical approaches were used, albeit the effect was not statistically significant (2 studies, WMD –6.84%, 95% CI –10.05%, 1.38%; I2=86%) (Figure 3). The heterogeneity was not materially affected by performing analyses by the above subgroups, suggesting that the SDF assay and surgical technique do not explain the inconsistency in the treatment effect across primary studies. Limitations, reasons for caution There were no randomized controlled trials comparing varicocelectomy to placebo for alleviating SDF levels. Heterogeneity was high, which may be explained by the low number of included studies. Pregnancy data are not available in most studies, thus the impact of reduced SDF after varicocelectomy on pregnancy rates unclear. Wider implications of the findings: Our study indicates a positive association between varicocelectomy and reduced postoperative SDF rates in men with clinical varicocele and infertility, independentetly of the assays used to measure SDF. These findings may help counsel and manage infertile men with varicocele and high SDF levels. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Hervá. Herrero ◽  
A Pacheco ◽  
R Rivera-Egea ◽  
M Gi. Julia ◽  
A Navarro-Gomezlechon ◽  
...  

Abstract Study question Does sperm DNA fragmentation (SDF) reduce the ratio of good-quality embryos in day 3 (D3) and day 5 (D5) of embryonic development? Summary answer High sperm DNA fragmentation (SDF &gt;15%) is associated with poor embryo quality at blastocyst-stage per cycle in unselected patients undergoing IVF and ICSI. What is known already It has been shown that the proportion of spermatozoa with DNA fragmentation is higher in infertile men than in semen from fertile men. However, the controversy regarding the impact that sperm genome damage can have on IVF or ICSI treatments is evident in the published literature. The effects of SDF would become evident after activation of the embryonic genome at 8-cell stage, compromising not only the quality of the embryos obtained, but also the reproductive outcomes, as reduced implantation rates, higher miscarriages rates and thus, a decreased chance of pregnancy. Study design, size, duration This multicentric observational retrospective study included 1339 couples who underwent 2759 IVF-ICSI cycles using autologous oocytes from January 2000 to March 2019. All men have an SDF test in their ejaculated spermatozoa by TUNEL assay (Terminal deoxynucleotidyl transferase dUTP nick end labeling). The subjects were divided into two groups according to their sperm DNA integrity: low (≤15%) (n = 2287 cycles) or high (&gt;15%) (n = 472) SDF. Participants/materials, setting, methods Embryo quality was assessed complying morphological standards at cleavage-stage on D3 and at blastocyst-stage on D5 (inner cell mass (ICM) and trophectoderm (TE) grade (A, B, C or D)) in according to ASEBIR’s embryo selection criteria, being embryos of good quality those categorized as A+B. The outcomes were calculated in relation to the total number of zygotes obtained. The results were compared by Student t test; p value &lt;0.05 was considered significant. Main results and the role of chance The SDF average of the low group was 5.8% (95% CI 5.6–5.9) whereas in high group was 23.7% (95% CI 23.0–24.4). The female age was equal, 37.1 years (95%CI 37.0–37.2) and 37.1 years (95% CI 36.8–37.4) respectively. A total of 9796 embryos were evaluated. The optimal cleavage-stage embryo rate per cycle was 25.0% (95% CI 21.7–28.3) (8.0 average cells number, 1.5 embryo fragmentation average, symmetry 1, mononucleated cells) versus 26.7% (95%CI 19.1–34.2) (7.9 average cells number, 1.8 embryo fragmentation average, symmetry 1, mononucleated cells) when comparing between groups (p &lt; 0.001). Blastocyst-stage arrival rate (number of embryos at D5) per cycle was 55.8% (95% CI 54.3–57.2) in ≤ 15% SDF group (embryo quality score was ICM A:12.1%, B:69.5%, C:8.8%, D:4.5%; TE A: 7.5%, B:42.2%, C:42.2%, D:8.1%) and 55.9% (95% CI 52.8–59.1) in the &gt;15% SDF group (ICM A:12.0%, B:68.7%, C:10.6%, D: 5.2%; TE A:9.1%, B:44.8%, C:37.8%, D:8.3%) (p &lt; 0.001). The good quality blastocyst rate per cycle was significantly higher in the group with SDF ≤15%, 27.7% (95%CI 26.5–29.0) versus SDF &gt;15% (27.4% (95%CI 24.6–30.2)). Of the total number of blastocysts, the proportion of A+B blastocyst was 60.5% (95% CI 58.3–62.7) and 64.2% (95% CI 59.2–69.2) (p &lt; 0.001), respectively. Limitations, reasons for caution The retrospective and multicenter nature of this study leads to uncontrolled biases derived from the clinical practice. Although the results were not adjusted for female’s age, it was not statistically different between groups. Embryo morphology evaluation was performed by senior embryologists, it still remains a subjective evaluation, though. Wider implications of the findings: In this study, a higher amount of data was compiled so that a large number of embryos were analyzed. The DNA integrity of the sperm may be an important consideration when poor quality embryos were obtained in the previous cycle when deciding on the next clinical strategy to apply. Trial registration number NA


2020 ◽  
Vol 114 (3) ◽  
pp. e372
Author(s):  
Assumpto Iaconelli ◽  
Daniela Paes de Almeida Ferreira Braga ◽  
Amanda Souza Setti ◽  
Rodrigo Rosa Provenza ◽  
Joana Noguères Simas ◽  
...  

2019 ◽  
Vol 300 (1) ◽  
pp. 207-215 ◽  
Author(s):  
Sevastiani Antonouli ◽  
Achilleas Papatheodorou ◽  
Yannis Panagiotidis ◽  
Stamatios Petousis ◽  
Nikos Prapas ◽  
...  

2015 ◽  
Vol 21 (1) ◽  
pp. 109-122 ◽  
Author(s):  
Monica Muratori ◽  
Lara Tamburrino ◽  
Sara Marchiani ◽  
Marta Cambi ◽  
Biagio Olivito ◽  
...  

2019 ◽  
Vol 39 (6) ◽  
pp. 955-962 ◽  
Author(s):  
Xiaolei Liang ◽  
Yifang Mao ◽  
Yiqing Wang ◽  
Shan Liu ◽  
Jiexi Yan

2016 ◽  
Vol 44 (6) ◽  
pp. 1283-1291 ◽  
Author(s):  
Lin-Tao Xue ◽  
Rui-Xue Wang ◽  
Bing He ◽  
Wei-Ying Mo ◽  
Li Huang ◽  
...  

Objective To investigate the effect of sperm DNA fragmentation on the fertilization rate, embryo development and pregnancy outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in a cohort of Chinese couples. Methods Infertile couples that had undergone assisted reproductive technology at our centre between January 2011 and December 2013 were included in this retrospective study. Fractions of prepared sperm samples were evaluated for sperm DNA fragmentation on the day of oocyte recovery. Results Of the 550 couples selected, 415 had undergone IVF and 135 ICSI. Sperm DNA fragmentation rate was significantly negatively correlated with the fertilization rate in the ICSI cycles but not the IVF cycles. No association was found between sperm DNA fragmentation and cleavage rate or good quality embryo formation rates in IVF or ICSI cycles. Receiver operating characteristic (ROC) curve analysis showed that the sperm DNA fragmentation rate was a statistically significant prognostic indicator of the clinical fertilization rate in ICSI cycles; a rate > 22.3% was associated with a lower fertilization rate following ICSI compared with a rate ≤ 22.3%. Conclusions High values of sperm DNA fragmentation were associated with a low fertilization rate following ICSI but were not associated with alterations in pregnancy or live birth rates in either ICSI or IVF in this cohort of Chinese couples.


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