Variation of DNA Fragmentation Levels During Density Gradient Sperm Selection for Assisted Reproduction Techniques: A Possible New Male Predictive Parameter of Pregnancy?

Variation of DNA Fragmentation Levels During Density Gradient Sperm Selection for Assisted Reproduction Techniques: A Possible New Male Predictive Parameter of Pregnancy?
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DOI:
10.1097/md.0000000000003624
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发表时间:
2016-05
期刊:
影响因子:
1.6
通讯作者:
Borini A
Borini A
中科院分区:
医学4区
文献类型:
--
作者:
Muratori M;Tarozzi N;Cambi M;Boni L;Iorio AL;Passaro C;Luppino B;Nadalini M;Marchiani S;Tamburrino L;Forti G;Maggi M;Baldi E;Borini A

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预测体外受精(IVF)/卵胞浆内单精子注射(ICSI)的结局是目前辅助生殖研究的主要目标之一。为了解密度梯度离心法(DGC)对精子DNA完整性和妊娠率(PR)的影响,我们前瞻性地评价了密度梯度离心法(DGC)前后精子DNA片段(SDF)的变化。在接受IVF/ICSI治疗的同一天,对90对不育夫妇进行了SDF研究。DGC后SDF增加41例(A组,SDF中位数:29.25%[四分位数范围,IQR:16.01~41.63],DGC后SDF增加60.40%[IQR:32.92~93.53];B组,SDF下降49例,DGC前:18.84%[IQR:13.70~35.47],IQR:8.98%[IQR:6.24~15.58])。A组和B组PR分别为17.1%和34.4%(优势比[OR]:2.58,95%可信区间[CI]:0.95~7.04,P = 0.056)。在调整了女性因素、男女年龄和女性体重指数后,估计的OR增加到3.12(95%CI:1.0 5~9.2 7,P = 0.041)。根据有无女性因素的亚组分析,A、B组与PR的关联存在异质性(无女性因素n = 59和有女性因素n = 31的OR分别为4.22,95%CI:1.16~15.30和OR:1.53,95%CI:0.23~10.40)。这项研究提供了第一个证据,表明DGC程序会增加大约一半接受IVF/ICSI的受试者的SDF,这些受试者的怀孕概率要低得多,这引发了人们对这种选择程序的安全性的担忧。评估DGC前后的SDF可作为预测IVF/ICSI妊娠结局的新指标。对于DGC后遭受损伤的受试者,建议采用替代的精子选择策略。
Predicting the outcome of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) is one main goal of the present research on assisted reproduction. To understand whether density gradient centrifugation (DGC), used to select sperm, can affect sperm DNA integrity and impact pregnancy rate (PR), we prospectively evaluated sperm DNA fragmentation (sDF) by TUNEL/PI, before and after DGC. sDF was studied in a cohort of 90 infertile couples the same day of IVF/ICSI treatment. After DGC, sDF increased in 41 samples (Group A, median sDF value: 29.25% [interquartile range, IQR: 16.01–41.63] in pre- and 60.40% [IQR: 32.92–93.53] in post-DGC) and decreased in 49 (Group B, median sDF value: 18.84% [IQR: 13.70–35.47] in pre- and 8.98% [IQR: 6.24–15.58] in post-DGC). PR was 17.1% and 34.4% in Group A and B, respectively (odds ratio [OR]: 2.58, 95% confidence interval [CI]: 0.95–7.04, P = 0.056). After adjustment for female factor, female and male age and female BMI, the estimated OR increased to 3.12 (95% CI: 1.05–9.27, P = 0.041). According to the subgroup analysis for presence/absence of female factor, heterogeneity in the association between the Group A and B and PR emerged (OR: 4.22, 95% CI: 1.16–15.30 and OR: 1.53, 95% CI: 0.23–10.40, respectively, for couples without, n = 59, and with, n = 31, female factor). This study provides the first evidence that the DGC procedure produces an increase in sDF in about half of the subjects undergoing IVF/ICSI, who then show a much lower probability of pregnancy, raising concerns about the safety of this selection procedure. Evaluation of sDF before and after DGC configures as a possible new prognostic parameter of pregnancy outcome in IVF/ICSI. Alternative sperm selection strategies are recommended for those subjects who undergo the damage after DGC.