背景:据推测,精子DNA片段化(SDF)在复发性妊娠丢失(RPL)的发病机制中起作用。不幸的是,已经发表的证据质量很低。
目的:通过尽可能限制混杂因素的干扰来研究SDF与特发性RPL之间的关系材料和方法:这是一项在意大利两家大学医院进行的回顾性多中心病例对照研究(即警察杰梅利,罗马和HumanitasS.PioX,米兰)从2020年7月到2022年3月。病例是属于受妊娠早期特发性RPL影响的夫妇的男性,RPL定义为先前失去两次或更多次妊娠。选择了两个对照组:i)属于具有证实生育能力的夫妇的男性(即,至少两次先前的足月怀孕)(对照组A);ii)属于已证实不孕症的夫妇的男性(即,在12个月或更长时间的常规无保护性交后未能实现妊娠)(对照组B)。SDF指数(sDFI)通过末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)测定来测量。
结果:我们包括74例,37名具有生育能力的男性(对照组A)和100名不育夫妇的男性(对照组B)。对照组A的sDFI中位数显着降低(17%,四分位数间距(IQR):14.3-20.6%)与两个病例组(24.5%,IQR:17-32%;p<0.0001)和对照组B(24%,IQR:18.9-30%;p=0.001)。在两个病例组中,sDFI>30%的受试者的比率显著高于(28%,95%置信区间(CI)[18,40%])和对照组B(26%,95CI[18,36%])与对照组A(0%,95%CI[0,10%])(p<0.001)。多变量回归模型在sDFI和RPL之间产生了显著关联(调整后的比值比(aOR)1.13,95CI[1.04,1.23],p=0.006),但未能显示sDFI与不孕症之间的关联(aOR1.13,95CI[1,1.29],p=0.05)。
结论:受RPL或不育症影响的夫妇中,男性的SDF发生率明显高于育龄对照组。然而,在调整协变量后,sDFI仅与RPL相关。本文受版权保护。保留所有权利。
Sperm DNA fragmentation was hypothesized to have a role in the pathogenesis of recurrent pregnancy loss. Unfortunately, the quality of already published evidence is low.
To investigate the association between sperm DNA fragmentation and idiopathic recurrent pregnancy loss by limiting, as much as possible, the interference of confounding factors.
This was a retrospective multicenter case-control study conducted in two Italian University Hospitals (i.e., Policlinico Gemelli, Rome and Humanitas S. Pio X, Milan) from July 2020 to March 2022. Cases were men belonging to couples affected by first trimester idiopathic recurrent pregnancy loss, defined as the previous loss of two or more pregnancies. Two control groups were selected: (i) men belonging to couples with proven fertility (i.e., at least two previous full-term pregnancies) (control group A); (ii) men belonging to couples with proven infertility (i.e., the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse) (control group B). The sperm DNA fragmentation index was measured by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay.
We included 74 cases, 37 men with proven fertility (control group A) and 100 men belonging to infertile couples (control group B). The median sperm DNA fragmentation index was significantly lower in control group A (17%, interquartile range: 14.3%-20.6%) compared to both case group (24.5%, interquartile range: 17%-32%; p < 0.0001) and control group B (24%, interquartile range: 18.9%-30%; p = 0.001). The rate of subjects with sperm DNA fragmentation index greater than 30% was significantly higher in both case groups (28%, 95% confidence interval [18%-40%]) and control group B (26%, 95% confidence interval [18%, 36%]) compared to control group A (0%, 95% confidence interval [0%-10%]) (p < 0.001). Multivariate regression models yielded a significant association between sperm DNA fragmentation index and recurrent pregnancy loss (adjusted odds ratio 1.13, 95% confidence interval [1.04-1.23], p = 0.006), but failed to show an association between sperm DNA fragmentation index and infertility (adjusted odds ratio 1.13, 95% CI [1-1.29], p = 0.05).
Men within couples affected by recurrent pregnancy loss or infertility had a significantly higher rate of sperm DNA fragmentation compared to fertile controls. However, after adjusting for covariates, sperm DNA fragmentation index was associated only with recurrent pregnancy loss.