Genetic diagnosis, sperm phenotype and ICSI outcome in case of severe asthenozoospermia with multiple morphological abnormalities of the flagellum
Genetic diagnosis, sperm phenotype and ICSI outcome in case of severe asthenozoospermia with multiple morphological abnormalities of the flagellum
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DOI：
10.1093/humrep/deab200
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发表时间：
2021-09-16
影响因子：
6.1
通讯作者：
Patrat, Catherine
中科院分区：
文献类型：
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作者：
Ferreux, Lucile;Bourdon, Mathilde;Patrat, Catherine
研究问题：在具有多种鞭毛形态异常（MMAF 表型）的严重弱精子症病例中，ICSI 结果是否会受到损害？总结答案：尽管偶尔会出现技术困难，但无论遗传缺陷如何，患有 MMAF 的夫妇的 ICSI 结果与其他需要 ICSI 的夫妇没有差异。 已知情况： 严重弱精子症，尤其是与MMAF 表型，导致男性不育。最近的研究结果证实，遗传病因通常是造成这种表型的原因。在这种情况下，可以使用 ICSI 来实现妊娠。然而，迄今为止，很少有研究对该表型背后的鞭毛超微结构缺陷、其遗传病因以及此类男性不育病例中的 ICSI 结果进行详细分析。 研究设计、规模、持续时间：我们对 25 名表现出与通过标准精液分析确定的 MMAF 表型相关的严重弱精子症的不育男性进行了回顾性研究。他们于 2009 年至 2017 年间在巴黎（法国）的辅助生殖学术中心招募。使用透射电子显微镜 (TEM) 和全外显子组测序 (WES) 分别确定精子超微结构表型和因果突变。最后，20 对患有 MMAF 的夫妇接受了基于 ICSI 的辅助生殖技术。 参与者/材料、环境、方法：与具有生育能力的对照男性的精子相比，由于精子前行活力降低以及鞭毛缺失、短、卷曲或不规则的频率增加，因此招募了 MMAF 患者。对 MMAF 患者和生育男性的几种超微结构缺陷进行了定量分析。将 20 对患有 MMAF 的夫妇获得的 ICSI 结果与 378 名患有少弱精子症但没有 MMAF 的男性作为 ICSI 对照组进行比较。主要结果和机会的作用：这些患者中发现的鞭毛异常的 TEM 分析和分类提供了有关弱精子症和精子尾部异常的结构缺陷的重要信息。特别是，中央一对轴丝微管的缺失是比对照精子更常见的主要异常现象（P
STUDY QUESTION: Are ICSI outcomes impaired in cases of severe asthenozoospermia with multiple morphological abnormalities of the flagellum (MMAF phenotype)?SUMMARY ANSWER: Despite occasional technical difficulties, ICSI outcomes for couples with MMAF do not differ from those of other couples requiring ICSI, irrespective of the genetic defect.WHAT IS KNOWN ALREADY: Severe asthenozoospermia, especially when associated with the MMAF phenotype, results in male infertility. Recent findings have confirmed that a genetic aetiology is frequently responsible for this phenotype. In such situations, pregnancies can be achieved using ICSI. However, few studies to date have provided detailed analyses regarding the flagellar ultrastructural defects underlying this phenotype, its genetic aetiologies, and the results of ICSI in such cases of male infertility.STUDY DESIGN, SIZE, DURATION: We performed a retrospective study of 25 infertile men exhibiting severe asthenozoospermia associated with the MMAF phenotype identified through standard semen analysis. They were recruited at an academic centre for assisted reproduction in Paris (France) between 2009 and 2017. Transmission electron microscopy (TEM) and whole exome sequencing (WES) were performed in order to determine the sperm ultrastructural phenotype and the causal mutations, respectively. Finally 20 couples with MMAF were treated by assisted reproductive technologies based on ICSI.PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with MMAF were recruited based on reduced sperm progressive motility and increased frequencies of absent, short, coiled or irregular flagella compared with those in sperm from fertile control men. A quantitative analysis of the several ultrastructural defects was performed for the MMAF patients and for fertile men. The ICSI results obtained for 20 couples with MMAF were compared to those of 378 men with oligoasthenoteratozoospermia but no MMAF as an ICSI control group.MAIN RESULTS AND THE ROLE OF CHANCE: TEM analysis and categorisation of the flagellar anomalies found in these patients provided important information regarding the structural defects underlying asthenozoospermia and sperm tail abnormalities. In particular, the absence of the central pair of axonemal microtubules was the predominant anomaly observed more frequently than in control sperm (P