State of the Art for Genetic Testing of Infertile Men
State of the Art for Genetic Testing of Infertile Men
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DOI：
10.1210/jc.2009-1925
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发表时间：
2010-03-01
影响因子：
5.8
通讯作者：
O'Bryan, Moira K.
中科院分区：
文献类型：
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作者：
McLachlan, Robert I.;O'Bryan, Moira K.
卵胞浆内单精子注射（ICSI）现在为许多严重的特发性生精障碍和梗阻性无精子症患者提供了生育能力。遗传原因必须通过对不育男性和受影响夫妇进行系统评估来寻找，并了解此类诊断对辅助生殖技术结果及其潜在后代的影响。这篇综述讨论了与生育实践有关的已建立和新出现的遗传疾病。在约7%的特发性生精障碍男性中发现染色体异常，主要是无精子症男性的数量/结构和少精子症男性的易位/倒位。对于精子密度低于1000万/ml的男性，即使没有其他临床表现，也建议进行常规核型分析，因为不育与射出精子或睾丸精子的非整倍体率较高以及ICSI后代染色体缺陷增加有关。Y染色体长臂微缺失是最常见的公认的不育遗传原因，约4%的男性精子密度低于500万/ml。建议使用严格的质量保证程序进行常规检测。无精子因子（AZF）-c缺失是Y染色体长臂微缺失的最常见形式，通常与射精或睾丸活检中精子水平低相关，而AZF a或AZF b +c缺失的男性通常不产生睾丸精子。当AZF缺失的精子可用并用于ICSI时，男性后代的生育缺陷似乎不可避免。双侧先天性输精管缺如与囊性纤维化跨膜受体突变的杂合性有关，因此对这对夫妇进行常规基因筛查和遗传咨询至关重要。与不同生殖功能障碍相关的不太常见的遗传关联/缺陷检测可能适用于特定患者，但尚未进入常规实践。（临床内分泌代谢杂志95：1013-1024，2010）
Intracytoplasmic sperm injection (ICSI) now provides fertility in many cases of severe idiopathic spermatogenic failure and obstructive azoospermia. Genetic causes must be sought by systematic evaluation of infertile men and affected couples informed about the implications of such diagnoses for assisted reproductive technology outcome and their potential offspring. This review discusses established and emerging genetic disorders related to fertility practice. Chromosomal anomalies are found in about 7% men with idiopathic spermatogenic failure, predominantly numerical/structural in azoospermic men and translocations/inversions in oligospermic men. Routine karyo-typing of men with sperm densities less than 10 million/ml, even in the absence of other clinical presentations, is recommended because infertility is associated with higher rates of aneuploidy in ejaculated or testicular sperm and increased chromosomal defects in ICSI offspring. The long arm of the Y chromosome microdeletions are the most common recognized genetic cause of infertility and are found in about 4% men with sperm densities less than 5 million/ml. Routine testing using strict quality assurance procedures is recommended. Azoospermia factor (AZF)-c deletions, the most common form of the long arm of the Y chromosome microdeletions, are usually associated with low levels of sperm in the ejaculate or in testis biopsies, whereas men with AZFa or AZFb+c deletions usually produce no testicular sperm. When AZF-deleted sperm are available and used for ICSI, fertility defects in male offspring seem inevitable. Bilateral congenital absence of the vas is associated with heterozygosity for cystic fibrosis transmembrane receptor mutations making routine gene screening and genetic counseling of the couple essential. Testing for less common genetic associations/defects linked with different reproductive dysfunction may be applicable to specific patients but have not entered routine practice. (J Clin Endocrinol Metab 95: 1013-1024, 2010)