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在染色体风险增加的两种情况下,即高龄患者和体外受精后反复种植失败的患者,卵母细胞非整倍体机制有所不同。

Oocyte aneuploidy mechanisms are different in two situations of increased chromosomal risk: older patients and patients with recurrent implantation failure after in vitro fertilization.

作者信息

Vialard François, Lombroso R, Bergere M, Gomes D Molina, Hammoud I, Bailly M, Selva J

机构信息

Department of Reproductive Biology, Centre Hospitalier Intercommunal de Poissy St-Germain 78, Poissy, France.

出版信息

Fertil Steril. 2007 Jun;87(6):1333-9. doi: 10.1016/j.fertnstert.2006.11.042. Epub 2007 May 7.

Abstract

OBJECTIVE

To clarify the mechanisms underlying oocyte abnormalities in meiosis: meiotic nondisjunction of a whole chromosome or premature separation of sister chromatids in two situations of increased chromosomal risk.

DESIGN

Preconception diagnosis by first polar-body analysis in two situations of increased chromosomal risk.

SETTING

Departments of reproductive biology, cytogenetics, gynecology, and obstetrics.

PATIENT(S): First polar body analysis was proposed to 76 patients (91 cycles) for advanced age (AMA; n = 30, 36 cycles), recurrent implantation failure (RIF; >10 embryos transferred without implantation; n = 32, 36 cycles), or both (AMA + RIF; n = 14, 19 cycles), before their intracytoplasmic sperm injection procedure.

INTERVENTION(S): First polar-body analysis using fluorescence in situ hybridization.

MAIN OUTCOME MEASURE(S): Mechanisms and frequency of aneuploidy.

RESULT(S): Three hundred eighty-four oocytes were analyzed by fluorescence in situ hybridization, 130 from women >38 years of age, 171 from women with RIF, and 83 from women with both indications. The oocyte abnormality rate was similar in the three groups, respectively, 38.5%, 40.4%, and 45.8%. The aneuploidy mechanisms were different for women >38 years of age who had no previous implantation failure (AMA) compared with women of whatever age who had implantation failure (P<.05 vs. RIF; P<.001 vs. AMA+RIF), with, respectively, for the AMA, RIF, and AMA+RIF groups, 72.2%, 56.6%, and 49.2% premature separation of sister chromatids and 27.8%, 43.4%, and 50.8% meiotic nondisjunction. In the two implantation-failure groups, we distinguished a subgroup (22% in the RIF group and 33% in AMA+RIF group) of patients with >2/3 abnormal oocytes, suggesting a meiosis alteration.

CONCLUSION(S): The mechanisms accounting for oocyte aneuploidy differed in the two clinical situations of advanced maternal age and RIF. Advanced maternal-age aneuploidy was linked to a loss of sister chromatid cohesion that led to one single chromatid abnormality, whereas implantation failure is a much more heterogeneous situation.

摘要

目的

阐明减数分裂过程中卵母细胞异常的潜在机制:在两种染色体风险增加的情况下,整条染色体的减数分裂不分离或姐妹染色单体的过早分离。

设计

在两种染色体风险增加的情况下,通过第一极体分析进行孕前诊断。

地点

生殖生物学、细胞遗传学、妇科和产科科室。

患者

对76例患者(91个周期)进行了第一极体分析,这些患者因高龄(AMA;n = 30,36个周期)、反复种植失败(RIF;移植超过10个胚胎未着床;n = 32,36个周期)或两者皆有(AMA + RIF;n = 14,19个周期),在其卵胞浆内单精子注射手术前进行。

干预措施

使用荧光原位杂交进行第一极体分析。

主要观察指标

非整倍体的机制和频率。

结果

通过荧光原位杂交分析了384个卵母细胞,其中130个来自年龄大于38岁的女性,171个来自反复种植失败的女性,83个来自具有两种指征的女性。三组的卵母细胞异常率相似,分别为38.5%、40.4%和45.8%。与有种植失败史的任何年龄女性相比,既往无种植失败史(AMA)的38岁以上女性的非整倍体机制不同(与RIF相比P<0.05;与AMA + RIF相比P<0.001),AMA组、RIF组和AMA + RIF组中姐妹染色单体过早分离分别为72.2%、56.6%和49.2%,减数分裂不分离分别为27.8%、43.4%和50.8%。在两个种植失败组中,我们区分出一个亚组(RIF组中占22%,AMA + RIF组中占33%),其卵母细胞异常率超过2/3,提示减数分裂改变。

结论

在高龄产妇和反复种植失败这两种临床情况下,卵母细胞非整倍体的机制不同。高龄产妇的非整倍体与姐妹染色单体凝聚力丧失有关,导致单一染色单体异常,而种植失败则是一种更为异质性的情况。

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