BACKGROUND Miscarriage describes the spontaneous loss of pregnancy before the threshold of viability; the vast majority occur before 12 weeks of gestation. Miscarriage affects one in four couples and is the most common complication of pregnancy. Chromosomal abnormalities of the embryo are identified in ∼50% of first trimester miscarriages; aneuploidy accounts for 86% of these cases. The majority of trisomic miscarriages are of maternal origin with errors occurring during meiotic division of the oocytes. Chromosome segregation errors in oocytes may be sporadic events secondary to advancing maternal age; however, there is increasing evidence to suggest possible maternal germline contributions to this. OBJECTIVE AND RATIONALE The objective of this review was to appraise critically the existing evidence relating to maternal germline factors associated with pregnancy loss secondary to embryo aneuploidy, identify limitations in the current evidence base and establish areas requiring further research. SEARCH METHODS The initial literature search was performed in September 2019 and updated in January 2021 using the electronic databases OVID MEDLINE, EMBASE and the Cochrane Library. No time or language restrictions were applied to the searches and only primary research was included. Participants were women who had suffered pregnancy loss secondary to numerical chromosomal abnormalities of the embryo. Study identification and subsequent data extraction were performed by two authors independently. The Newcastle–Ottawa Scale was used to judge the quality of the included studies. The results were synthesized narratively. OUTCOMES The literature search identified 2198 titles once duplicates were removed, of which 21 were eligible for inclusion in this systematic review. They reported on maternal germline factors having variable degrees of association with pregnancy loss of aneuploid origin. The Online Mendelian Inheritance in Man (OMIM) gene ontology database was used as a reference to establish the functional role currently attributed to the genes reported. The majority of the cases reported and included were secondary to the inheritance of maternal structural factors such as Robertsonian translocations, deletions and insertions. Germline factors with a plausible role in aneuploid pregnancy loss of maternal origin included skewed X-inactivation and CGG repeats in the fragile X mental retardation (FMR1) gene. Studies that reported the association of single gene mutations with aneuploid pregnancy loss were conflicting. Single gene mutations with an uncertain or no role in aneuploid pregnancy loss included mutations in synaptonemal complex protein 3 (SYCP3), mitotic polo-like kinase 4 (PLK4) and meiotic stromal antigen 3 (STAG3) spindle integrity variants and 5,10-methylenetetrahydrofolate reductase (MTHFR). WIDER IMPLICATIONS Identifying maternal genetic factors associated with an increased risk of aneuploidy will expand our understanding of cell division, non-disjunction and miscarriage secondary to embryo aneuploidy. The candidate germline factors identified may be incorporated in a screening panel for women suffering miscarriage of aneuploidy aetiology to facilitate counselling for subsequent pregnancies.

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与非整倍体流产相关的母体生殖系因素：系统评价

背景 流产描述了在生存能力阈值之前的自发性流产。绝大多数发生在妊娠 12 周之前。流产影响四分之一的夫妇，是最常见的妊娠并发症。约 50% 的妊娠早期流产中发现了胚胎染色体异常；非整倍体占这些病例的 86%。大多数三体流产是母体起源的，在卵母细胞减数分裂期间发生错误。卵母细胞中的染色体分离错误可能是继发于母体年龄增长的偶发事件；然而，越来越多的证据表明母体种系可能对此做出了贡献。目的和理由 本综述的目的是批判性地评估与继发于胚胎非整倍体的妊娠丢失相关的母体生殖系因素的现有证据，确定当前证据基础的局限性并确定需要进一步研究的领域。检索方法 最初的文献检索于 2019 年 9 月进行，并于 2021 年 1 月使用电子数据库 OVID MEDLINE、EMBASE 和 Cochrane 图书馆进行更新。搜索没有时间或语言限制，只包括初级研究。参与者是因胚胎数量染色体异常而遭受流产的妇女。研究鉴定和随后的数据提取由两位作者独立进行。采用纽卡斯尔-渥太华量表来判断纳入研究的质量。结果以叙述方式综合。结果 删除重复后，文献检索确定了 2198 个标题，其中 21 个符合纳入本系统评价的条件。他们报告了与非整倍体来源的妊娠丢失具有不同程度关联的母体生殖系因素。在线人类孟德尔遗传 (OMIM) 基因本体数据库被用作参考来确定目前归因于所报告基因的功能作用。报告和纳入的大多数病例继发于母体结构因素的遗传，例如罗伯逊易位、缺失和插入。在母体来源的非整倍体妊娠丢失中具有合理作用的种系因素包括偏斜的 X 失活和脆性 X 智力迟钝 (FMR1) 基因中的 CGG 重复。报告单基因突变与非整倍体流产相关的研究相互矛盾。单基因突变在非整倍体妊娠丢失中的作用不确定或没有作用，包括联会复合蛋白 3 (SYCP3)、有丝分裂 polo 样激酶 4 (PLK4) 和减数分裂基质抗原 3 (STAG3) 纺锤体完整性变异体和 5,10-亚甲基四氢叶酸突变还原酶（MTHFR）。更广泛的意义 识别与非整倍体风险增加相关的母体遗传因素将扩大我们对胚胎非整倍体继发的细胞分裂、不分离和流产的理解。