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父亲年龄与非整倍体率之间是否存在相关性?对 3118 个来自年轻卵子供体的胚胎进行的分析。

Is there a correlation between paternal age and aneuploidy rate? An analysis of 3,118 embryos derived from young egg donors.

机构信息

CReATe Fertility Centre, Toronto, Ontario Canada; Department of Obstetrics and Gynecology, Women's College Hospital, Toronto, Ontario Canada.

CReATe Fertility Centre, Toronto, Ontario Canada.

出版信息

Fertil Steril. 2020 Aug;114(2):293-300. doi: 10.1016/j.fertnstert.2020.03.034. Epub 2020 Jul 9.

DOI:10.1016/j.fertnstert.2020.03.034
PMID:32654815
Abstract

OBJECTIVE

To investigate a possible correlation between chromosomal aberrations and paternal age, analyzing embryos derived from young oocyte donors, with available preimplantation genetic testing for aneuploidy results from day 5/6 trophectoderm biopsy obtained by next-generation sequencing for all 24 chromosomes.

DESIGN

Retrospective cohort study.

SETTING

Canadian fertility centre.

PATIENT(S): A total of 3,118 embryos from 407 male patients, allocated into three paternal age groups: group A, ≤39 years (n = 203); group B, 40-49 years (n = 161); group C, ≥50 years (n = 43).

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): The primary outcomes were aneuploidy, euploidy, mosaicism, and blastocyst formation rates. Secondary endpoints were comparison of specific chromosome aneuploidy, segmental and complex (involving two chromosomes + mosaicism >50%) aneuploidy, and analysis of overall percentage of chromosomal gains and losses within each group.

RESULT(S): The study included 437 in vitro fertilization (IVF) antagonist cycles using 302 oocyte donors in which preimplantation genetic testing for aneuploidy was performed. Overall, 70.04% of embryos were euploid, 13.9% were aneuploid, and 16.06% were mosaic. No significant differences among paternal age groups A, B, and C were found in euploidy rates (69.2%, 70.6%, 71.4%, respectively), aneuploidy rates (14.7%, 12.8%, 13.9%, respectively) or mosaicism rates (16.1%, 16.6%, 13.6%; respectively). The fertilization rate was lower in group C compared with group B (76.35% vs. 80.09%). No difference was found in blastocyst formation rate between the study groups (median 52% [interquartile range, 41%, 67%] vs. 53% [42%, 65%] vs. 52% [42%, 64%], respectively). A generalized linear mixed model regression analysis for embryo ploidy rates found older oocyte donor age to be independently associated with embryo aneuploidy (odds ratio = 1.041; 95% CI, 1.009-1.074). The rate of segmental aneuploidies was significantly higher in the older versus younger paternal age group (36.6% vs. 19.4%).

CONCLUSION(S): No association was found between paternal age and aneuploidy rates in embryos derived from IVF cycles using young oocyte donors, after adjusting for donor, sperm, and IVF cycle characteristics. Advanced paternal age ≥ 50, compared with younger paternal ages, was associated with a lower fertilization rate and increased rate of segmental aberrations.

摘要

目的

通过分析来自年轻卵母细胞供体的胚胎,探讨染色体畸变与父龄之间的可能相关性,这些胚胎可通过下一代测序对第 5/6 天的滋养外胚层进行胚胎植入前遗传学检测,获得所有 24 条染色体的非整倍体结果。

设计

回顾性队列研究。

地点

加拿大生育中心。

患者

407 名男性患者的共 3118 个胚胎,分为三组:A 组,≤39 岁(n = 203);B 组,40-49 岁(n = 161);C 组,≥50 岁(n = 43)。

干预措施

无。

主要观察指标

主要结局为非整倍体、整倍体、嵌合体和囊胚形成率。次要终点为比较特定染色体非整倍体、节段性和复杂性(涉及两条染色体+嵌合体>50%)非整倍体,并分析每组内染色体整体增益和缺失的百分比。

结果

本研究纳入了 437 个采用抗结剂方案的体外受精(IVF)周期,其中有 302 个卵母细胞供体进行了胚胎植入前遗传学检测非整倍体。总体而言,70.04%的胚胎为整倍体,13.9%为非整倍体,16.06%为嵌合体。在 A、B 和 C 组中,父龄与整倍体率(分别为 69.2%、70.6%、71.4%)、非整倍体率(分别为 14.7%、12.8%、13.9%)或嵌合体率(分别为 16.1%、16.6%、13.6%)均无显著差异。与 B 组相比,C 组的受精率较低(76.35%比 80.09%)。研究组之间的囊胚形成率无差异(中位数 52%[四分位距,41%,67%]比 53%[42%,65%]比 52%[42%,64%])。胚胎倍性率的广义线性混合模型回归分析发现,卵母细胞供体年龄越大,胚胎非整倍体的可能性越高(优势比=1.041;95%可信区间,1.009-1.074)。与年轻父龄组相比,年龄较大的父龄组节段性非整倍体发生率显著更高(36.6%比 19.4%)。

结论

在调整了供体、精子和 IVF 周期特征后,我们发现,使用年轻卵母细胞供体的 IVF 周期中,父龄与胚胎非整倍体率之间无关联。与年轻父龄相比,高龄≥50 岁与受精率降低和节段性畸变发生率增加有关。

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