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母亲年龄是否会影响整倍体胚胎移植后辅助生殖技术的成功率?系统评价和荟萃分析。

Does maternal age affect assisted reproduction technology success rates after euploid embryo transfer? A systematic review and meta-analysis.

机构信息

Department of Women and Children's Health, Unit of Gynecology and Obstetrics, University of Padua, Padua, Italy.

Infertility Unit, ASST Lariana, Cantù (Como), Italy.

出版信息

Fertil Steril. 2023 Aug;120(2):251-265. doi: 10.1016/j.fertnstert.2023.02.036. Epub 2023 Mar 5.

DOI:10.1016/j.fertnstert.2023.02.036
PMID:36878347
Abstract

IMPORTANCE

Maternal age-related embryo aneuploidy is considered the most significant limiting factor for a favorable outcome after assisted reproduction technology (ART) procedures. Thus, preimplantation genetic testing for aneuploidies has been proposed as a strategy to genetically evaluate embryos before transfer to the uterus. However, whether embryo ploidy justifies all the aspects of age-related fertility decline remains controversial.

OBJECTIVE

To investigate the effect of different maternal ages on ART success rates after transfer of euploid embryos.

DATA SOURCES

ScienceDirect, PubMed, Scopus, Embase, the Cochrane library, Clinicaltrials.gov, EU Clinical Trials Register, and World Health Organization International Clinical Trials Registry were searched from inception until November 2021 using combinations of relevant keywords.

STUDY SELECTION AND SYNTHESIS

Observational and randomized controlled studies were included if they investigated the impact of maternal age on ART outcomes after the transfer of euploid embryos and reported frequencies of women achieving ongoing pregnancy or live birth.

MAIN OUTCOMES

The ongoing pregnancy rate or live birth rate (OPR/LBR) after euploid embryo transfer comparing women <35 vs. women ≥35 years old was the primary outcome. Secondary outcomes included implantation rate and miscarriage rate. Subgroup and sensitivity analyses were also planned to explore the sources of inconsistency among studies. The quality of studies was assessed using a modified version of the Newcastle-Ottawa Scale, and body of evidence was evaluated using the Grading of Recommendations Assessment Development and Evaluation working group methodology.

RESULTS

A total of 7 studies were included (n = 11,335 ART embryo transfers of euploid embryos). A higher OPR/LBR (odds ratio, 1.29; 95% confidence interval [CI], 1.07-1.54; I = 40%) in women aged <35 years than in women ≥35 with a risk difference equal to 0.06 (95% CI, 0.02-0.09) was found. In line, implantation rate was higher in the youngest group (odds ratio, 1.22; 95% CI, 1.12-1.32; I = 0%). A statistically significant higher OPR/LBR was also found comparing women aged <35 to women 35-37, 38-40, or 41-42. A gradient relationship between age and OPR/LBR could be observed in proportion meta-analysis, especially if restricted to studies with low risk of bias.

CONCLUSION AND RELEVANCE

Increasing maternal age is associated with a decline in ART success rates independent of embryo ploidy. This message contributes to an appropriate patient's counseling before starting preimplantation genetic testing for aneuploidies procedures.

PROSPERO REGISTRATION NUMBER

CRD42021289760.

摘要

重要性

胚胎非整倍体与母体年龄相关,被认为是辅助生殖技术(ART)后获得良好结果的最显著限制因素。因此,胚胎植入前遗传学检测已被提议作为一种在胚胎转移到子宫之前对其进行遗传评估的策略。然而,胚胎倍性是否能解释与年龄相关的生育能力下降的所有方面仍存在争议。

目的

探讨不同母体年龄对胚胎整倍体转移后 ART 成功率的影响。

数据来源

从建库至 2021 年 11 月,通过相关关键词的组合,在 ScienceDirect、PubMed、Scopus、Embase、Cochrane 图书馆、Clinicaltrials.gov、EU 临床试验注册处和世界卫生组织国际临床试验注册平台上搜索了观察性和随机对照研究。

研究选择和综合

如果研究调查了母体年龄对胚胎整倍体转移后 ART 结局的影响,并报告了实现持续妊娠或活产的女性频率,则纳入观察性和随机对照研究。

主要结局

比较<35 岁与≥35 岁女性胚胎整倍体转移后的持续妊娠率或活产率(OPR/LBR)是主要结局。次要结局包括着床率和流产率。还计划进行亚组和敏感性分析,以探讨研究间不一致的来源。使用改良的纽卡斯尔-渥太华量表评估研究质量,使用推荐评估、制定与评价工作组方法评估证据质量。

结果

共纳入 7 项研究(n=11335 例胚胎整倍体转移的 ART 胚胎)。<35 岁的女性的 OPR/LBR (优势比,1.29;95%置信区间 [CI],1.07-1.54;I=40%)高于≥35 岁的女性,风险差异为 0.06(95%CI,0.02-0.09)。同样,最年轻组的着床率更高(优势比,1.22;95%CI,1.12-1.32;I=0%)。<35 岁的女性与 35-37 岁、38-40 岁或 41-42 岁的女性相比,OPR/LBR 也有统计学意义上的提高。在比例荟萃分析中可以观察到年龄与 OPR/LBR 之间的梯度关系,尤其是在限制于低偏倚风险的研究中。

结论和相关性

母体年龄的增加与胚胎整倍体转移后的 ART 成功率下降有关,这与胚胎倍性无关。这一信息有助于在开始胚胎植入前非整倍体遗传学检测程序之前,为患者提供适当的咨询。

前瞻性注册号

CRD42021289760。

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