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更多更好吗?ICSI 后卵母细胞产量较高与第三天整倍体胚胎数量增多独立相关。

Is more better? A higher oocyte yield is independently associated with more day-3 euploid embryos after ICSI.

机构信息

Centre for Big Data Research in Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

出版信息

Hum Reprod. 2019 Jan 1;34(1):79-83. doi: 10.1093/humrep/dey342.

DOI:10.1093/humrep/dey342
PMID:30476100
Abstract

STUDY QUESTION

Is the number of oocytes retrieved after ovarian stimulation for ICSI independently associated with the number of day-3 euploid embryos (EE)?

SUMMARY ANSWER

A larger oocyte yield is independently associated with more day-3 EE, although the expected benefit decreases significantly with advancing age.

WHAT IS KNOWN ALREADY

Although traditionally ovarian stimulation aims at collecting more than one oocyte in order to increase the chance of pregnancy, there is evidence suggesting that excessive ovarian response leads to lower live birth rates. Whether a larger oocyte yield after ovarian stimulation is associated with the genetic composition of the resulting embryos and therefore with their reproductive potential is still largely unknown.

STUDY DESIGN, SIZE, DURATION: This is a multi-centered retrospective cohort study analyzing 724 cycles of preimplantation genetic testing for aneuploidy (PGT-A) cycles using day-3 biopsy and array-comparative genomic hybridization between March 2011 and December 2016 in three laboratories.

PARTICIPANTS/MATERIALS, SETTING, METHODS: The primary outcome measure was the number of EE on day-3. Statistical analysis was performed using the generalized estimating equations (GEE) framework and multivariate regression models to control for the clustered nature of the data while adjusting for potential confounders.

MAIN RESULTS AND THE ROLE OF CHANCE

A multivariate regression GEE model including all significant population and stimulation characteristics as covariates as well as an interaction term between female age and number of oocytes revealed that the number of oocytes retrieved was still positively associated with the number of EE (coeff: +0.40, 95% CI: 0.24-0.56). The interaction term was highly significant (coeff: -0.01, P < 0.001) indicating an effect modifying role of female age on the association of oocytes retrieved with the number of EE. The number of oocytes retrieved was also positively associated with cumulative live birth rates (odds ratio: 1.07, 95% CI: 1.03-1.12).

LIMITATIONS, REASONS FOR CAUTION: This study is retrospective and the presence of residual unknown bias cannot be excluded. Furthermore, the population analyzed in this study might not be completely representative of the general population undergoing ICSI.

WIDER IMPLICATIONS OF THE FINDINGS

These results provide an explanatory mechanism for the recently published positive association between the number of oocytes retrieved and cumulative live birth rates.

STUDY FUNDING/COMPETING INTEREST(S): CAV is supported by a NHMRC Early Career Fellowship (GNT1147154)/ No competing interests to declare.

摘要

研究问题

在接受 ICSI 的卵巢刺激后获得的卵母细胞数量是否与第 3 天的整倍体胚胎 (EE) 数量独立相关?

总结答案

更多的卵母细胞产量与第 3 天的 EE 数量更多相关,尽管随着年龄的增长,预期的益处显著下降。

已知的事实

尽管传统的卵巢刺激旨在采集多个卵母细胞以增加怀孕的机会,但有证据表明过度的卵巢反应会导致活产率降低。卵巢刺激后获得的更大的卵母细胞产量是否与随后胚胎的遗传组成相关,因此与它们的生殖潜力相关,在很大程度上仍然未知。

研究设计、规模、持续时间:这是一项多中心回顾性队列研究,分析了 2011 年 3 月至 2016 年 12 月期间三个实验室中使用第 3 天活检和基于阵列的比较基因组杂交进行的 724 个胚胎植入前遗传检测整倍体 (PGT-A) 周期。

参与者/材料、设置、方法:主要结局测量指标为第 3 天的 EE 数量。使用广义估计方程 (GEE) 框架和多元回归模型进行统计分析,在调整潜在混杂因素的同时,控制数据的聚类性质。

主要结果和机会作用

一个包含所有重要人口和刺激特征作为协变量的多元回归 GEE 模型,以及女性年龄和卵母细胞数量之间的交互项,表明获得的卵母细胞数量与 EE 的数量仍呈正相关(系数:+0.40,95%CI:0.24-0.56)。交互项具有高度显著性(系数:-0.01,P<0.001),表明女性年龄对获得的卵母细胞数量与 EE 数量之间的关联具有修饰作用。获得的卵母细胞数量也与累积活产率呈正相关(优势比:1.07,95%CI:1.03-1.12)。

局限性、谨慎的原因:本研究为回顾性研究,不能排除存在残余未知偏倚的可能性。此外,本研究分析的人群可能不完全代表接受 ICSI 的一般人群。

研究结果的广泛意义

这些结果为最近发表的获得的卵母细胞数量与累积活产率之间存在正相关的研究结果提供了一个解释机制。

研究资金/竞争利益:CAV 得到了 NHMRC 早期职业研究员奖学金(GNT1147154)的支持/没有竞争利益需要声明。

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