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采用匹配倾向评分设计比较胚胎植入前遗传学检测非整倍体的妊娠结局。

Comparison of pregnancy outcomes following preimplantation genetic testing for aneuploidy using a matched propensity score design.

机构信息

Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

出版信息

Hum Reprod. 2020 Oct 1;35(10):2356-2364. doi: 10.1093/humrep/deaa161.

Abstract

STUDY QUESTION

Does preimplantation genetic testing for aneuploidy (PGT-A) increase the likelihood of live birth among women undergoing autologous IVF who have fertilized embryos?

SUMMARY ANSWER

PGT-A is associated with a greater probability of live birth among women 35 years old and older who are undergoing IVF.

WHAT IS KNOWN ALREADY

Previous studies evaluating the association between PGT-A and the incidence of live birth may be prone to confounding by indication, as women whose embryos undergo PGT-A may have a lower probability of live birth due to other factors associated with their increased risk of aneuploidy (e.g. advancing age, history of miscarriage). Propensity score matching can reduce bias where strong confounding by indication is expected.

STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study utilizing data from women who underwent autologous IVF treatment, had their first oocyte retrieval at our institution from 1 January 2011 through 31 October 2017 and had fertilized embryos from this retrieval. If a woman elected to use PGT-A, all good quality embryos (defined as an embryo between Stages 3 and 6 with Grade A or B inner or outer cell mass) were tested. We only evaluated cycles associated with the first oocyte retrieval in this analysis.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Our analytic cohort included 8227 women. We used multivariable logistic regression to calculate a propensity score for PGT-A based on relevant demographic and clinical factors available to the IVF provider at the time of PGT-A or embryo transfer. We used the propensity score to match women who did and did not utilize PGT-A in a 1:1 ratio. We then used log-binomial regression to compare the cumulative incidence of embryo transfer, clinical pregnancy, miscarriage and live birth between women who did and did not utilize PGT-A. Because the risk of aneuploidy increases with age, we repeated these analyses among women <35, 35-37 and ≥38 years old based on the Society for Assisted Reproductive Technology's standards.

MAIN RESULTS AND THE ROLE OF CHANCE

Overall, women with fertilized embryos who used PGT-A were significantly less likely to have an embryo transfer (risk ratios (RR): 0.78; 95% CI: 0.73, 0.82) but were more likely to have a cycle that resulted in a clinical pregnancy (RR: 1.15; 95% CI: 1.04, 1.28) and live birth (RR: 1.21; 95% CI: 1.08, 1.35) than women who did not use PGT-A. Among women aged ≥38 years, those who used PGT-A were 67% (RR: 1.67; 95% CI: 1.31, 2.13) more likely to have a live birth than women who did not use PGT-A. Among women aged 35-37 years, those who used PGT-A were also more likely to have a live birth (RR: 1.27; 95% CI: 1.05, 1.54) than women who did not use PGT-A. In contrast, women <35 years old who used PGT-A were as likely to have a live birth (RR: 0.91; 95% CI: 0.78, 1.06) as women <35 years old who did not use PGT-A.

LIMITATIONS, REASONS FOR CAUTION: We were unable to abstract several potential confounding variables from patients' records (e.g. anti-Mullerian hormone levels and prior IVF treatment), which may have resulted in residual confounding. Additionally, by restricting our analyses to cycles associated with the first oocyte retrieval, we were unable to estimate the cumulative incidence of live birth over multiple oocyte retrieval cycles.

WIDER IMPLICATIONS OF THE FINDINGS

Women aged 35 years or older are likely to benefit from PGT-A. Larger studies might identify additional subgroups of women who might benefit from PGT-A.

STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. D.S. reports that he is a member of the Cooper Surgical Advisory Board. The other authors report no conflicts of interest.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

胚胎植入前遗传学检测(PGT-A)是否会增加 35 岁以上接受自体 IVF 的女性受精胚胎活产的可能性?

总结答案

PGT-A 与 35 岁及以上接受 IVF 的女性活产的可能性增加相关。

已知情况

以前评估 PGT-A 与活产发生率之间关联的研究可能容易受到指示性混杂的影响,因为接受 PGT-A 的胚胎的女性由于其他与较高非整倍体风险相关的因素,可能具有较低的活产可能性(例如,年龄较大、流产史)。倾向评分匹配可以减少预期存在强烈指示性混杂的偏倚。

研究设计、大小和持续时间:我们进行了一项回顾性队列研究,使用了 2011 年 1 月 1 日至 2017 年 10 月 31 日期间在我们机构接受自体 IVF 治疗、第一次卵母细胞取出的女性的数据,以及这些取出的受精胚胎。如果女性选择使用 PGT-A,则对所有优质胚胎(定义为 3 期至 6 期胚胎,内细胞团或外细胞团 A 级或 B 级)进行检测。在这项分析中,我们仅评估了与第一次卵母细胞取出相关的周期。

参与者/材料、设置、方法:我们的分析队列包括 8227 名女性。我们使用多变量逻辑回归根据 IVF 提供者在 PGT-A 或胚胎转移时可用的相关人口统计学和临床因素计算 PGT-A 的倾向评分。我们使用倾向评分以 1:1 的比例匹配使用和未使用 PGT-A 的女性。然后,我们使用对数二项式回归比较使用和未使用 PGT-A 的女性之间的胚胎转移、临床妊娠、流产和活产的累积发生率。由于非整倍体风险随年龄增加而增加,我们根据辅助生殖技术协会的标准,在<35 岁、35-37 岁和≥38 岁的女性中重复了这些分析。

主要结果和机会的作用

总体而言,使用 PGT-A 的有受精胚胎的女性进行胚胎转移的可能性显著降低(风险比(RR):0.78;95%CI:0.73,0.82),但更有可能经历导致临床妊娠(RR:1.15;95%CI:1.04,1.28)和活产(RR:1.21;95%CI:1.08,1.35)的周期。在≥38 岁的女性中,使用 PGT-A 的女性活产的可能性比未使用 PGT-A 的女性高 67%(RR:1.67;95%CI:1.31,2.13)。在 35-37 岁的女性中,使用 PGT-A 的女性也比未使用 PGT-A 的女性更有可能活产(RR:1.27;95%CI:1.05,1.54)。相比之下,35 岁以下使用 PGT-A 的女性活产的可能性与 35 岁以下未使用 PGT-A 的女性相同(RR:0.91;95%CI:0.78,1.06)。

局限性、谨慎的原因:我们无法从患者的记录中提取几个潜在的混杂变量(例如,抗苗勒管激素水平和之前的 IVF 治疗),这可能导致残留混杂。此外,通过将我们的分析仅限于与第一次卵母细胞取出相关的周期,我们无法估计多次卵母细胞取出周期中活产的累积发生率。

研究结果的更广泛意义

35 岁或以上的女性可能受益于 PGT-A。更大的研究可能会确定其他可能受益于 PGT-A 的女性亚组。

研究资助/利益冲突:本研究未获得任何资金。D.S. 报告他是库珀外科咨询委员会的成员。其他作者报告没有利益冲突。

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