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胚胎活检与单胎妊娠围产结局:一项对生殖技术学会临床结局报告系统中 16246 个冷冻胚胎移植周期的分析。

Embryo biopsy and perinatal outcomes of singleton pregnancies: an analysis of 16,246 frozen embryo transfer cycles reported in the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System.

机构信息

Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Reproductive Medicine Associates of Northern California, San Francisco, CA.

出版信息

Am J Obstet Gynecol. 2021 May;224(5):500.e1-500.e18. doi: 10.1016/j.ajog.2020.10.043. Epub 2020 Oct 28.

Abstract

BACKGROUND

Preimplantation genetic testing is commonly performed by removing cells from the trophectoderm, the outer layer of the blastocyst, which subsequently forms the placenta. Because preimplantation genetic testing removes the cells that are destined to form the placenta, it is possible that preimplantation genetic testing could be associated with an increased risk for adverse outcomes associated with abnormal placentation. Despite the increasing utilization of preimplantation genetic testing, few studies have investigated the perinatal outcomes, with published studies yielding contradictory findings and using small sample sizes.

OBJECTIVE

This study aimed to compare the perinatal outcomes of singleton pregnancies conceived following frozen embryo transfer of a single, autologous blastocyst either with or without preimplantation genetic testing.

STUDY DESIGN

This was a retrospective analysis of autologous frozen embryo transfer cycles that led to singleton live births per the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System, including cycles initiated between 2014 and 2015. The perinatal outcomes, including birthweight, Z-score, small for gestational age, large for gestational age, macrosomia, and preterm birth, were compared between pregnancies with or without preimplantation genetic testing. We conducted multivariable linear regression analyses for the birthweight and Z-score and logistic regression for the binary outcomes. A false discovery rate was adjusted to decrease the type I error from multiple hypothesis testing.

RESULTS

Of the 16,246 frozen embryo transfers resulting in singleton births included in this analysis, 6244 involved the transfer of a single blastocyst that had undergone preimplantation genetic testing, and the remainder (n=10,002) involved the transfer of a single blastocyst that had not undergone a biopsy. When compared with the women from the nonpreimplantation genetic testing group, the average maternal age (35.8±4.1 vs 33.7±3.9; P<.001) and prevalence of prior spontaneous abortion (37.3% vs 27.7%; P<.001) were higher among women from the preimplantation genetic testing group. Bivariate analysis revealed a higher prevalence of small-for-gestational-age newborns (4.8% vs 4.0%; P=.008) and premature delivery (14.1% vs 12.5%; P=.005) and a lower prevalence of large-for-gestational-age newborns (16.3% vs 18.2%; P=.003) and macrosomia (11.1% vs 12.4%; P=.013) among the preimplantation genetic testing pregnancies. Multivariate regression analyses, adjusting for the year of transfer, maternal age, maternal body mass index, smoking status (3 months before the treatment cycle), obstetrical histories (full-term birth, preterm birth, and spontaneous abortion), infertility diagnosis, and infant sex suggested a significantly increased odds of preterm birth (adjusted odds ratio, 1.20; 95% confidence interval, 1.09-1.33; P<.001) from preimplantation genetic testing blastocysts. Birthweight (-14.63; 95% confidence interval, -29.65 to 0.38; P=.056), birthweight Z-score (-0.03; 95% confidence interval, -0.06 to 0.00; P=.081), and odds of small-for-gestational-age newborns (adjusted odds ratio, 1.17; 95% confidence interval, 0.99-1.38; P=.066), large-for-gestational-age newborns (adjusted odds ratio, 0.96; 95% confidence interval, 0.88-1.06; P=.418), and macrosomia (adjusted odds ratio, 0.96; 95% confidence interval, 0.85-1.07; P=.427) did not differ between the frozen transfer cycles with or without preimplantation genetic testing in the analysis adjusted for the confounders. Subgroup analysis of the cycles with a stated infertility diagnosis (n=14,285) yielded consistent results.

CONCLUSION

Compared with frozen embryo transfer cycles without preimplantation genetic testing, the frozen embryo transfer cycles with preimplantation genetic testing was associated with a small increase in the likelihood of preterm birth. Although the increase in the risk for prematurity was modest in magnitude, further investigation is warranted.

摘要

背景

胚胎植入前遗传学检测通常通过从囊胚的外层滋养外胚层中去除细胞来进行,囊胚随后形成胎盘。 因为胚胎植入前遗传学检测会去除注定要形成胎盘的细胞,所以胚胎植入前遗传学检测可能与与异常胎盘形成相关的不良围产期结局的风险增加有关。 尽管胚胎植入前遗传学检测的使用越来越多,但很少有研究调查围产期结局,已发表的研究结果存在矛盾,且样本量较小。

目的

本研究旨在比较冷冻胚胎移植中,使用或不使用胚胎植入前遗传学检测的单胎妊娠的围产期结局。

研究设计

这是一项对按照辅助生殖技术协会临床结局报告系统报告的,通过冻融胚胎移植导致单胎活产的自体冷冻胚胎移植周期的回顾性分析,包括 2014 年至 2015 年期间启动的周期。比较了有或没有胚胎植入前遗传学检测的妊娠的围产期结局,包括出生体重、Z 评分、小于胎龄儿、大于胎龄儿、巨大儿和早产。我们对出生体重和 Z 评分进行了多变量线性回归分析,对二元结局进行了逻辑回归分析。假发现率被调整以减少多重假设检验的 I 型错误。

结果

在本分析中,纳入了 16246 个导致单胎活产的冷冻胚胎移植,其中 6244 个涉及接受胚胎植入前遗传学检测的单个囊胚的移植,其余 10002 个涉及未接受活检的单个囊胚的移植。与非胚胎植入前遗传学检测组的女性相比,接受胚胎植入前遗传学检测组的女性平均年龄(35.8±4.1 岁比 33.7±3.9 岁;P<.001)和既往自然流产发生率(37.3%比 27.7%;P<.001)更高。单变量分析显示,接受胚胎植入前遗传学检测的妊娠中,小于胎龄儿的发生率(4.8%比 4.0%;P=.008)和早产率(14.1%比 12.5%;P=.005)较高,而大于胎龄儿的发生率(16.3%比 18.2%;P=.003)和巨大儿的发生率(11.1%比 12.4%;P=.013)较低。多变量回归分析,调整了移植年份、母亲年龄、母亲体重指数、吸烟状况(治疗周期前 3 个月)、产科史(足月分娩、早产和自然流产)、不孕诊断和婴儿性别,表明胚胎植入前遗传学检测的囊胚与早产的几率显著增加(调整后的优势比,1.20;95%置信区间,1.09-1.33;P<.001)。出生体重(-14.63;95%置信区间,-29.65 至 0.38;P=.056)、出生体重 Z 评分(-0.03;95%置信区间,-0.06 至 0.00;P=.081)以及小于胎龄儿(调整后的优势比,1.17;95%置信区间,0.99-1.38;P=.066)、大于胎龄儿(调整后的优势比,0.96;95%置信区间,0.88-1.06;P=.418)和巨大儿(调整后的优势比,0.96;95%置信区间,0.85-1.07;P=.427)的几率在调整了混杂因素的分析中,在有或没有胚胎植入前遗传学检测的冷冻胚胎移植周期之间没有差异。有明确不孕诊断的周期(n=14285)的亚组分析得出了一致的结果。

结论

与没有胚胎植入前遗传学检测的冷冻胚胎移植周期相比,使用胚胎植入前遗传学检测的冷冻胚胎移植周期与早产的可能性略有增加。虽然早产风险的增加幅度较小,但仍需要进一步研究。

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