Table_2_Day-3-embryo fragmentation is associated with singleton birth weight following fresh single blastocyst transfer: A retrospective study.docx

BackgroundPrevious studies have arguably associated poor embryo morphology with low birth weight in singletons following single embryo transfer. However, the association between birth weight and specific morphological features in the cleavage stage remains less known. The purpose of the study was to investigate whether morphological features of embryos at the cleavage stage affect birth weight following blastocyst transfer.
MethodsThe single-center retrospective cohort study included 4,226 singletons derived from fresh single cleavage-stage embryo transfer (ET; n = 1,185), fresh single blastocyst transfer (BT; n = 787), or frozen-thawed single blastocyst transfer (FBT; n = 2,254) between 2016 and 2019. Morphological parameters including early cleavage, day-3 fragmentation, symmetry, blastomere number, and blastocyst morphology were associated with neonatal birth weight and birth weight z-score in multivariate regression models. The models were adjusted for maternal age, body mass index (BMI), parity, peak estradiol level, endometrial thickness, insemination protocol, female etiologies, order of transfer, mode of delivery, and year of treatment.
ResultsAdjusted for confounders, day-3 fragmentation was the only morphological feature associated with birth weight and birth weight z-score, while early cleavage, symmetry, blastomere number, and blastocyst morphology were not. Day-3 fragmentation increased the birth weight in both the ET (115.4 g, 95% CI: 26.6–204.2) and BT groups (168.8 g, 95% CI: 48.8–288.8) but not in the FBT group (7.47 g, 95% CI: -46.4 to 61.3). The associations between birth weight and these morphological parameters were confirmed through birth weight z-score analyses. The adjusted odds of large for gestational age (LGA) and high birth weight were also significantly greater in singletons following the transfer of fragmented embryos in the BT group [odds ratio (OR) 3, 95% CI: 1.2–7.51 and OR 3.65, 95% CI: 1.33–10, respectively]. The presence of fragmentation at the cleavage stage also affected the association between the blastocyst morphology and birth weight. Inner cell mass grades were negatively associated with birth weight in blastocysts with day-3 fragmentation but not in blastocysts without.
ConclusionsThe birth weight following blastocyst transfer was found to be positively associated with fragmentation at the cleavage stage. The data did not support the argument that transferring a poor-looking embryo may increase the risks of low birth weight. However, concerns for LGA infants remain.

背景 既往研究认为，单胚胎移植后单胎新生儿的不良胚胎形态与低出生体重存在关联，但目前学界对卵裂期（cleavage stage）特异性胚胎形态特征与出生体重间的关联仍知之甚少。本研究旨在探讨卵裂期胚胎的形态特征是否会影响囊胚移植（blastocyst transfer）后新生儿的出生体重。
方法 本研究为单中心回顾性队列研究，纳入2016至2019年间接受新鲜单卵裂期胚胎移植（embryo transfer, ET；n=1185）、新鲜单囊胚移植（blastocyst transfer, BT；n=787）或冻融单囊胚移植（frozen-thawed single blastocyst transfer, FBT；n=2254）的4226名单胎新生儿。研究采用多因素回归模型，分析早期卵裂、第3天胚胎碎片、对称性、卵裂球数目及囊胚形态等形态学参数与新生儿出生体重及出生体重z评分（birth weight z-score）的关联。模型校正了产妇年龄、体质量指数（body mass index, BMI）、产次、雌二醇峰值水平、子宫内膜厚度、授精方案、女性不孕病因、移植顺序、分娩方式及治疗年份等混杂因素。
结果 校正混杂因素后，第3天胚胎碎片是唯一与出生体重及出生体重z评分存在关联的形态学特征，早期卵裂、对称性、卵裂球数目及囊胚形态均未显示出此类关联。第3天胚胎碎片可提升ET组（115.4g，95%置信区间：26.6~204.2）与BT组（168.8g，95%置信区间：48.8~288.8）新生儿的出生体重，但对FBT组无显著影响（7.47g，95%置信区间：-46.4~61.3）。出生体重z评分分析进一步验证了上述形态学参数与出生体重间的关联。BT组中，移植带有碎片的胚胎的单胎新生儿，其大于胎龄儿（large for gestational age, LGA）及高出生体重的校正后比值比（odds ratio, OR）均显著升高[OR=3，95%置信区间：1.2~7.51；OR=3.65，95%置信区间：1.33~10]。卵裂期胚胎碎片的存在还会影响囊胚形态与出生体重间的关联：在存在第3天胚胎碎片的囊胚中，内细胞团评分与出生体重呈负相关，而在无碎片的囊胚中则无此关联。
结论 本研究发现，囊胚移植后的新生儿出生体重与卵裂期胚胎碎片呈正相关。研究数据不支持“移植外观不良的胚胎会增加低出生体重儿风险”这一观点，但临床仍需警惕大于胎龄儿的发生风险。