高龄与非高龄患者胚胎移植术后自然流产胚胎染色体核型异常多因素回归分析

Logistic regression analysis of risk factors associated with embryo chromosomal abnormalities after embryo transfer in advanced age and young patients

目的分析不同年龄段患者行辅助生殖技术(assisted reproductive technology,ART)助孕后自然流产胚胎染色体核型异常的发生率及其相关危险因素。方法回顾性队列分析2016年1月—2018年6月期间于中山大学附属第六医院生殖中心行体外受精/卵母细胞质内单精子注射-胚胎移植(in vitro fertilization/intracytoplasmic sperm injection-embryo transfer,IVF/ICSI-ET)后自然流产并行绒毛染色体核型检测的患者资料。基于患者年龄,分成高龄组(≥35岁)和年轻组(<35岁),分别分析染色体核型异常胚胎在ART术后自然流产胚胎中所占比例。根据染色体核型检测结果,分为染色体核型异常组和正常组,进行单因素分析及二变量逻辑回归分析,探索胚胎染色体核型异常发生的高危因素。结果共纳入506例年轻患者及371例高龄患者,胚胎染色体核型异常率分别为42.09%及62.80%。在高龄和年轻的患者中,冷冻胚胎移植周期比例和ICSI比例在胚胎染色体核型异常组和正常组间差异无统计学意义。年轻组和高龄组胚胎染色体核型异常患者的年龄[(31.1±3.1)岁,(39.6±2.5)岁]均高于染色体核型正常组[(30.4±3.0)岁,(37.4±2.1)岁](P=0.018,P<0.001),而抗苗勒管激素(anti-Müllerian hormone,AMH)[3.68(3.80)μg/L,2.13(2.23)μg/L]及窦卵泡数(13.72±7.77,9.76±5.91)均显著低于染色体核型正常组[4.18(4.24)μg/L,3.12(2.86)μg/L;15.58±8.04,11.56±7.29],差异有统计学意义(P=0.013,P=0.019;P=0.010,P=0.014)。移植胚胎质量、移植胚胎发育类型等组间差异均无统计学意义。进一步逻辑回归分析显示,在年轻患者中,仅血清AMH与自然流产胚胎染色体异常的发生密切相关(OR=1.021,P=0.010)。纠正AMH后,年龄与自然流产胚胎染色体异常的发生无相关性。而在高龄患者中,年龄与自然流产胚胎染色体异常的发生密切相关(OR=0.789,P=0.001)。纠正年龄后,AMH与自然流产胚胎染色体异常的发生无相关性。结论玻璃化冷冻技术及ICSI技术不增加胚胎染色体核型异常的发生率。对于<35岁患者,基础AMH水平与胚胎染色体核型异常密切相关。对于≥35岁患者,高龄是患者胚胎染色体核型异常的主要高危因素。

Objective To analyze embryo chromosomal abnormalities rate and its risk factors after assisted reproductive technology (ART) in different age groups. Methods This was a retrospective cohort study on 877 patients undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in Reproductive Medicine Center of the Sixth Affiliated Hospital of Sun Yat-Sen University between January 2016 and June 2018. All patients had embryo chromosomes tested after spontaneous abortion. Clinical data were compared between the patients with normal chromosome karyotype and those with abnormal chromosome karyotype using univariate and multivariate analysis for risk factors of abnormal chromosome karyotype in young (<35 years old) and advanced age (≥35 years old) patients. Results In total, 506 young and 371 advanced age patients were enrolled, whose abnormal chromosome karyotype rate was 42.09% and 62.80%, respectively. Whether young or advanced age patients, there was no statistically significant difference in the rate of freezing embryo transfer and ICSI between abnormal and normal chromosome karyotype groups. No matter young or advanced age patients, patients with abnormal chromosome karyotype were significantly older [(31.1±3.1) years old,(39.6±2.5) years old] than those with normal chromosome karyotype [(30.4±3.0) years old,(37.4±2.1)years old](P=0.018, P<0.001), whereas anti-Müllerian hormone (AMH)[3.68(3.80)μg/L, 2.13(2.23)μg/L] and AFC (13.72±7.77, 9.76±5.91) were significantly lower in patients with abnormal chromosome karyotype [4.18(4.24)μg/L, 3.12(2.86)μg/L;15.58±8.04, 11.56±7.29](P=0.013, P=0.019;P=0.010, P=0.014). The further logistic regression analysis confirmed that only AMH was the risk factor of abnormal chromosome karyotype in young patients (OR=1.021, P=0.010), while age was the risk factor of abnormal chromosome karyotype in advanced age patients after spontaneous abortion (OR=0.789, P=0.001). Conclusion Neither vitrified cryopreservation nor ICSI would increase incidence of abnormal chromosome karyotype. For patients younger than 35 years old, basal serum AMH was independently related to chromosomal abnormalities. For those older than 35 years old, age was the mayor risk factor for chromosomal abnormalities.