基于囊胚期活检的胚胎植入前非整倍体遗传学检测对高龄女性母婴结局的影响

Maternal and perinatal outcomes after preimplantation genetic testing for aneuploidies using blastocyst biopsy for women of advanced age

目的探讨基于囊胚期活检的胚胎植入前非整倍体遗传学检测(preimplantation genetic testing for aneuploidies,PGT-A)对高龄女性妊娠结局及子代健康的影响。方法采用回顾性队列研究,选取2016年1月至2018年12月期间在北京大学第三医院妇产科生殖医学中心采用卵胞质内单精子注射(intracytoplasmic sperm injection,ICSI)后行PGT-A(记为PGT-A组)或单纯ICSI(记为对照组)助孕、年龄≥35岁、单囊胚解冻移植的患者。同时根据年龄进一步分为35~37岁亚组和≥38岁亚组。主要结局为活产,次要结局包括人绒毛膜促性腺激素(human chorionic gonadotropin,hCG)阳性、临床妊娠、妊娠丢失、妊娠期糖尿病、妊娠期高血压、胎龄、早产、剖宫产、低出生体质量儿、巨大儿、小于胎龄儿及大于胎龄儿等。结果对于高龄患者,PGT-A组的活产率显著高于对照组[38.0%(89/234)比26.8%(237/885),OR(95%CI)=1.49(1.13~1.97),P=0.047],其流产率显著低于对照组[17.6%(19/108)比29.0%(116/443),OR(95%CI)=0.45(0.24~0.85),P=0.013]。≥38岁亚组患者PGT-A组的活产率[OR(95%CI)=3.01(1.67~5.44),P<0.001]、hCG阳性率[OR(95%CI)=2.08(1.25~3.47),P=0.005]、临床妊娠率[OR(95%CI)=2.39(1.40~4.07),P=0.001]均显著高于对照组,且PGT-A组的流产率显著低于对照组[OR(95%CI)=0.34(0.13~0.85),P=0.022];而35~37岁亚组患者,其妊娠结局在两组间差异均无统计学意义(均P>0.05)。高龄女性的产科并发症及其新生儿结局发生情况在PGT-A组和对照组间差异均无统计学意义(均P>0.05),根据年龄进行的亚组分析也得出了一致结论。结论基于囊胚期活检的PGT-A可显著提高≥38岁患者在单囊胚解冻移植周期中的hCG阳性率、临床妊娠率及活产率,并显著降低流产率,但并未显示PGT-A对35~37岁患者的妊娠结局有改善效果。此外,PGT-A的使用并不会增加高龄女性产科并发症及其新生儿不良结局的发生风险。

Objective To examine the effects of preimplantation genetic testing for aneuploidies(PGT-A)using blastocyst biopsy on maternal and perinatal outcomes for women of advanced age.Methods A retrospective cohort study was conducted during January 2016 to December 2018 at Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital.Women who were aged≥35 years,underwent intracytoplasmic sperm injection(ICSI,control group)or PGT-A after ICSI(PGT-A group)with single frozen-thawed blastocyst transferred were eligible in this study.They were further divided into 35-37 years old subgroup and≥38 years old subgroup according to age.The primary outcome was live birth,and the secondary outcomes were human chorionic gonadotropin(hCG)positivity,clinical pregnancy,pregnancy loss,hypertension in pregnancy,gestational diabetes mellitus,gestational age,preterm birth,caesarean section,low birth weight,small gestational age,and large gestational age.Results For women aged≥35 years,the live birth rate in PGT-A group was significantly higher than that in control group[38.0%(89/234)vs.26.8%(237/885),OR(95%CI)=1.49(1.13-1.97),P=0.047],the miscarriage rate was significantly lower than that in control group[17.6%(19/108)vs.29.0%(116/443),OR(95%CI)=0.45(0.24-0.85),P=0.013].We found that for women who aged≥38 years,the live birth rate[OR(95%CI)=3.01(1.67-5.44),P<0.001],hCG positivity rate[OR(95%CI)=2.08(1.25-3.47),P=0.005],clinical pregnancy rate[OR(95%CI)=2.39(1.40-4.07),P=0.001]in PGT-A group were significantly higher than those in control group,and the miscarriage rate in PGT-A group was significantly lower than that in control group[OR(95%CI)=0.34(0.13-0.85),P=0.022];for women aged 35-37 years,there were no statistically significant differences in pregnancy outcomes between the two groups(all P>0.05).Moreover,there were no statistically significant differences in the rates of obstetric complications and perinatal outcomes for women aged≥35 years between PGT-A group and control group(all P>0.05),and similar results were found in the subgroup analyses for women who aged 35-37 years or≥38 years.Conclusion PGT-A using blastocyst stage biopsy strategy in single blastocyst thaw transferred cycles could significantly improve the rates of hCG positivity,clinical pregnancy,and live birth,and significantly reduce the miscarriage rate for women aged≥38 years,but could not improve the pregnancy outcomes for women aged 35-37 years.In addition,the use of PGT-A does not increase the risk of obstetric complications and perinatal outcomes for women of advanced age.