低分子肝素及胚胎植入前非整倍体检测对不明原因复发性流产患者妊娠结局的影响

Effect of low molecular heparin and preimplantation genetic testing for aneuploidies on pregnancy outcome in patients with unexplained recurrent spontaneous abortion.

目的:比较行胚胎植入前非整倍体检测(PGT-A)助孕和未行PGT-A助孕的不明原因复发性流产(URSA)患者应用低分子肝素(LMWH)后临床结局的差异。方法:回顾分析2016年1月1日至2022年5月17日URSA患者于郑州大学第三附属医院生殖医学科首次移植冷冻囊胚共1158个周期的临床资料,按移植前是否行PGT-A分为PGT-A组(行PGT-A+ICSI,315例)和非PGT-A组(行IVF/ICSI,843例),再根据移植日是否使用LMWH分为肝素组和非肝素组,为调整混杂因素进行1∶5倾向性评分匹配(PSM),对PSM后患者数据进行分析,比较两组患者种植率、临床妊娠率、流产率、早期流产率、活产率及单胎活产围产结局的差异。对非PGT-A组和PGT-A组PSM前数据、肝素PGT-A组和肝素非PGT-A组临床妊娠结局进行多因素logistic回归分析。结果:非PGT-A组中,肝素组和非肝素组的不孕年限差异有统计学意义(P<0.05),种植率(33.8%vs 32.1%,P=0.610)、临床妊娠率(45.4%vs 43.8%,P=0.733)、流产率(28.0%vs 28.4%,P=0.958)、早期流产率(23.8%vs 25.4%,P=0.797)、活产率(31.9%vs 30.1%,P=0.671)比较差异无统计学意义(P>0.05)。PGT-A组中,肝素组和非肝素组的女方体质量指数(BMI)比较差异有统计学意义(P<0.05),种植率(59.8%vs 57.6%,P=0.763)、临床妊娠率(59.4%vs 57.6%,P=0.806)、流产率(20.4%vs 14.7%,P=0.448)、早期流产率(16.4%vs 14.7%,P=0.803)、活产率(46.9%vs 49.2%,P=0.752)比较差异无统计学意义(P>0.05)。非PGT-A组中,肝素组和非肝素组内获得单胎活产患者的围产期结局比较差异均无统计学意义(P>0.05);PGT-A组中,肝素组较非肝素组小于胎龄儿(10.3%vs 0.8%,P=0.023),差异有统计学意义(P<0.05),余获得单胎活产患者的围产期结局差异均无统计学意义(P>0.05)。结论:行PGT-A助孕和未行PGT-A助孕的URSA患者应用LMWH并不能改善其妊娠结局,且行PGT-A助孕应用LMWH患者的围产期小于胎龄儿发生风险显著升高。

Objective:To compare the differences in clinical outcomes after application of low molecular weight heparin(LMWH)in patients with unexplained recurrent spontaneous abortion(URSA)who underwent preimplantation genetic testing for aneuploidies(PGT-A)for conception and those who did not undergo PGT-A.Methods:The clinical data of URSA patients who had their first frozen blastocyst transfer in the Department of Reproductive Medicine of the Third Affiliated Hospital of Zhengzhou University for a total of 1158 cycles from January 12016 to May 172022 were retrospectively analysed,and were divided into the PGT-A group(PGT-A+ICSI,315 cases)and the non-PGT-A group(IVF/ICSI,843 cases),and then divided into heparin and non-heparin subgroups according to whether LMWH was used on the day of transplantation.1∶5 propensity score matching(PSM)was performed to adjust for confounders,and the data of the patients after PSM were analysed to compare the differences in implantation rate,clinical pregnancy rate,miscarriage rate,early miscarriage rate,live birth rate,and perinatal outcome of singleton live births between the two groups.Multifactorial logistic regression analyses were performed on the pre-PSM data of the non-PGT-A and PGT-A groups,and the clinical pregnancy outcomes of the heparin PGT-A and heparin non-PGT-A groups.Results:The difference in infertility duration between the two subgroups of non-PGT-A group was statistically significant(P<0.05),and the rates of implantation(33.8%vs 32.1%,P=0.610),clinical pregnancy(45.4%vs 43.8%,P=0.733),miscarriage(28.0%vs 28.4%,P=0.958),early miscarriage(23.8%vs 25.4%,P=0.797),and live birth rate(31.9%vs 30.1%,P=0.671)were not statistically significant(P>0.05).There was a statistically significant difference in female body mass index between the two subgroups of PGT-A group(P<0.05).And within the two subgroups of PGT-A group,the implantation rate(59.8%vs 57.6%,P=0.763),clinical pregnancy rate(59.4%vs 57.6%,P=0.806),miscarriage rate(20.4%vs 14.7%,P=0.448),early miscarriage rate(16.4%vs 14.7%,P=0.803),and live birth rate(46.9%vs 49.2%,P=0.752)were not statistically different(P>0.05).The difference in perinatal outcomes of patients who obtained a singleton live birth within the two subgroups of non-PGT-A group was not statistically significant(P>0.05).The difference in small for gestational age(SGA)in the PGT-A heparin subgroup compared to the non-heparin subgroup(10.3%vs 0.8%,P=0.023)was statistically significant(P<0.05),and the difference in perinatal outcomes of the remaining patients who obtained a singleton live birth was not statistically significant(P>0.05).Conclusion:Performing PGT-A to assist conception or applying LMWH did not improve the pregnancy outcome of patients with URSA,and the risk of perinatal SGA was significantly higher in patients applying LMWH.