Y染色体AZFc区不同部分缺失对严重少弱精子症患者ICSI结局的影响

Effect of the different partial deletions in the AZFc locus of Y-chromosome on the ICSI outcome of severe oligoasthenozoospermia patients

目的探讨Y染色体无精子因子(azoospermia factor, AZF)c区不同部分缺失对严重少弱精子症患者卵胞质内单精子显微注射(intracytoplasmic sperm injection, ICSI)临床结局的影响。方法本研究为回顾性队列研究, 分析在河南省人民医院生殖医学中心2017年12月至2020年7月期间经Y染色体AZF区高通量测序筛查、精子浓度<5×106/mL且行射精精子ICSI助孕的严重少弱精子症患者的临床资料, 根据筛查结果将携带AZFc缺失的患者纳入缺失组(n=108), 无AZFc缺失的患者纳入对照组(n=445), 同时按照缺失位点类型将AZFc缺失组分为b2/b4缺失(n=19)、b2/b3缺失(n=30)、gr/gr缺失(n=43)3个亚组, 分别比较各组间及亚组间胚胎发育及妊娠结局情况。结果存在AZFc缺失的患者第3日(day 3, D3)可利用胚胎率、优质胚胎率以及囊胚形成率均低于对照组, 差异均有统计学意义[(70.4%(556/790)比78.5%(2867/3651), P<0.001;24.7%(199/807)比34.3%(1284/3747), P<0.001;51.7%(277/536)比58.0%(1540/2592), P=0.007];种植率、临床妊娠率、移植周期活产率两组间比较差异均无统计学意义(均P>0.05)。AZFc区域b2/b3缺失亚组D3可利用胚胎率、优质胚胎率、囊胚形成率、种植率、临床妊娠率及活产率与对照组比较, 差异均无统计学意义(均P>0.05);b2/b4缺失亚组优质胚胎率[23.2%(32/138)]低于对照组(P=0.004), 而D3可利用胚胎率、囊胚形成率、种植率、临床妊娠率及活产率与对照组相比, 差异均无统计学意义(均P>0.05);gr/gr缺失亚组D3可利用胚胎率[71.6%(280/391)]、优质胚胎率[20.8%(84/403)]以及囊胚形成率[48.7%(133/273)]均低于对照组(P=0.002、P<0.001、P<0.001), 而种植率、临床妊娠率及活产率与对照组比较, 差异均无统计学意义(均P>0.05)。结论 Y染色体AZFc区域b2/b3缺失和b2/b4缺失对严重少弱精子症患者ICSI胚胎发育及妊娠结局均无显著影响, gr/gr缺失对胚胎发育不利影响最大, 但对妊娠结局无影响。

Objective To investigate the effects of different partial deletions in azoospermia factor(AZF)locus of Y-chromosome on the clinical outcome of severe oligoasthenozoospermia patients by intracytoplasmic sperm injection(ICSI).Methods A retrospective cohort study was conducted on the patients undergoing high-throughput sequencing for Y chromosome microdeletion screening and ICSI treatment in Reproductive Medicine Center of Henan Provincial People's Hospital from December 2017 to July 2020.According to whether carrying AZFc microdeletions or not,the patients were divided into the AZFc-deletion group and control group.And AZFc-deletion group was divided into 3 subgroups,b2/b3 deletion,b2/b4 deletion and gr/gr deletions subgroup,by the types of partial deletion.Results The day 3(D3)available embryo rate,the high-quality embryo rate,and the blastocyst formation rate in patients with AZFc deletion were statistically lower than those in control group[70.4%(556/790)vs.78.5%(2867/3651),P<0.001;24.7%(199/807)vs.34.3%(1284/3747),P<0.001;51.7%(277/536)vs.58.0%(1540/2592),P=0.007],and there were no statistical differences in implantation rate,clinical pregnancy rate,live birth rate during transplantation cycle between the two groups(all P>0.05).The AZFc b2/b3 deletion subgroup had no significant differences in D3 available embryo rate,high-quality embryo rate,blastocyst formation rate,implantation rate,clinical pregnancy rate and live birth rate,compared with control group(all P>0.05).The rate of high-quality embryos in patients with the b2/b4 deletion subgroup[23.2%(32/138)]was lower than that of control group(P=0.004),but there were no statistical differences in D3 available embryo rate,blastocyst formation rate,implantation rate,clinical pregnancy rate and live birth rate(all P>0.05).The D3 available embryo rate[71.6%(280/391)],the high-quality embryo rate[20.8%(84/403)]and the blastocyst formation rate[48.7%(133/273)]in patients of gr/gr deletion subgroup were significantly lower than those in control group(P=0.002,P<0.001,P<0.001),but there were no statistical differences in implantation rate,clinical pregnancy rate and live birth rate(all P>0.05).Conclusion AZFc b2/b3 deletion and b2/b4 deletion in the AZFc locus of Y chromosome have no significant effect on embryonic development and pregnancy outcome in patients with severe oligoasthenozoospermia undergoing ICSI.Gr/gr deletion has most adverse effect on embryonic development but no effect on pregnancy outcome.