抗着丝点抗体阳性患者体外受精结局分析

Pregnancy outcomes of patients with positive anticentromere antibodies receiving in vitro fertilization-embryo transfer

目的:通过观察抗着丝点抗体(ACA)阳性患者体外受精-胚胎移植和自然试孕结局,探讨此类患者的生育策略。方法:采用病例对照研究回顾性分析2016年6月至2023年6月在浙江省人民医院接受体外受精-胚胎移植治疗且有抗核抗体(ANA)谱检查结果的3955例患者的临床资料。根据ACA结果将所纳入患者分为ACA阳性组和ACA阴性组。采用倾向评分匹配方法对两组进行1∶3配对,分别比较两组体外受精的胚胎结局;并采用自身对照分析不同授精方法和是否应用免疫抑制剂对结局的影响;对ACA阳性患者体外受精失败后的自然试孕和疾病进展进行随访。结果:ACA阳性患者34例,占总病例数的0.86%,占ANA阳性体外受精患者数的2.51%。无论是接受常规体外受精(c-IVF)还是卵胞质内单精子注射(ICSI)的患者,ACA阳性组卵母细胞成熟度和受精情况均与ACA阴性组有明显差异(均P<0.01),且ACA阳性组授精后第三日(D3)次优胚数和D3优胚数均减少(均P<0.05)。5例ACA阳性患者自身ICSI周期相比c-IVF周期双原核(2PN)率未提高(P>0.05),D3优胚数和D3次优胚数减少(均P<0.05)。12例ACA阳性患者经过免疫抑制剂治疗1~2个月后再行c-IVF/ICSI,用药前后获卵和受精情况均未改变(均P>0.05),2PN胚胎卵裂率改善(P<0.05)。ACA阳性组与ACA阴性组移植胚胎数相近,但ACA阳性组胚胎着床率、临床妊娠率显著低于ACA阴性组(均P<0.05),流产率差异无统计学意义(P>0.05)。27例ACA阳性患者体外受精失败后尝试自然试孕或人工授精,共获临床妊娠7例。结论:血清ACA阳性会干扰卵母细胞的成熟和正常受精过程,使用ICSI和免疫抑制剂不能改善受精结局,但ACA阳性患者有可能获得自然妊娠。

Objective:To analyze the pregnancy outcomes in patients with positive anti-centromere antibodies(ACA)receiving in vitro fertilization(IVF)-embryo transfer(ET)and natural conception.Methods:A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received IVF-ET therapy and had the results of antinuclear antibody(ANA)spectrum at Zhejiang Provincial People’s Hospital from June 2016 to June 2023.Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching.Embryo outcomes of IVF were compared between the two groups,and the impact of different fertilization methods and the use of immunosuppressants on pregnancy outcomes were analyzed using selfmatching.The natural conception and disease progress were followed up for ACApositive patients after IVF failure.Results:The ACA-positive patients accounted for 0.86%of all IVF patients(34/3955)and 2.51%of total ANA-positive IVF patients.Regardless of whether patients received conventional IVF(c-IVF)or intracytoplasmic sperm injection(ICSI),the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group(both P<0.01).Moreover,the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos(both P<0.05).In 5 cases of ACA-positive patients who underwent ICSI cycles,the two pronucleus(2PN)rate did not increase compared to c-IVF cycles(P>0.05),and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos(both P<0.05).After 1-2 months of immunosuppressant treatment,12 ACA-positive patients underwent c-IVF/ICSI again,and there were no changes in egg retrieval and fertilization before and after medication(both P>0.05),but there was an improvement in the 2PN embryo cleavage rate(P<0.05).The number of embryos transferred was similar between the ACA-positive and negative groups,but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group(both P<0.05),with no significant differences in the miscarriage rate between the two groups(P>0.05).Twentyseven ACA-positive patients attempted natural conception or artificial insemination after IVF failure,resulting in a total of 7 cases of clinical pregnancy.Conclusions:Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes,with no improvement observed with ICSI and immunosuppressant use.However,ACA-positive patients may still achieve natural pregnancy.