STUDY QUESTION Can antinuclear antibodies (ANA) affect the subsequent live birth rate (LBR) in patients with unexplained recurrent pregnancy loss (RPL) in the absence of antiphospholipid antibodies (aPL)? SUMMARY ANSWER Women with unexplained RPL have a high probability of live birth following a positive pregnancy test (>70%), being similar between those with positive and negative ANA testing, regardless of the cut-off value. WHAT IS KNOWN ALREADY The RPL guidelines of the ESHRE state that ‘ANA testing can be considered for explanatory purposes’. However, there have been a limited number of studies on this issue and sample sizes have been small, and the impact of ANA on the pregnancy prognosis is unclear. STUDY DESIGN, SIZE, DURATION A retrospective cohort study was conducted at Nagoya City University Hospital between 2006 and 2019. The study included 1021 women with RPL without known cause. PARTICIPANTS/MATERIALS, SETTING, METHODS Hysterosalpingography or 3D-ultrasound, chromosome analysis for both partners, blood tests for aPL, ANA, hypothyroidism, and diabetes mellitus were performed before a subsequent pregnancy. ANAs were measured by indirect immunofluorescence on Hep-2 cell slides. The cutoff dilution used was 1:40. In addition, patients were classified according to the ANA pattern on immunofluorescence staining: homogeneous, speckled, nucleolar, centromeric, peripheral, cytoplasmic, and others. LBRs were compared between ANA-positive and ANA-negative patients after excluding patients with antiphospholipid antibody syndrome, an abnormal chromosome in either partner and a uterine anomaly. MAIN RESULTS AND THE ROLE OF CHANCE Considering the cut-off value = 1:40 dilution, the subsequent LBRs were 72.5% (256/353) for the ANA-positive group and 73.2% (489/668) for the ANA-negative group; odds ratio (OR) = 0.97, 95% CI = 0.72–1.29. After excluding the miscarriages occurring from embryonic aneuploidy, the biochemical pregnancy losses, and the ectopic pregnancies, LBRs were 92.8% (256/276) for the ANA-positive group and 93.0% (489/526) for the ANA-negative group: OR = 0.97 (95% CI = 0.55–1.70). Considering the cut-off value = 1:80 dilution, the subsequent LBRs were 75.0% (87/116) for the ANA-positive group and 72.7% (658/905) for the ANA-negative group; OR = 1.13 (95% CI = 0.72–1.76). After excluding the miscarriages occurring from embryonic aneuploidy, the biochemical pregnancy losses, and the ectopic pregnancies, LBRs were 89.7% (87/97) for the ANA-positive group and 93.3% (658/705) for the ANA-negative group: OR = 0.62 (95% CI = 0.30–1.27). Considering the cut-off value = 1:160 dilution, the subsequent LBRs were 82.4% (28/34) for the ANA-positive group and 72.6% (717/987) for the ANA-negative group; OR = 1.76 (95% CI = 0.72–4.29). After excluding the miscarriages occurring from embryonic aneuploidy, the biochemical pregnancy losses, and the ectopic pregnancies, LBR were 93.3% (28/30) for the ANA-positive group and 92.9% (717/772) for the ANA-negative group: OR = 1.07 (95% CI = 0.25–4.63). There was no difference in LBR between the 2 groups before or after adjustment for age and BMI, but ANA-positive patients were significantly older than ANA-negative patients when using the 1:40 dilution, and ANA-positive patients had significantly lower BMIs than ANA-negative patients when using the 1:80 dilution. LIMITATIONS, REASONS FOR CAUTION A healthy control group was not established, making it impossible to compare ANA positivity rates between healthy controls and RPL patients. There were significant differences in age (1:40 dilution) and BMI (1:160 dilution) between the ANA-positive and ANA-negative groups. WIDER IMPLICATIONS OF THE FINDINGS Our results suggest that ANA testing is not useful to predict future pregnancy loss in women with RPL without known cause. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by MEXT Promotion of Distinctive Joint Research Center Program, Grant Number JPMXP0621467963 and used for English proofreading costs. There are no competing interests for all authors. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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抗核抗体与复发性流产患者妊娠预后的相关性


研究问题 在没有抗磷脂抗体 （aPL） 的情况下，抗核抗体 （ANA） 会影响不明原因的复发性流产 （RPL） 患者随后的活产率 （LBR） 吗？摘要 答案 不明原因 RPL 女性在妊娠试验阳性后活产的可能性很高 （>70%），无论临界值如何，ANA 检测阳性和阴性的女性都相似。已知的ESHRE 的 RPL 指南指出，“出于解释目的，可以考虑进行 ANA 测试”。然而，关于这个问题的研究数量有限，样本量也很小，ANA 对妊娠预后的影响尚不清楚。研究设计、规模、持续时间 2006 年至 2019 年期间在名古屋市立大学医院进行了一项回顾性队列研究。该研究包括 1021 名原因不明的 RPL 女性。参与者/材料、地点、方法、伴侣双方的染色体分析、aPL、ANA、甲状腺功能减退症和糖尿病的血液检查在随后的怀孕前进行。通过在 Hep-2 细胞载玻片上间接免疫荧光测量 ANA。使用的临界稀释度为 1：40。此外，根据免疫荧光染色的 ANA 模式对患者进行分类：均质、斑点、核仁、着丝粒、外周、细胞质等。在排除抗磷脂抗体综合征患者、任何一方染色体异常和子宫异常患者后，比较 ANA 阳性和 ANA 阴性患者之间的 LBR。主要结果和机会的作用考虑到临界值 = 1：40 稀释度，ANA 阳性组随后的 LBR 为 72.5% （256/353） 和 73。ANA 阴性组为 2% （489/668）;比值比 （OR） = 0.97,95% CI = 0.72–1.29。在排除胚胎非整倍体流产、生化妊娠丢失和异位妊娠后，ANA 阳性组的 LBR 为 92.8% （256/276），ANA 阴性组为 93.0% （489/526）：OR = 0.97 （95% CI = 0.55-1.70）。考虑到临界值 = 1：80 稀释度，ANA 阳性组随后的 LBR 为 75.0% （87/116），ANA 阴性组为 72.7% （658/905）;OR = 1.13 （95% CI = 0.72–1.76）。在排除胚胎非整倍体流产、生化妊娠丢失和异位妊娠后，ANA 阳性组的 LBR 为 89.7% （87/97），ANA 阴性组为 93.3% （658/705）：OR = 0.62 （95% CI = 0.30-1.27）。考虑到临界值 = 1：160 稀释度，ANA 阳性组随后的 LBR 为 82.4% （28/34），ANA 阴性组为 72.6% （717/987）;OR = 1.76 （95% CI = 0.72–4.29）。在排除胚胎非整倍体流产、生化妊娠丢失和异位妊娠后，ANA 阳性组的 LBR 为 93.3% （28/30），ANA 阴性组为 92.9% （717/772）：OR = 1.07 （95% CI = 0.25-4.63）。调整年龄和 BMI 前后 2 组之间的 LBR 无差异，但使用 1：40 稀释液时，ANA 阳性患者显著大于 ANA 阴性患者，使用 1：80 稀释液时，ANA 阳性患者的 BMI 显著低于 ANA 阴性患者。局限性，谨慎的原因 没有建立健康对照组，因此无法比较健康对照组和 RPL 患者之间的 ANA 阳性率。 ANA 阳性组和 ANA 阴性组之间的年龄 （1：40 稀释） 和 BMI （1：160 稀释） 存在显著差异。研究结果的更广泛意义 我们的结果表明，ANA 检测对于预测原因不明的 RPL 女性未来的流产没有用。研究资金/竞争利益 本研究得到了文部科学省独特联合研究中心计划推广的支持，资助号 JPMXP0621467963 并用于英文校对费用。所有作者都没有利益争夺。试验注册号 N/A。