Yoshihara H, Goto S, Kitaori Tamao, Sugiura-Ogasawara M
Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan.
Hum Reprod. 2025 Feb 1;40(2):236-243. doi: 10.1093/humrep/deae280.
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)?
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.
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.
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.
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.
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在无抗磷脂抗体（aPL）的不明原因复发性流产（RPL）患者中，抗核抗体（ANA）是否会影响随后的活产率（LBR）？
不明原因RPL且妊娠试验呈阳性的女性有较高的活产概率（>70%），ANA检测呈阳性和阴性的女性之间活产概率相似，与临界值无关。
欧洲人类生殖与胚胎学会（ESHRE）的RPL指南指出，“可考虑进行ANA检测以作解释之用”。然而，关于此问题的研究数量有限，样本量较小，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。该研究纳入了1021名原因不明的RPL女性。
研究对象/材料、研究环境、方法：在随后妊娠前进行子宫输卵管造影或三维超声检查、双方染色体分析、aPL、ANA、甲状腺功能减退和糖尿病的血液检查。ANA通过在人喉癌（Hep-2）细胞玻片上进行间接免疫荧光法检测。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：均质型、斑点型、核仁型、着丝粒型、周边型、胞浆型及其他类型。在排除抗磷脂抗体综合征患者、任何一方染色体异常患者及子宫异常患者后，比较ANA阳性和阴性患者的活产率。
考虑临界值 = 1:40稀释度时，ANA阳性组随后的活产率为72.5%（256/353），ANA阴性组为73.2%（489/668）；优势比（OR） = 0.97，95%置信区间（CI） = 0.72 - 1.29。排除胚胎非整倍体流产、生化妊娠丢失和异位妊娠后，ANA阳性组活产率为92.8%（256/276），ANA阴性组为93.0%（489/526）：OR = 0.97（95%CI = 0.55 - 1.70）。考虑临界值 = 1:80稀释度时，ANA阳性组随后的活产率为75.0%（87/116），ANA阴性组为72.7%（658/905）；OR = 1.13（95%CI = 0.72 - 1.76）。排除胚胎非整倍体流产、生化妊娠丢失和异位妊娠后，ANA阳性组活产率为89.7%（87/97），ANA阴性组为93.3%（658/705）：OR = 0.62（95%CI = 0.30 - 1.27）。考虑临界值 = 1:160稀释度时，ANA阳性组随后的活产率为82.4%（28/34），ANA阴性组为72.6%（717/987）；OR = 1.76（95%CI = 0.72 - 4.29）。排除胚胎非整倍体流产、生化妊娠丢失和异位妊娠后，ANA阳性组活产率为93.3%（28/30），ANA阴性组为92.9%（717/772）：OR = 1.07（95%CI = 0.25 - 4.63）。在调整年龄和体重指数（BMI）前后，两组的活产率均无差异，但使用1:40稀释度时，ANA阳性患者年龄显著大于ANA阴性患者，使用1:80稀释度时，ANA阳性患者的BMI显著低于ANA阴性患者。
局限性、谨慎原因：未设立健康对照组，无法比较健康对照与RPL患者之间的ANA阳性率。ANA阳性组和阴性组之间在年龄（1:40稀释度）和BMI（1:160稀释度）方面存在显著差异。
我们的结果表明，ANA检测对于预测原因不明的RPL女性未来的妊娠丢失并无帮助。
研究资助/利益冲突：本研究由日本文部科学省（MEXT）特色联合研究中心推进项目资助，资助编号JPMXP0621467963，用于英文校对费用。所有作者均无利益冲突。
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