Association between antinuclear antibodies and pregnancy prognosis in recurrent pregnancy loss patients

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.

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.

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.

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.

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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