Salvatore Terrazzino

Background In order to clarify the role of the maternal apolipoprotein E (ApoE) genotype and the risk of recurrent pregnancy loss (RPL), we herein performed an updated systematic review and meta‐analysis to reevaluate the evidence on this association. Methods A comprehensive literature search was performed on PubMed, Web of Knowledge and the Cochrane library up to September 2022. Methodological study quality was assessed using the Newcastle–Ottawa Scale and the credibility of significant pooled odds ratios (ORs) was estimated by the false positive report probability and the Bayesian false discovery probability. Results Twelve studies published from 2009 to 2022 fulfilled the inclusion criteria. In the overall analysis, the ε 4 allele was found to confer an increased risk of RPL compared to the ε 3 allele (OR 1.60, 95% CI 1.00–2.55, p = 0.049) and women carrying the ApoE ε 4 allele displayed a higher risk of RPL compared with those carrying the ε 2 and ε 3 alleles (OR 1.75, 95% CI 1.06–2.87, p = 0.028). Subgroup analysis based on subjects’ ethnicity revealed that these associations were restricted to the Asian population ( ε 4 allele vs. ε 3 allele, OR 5.93, 95% CI 1.79–19.61, p = 0.004; ε 4 allele carriers vs. carriers of ε 2 and ε 3 alleles, OR 8.42, 95% CI 1.47–48.12, p = 0.017). None of the associations detected were found to be noteworthy under false positive report probability or Bayesian false discovery probability at a prior probability of 0.001. Conclusions This updated meta‐analysis highlights an association between maternal ApoE genotype and RPL risk in Asians, but not in Caucasians. Further case–control studies are warranted in women of Asian ancestry to exclude the possibility of false ‐ positive findings.