Association of Interleukin-33 with Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis Study

Recurrent pregnancy loss (RPL) is a condition in which a woman experiences two or more consecutive miscarriages before reaching 20 weeks of gestation. The present study was designed to explore the potential link between the interleukin (IL)-33 and RPL. To achieve this goal, we conducted a comprehensive search across the ISI, PubMed, Embase, and Scopus databases.

We reviewed studies that examined the relationship between specific IL-33 polymorphisms and RPL using the appropriate keywords. The comparator in our study consisted of a control group that included women without RPL. This group was used to assess the differences in genetic polymorphisms and IL-33 serum levels compared to women who experienced RPL. We analyzed the collected data using a random-effects model in STATA (version 14). Five case-control studies were eligible, yielding a total sample size of 1,831 participants (891 cases and 940 controls).

The results revealed a significant association between the GG genotype of IL-33 polymorphisms rs16924159 and rs1929992 [odds ratio (OR)=0.72, 95% confidence intervals (CI)=0.51-1.02, I²=58.2, P=0.068] and RPL. The presence of the GG genotype of IL-33 polymorphisms rs16924159 and rs1929992 in women was associated with a 0.72-fold increased risk of RPL. Additionally, no statistically significant correlation was noted between IL-33 GA (OR=1.19, 95% CI=75-1.88, I²=80.7, P=0.001) and AA (OR=1.02, 95% CI=0.81-1.29, I²=71.8, P=0.029) genotypes and RPL. Analysis of IL-33 serum levels indicated a significant association with RPL (OR=-0.45, 95% CI=-0.67-(- 0.23), I²=57.3, P=0.128).

Our findings demonstrate an association between the GG genotype of IL-33 polymorphisms and an increased risk of RPL. Moreover, higher serum levels of IL-33 are likely protective against RPL.