Associations of Chlamydia trachomatis serology with fertility-related and pregnancy adverse outcomes in women: a systematic review and meta-analysis of observational studies

Abstract

Background: Chlamydia trachomatis (CT) infection has an increased risk for fertility-related and pregnancy adverse outcomes partly due to mechanisms related to a pro-inflammatory response to CT-, or cHSP60-induced delayed hypersensitivity. This study aimed to assess the evidence on the association between CT serology and adverse outcomes.

Methods: PubMed/Medline, Embase and Web of Science databases were searched for observational studies on the association of CT-specific antibodies (e. g. IgG, IgA, IgM, etc.) with infertility, tubal factor infertility (TFIF), ectopic pregnancy (EP), spontaneous abortion (SA), or preterm labor (PL) that were published from database inception to 31 August 2022. Pooled adjusted odds ratios or relative risks with corresponding 95% confidence intervals were calculated using a random effects model. This study was registered with PROSPERO (CRD42022368366).

Findings: We identified 128 studies that met the inclusion criteria, comprising 87 case-control, 34 cross-sectional and 7 cohort studies, for a total of 167 records involving 128,625 women participants included into the meta-analyses. Based on the adjusted estimates, it was found that CT-specific IgG was significantly associated with TFIF (pooled adjusted OR = 2.09, 95% CI 1.33-3.27, I² = 63.8%) or EP (pooled adjusted OR = 3.00, 95% CI 1.66-5.40, I² = 93.0%). Analyses of the unadjusted estimates indicated significant associations between CT-specific IgG and infertility, TFIF, EP or SA (four pooled unadjusted ORs ranging between 1.60 and 5.14, I² ranging between 40% and 83%); IgA and infertility, TFIF, EP (three pooled unadjusted ORs ranging between 3.64 and 4.91, I² ranging between 0% and 74%); IgM and TFIF (pooled unadjusted OR = 5.70, 95% CI 1.58-20.56, I² = 56%); or cHSP60 and TFIF (pooled unadjusted OR = 7.83, 95% CI 5.42-11.31, I² = 49%).

Interpretation: A broad range of CT-specific antibodies have been studied in association with fertility-related and pregnancy adverse outcomes. However, our study identified a low- or moderate-quality evidence for an association of CT serology with the outcomes. There are substantial research gaps in relation to the clinical implications of CT serological biomarkers.

Funding: The work was supported by the Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2016-I2M-3-021).

Keywords: Chlamydia trachomatis; Meta-analysis; Outcome; Serology.

Fig. 1

Study selection. ∗Other reasons for exclusion after full-text assessment are shown in Appendix 2. ∗∗ Full citations of the 128 included studies are in Appendix 13. The selection work was done by two authors (ZY and TY) respectively and the final results was decided after the crosscheck and discussion by the two authors.

Fig. 2

Odds ratio of tubal factor infertility or ectopic pregnancy with Chlamydia trachomatis-specific antibody IgG (adjusted). The figure shows the pooled adjusted estimates that compared the chlamydial IgG conditions on the risk of tubal factor infertility (A) or ectopic pregnancy (B). Solid diamonds and horizontal lines represent point estimates and corresponding 95% confidence intervals (CIs) of the individual studies. Transparent diamonds represent the overall estimates and 95% CIs. Full citations of the included studies are in Appendix 13.