Changes in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data

Background

Hormonal changes during the menstrual cycle appear to play a key role in shaping immunity in the cervicovaginal tract and may influence the risk of sexually transmitted infections. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle but have often shown conflicting results. Thus, our understanding of the immunological correlates of the menstrual cycle remains vague and could be improved by a meta-analysis of all available data sets.

Results

We present a protocol for a systematic review and meta-analysis of individual participant data of cervicovaginal immune mediators during the menstrual cycle. Our primary objective is to estimate the differences in concentrations of immune mediators between the follicular and luteal phases of the menstrual cycle. Our secondary objectives are to compare how four technical factors (sample type, assay type, method of determining menstrual cycle phase, and normalization of immune mediator concentrations to total protein) affect the estimated differences across the menstrual cycle phases. In addition to summarizing previous studies, we will perform a new study, measuring select immune mediators in 200 paired cervicovaginal lavage samples. This additional study will strengthen the evidence and test the validity of the meta-analysis.

Conclusions

Our systematic review and meta-analysis will provide precise estimates of immune mediator concentrations throughout the menstrual cycle. This improved understanding of cervicovaginal immunity across the menstrual cycle will provide important baseline knowledge for the design of clinical trials of vaginal interventions, including hormonal contraception and prevention tools for sexually transmitted infections.