Genome-wide analysis of cervical secretions obtained during embryo transfer reveals the association between deoxyribonucleic acid methylation and pregnancy outcomes

Objective: To study whether the methylation status of cervical secretions can reflect the ability of the endometrium to allow embryo implantation. Design: Case-control study. Setting: In vitro fertilization centers. Patient(s): Women undergoing embryo transfer cycles, in which at least 1 good-quality embryo was transferred. Intervention(s): Collection of cervical secretions during the procedure of embryo transfer. Main Outcome Measure(s): Methylation profiles of cervical secretions in relation to pregnancy outcomes. Result(s): Genome-wide methylation profiles differ between cervical secretions from pregnancy and nonpregnancy cycles. Clustering analysis on the basis of the top 2,000 differentially methylated probes of cervical secretions from 28 pregnancy and 29 nonpregnancy cycles correctly categorized 86.0% of the samples in terms of conceptional status, which was verified in selected genes by quantitative methylation-specific polymerase chain reaction and validated in another independent sample set. The combination of selected genes was estimated to predict pregnancy outcomes with a maximal area under the receiver operating characteristic curve of 0.83. Conclusion(s): The methylation profiles of cervical secretions were associated with pregnancy outcomes in embryo transfer cycles. Although not clinically useful at present, deoxyribonucleic acid methylation in cervical secretions may shed new light on the less invasive assessment of endometrial receptivity.