Cervical Secretion Methylation Is Associated with the Pregnancy Outcome of Frozen-Thawed Embryo Transfer

Yi Xuan Lee, Po Hsuan Su, Anh Q. Do, Chii Ruei Tzeng, Yu Ming Hu, Chi Huang Chen, Chien Wen Chen, Chi Chun Liao, Lin Yu Chen, Yu Chun Weng, Hui Chen Wang, Hung Cheng Lai

Research output: Contribution to journalArticlepeer-review


The causes of implantation failure remain a black box in reproductive medicine. The exact mechanism behind the regulation of endometrial receptivity is still unknown. Epigenetic modifications influence gene expression patterns and may alter the receptivity of human endometrium. Cervical secretions contain endometrial genetic material, which can be used as an indicator of the endometrial condition. This study evaluates the association between the cervical secretion gene methylation profile and pregnancy outcome in a frozen-thawed embryonic transfer (FET) cycle. Cervical secretions were collected from women who entered the FET cycle with a blastocyst transfer (36 pregnant and 36 non-pregnant women). The DNA methylation profiles of six candidate genes selected from the literature review were measured by quantitative methylation-specific PCR (qMSP). Bioinformatic analysis of six selected candidate genes showed significant differences in DNA methylation between receptive and pre-receptive endometrium. All candidate genes showed different degrees of correlation with the pregnancy outcomes in the logistic regression model. A machine learning approach showed that the combination of candidate genes’ DNA methylation profiles could differentiate pregnant from non-pregnant samples with an accuracy as high as 86.67% and an AUC of 0.81. This study demonstrated the association between cervical secretion methylation profiles and pregnancy outcomes in an FET cycle and provides a basis for potential clinical application as a non-invasive method for implantation prediction.

Original languageEnglish
Article number1726
JournalInternational journal of molecular sciences
Issue number2
Publication statusPublished - Jan 2023


  • cervical secretion
  • implantation
  • methylation
  • non-invasive

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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