Relationship between early and mid-lateal phase progesterone levels and the DNA methylation of WOI-related genes in cervical secretions in fresh and frozen IVF cycles

Abstract

Objective

To study the association between serum progesterone (P4) levels on the day of embryo transfer (ET) and the deoxyribonucleic acid methylation of window of implantation-related genes in cervical secretions, in both fresh and frozen ET cycles among women undergoing in vitro fertilization (IVF) treatment.

Design

Single-center retrospective cohort study.

Subjects

Women undergoing ET cycles.

Exposure

Cervicovaginal materials have been used as a noninvasive surrogate in investigations of endometrial conditions and progesterone levels on the day of ET.

Main Outcome Measures

Progesterone levels and methylation changes.

Results

A total of 40 eligible women undergoing IVF-ET cycles were evaluated. On the basis of methylation analyses of CXCL14, EMCN, RARRES1, PAEP, THBS2, and GPX3, no statistically significant correlation was found with the median serum P4 levels on the day of ET. When participants were grouped into quartiles on the basis of P4 levels on the day of ET, no statistically significant differences were observed in the methylation levels of CXCL14, SERPING1, EMCN, RARRES1, PAEP, THBS2, and GPX3. The median P4 levels were significantly lower in the thawed ET group (median, 21.4 ng/mL; interquartile range, 13.3–24.0) than in the fresh transfer group (median, 24.0 ng/mL; interquartile range, 18.0–45.0). No significant differences in gene methylation levels were observed between fresh and thawed transfer types, except for THBS2, which showed significantly lower methylation levels in the thawed group than in the fresh group. Although the median P4 levels were lower on day 3 transfers (16.6 ng/mL) than on day 5 transfers (22.4 ng/mL), the difference was not statistically significant. Similarly, no significant differences in methylation levels were detected when comparing day 3 vs. day 5 ET groups.

Conclusion

No association was found between early and mid-luteal phase P4 levels and methylation changes of implantation-related genes in cervical secretions during both fresh and frozen IVF cycles.