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 levels on the day of embryo transfer and the DNA methylation of window of implantation (WOI)-related genes in cervical secretions, in both fresh and frozen embryo transfer cycles among women undergoing in vitro fertilization (IVF) treatment.

Design: Single-centre retrospective cohort study SUBJECTS: Women undergoing embryo transfer cyles.

Exposure: Cervicovaginal materials have been used as a noninvasive surrogate in investigations of endometrial conditions and progesteron levels on day embryo transfer.

Main outcome measure(s): Progesterone levels, methylation changes, RESULTS: A total of 40 eligible women undergoing in vitro fertilization (IVF) embryo transfer cycles were evaluated. Based on methylation analyses of CXCL14, EMCN, RARRES1, PAEP, THBS2, and GPX3, no statistically significant correlation was found with median serum progesterone (P4) levels on the day of embryo transfer (p > 0.05). When participants were grouped into quartiles based on P4 levels on the day of embryo transfer, no statistically significant differences were observed in the methylation levels of CXCL14, SERPING1, EMCN, RARRES1, PAEP, THBS2, and GPX3 (p > 0.05 for all comparisons). Median P4 levels were significantly lower in the thawed embryo transfer group (median: 21.4 ng/mL; interquartile range [IQR]: 13.3-24.0) compared to the fresh transfer group (median: 24.0 ng/mL; IQR: 18.0-45.0) (p = 0.039). 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 compared to the fresh group (p = 0.013). Although median P4 levels were lower on day 3 transfers (16.6 ng/mL) compared to day 5 transfers (22.4 ng/mL), the difference was not statistically significant (p > 0.05). Similarly, no significant differences in methylation levels were detected when comparing day 3 vs. day 5 embryo transfer groups.

Conclusions: There is no association was found between early and mid-luteal phase progesterone levels and methylation changes of implantation-related genes in cervical secretions during both fresh and frozen IVF cycles.