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

Chen, Chien-Wen; Huang, Rui-Lan; Q., Anh; Wang, Hui-Chen; Lee, Yi-Xuan; Wang, Chia-Woei; Hsieh, Chang-Chih; Tzeng, Chii‐Ruey; Hu, Yu-Ming; Chen, Chi-Huang; Weng, Yu-Chun; Su, Po-Hsuan; Chen, Lin-Yu; Lai, Hung Cheng

doi:10.1016/j.xfss.2021.12.004

Cited by 3 publications

(11 citation statements)

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“…In our previous work, we found that the genome-wide methylation profiles in cervical secretions differ between pregnancy and non-pregnancy cycles [ 41 ]. Since endometrial receptivity constitutes the ability of the endometrium to allow blastocysts to successfully implant themselves and to be nourished and sustained, we assumed that the methylation pattern of candidate genes might be associated with the pregnancy outcome in the FET cycle.…”

Section: Resultsmentioning

confidence: 99%

“…Since endometrial receptivity constitutes the ability of the endometrium to allow blastocysts to successfully implant themselves and to be nourished and sustained, we assumed that the methylation pattern of candidate genes might be associated with the pregnancy outcome in the FET cycle. To this end, we collected cervical secretion DNA methylome data from 41 women receiving FET [ 41 ]. Of the 41 women, 24 were successful in pregnancy, and 17 were not.…”

Section: Resultsmentioning

confidence: 99%

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

Lee

et al. 2023

IJMS

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Lee

et al. 2023

IJMS

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“…Previously, using a genome-wide analysis of methylation profiles from cervical secretions in embryo transfer cycles, we showed that unsupervised clustering using 2000 DMPs could correctly classify 86% of samples [ 34 ]. Consistent with that evidence, the results herein support the conclusion that DNA methylation changes detected from cervical secretions are highly relevant to the IVF-ET outcome.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, it is evident that DNA methylation markers from cervicovaginal materials can be used to detect endometrial cancer with high accuracy [ 31 , 32 , 33 ]. Furthermore, our previous study showed that DNA methylation profiles of mid-secretory cervical secretions are associated with IVF-ET outcome [ 34 ]. Herein, we hypothesized that the DNA methylation status of WOI genes from cervical secretions can be used to predict ongoing pregnancy in embryo transfer cycles.…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation of Window of Implantation Genes in Cervical Secretions Predicts Ongoing Pregnancy in Infertility Treatment

Chen³

et al. 2023

IJMS

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Window of implantation (WOI) genes have been comprehensively identified at the single cell level. DNA methylation changes in cervical secretions are associated with in vitro fertilization embryo transfer (IVF-ET) outcomes. Using a machine learning (ML) approach, we aimed to determine which methylation changes in WOI genes from cervical secretions best predict ongoing pregnancy during embryo transfer. A total of 2708 promoter probes were extracted from mid-secretory phase cervical secretion methylomic profiles for 158 WOI genes, and 152 differentially methylated probes (DMPs) were selected. Fifteen DMPs in 14 genes (BMP2, CTSA, DEFB1, GRN, MTF1, SERPINE1, SERPINE2, SFRP1, STAT3, TAGLN2, TCF4, THBS1, ZBTB20, ZNF292) were identified as the most relevant to ongoing pregnancy status. These 15 DMPs yielded accuracy rates of 83.53%, 85.26%, 85.78%, and 76.44%, and areas under the receiver operating characteristic curves (AUCs) of 0.90, 0.91, 0.89, and 0.86 for prediction by random forest (RF), naïve Bayes (NB), support vector machine (SVM), and k-nearest neighbors (KNN), respectively. SERPINE1, SERPINE2, and TAGLN2 maintained their methylation difference trends in an independent set of cervical secretion samples, resulting in accuracy rates of 71.46%, 80.06%, 80.72%, and 80.68%, and AUCs of 0.79, 0.84, 0.83, and 0.82 for prediction by RF, NB, SVM, and KNN, respectively. Our findings demonstrate that methylation changes in WOI genes detected noninvasively from cervical secretions are potential markers for predicting IVF-ET outcomes. Further studies of cervical secretion of DNA methylation markers may provide a novel approach for precision embryo transfer.

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“…Many epigenetical mechanisms are involved as well, such as DNA methylation [ 256 ], m 6 A methylation [ 166 ], or interaction with ncRNAs secreted from exosomes [ 257 ]. It has even been suggested that DNA methylation profiles of cervical secretion could serve in the future as an alternative way for diagnosing endometrial receptivity [ 258 ]. Decidualization, the process of endometrial preparation for blastocyst implantation, is suppressed in human endometrial stromal cells by an ncRNA, the miR-542-3p.…”

Section: In Utero Epigenetics Beyond Art?mentioning

confidence: 99%

An Interplay between Epigenetics and Translation in Oocyte Maturation and Embryo Development: Assisted Reproduction Perspective

2022

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Germ cell quality is a key prerequisite for successful fertilization and early embryo development. The quality is determined by the fine regulation of transcriptomic and proteomic profiles, which are prone to alteration by assisted reproduction technology (ART)-introduced in vitro methods. Gaining evidence shows the ART can influence preset epigenetic modifications within cultured oocytes or early embryos and affect their developmental competency. The aim of this review is to describe ART-determined epigenetic changes related to the oogenesis, early embryogenesis, and further in utero development. We confront the latest epigenetic, related epitranscriptomic, and translational regulation findings with the processes of meiotic maturation, fertilization, and early embryogenesis that impact the developmental competency and embryo quality. Post-ART embryo transfer, in utero implantation, and development (placentation, fetal development) are influenced by environmental and lifestyle factors. The review is emphasizing their epigenetic and ART contribution to fetal development. An epigenetic parallel among mouse, porcine, and bovine animal models and human ART is drawn to illustrate possible future mechanisms of infertility management as well as increase the awareness of the underlying mechanisms governing oocyte and embryo developmental complexity under ART conditions.

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

Cited by 3 publications

References 58 publications

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

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

DNA Methylation of Window of Implantation Genes in Cervical Secretions Predicts Ongoing Pregnancy in Infertility Treatment

An Interplay between Epigenetics and Translation in Oocyte Maturation and Embryo Development: Assisted Reproduction Perspective

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