Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Lee YX

PROVIDER: S-EPMC9863254 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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

Lee Yi-Xuan YX Su Po-Hsuan PH Do Anh Q AQ Tzeng Chii-Ruei CR Hu Yu-Ming YM Chen Chi-Huang CH Chen Chien-Wen CW Liao Chi-Chun CC Chen Lin-Yu LY Weng Yu-Chun YC Wang Hui-Chen HC Lai Hung-Cheng HC

International journal of molecular sciences 20230115 2

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 pr ...[more]

PMID: 36675243

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Project description:Background: Nowadays, frozen-thawed embryo transfer (FET) cycles represent a high proportion of fertility treatments worldwide. Recent studies suggest differences in pregnancy outcomes depending on the FET treatment protocol used. The reason for this is still unclear, but the number of corpora lutea (CL) at conception is discussed as a possible factor. This study aims to investigate whether maternal and neonatal outcomes for pregnancies following FET lacking a CL differ from FET with one or more CL in order to explore a potential link between CL absence and adverse pregnancy outcomes. Methods: The study was designed as a retrospective, multi-center observational study with two cohorts after singleton live birth [0 CL cohort (FET in a programmed cycle, n = 114) and ≥ 1 CL cohort (FET in a natural or stimulated cycle, n = 68)]. Participants completed a questionnaire on the outcome of pregnancy and birth records were analyzed in a descriptive way. Multivariable logistic and linear regressions were performed in order to explore associations between CL absence and pregnancy outcomes. The strength of the agreement between the information in the survey and the diagnoses extracted from the files was assessed by Cohen's Kappa. Results: The risk of hypertensive disorders of pregnancy was higher after FET in the absence of a CL compared to FET with CL presence (aOR 5.56, 95% CI 1.12 - 27.72). Birthweights and birthweight percentiles were significantly higher in the 0 CL group. CL absence was a predictor of higher birthweight (adjusted coefficient B 179.74, 95% CI 13.03 - 346.44) and higher birthweight percentiles (adjusted coefficient B 10.23, 95%, 95% CI 2.28 - 18.40) particularly in female newborns of the 0 CL cohort. While the strength of the agreement between the reported information in the survey and the actual diagnoses extracted from the files was good for the majority of outcomes of interest it was fair in terms of hypertension (κ = 0.38). Conclusion: This study supports observations suggesting a potential link between a lack of CL at conception and adverse maternal and neonatal outcomes. Further investigations on causes and pathophysiological relationships are yet to be conducted.

Project description:BackgroundAcupuncture is increasingly used as adjuvant therapy for infertile women undergoing frozen-thawed embryo transfer (FET); however, its effects and safety are highly controversial. This study aimed to evaluate the pooled effects of adjuvant acupuncture on FET pregnancy outcomes.MethodsWe considered only randomized controlled trials (RCTs) that compared acupuncture with sham acupuncture or no adjuvant treatment during FET and the primary outcome was clinical pregnancy rate. Two authors separately selected studies, extracted data, and performed a risk of bias assessment. Pooled data were expressed as risk ratio (RR) or mean difference (MD), with a 95% confidence interval (CI). In addition, we conducted subgroup and sensitivity analyses to investigate the sources of heterogeneity, and we also constructed funnel plots to assess the likelihood of publication bias. Finally, Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) was applied to evaluate the quality of evidence.ResultsA total of 14 RCTs with a total of 1,130 participants were included in the study. We found significant effects of acupuncture adjuvant to FET on the outcomes of clinical pregnancy rate (RR = 1.54, 95% CI [1.28, 1.85], I 2 = 34%; 14 trials), biochemical pregnancy rate (RR = 1.51, 95% CI [1.21, 1.89]; 5 trials), endometrial thickness (MD = 0.97, 95% CI [0.43, 1.51]; 12 trials), and endometrial pattern (RR = 1.41, 95% CI [1.13, 1.75]; 7 trials). For live birth rate (RR = 1.48, 95% CI [0.90, 2.43], 4 trials), there were no statistical effectiveness. For subgroup analyses, most variables had tolerable heterogeneity (I 2 = 0%) except for trials that were sham-controlled, performed acupuncture only after FET, or <5 times, which appeared to interpret most of the heterogeneity. Additionally, the quality of evidence of all outcomes in this review ranged from low to moderate.ConclusionAcupuncture could be instrumental in the pregnancy outcomes of FET, and has very few risks of severe adverse events; however, the quality of evidence is unsatisfactory. Further research with rigorous methodological quality should be considered, and the protocols of acupuncture also need more investigations (e.g., appropriate control groups, sessions, and times).

Project description:Background: Nowadays, the choice of frozen embryo transfer (FET) regimens is mainly guided by personal convenience. Clinicians prefer the predictability and reliability of artificial cycle (AC) FET and have extended its usage to general in vitro fertilization population. More recent primary studies are beginning to challenge the comparability of AC-FET and suggest reduced clinical pregnancy rate and live birth rate (LBR) compared with those in modified natural cycle (mNC) FET (ovulation triggered by human chorionic gonadotrophin) and stimulated cycle (SC) FET. Objective: To assess the pregnancy outcomes within matched mNC-FET, SC-FET, and AC-FET cycles by using propensity score matching (PSM) in a larger cohort. Methods: A total of 16,946 women who underwent their first autologous FET cycle between July 2014 and July 2017 were evaluated. PSM, using the nearest neighbor matching, were established to adjust the baseline features within the three protocols in proportion of 1:1 (mNC-FET vs. SC-FET, mNC-FET vs. AC-FET, SC-FET vs. AC-FET). Furthermore, there were 3,567, 2,917, and 3,964 cycles compared between matched mNC-FET and SC-FET, mNC-FET and AC-FET, and SC-FET and AC-FET after the PSM, respectively. Results: LBR was significant lower in the AC-FET group than that in the mNC-FET (40.0 vs. 43.3%) and SC-FET groups (40.9 vs. 46.5%). The adjusted odds ratios (95% CIs) were 1.11 (1.00, 1.24) for mNC/AC (P = 0.044) and 0.84 (0.76, 0.92) for AC/SC (P < 0.001), which indicated that the AC-FET group was associated with lowest LBR. The LBR was comparable between matched mNC-FET and SC-FET after adjusting for endometrial thickness. Moreover, a lower clinical pregnancy rate and a higher risk of early pregnancy loss were discovered in AC-FET cycles compared with those in SC-FET. Conclusion: In view of our data, AC used for scheduling FET was associated with lower LBR compared with SC and modified natural cycle. This interpretation requires future verification from well-designed prospective multicenter randomized clinical trials, although the comparisons in our study were conducted in the homogenous population after the PSM.

Project description:IntroductionAlthough it is well-known that obesity increases the risk of gestational hypertension (GH) in both spontaneous and assisted reproductive technology (ART) pregnancies. Recent data show that, in ART pregnancies, frozen-thawed embryo transfer (FET) is associated with an even higher risk of GH compared with fresh transfer. However, the relationship between pre-gravid body mass index (BMI) and GH in FET pregnancies has seldom been reported.ObjectiveThe aim of this study is to examine the effect of pre-gravid BMI on GH in singleton pregnancy following FET.MethodsA retrospective cohort study at a tertiary hospital, including a total of 7,502 women who achieved singleton pregnancy after FET, was included. All patients were enrolled only once. On the basis of the BMI definitions of the Working Group on Obesity in China (WGOC) and the World Health Organization, the women were divided into normal BMI, overweight, and obese groups. The main outcome was GH, and the effect of pre-pregnancy BMI on GH was assessed by generalized linear model.ResultsThe risk of GH in our study population was 6.15%. According to the BMI definitions of the WGOC, the risk of GH in the obese group (15.55%) was significantly higher than that of the overweight group (8.26%, P < 0.001) and the normal BMI group (4.68%, P < 0.001). Pre-gravid overweight and obesity were associated with higher GH risk (OR, 1.77; 95% CI, 1.41-2.20; P < 0.001; OR, 3.69; 95% CI, 2.77-4.91; P < 0.001). A non-linear relationship between pre-gravid BMI and GH was observed. The risk of GH decreased with pre-gravid BMI level up to the turning point of BMI = 28.6 kg/m2 (OR, 1.16; 95% CI, 1.12-1.21; P < 0.001).ConclusionPre-gravid overweight and obesity are associated with higher GH risk among singleton pregnancy following FET. Before the turning point of BMI = 26.8 kg/m2, the risk of GH may increase 16.4% with each one-unit increment of maternal BMI. Women preparing for FET should maintain a normal BMI to lower the chances of GH.

Dataset Information

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

Publications

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

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