Transcriptome sequencing of endometrium revealed alterations in mRNAs and lncRNAs after ovarian stimulation

Li, Lingxiu; Wang, Peng; Liu, Shan; Bai, Xueyan; Zou, Binbin; Li, Yuan

doi:10.1007/s10815-019-01616-5

Cited by 13 publications

(8 citation statements)

References 59 publications

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“…During the fresh embryo transfer scheme, the hyper-physiological levels of E 2 elevated the P 4 levels, which reduced endometrial receptivity (Wu et al, 2012). Li et al confirmed that in IVF/ICSI patients, the supra-physiological E 2 concentration in COH affected endometrial transcriptome profiles, resulting in a shift of the embryo transfer window via endometrial mRNA and lncRNA sequencing (Li et al, 2020). Other researchers found that there was not sufficient evidence to confirm or deny the effect of E 2 levels on clinical outcomes during the IVF/ICSI cycle on the day of hCG administration (Kosmas, Kolibianakis & Devroey, 2004).…”

Section: Discussionmentioning

confidence: 99%

Clinical and perinatal outcomes of fresh single-blastocyst-transfer cycles under an early follicular phase prolonged protocol according to day of trigger estradiol levels

Ying

Zhang

et al. 2021

PeerJ

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Backgroud This study’s objectives were to compare the clinical, perinatal, and obstetrical outcomes of patients with different estradiol (E2) levels in fresh single-blastocyst-transfer (SBT) cycles under an early follicular phase prolonged regimen on the day of trigger. Methods We recruited patients in fresh SBT cycles (n = 771) undergoing early follicular phase prolonged protocols with β-hCG values above 10 IU/L between June 2016 and December 2018. Patients who met the inclusion and exclusion criteria were divided into four groups according to their serum E2 level percentages on the day of trigger: <25th, 25th–50th, 51st–75th, and >75th percentile groups. Results Although the rates of clinical pregnancy (85.57% (166/194)), embryo implantation 86.60% (168/194), ongoing pregnancy (71.13% (138/194)), and live birth (71.13% (138/194)) were lowest in the >75th percentile group, we did not observe any significant differences (all P > 0.05). We used this information to predict the rate of severe ovarian hyperstimulation syndrome (OHSS) area under the curve (AUC) = 72.39%, P = 0.029, cut off value of E2 = 2,893 pg/ml with the 75% sensitivity and 70% specificity. The 51st–75th percentile group had the highest rates of low birth weight infants (11.73% (19/162), P = 0.0408), premature delivery (11.43% (20/175), P = 0.0269), admission to the neonatal intensive care unit (NICU) (10.49% (17/162), P = 0.0029), twin pregnancies (8.57% (15/175), P = 0.0047), and monochorionic diamniotic pregnancies (8.57% (15/175); P = 0.001). We did not observe statistical differences in obstetrics complications, including gestational diabetes mellitus (GDM), gestational hypertension, placenta previa, premature rupture of membranes (PROM), and preterm premature rupture of membranes (PPROM). Conclusion We concluded that serum E2 levels on the day of trigger were not good predictors of live birth rate or perinatal and obstetrical outcomes. However, we found that high E2 levels may not be conducive to persistent pregnancies. The E2 level on the day of trigger can still be used to predict the incidence of early onset severe OHSS in the fresh SBT cycle.

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Section: Discussionmentioning

confidence: 99%

Clinical and perinatal outcomes of fresh single-blastocyst-transfer cycles under an early follicular phase prolonged protocol according to day of trigger estradiol levels

Ying

Zhang

et al. 2021

PeerJ

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“…Cycles were excluded if: (1) the E2 level on trigger day was unavailable; (2) there were abnormal karyotypes in either of the couple; (3) embryos were generated using frozen or donor gametes, oocytes in vitro maturation, or non‐ejaculated sperms; (4) two or more fertilization methods were applied in a cycle; (5) embryo biopsies; (6) women with the diagnosis of adenomyosis, leiomyomas, intrauterine adhesion, endometrial polyps, uterine malformation, and cervical excisions. A complete cycle refers to a fresh cycle and subsequent FET cycles when all embryos are used, or at least one live birth is achieved 5 . The cycles were divided into six groups according to the E2 level on trigger day 13 : <1000, 1000–2000, 2000–3000, 3000–4000, 4000–5000 and ≥5000 pg/mL 13 …”

Section: Methodsmentioning

confidence: 99%

Estradiol on trigger day: Irrelevant to live birth rates of fresh cycles but positively associated with cumulative live birth rates

Wang,

Jin,

Shi

et al. 2023

Intl J Gynecology & Obste

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ObjectiveTo assess the effects of estradiol (E2) on trigger day on cumulative live birth rates (CLBRs), and pregnancy outcomes after fresh and frozen–thawed embryo transfer (FET).MethodsThis multicenter retrospective cohort study included 42 315 patients from five reproductive centers. Six subgroups were divided according to E2 on trigger day (<1000, 1000–2000, 2000–3000, 3000–4000, 4000–5000, >5000 pg/mL). Smooth curve fitting and nonlinear mixed‐effects models were used.ResultsWhen E2 was <5500 pg/mL, the CLBR increased by 10% for every 1000 pg/mL increase in E2. When E2 was between 5500 and 13 281 pg/mL, CLBR increased by 1.8% for every 1000 pg/mL increase in E2. When E2 was >13 281 pg/mL, CLBR decreased by 3% for every 1000 pg/mL increase in E2. From group E2 < 1000 to group E2 > 5000 pg/mL, pregnancy and live birth rates in fresh cycles were not related to E2. The live birth rate after FET was higher in the E2 ≥ 5000 pg/mL group than in the E2 < 1000 pg/mL group (odds ratio [OR] 4.03, and 95% confidence interval [CI] 3.74–4.35; adjusted OR 1.20, 95% CI 1.05–1.37).ConclusionCLBR is associated with E2 on trigger day in a segmented manner. Pregnancy and live birth rates in fresh cycles were not associated with E2. The live birth rate in FET cycles was highest when E2 ≥ 5000 pg/mL.

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“…Another lncRNA, ENST00000433673 , is expressed in epithelial and stromal endometrial cells to enhance the synthesis of ITGAL and ICAM1, two proteins required for the adhesion of the trophoblast to the endometrium [ 192 ]. LncRNAs have also been proposed as biomarkers of endometrial receptivity, such as LINC01060 and LINC01104 , whose specific functions remain to be elucidated [ 193 ].…”

Section: Non-coding Rnasmentioning

confidence: 99%

The role of epigenetic mechanisms in the regulation of gene expression in the cyclical endometrium

et al. 2021

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Background The human endometrium is a highly dynamic tissue whose function is mainly regulated by the ovarian steroid hormones estradiol and progesterone. The serum levels of these and other hormones are associated with three specific phases that compose the endometrial cycle: menstrual, proliferative, and secretory. Throughout this cycle, the endometrium exhibits different transcriptional networks according to the genes expressed in each phase. Epigenetic mechanisms are crucial in the fine-tuning of gene expression to generate such transcriptional networks. The present review aims to provide an overview of current research focused on the epigenetic mechanisms that regulate gene expression in the cyclical endometrium and discuss the technical and clinical perspectives regarding this topic. Main body The main epigenetic mechanisms reported are DNA methylation, histone post-translational modifications, and non-coding RNAs. These epigenetic mechanisms induce the expression of genes associated with transcriptional regulation, endometrial epithelial growth, angiogenesis, and stromal cell proliferation during the proliferative phase. During the secretory phase, epigenetic mechanisms promote the expression of genes associated with hormone response, insulin signaling, decidualization, and embryo implantation. Furthermore, the global content of specific epigenetic modifications and the gene expression of non-coding RNAs and epigenetic modifiers vary according to the menstrual cycle phase. In vitro and cell type-specific studies have demonstrated that epithelial and stromal cells undergo particular epigenetic changes that modulate their transcriptional networks to accomplish their function during decidualization and implantation. Conclusion and perspectives Epigenetic mechanisms are emerging as key players in regulating transcriptional networks associated with key processes and functions of the cyclical endometrium. Further studies using next-generation sequencing and single-cell technology are warranted to explore the role of other epigenetic mechanisms in each cell type that composes the endometrium throughout the menstrual cycle. The application of this knowledge will definitively provide essential information to understand the pathological mechanisms of endometrial diseases, such as endometriosis and endometrial cancer, and to identify potential therapeutic targets and improve women’s health.

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Transcriptome sequencing of endometrium revealed alterations in mRNAs and lncRNAs after ovarian stimulation

Cited by 13 publications

References 59 publications

Clinical and perinatal outcomes of fresh single-blastocyst-transfer cycles under an early follicular phase prolonged protocol according to day of trigger estradiol levels

Clinical and perinatal outcomes of fresh single-blastocyst-transfer cycles under an early follicular phase prolonged protocol according to day of trigger estradiol levels

Estradiol on trigger day: Irrelevant to live birth rates of fresh cycles but positively associated with cumulative live birth rates

The role of epigenetic mechanisms in the regulation of gene expression in the cyclical endometrium

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