scholarly journals Uterine fluid proteins for minimally invasive assessment of endometrial receptivity

2019 ◽  
Author(s):  
Sergo Kasvandik ◽  
Merilin Saarma ◽  
Tanel Kaart ◽  
Ilmatar Rooda ◽  
Agne-Velthut Meikas ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Embryo Transfer ◽  
Endometrial Receptivity ◽  
Uterine Receptivity ◽  
Recurrent Implantation Failure ◽  
Secretory Phase ◽  
Minimal Invasiveness ◽  
Specificity And Sensitivity ◽  
Uterine Fluid ◽  
Secretory Endometrium

Abstract Context Clinically used endometrial (EM) receptivity assays are based on transcriptomic patterning of biopsies at mid-secretory endometrium (MSE) to identify the possible displacement or disruption of window of implantation (WOI) in patients with recurrent implantation failure (RIF). However, biopsies are invasive and cannot be performed in the same cycle with IVF embryo transfer, while uterine fluid (UF) analysis is considered minimally invasive and can immediately precede embryo transfer. Objective To determine whether UF proteome can be used for WOI monitoring and whether it would highlight the etiology of RIF. Patients Paired early secretory endometrial (ESE) and MSE UF samples from six fertile control women for discovery, and additional 11 paired ESE/MSE samples from controls and 29 MSE samples from RIF patients for validation. Results Using discovery mass spectrometry (MS) proteomics we detected 3,158 proteins from secretory phase UF of which 367 undergo significant (q < 0.05) proteomic changes while transitioning from ESE to MSE. 45 proteins were further validated with targeted MS, and 21 were found to display similar levels between control ESE and RIF MSE, indicating displacement of the WOI. Panel of PGR, NNMT, SLC26A2 and LCN2 demonstrated specificity and sensitivity of 91.7% for distinguishing MSE from ESE samples. The same panel distinguished control MSE samples from RIF MSE with a 91.7% specificity and 96.6% sensitivity. Conclusion UF proteins can be used for estimating uterine receptivity with minimal invasiveness. Women with RIF appear to have altered MSE UF profiles that may contribute to their low IVF success rate.

scholarly journals Uterine fluid proteins for minimally invasive assessment of endometrial receptivity

2019 ◽  
Author(s):  
Sergo Kasvandik ◽  
Merilin Saarma ◽  
Tanel Kaart ◽  
Ilmatar Rooda ◽  
Agne-Velthut Meikas ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Embryo Transfer ◽  
Endometrial Receptivity ◽  
Uterine Receptivity ◽  
Recurrent Implantation Failure ◽  
Secretory Phase ◽  
Minimal Invasiveness ◽  
Specificity And Sensitivity ◽  
Uterine Fluid ◽  
Secretory Endometrium

Abstract Context Clinically used endometrial (EM) receptivity assays are based on transcriptomic patterning of biopsies at mid-secretory endometrium (MSE) to identify the possible displacement or disruption of window of implantation (WOI) in patients with recurrent implantation failure (RIF). However, biopsies are invasive and cannot be performed in the same cycle with IVF embryo transfer, while uterine fluid (UF) analysis is considered minimally invasive and can immediately precede embryo transfer. Objective To determine whether UF proteome can be used for WOI monitoring and whether it would highlight the etiology of RIF. Patients Paired early secretory endometrial (ESE) and MSE UF samples from six fertile control women for discovery, and additional 11 paired ESE/MSE samples from controls and 29 MSE samples from RIF patients for validation. Results Using discovery mass spectrometry (MS) proteomics we detected 3,158 proteins from secretory phase UF of which 367 undergo significant (q < 0.05) proteomic changes while transitioning from ESE to MSE. 45 proteins were further validated with targeted MS, and 21 were found to display similar levels between control ESE and RIF MSE, indicating displacement of the WOI. Panel of PGR, NNMT, SLC26A2 and LCN2 demonstrated specificity and sensitivity of 91.7% for distinguishing MSE from ESE samples. The same panel distinguished control MSE samples from RIF MSE with a 91.7% specificity and 96.6% sensitivity. Conclusion UF proteins can be used for estimating uterine receptivity with minimal invasiveness. Women with RIF appear to have altered MSE UF profiles that may contribute to their low IVF success rate.

Uterine Fluid Proteins for Minimally Invasive Assessment of Endometrial Receptivity

2019 ◽  
Vol 105 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Sergo Kasvandik ◽  
Merilin Saarma ◽  
Tanel Kaart ◽  
Ilmatar Rooda ◽  
Agne Velthut-Meikas ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Embryo Transfer ◽  
Uterine Receptivity ◽  
Recurrent Implantation Failure ◽  
Secretory Phase ◽  
Vitro Fertilization ◽  
Minimal Invasiveness ◽  
Specificity And Sensitivity ◽  
Uterine Fluid

Abstract Context Clinically used endometrial (EM) receptivity assays are based on transcriptomic patterning of biopsies at midsecretory endometrium (MSE) to identify the possible displacement or disruption of window of implantation (WOI) in patients with recurrent implantation failure (RIF). However, biopsies are invasive and cannot be performed in the same cycle with in vitro fertilization embryo transfer, while uterine fluid (UF) analysis is considered minimally invasive and can immediately precede embryo transfer. Objective To determine whether UF proteome can be used for WOI monitoring and whether it would highlight the etiology of RIF. Patients Paired early secretory endometrial (ESE) and MSE UF samples from six fertile control women for discovery, and an additional 11 paired ESE/MSE samples from controls and 29 MSE samples from RIF patients for validation. Results Using discovery mass spectrometry (MS) proteomics we detected 3158 proteins from secretory phase UF of which 367 undergo significant (q &lt; 0.05) proteomic changes while transitioning from ESE to MSE. Forty-five proteins were further validated with targeted MS, and 21 were found to display similar levels between control ESE and RIF MSE, indicating displacement of the WOI. A panel of PGR, NNMT, SLC26A2 and LCN2 demonstrated specificity and sensitivity of 91.7% for distinguishing MSE from ESE samples. The same panel distinguished control MSE samples from RIF MSE with a 91.7% specificity and 96.6% sensitivity. Conclusion UF proteins can be used for estimating uterine receptivity with minimal invasiveness. Women with RIF appear to have altered MSE UF profiles that may contribute to their low IVF success rate.

scholarly journals A Two-Cohort RNA-seq Study Reveals Changes in Endometrial and Blood miRNome in Fertile and Infertile Women

Genes ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 574 ◽  
Author(s):  
Kadri Rekker ◽  
Signe Altmäe ◽  
Marina Suhorutshenko ◽  
Maire Peters ◽  
Juan F. Martinez-Blanch ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Small Rna Sequencing ◽  
Rna Seq ◽  
Recurrent Implantation Failure ◽  
Secretory Phase ◽  
Blood Samples ◽  
Infertile Women ◽  
Secretory Endometrium ◽  
Fertile Women

The endometrium undergoes extensive changes to prepare for embryo implantation and microRNAs (miRNAs) have been described as playing a significant role in the regulation of endometrial receptivity. However, there is no consensus about the miRNAs involved in mid-secretory endometrial functions. We analysed the complete endometrial miRNome from early secretory (pre-receptive) and mid-secretory (receptive) phases from fertile women and from patients with recurrent implantation failure (RIF) to reveal differentially expressed (DE) miRNAs in the mid-secretory endometrium. Furthermore, we investigated whether the overall changes during early to mid-secretory phase transition and with RIF condition could be reflected in blood miRNA profiles. In total, 116 endometrial and 114 matched blood samples collected from two different population cohorts were subjected to small RNA sequencing. Among fertile women, 91 DE miRNAs were identified in the mid-secretory vs. early secretory endometrium, while no differences were found in the corresponding blood samples. The comparison of mid-secretory phase samples between fertile and infertile women revealed 21 DE miRNAs from the endometrium and one from blood samples. Among discovered novel miRNAs, chr2_4401 was validated and showed up-regulation in the mid-secretory endometrium. Besides novel findings, we confirmed the involvement of miR-30 and miR-200 family members in mid-secretory endometrial functions.

scholarly journals Clinical applications of endometrial receptivity tests in patients with recurrent implantation failure

2021 ◽  
Vol 16 (1) ◽  
pp. 79-85
Author(s):  
Ioan BOLEAC ◽  
◽  
Manuela NEAGU ◽  
Anca CORICOVAC ◽  
Dorina CODREANU ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Embryo Transfer ◽  
Expression Profile ◽  
Clinical Applications ◽  
Endometrial Receptivity ◽  
Clinical Pregnancy ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Endometrial Cells

Recurrent implantation failure is represented by the failure to achieve a clinical pregnancy after transfer of at least 4 good-quality embryos in a minimum of 3 fresh or frozen cycles in a woman under the age of 40 years. One of the recent approaches in studying the window of implantation was building the expression profile of the genes of the endometrial cells. We performed a retrospective study which investigated if endometrial receptivity tests improved the outcomes of IVF procedures in patients with recurrent implantation failure. We enrolled 47 couples with RIF and divided them in 2 groups: the first group of 22 couples performed the ERA test and the embryo transfer according to the result of the test; the second group of 27 couples had the embryo transfer done without the ERA test. Our conclusion was that the ERA test did not improve the outcomes for patients with recurrent implantation failure.

scholarly journals Evaluation of Pregnancy Outcomes of Vitrified-Warmed Blastocyst Transfer before and after Endometrial Receptivity Analysis in Identical Patients with Recurrent Implantation Failure

2021 ◽  
pp. 1-7
Author(s):  
Yuta Kasahara ◽  
Tomoko Hashimoto ◽  
Ryo Yokomizo ◽  
Yuya Takeshige ◽  
Koki Yoshinaga ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
Endometrial Receptivity ◽  
Pregnancy Rates ◽  
Blastocyst Transfer ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Clinical Value ◽  
Ongoing Pregnancy Rate

Background:The clinical value of personalized embryo transfer (pET) guided by the endometrial receptivity analysis (ERA) tests for recurrent implantation failure (RIF) cases is still unclear. The aim of this study is to clarify the efficacy of ERA leading to personalization of the day of embryo transfer (ET) in RIF patients. Methods: A retrospective study was performed for 94 patients with RIF who underwent ERA between July 2015 and December 2019. Pregnancy outcomes in a previous vitrified-warmed blastocyst transfer (previous VBT) and a personalized vitrified-warmed blastocyst transfer (pVBT) in identical patients were compared. The details of each pVBT were further analyzed between patients in a non-displaced group, which indicated “receptive” cases in ERA results and those who were in the displaced group, which indicated “non-receptive” cases. Results:When the pregnancy rate, both per patient and per transfer cycle, of previous VBT and pVBT were compared, a significant increase in pVBT was observed between the two methods (5.3% vs. 62.8%, 4.4% vs. 47.9%, respectively). The pregnancy rates, implantation rates, and clinical pregnancy rates of the first pVBT were significantly higher in the displaced group than the non-displaced group. The cumulative ongoing pregnancy rate of the displaced group tended to be higher compared to that of the non-displaced group in the first pVBT, although the difference was not statistically significant (51.0% vs. 31.1%, [Formula: see text] = 0.06). Conclusions:Our study demonstrates that pVBT guided by ERA tests may improve pregnancy outcomes in RIF patients whose window of implantation (WOI) is displaced, and its effect may be more pronounced at the first pVBT. The displacement of WOI may be considered to be one of the causes of RIF, and its adjustment may contribute to the improvement of pregnancy outcomes in RIF patients.

P–387 Serum progesterone levels on the day of the endometrial receptivity analysis (ERA) biopsy do not correlate with the biopsy results

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S Ahuja ◽  
A Taranissi ◽  
M Taranissi
Keyword(s):  
Embryo Transfer ◽  
Essential Element ◽  
Endometrial Biopsy ◽  
Endometrial Receptivity ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Serum Progesterone ◽  
Endometrial Cells ◽  
Live Births ◽  
Negative Results

Abstract Study question Do the serum progesterone levels on the day of the endometrial receptivity analysis (ERA) biopsy correlate with the results of the ERA? Summary answer Serum progesterone levels on the day of the endometrial receptivity analysis biopsy do not correlate with the biopsy results. What is known already Endometrial receptivity is a time sensitive window characterised by maturation of the endometrium, during which the trophectodermal cells attach to the endometrial cells and invade the endometrial stromal vasculature. Progesterone is an essential element for receptivity and pregnancy. There is no consensus regarding the optimal progesterone levels in the luteal phase, for a successful pregnancy. Endometrial receptivity analysis is a diagnostic tool developed by profiling the transcriptome of over 238 genes that are expressed at different stages of the endometrial cycle. The results are reported as receptive, pre-receptive, early receptive, etc and are used to direct a personalised embryo transfer. Study design, size, duration We report a prospective study of 30 patients with a history of recurrent implantation failure (RIF). They underwent ERA testing in a medicated cycle, between early 2018 and late 2020. Participants/materials, setting, methods A large proportion of the patients we treat in our clinic (ARGC) have recurrent implantation failure. Thirty patients with RIF underwent ERA testing in a medicated cycle.They all followed the same protocol with down regulation, followed by estrogenic preparation for about 12–14 days, followed by progesterone for about 120 hours. An endometrial biopsy was taken at about 120 hours after progesterone exposure. Main results and the role of chance An ERA result was available on 28/30 patients. Eighteen were reported to be pre-receptive, seven receptive, 3 early receptive and 2 could not be analysed. The progesterone levels within 24 hours of the biopsy for the pre-receptive group ranged from 21.2–472 nmol/l, for the receptive group ranged from 27.8–152 nmol/l and for the early receptive group ranged from 54.9–162 nmol/l. Though the number of cases is small, we found no co-relation between the serum progesterone levels with the ERA results. Eighteen women underwent an embryo transfer based on the ERA results (pET-personalised embryo transfer). Eleven were positive with four live births, one early ongoing pregnancy, three miscarriages, one ectopic pregnancy, two biochemical pregnancies and seven negative results. Seven women had euploid embryo transfers-three had live births, one is viable at 11 weeks, one had a missed miscarriage and two were negative. There are no studies correlating the serum progesterone levels and the ERA results. In practice, we plan embryo transfers for women in frozen cycles by monitoring the serum progesterone levels alongside the day of the cycle. Hence, we wanted to review if the combination of the progesterone levels along with biopsy results would allow us the improve the results further. Limitations, reasons for caution This is a small study. Larger datasets are required to draw meaningful conclusions. Wider implications of the findings: If the above findings are confirmed by larger studies, we may not need to monitor serum progesterone levels during ERA biopsy cycles. Trial registration number NA

P–313 Endometrial receptivity analysis for personalized embryo transfer in patients with recurrent implantation failure: a retrospective analysis of a Chinese cohort

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Jia ◽  
Y L Sha ◽  
Z Qiu ◽  
Y H Guo ◽  
A X Tan ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Retrospective Analysis ◽  
Embryo Transfer ◽  
Chinese Women ◽  
Endometrial Receptivity ◽  
Control Group ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Biochemical Pregnancy ◽  
Implantation Rates

Abstract Study question To quantify the effectiveness of endometrial receptivity analysis (ERA)-guided personalized embryo transfer (pET) in Chinese women. Summary answer ERA-guided pET may remarkably improve pregnancy and implantation rates among Chinese women with Recurrent implantation failure (RIF). What is known already RIF is a major cause of infertility, and endometrial receptivity is widely accepted to impact implantation failure. Precision prediction of the WOI, the time when the endometrium is most receptive to the implantation of the embryo, is, therefore, of great significance to improve implantation prospects. Previous studies have shown the effectiveness of ERA for the prediction of the WOI, and how pET, timed by ERA, improves implantation and pregnancy rates; however, the efficacy of ERA-guided pET remains unknown for Chinese women. Study design, size, duration Patients in Chengdu Xi’nan Gynecology Hospital (Chengdu, China) who were undergoing frozen embryo transfer (FET) at the blastocyst stage on day five or day six during the period from November 2019 through September 2020 were recruited for this study. A total of 145 eligible patients were included in the study and assigned to the ERA group (n = 67) or the control group (n = 78). Clinical pregnancy outcomes were compared between the two groups. Participants/materials, setting, methods Endometrial specimens were collected the from ERA group. Total RNA was extracted from endometrial specimens, the transcriptomic sequencing data were processed using RNA-Seq and the endometrial receptivity status was assessed by the ERA predictor. The endometrium was classified as receptive or non-receptive according to the ERA assessment, and pET was done at the time determined by ERA in the ERA group. Subjects in the control group did not receive ERA and underwent blastocyst transfer normally. Main results and the role of chance The demographic and clinical characteristics were comparable between the ERA and control groups (P &gt; 0.05). The ERA test identified 10.45% of samples as receptive and 89.55% of samples as non-receptive in the ERA group, with 70.15% of samples presenting a pre-receptive profile. We observed higher cumulative pregnancy (74.63% vs. 64.10%) and cumulative implantation rate (47.32% vs. 21.68%) rates, and a lower biochemical pregnancy rate (18.00% vs. 34.00%) in the ERA group when compared to the control group (P &lt; 0.05). Additionally, we found higher pregnancy (67.16% vs. 39.74%) and implantation (46.54% vs. 16.94%) rates as well as a lower biochemical pregnancy rate (17.78% vs. 45.16%) after the first ERA test in the ERA group when compared to the control group (P &lt; 0.01). Limitations, reasons for caution First, this is a retrospective analysis, which is relatively more biased than prospective clinical trials. Second, the study sample is considerably small. Third, only 10.45% of the subjects were identified as presenting a receptive profile, which limits the comparisons of clinical outcomes between patients with receptive and non-receptive endometria. Wider implications of the findings: This study demonstrates that the ERA test helps to determine the optimal timing for embryo transfer, improve pregnancy and implantation rates in patients with RIF, and guides the clinical application of the ERA test. Trial registration number approval No. 2020–018

scholarly journals Decreased CD44v3 Expression Impairs Endometrial Stromal Cell Decidualization in Women With Recurrent Implantation Failure

2021 ◽  
Author(s):  
Xiaowei Zhou ◽  
Yi Cao ◽  
mingjuan Zhou ◽  
Mi Han ◽  
mengyu Liu ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Culture System ◽  
Embryo Implantation ◽  
Group Identification ◽  
Endometrial Receptivity ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Secretory Phase ◽  
Endometrial Stromal Cells ◽  
Cd44 Isoforms

Abstract BackgroundThe precise pathogenesis of poor endometrial receptivity in recurrent implantation failure (RIF) still remains unclear. This study aims to explore the effects of different CD44 isoforms in the mid-secretory phase endometrium on endometrial receptivity in women with RIF.MethodsMid-secretory phase endometrial tissue samples were obtained from two groups of women who had undergone IVF: a) 24 patients with RIF, b) 18 patients with infertility due to tubal obstruction, who had achieved a successful clinical pregnancy after the first embryo transfer in IVF (control group). Identification of differentially expressed CD44 isoforms in endometrial tissues was assessed with immunohistochemistry, qPCR and western blotting. Effects of CD44v3 overexpression and knockdown on proliferation and decidualization of Immortalized human endometrial stromal cells (T-HESCs) and primary HESCs were investigated by qPCR and Western blot. A heterologous co-culture system of embryo implantation was constructed to mimics the process of trophoblast invasion during implantation.ResultsCD44v3 was significantly higher expressed in mid-secretory phase of endometrial stromal cells than proliferation phase, but was notably lower in RIF patients. The expression of decidualization markers, prolactin (PRL) and insulin like growth factor binding protein-1 (IGFBP1), was notably decreased following CD44v3 knockdown, whereas the expression levels of both PRL and IGFBP1 increased after CD44v3 overexpression in HESCs. Furthermore, the CD44v3-knockdown HESCs displayed a significantly deficiency in supporting trophoblast outgrowth through a co-culture system of embryo implantation; however, CD44v3 overexpression in HESCs promoted trophoblast outgrowth.ConclusionThe reduced expression of CD44v3 suppresses HESCs proliferation and decidualization, which might play a pivotal role in poor endometrial receptivity in women with RIF.

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