The Role of Endometrial Biopsy in the Evaluation of Recurrent Implantation Failure

2005 ◽  
Vol 84 ◽  
pp. S272
Author(s):  
J.M. Hartnett ◽  
L. Engmann ◽  
M.M. Sanders ◽  
D. Maier ◽  
J. Nulsen ◽  
...  
Keyword(s):  
Endometrial Biopsy ◽  
Implantation Failure ◽  
Recurrent Implantation Failure

scholarly journals Role of T cells in intrauterine administration of activated peripheral blood mononuclear cells in recurrent implantation failure.

2021 ◽  
Author(s):  
Guillaume Ricaud ◽  
Cathy Vaillancourt ◽  
Veronique Blais ◽  
Marjorie Disdier ◽  
Fabien Joao ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Treg Cells ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Intrauterine administration of autologous peripheral blood mononuclear cells (PBMC) has been recently proposed as new immunotherapy for patients with unexplained recurrent implantation failure (RIF). In these patients, administration of activated PBMC 24-h or 72-h before embryo transfer resulted in a 3-fold increase in biochemical pregnancy rate. In this study we evaluated the role of T cells to promotes human endometrial receptivity. On the day of ovulation, PBMC were isolated from and activated with T cells mitogen, the phytohemagglutinin (PHA) and hCG for 48-h in a conditioned culture medium. Distributions of CD4+ T cells were characterized in 157 patients by flow cytometry before and after PHA/hCG activation. Cytokine production was analyzed by cytometric beads array. We observed in RIF patients a significant decrease in Th2 and natural Treg cells before activation with PHA/hCG and an increase of Th17 cells after activation compared to intrauterine sperm insemination (IUI) and in vitro fertilization (IVF) groups. Furthermore, the hCG/PHA treatment increases anti-inflammatory T cells (Th2 and Treg cells) compared to non-treated T cells. Principal component analysis (PCA) performed on CD4 T cell subtypes revealed a different cellular profile in the RIF compared to the IUI and IVF groups. This inflammatory state change could explain how endometrium immunomodulation by hCG-activated PBMC helps patients with unexplained RIF to reach implantation.

scholarly journals The role of G-CSF in recurrent implantation failure: A randomized double blind placebo control trial

2016 ◽  
Vol 14 (12) ◽  
pp. 737-742 ◽  
Author(s):  
Fatemeh Davari-tanha ◽  
Ensieh Shahrokh Tehraninejad ◽  
Mohadese Ghazi ◽  
Zahra Shahraki ◽  
◽  
...  
Keyword(s):  
Placebo Control Trial ◽  
Placebo Control ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Double Blind ◽  
Double Blind Placebo

P–388 Endometrial extracellular vesicles from recurrent implantation failure patients inhibited embryonic growth and implantation via miR–6131/PAK2 pathway

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Liu
Keyword(s):  
Extracellular Vesicles ◽  
Migration And Invasion ◽  
Hatching Rate ◽  
Implantation Failure ◽  
Trophoblast Cells ◽  
Recurrent Implantation Failure ◽  
Endometrial Cells ◽  
Blastocyst Rate ◽  
Fertile Women

Abstract Study question Could endometrial extracellular vesicles from recurrent implantation failure patients (RIF-EVs) attenuate the growth and implantation potentials of embryos and what are the mechanisms? Summary answer: RIF-EVs inhibited embryonic growth and decreased the trophoblast functions via miR–6131/PAK2 pathway. What is known already Recurrent implantation failure (RIF) is characterized by repeated embryo transfers without pregnancy. To date, the etiology of RIF remains poorly understood. Recent evidence indicated that extracellular vesicles (EVs) secreted by endometrial cells, played a crucial role in the implantation by regulating the development and implantation of embryos. Study design, size, duration Endometrial cells isolated from endometrial tissues of RIF patients (n = 25) and fertile women (n = 16) were cultured and modulated via hormones. Endometrial EVs from RIF patients (RIF-EVs) or fertile women (FER-EVs) were isolated from the conditioned medium. The influence of EVs on embryonic development and implantation was investigated by co-culture models of EVs and 2-cell murine embryos or HTR8/SVneo cells, respectively. High-through put sequencing was performed to identify the miRNA profile in the RIF-EVs. Participants/materials, setting, methods RIF-EVs and FER-EVs were characterized using western blotting, nanoparticle tracking analysis, and transmission electron microscopy. After co-culture with EVs, embryonic blastocyst rate and hatching rate were calculated. Besides, the proliferation, migration, and invasion of EV-treated trophoblast cells were evaluated by CCK–8, wound healing, and transwell invasion assays. miRNA expression profiles were compared between RIF-EVs and FER-EVs, and the regulatory role of significantly upregulated miR–6131 in RIF-EVs was investigated in the trophoblast cells. Main results and the role of chance RIF-EVs and FER-EVs are round bilayer vesicles, ranging mainly at 100 nm and enriched in TSG101, Alix, and CD9. Both RIF-EVs and FER-EVs entered embryonic or trophoblast cytoplasm. The blastocyst rate in the RIF-EV groups was significantly decreased compared to that in the FER-EV groups, at concentrations of 5, 10, and 20 μg/ml. The hatching rate was decreased significantly in embryos treated with 10 or 20 μg/ml RIF-EVs compared to those treated with FER-EVs at the same concentration (p < 0.05). The proliferation, migration, and invasion of trophoblasts were significantly decreased in the RIF-EV group at 20 μg/mL. A total of 11 differently expressed (fold change >2 and p < 0.05) miRNAs were found in the RIF-EVs, and two of them were validated in a larger set of EV samples using RT-PCR. The most significantly different miRNA, 6131, was increased in the RIF-EV-treated HTR8/SVneo cells. The up-regulation of miR–6131 inhibited the growth and invasion of HTR8/SVneo. Bioinformatics coupled with luciferase and western blot assays revealed that PAK2 is a direct target of miR–6131, and the overexpression of PAK2 can rescue the phenotype changes induced by miR–6131 overexpression. Limitations, reasons for caution Our study indicated miRNA in the RIF-EVs dysregulating the growth and function of embryonic cells. However, EVs contained a wide spectrum of bioactive molecules, including proteins, mRNAs, and DNA, which may play an important role in the implantation. Further studies are required to investigate the mechanisms. Wider implications of the findings: This work indicates an important role of EVs from women with RIF in embryonic implantation, potentially providing a novel insight to understand the pathophysiology of RIF. Trial registration number Not applicable

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-388 Pre-selected for an award: Endometrial extracellular vesicles from recurrent implantation failure patients inhibited embryonic growth and implantation via miR-6131/PAK2 pathway

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Liu
Keyword(s):  
Extracellular Vesicles ◽  
Migration And Invasion ◽  
Hatching Rate ◽  
Implantation Failure ◽  
Trophoblast Cells ◽  
Recurrent Implantation Failure ◽  
Endometrial Cells ◽  
Blastocyst Rate ◽  
Fertile Women

Abstract Study question Could endometrial extracellular vesicles from recurrent implantation failure patients (RIF-EVs) attenuate the growth and implantation potentials of embryos and what are the mechanisms?  Summary answer RIF-EVs inhibited embryonic growth and decreased the trophoblast functions via miR-6131/PAK2 pathway. What is known already Recurrent implantation failure (RIF) is characterized by repeated embryo transfers without pregnancy. To date, the etiology of RIF remains poorly understood. Recent evidence indicated that extracellular vesicles (EVs) secreted by endometrial cells, played a crucial role in the implantation by regulating the development and implantation of embryos. Study design, size, duration Endometrial cells isolated from endometrial tissues of RIF patients (n = 25) and fertile women (n = 16) were cultured and modulated via hormones. Endometrial EVs from RIF patients (RIF-EVs) or fertile women (FER-EVs) were isolated from the conditioned medium. The influence of EVs on embryonic development and implantation was investigated by co-culture models of EVs and 2-cell murine embryos or HTR8/SVneo cells, respectively. High-through put sequencing was performed to identify the miRNA profile in the RIF-EVs. Participants/materials, setting, methods RIF-EVs and FER-EVs were characterized using western blotting, nanoparticle tracking analysis, and transmission electron microscopy. After co-culture with EVs, embryonic blastocyst rate and hatching rate were calculated. Besides, the proliferation, migration, and invasion of EV-treated trophoblast cells were evaluated by CCK-8, wound healing, and transwell invasion assays. miRNA expression profiles were compared between RIF-EVs and FER-EVs, and the regulatory role of significantly upregulated miR-6131 in RIF-EVs was investigated in the trophoblast cells. Main results and the role of chance RIF-EVs and FER-EVs are round bilayer vesicles, ranging mainly at 100 nm and enriched in TSG101, Alix, and CD9. Both RIF-EVs and FER-EVs entered embryonic or trophoblast cytoplasm. The blastocyst rate in the RIF-EV groups was significantly decreased compared to that in the FER-EV groups, at concentrations of 5, 10, and 20 μg/ml. The hatching rate was decreased significantly in embryos treated with 10 or 20 μg/ml RIF-EVs compared to those treated with FER-EVs at the same concentration (p < 0.05). The proliferation, migration, and invasion of trophoblasts were significantly decreased in the RIF-EV group at 20 μg/mL. A total of 11 differently expressed (fold change >2 and p < 0.05) miRNAs were found in the RIF-EVs, and two of them were validated in a larger set of EV samples using RT-PCR. The most significantly different miRNA, 6131, was increased in the RIF-EV-treated HTR8/SVneo cells. The up-regulation of miR-6131 inhibited the growth and invasion of HTR8/SVneo. Bioinformatics coupled with luciferase and western blot assays revealed that PAK2 is a direct target of miR-6131, and the overexpression of PAK2 can rescue the phenotype changes induced by miR-6131 overexpression. Limitations, reasons for caution Our study indicated miRNA in the RIF-EVs dysregulating the growth and function of embryonic cells. However, EVs contained a wide spectrum of bioactive molecules, including proteins, mRNAs, and DNA, which may play an important role in the implantation. Further studies are required to investigate the mechanisms. Wider implications of the findings This work indicates an important role of EVs from women with RIF in embryonic implantation, potentially providing a novel insight to understand the pathophysiology of RIF. Trial registration number not applicable

scholarly journals The Role of Uterine Natural Killer Cells on Recurrent Miscarriage and Recurrent Implantation Failure: From Pathophysiology to Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1425
Author(s):  
Konstantinos Sfakianoudis ◽  
Anna Rapani ◽  
Sokratis Grigoriadis ◽  
Agni Pantou ◽  
Evangelos Maziotis ◽  
...  
Keyword(s):  
Natural Killer ◽  
Recurrent Miscarriage ◽  
Current Evidence ◽  
Routine Practice ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Causative Relationship ◽  
Unk Cells ◽  
Uterine Natural Killer

Uterine natural killer (uNK) cells constitute a unique uterine leucocyte subpopulation facilitating implantation and maintaining pregnancy. Herein, we critically analyze current evidence regarding the role of uNK cells in the events entailed in recurrent implantation failure (RIF) and recurrent miscarriages (RM). Data suggest an association between RIF and RM with abnormally elevated uNK cells’ numbers, as well as with a defective biological activity leading to cytotoxicity. However, other studies do not concur on these associations. Robust data suggesting a definitive causative relationship between uNK cells and RIF and RM is missing. Considering the possibility of uNK cells involvement on RIF and RM pathophysiology, possible treatments including glucocorticoids, intralipids, and intravenous immunoglobulin administration have been proposed towards addressing uNK related RIF and RM. When considering clinical routine practice, this study indicated that solid evidence is required to report on efficiency and safety of these treatments as there are recommendations that clearly advise against their employment. In conclusion, defining a causative relationship between uNK and RIF–RM pathologies certainly merits investigation. Future studies should serve as a prerequisite prior to proposing the use of uNK as a biomarker or prior to targeting uNK cells for therapeutic purposes addressing RIF and RM.

scholarly journals Identification of a lncRNA-Related Competing Endogenous RNA Network in Recurrent Implantation Failure

2021 ◽  
Author(s):  
Kai Huang ◽  
Ying Shi ◽  
Gezi Chen
Keyword(s):  
Underlying Mechanism ◽  
Control Group ◽  
Implantation Failure ◽  
Rna Seq ◽  
Recurrent Implantation Failure ◽  
Cerna Network ◽  
Regulation Network ◽  
Competing Endogenous Rnas ◽  
Competing Endogenous Rna Network

Abstract Background Impaired endometrial receptivity is supposed to be a major element leading to recurrent implantation failure (RIF). Numerous studies have identified that the lncRNAs-miRNAs-mRNAs regulation network functions in the generation of receptive uterus. Long non-coding RNAs could act as competing endogenous RNAs in the pathogenesis of RIF. However, our understanding of the underlying mechanism is still limited. Results Based on the RNA-Seq results, 617 DEmRNAs, 69 DElncRNAs and 107 DEmiRNAs were identified in the RIF group compared with the control group. To investigate the role of lncRNAs in RIF, we constructed a lncRNA related ceRNA network. A total of 3 lncRNAs, 8 miRNAs and 69 genes were identified. Above all, our study obtained 120 lncRNAs-miRNAs-mRNAs relationships in the ceRNA network. Among three hub lncRNAs, PART1 and PWRN1 were upregulated whereas PGM5P3-AS1 was downregulated in RIF endometrium. Meanwhile, three down-regulated miRNAs (hsa-miR-1207-5p, hsa-miR-134-5p, hsa-miR-1225-5p) and five up-regulated miRNAs (hsa-miR-30c-5p, hsa-miR-30b-5p, hsa-miR-145-5p, hsa-miR-21-5p, hsa-miR-196b-5p) were shown. Conclusions We constructed a lncRNA-related ceRNA network and identified three hub lncRNAs in recurrent implantation failure. The results may provide further understanding in the pathogenesis of RIF as well as potential diagnostic and therapeutic targets.

The role of prokineticins in recurrent implantation failure

2020 ◽  
Vol 49 (9) ◽  
pp. 101835
Author(s):  
Abdullah Karaer ◽  
Gorkem Tuncay ◽  
Onur Uysal ◽  
Tuğba Semerci Sevimli ◽  
Nurhan Sahin ◽  
...  
Keyword(s):  
Implantation Failure ◽  
Recurrent Implantation Failure
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