scholarly journals Human platelet lysates stimulate in vitro proliferation of human endometrial cells from patients with a history of recurrent implantation failure

F&S Science ◽  
2022 ◽  
Author(s):  
Tina Tu-Thu Ngoc Nguyen ◽  
Mitchell MacDougall ◽  
Yat Sze Sheila Kwok ◽  
Stewart J. Russell ◽  
Clifford L. Librach
Keyword(s):  
Human Platelet ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
In Vitro Proliferation ◽  
Endometrial Cells ◽  
History Of

scholarly journals Association between HOX Transcript Antisense RNA Single-Nucleotide Variants and Recurrent Implantation Failure

2021 ◽  
Vol 22 (6) ◽  
pp. 3021
Author(s):  
Jeong Yong Lee ◽  
Eun Hee Ahn ◽  
Hyeon Woo Park ◽  
Ji Hyang Kim ◽  
Young Ran Kim ◽  
...  
Keyword(s):  
Antisense Rna ◽  
Coagulation Factors ◽  
Healthy Controls ◽  
Implantation Failure ◽  
Single Nucleotide Variants ◽  
Recurrent Implantation Failure ◽  
Single Nucleotide ◽  
Vitro Fertilization ◽  
And Control

Recurrent implantation failure (RIF) refers to the occurrence of more than two failed in vitro fertilization–embryo transfers (IVF-ETs) in the same individual. RIF can occur for many reasons, including embryo characteristics, immunological factors, and coagulation factors. Genetics can also contribute to RIF, with some single-nucleotide variants (SNVs) reported to be associated with RIF occurrence. We examined SNVs in a long non-coding RNA, homeobox (HOX) transcript antisense RNA (HOTAIR), which is known to affect cancer development. HOTAIR regulates epigenetic outcomes through histone modifications and chromatin remodeling. We recruited 155 female RIF patients and 330 healthy controls, and genotyped HOTAIR SNVs, including rs4759314, rs920778, rs7958904, and rs1899663, in all participants. Differences in these SNVs were compared between the patient and control groups. We identified significant differences in the occurrence of heterozygous genotypes and the dominant expression model for the rs1899663 and rs7958904 SNVs between RIF patients and control subjects. These HOTAIR variants were associated with serum hemoglobin (Hgb), luteinizing hormone (LH), total cholesterol (T. chol), and blood urea nitrogen (BUN) levels, as assessed by analysis of variance (ANOVA). We analyzed the four HOTAIR SNVs and found significant differences in haplotype patterns between RIF patients and healthy controls. The results of this study showed that HOTAIR is not only associated with the development of cancer but also with pregnancy-associated diseases. This study represents the first report showing that HOTAIR is correlated with RIF.

P–394 Intralipid infusion at time of embryo transfer in women with history of recurrent implantation failure: a systematic review and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M P Rimmer ◽  
N Black ◽  
S Keay ◽  
S Quenby ◽  
B. H.A Wattar
Keyword(s):  
Systematic Review ◽  
Embryo Transfer ◽  
Meta Analysis ◽  
Small Sample ◽  
Risk Of Bias ◽  
Population Characteristics ◽  
Implantation Failure ◽  
Randomised Trials ◽  
Recurrent Implantation Failure ◽  
History Of

Abstract Study question What is the effectiveness of IV Intralipid (IVI) in improving pregnancy rates in women undergoing IVF with history of Recurrent implantation failure (RIF) to improve reproductive outcomes. Summary answer The evidence to support the use of IVI at the time of embryo transfer in women with RIF is limited. More RCTs are needed. What is known already: Optimising the implantation process following embryo transfer remains a clinical challenge with 10% of couples undergoing IVF affected by (RIF). Immunotherapy could help to optimise endometrial receptivity and increase the chances for successful conception in women with history of RIF. Intra-venous Intralipid (IVI), a fat-based emulsion of soybean oil, glycerine, phospholipids, egg, and polyunsaturated fatty acids, has been evaluated in several trials as a potential intervention to downregulate the uNK cells and macrophages as well as inhibit the pro-inflammatory mediators including T1 helper cells. Evidence synthesis is needed to evaluate the effectiveness of this intervention. Study design, size, duration We performed this systematic review using a prospectively registered protocol (CRD42019148517) and reported in accordance with the PRISMA guidelines. Participants/materials, setting, methods: We searched MEDLINE, EMBASE and CENTRAL for any randomised trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta-analysed data using a random effect model and reported on dichotomous outcomes using risk ratio (RR) and 95% confidence interval (CI). Main results and the role of chance We included five randomised trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, RR 1.55, 95%CI 1.16–2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95%CI 1.42–2.35, I2 0%) post treatment compared to no intervention. Limitations, reasons for caution Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics. Wider implications of the findings: Our meta-analysis offers an overview on the value of IVI to help women affected by RIF. Given the limitations and the quality of included trials, adopting the use of IVI a-la-carte to couples undergoing IVF remains immature. IVI should not be offered until larger RCTs demonstrate a persistent benefit. Trial registration number CRD42019148517

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.

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

scholarly journals Intralipid Immunotherapy for Repeated IVF Failure

2019 ◽  
Vol 01 (04) ◽  
pp. 154-160 ◽  
Author(s):  
Romy Ehrlich ◽  
M. Louise Hull ◽  
Jane Walkley ◽  
Gavin Sacks
Keyword(s):  
Adverse Events ◽  
Pregnancy Outcomes ◽  
Pregnancy Loss ◽  
Safety Concern ◽  
In Vitro Fertilisation ◽  
Implantation Failure ◽  
Definitive Evidence ◽  
History Of ◽  
Randomised Controlled

The intravenous fat emulsion, intralipid, has been hypothesised to be an effective and safe treatment for repeated in vitro fertilisation (IVF), implantation failure and pregnancy loss. This exploratory, retrospective cohort study determined pregnancy outcomes and documented adverse events associated with intralipid use. Ninety-three women were identified as having received intralipid for a history of repeated unsuccessful IVF cycles and pre-viable pregnancy loss in two Australian IVF units that independently recruited between October 2014 and July 2016. Pregnancy outcomes and adverse events were recorded in fresh and frozen embryo transfer cycles in which the infusion was administered. The 93 women who received intralipid had a clinical pregnancy rate of 40.0%, compared with 35.0% in 651 age-matched controls undergoing IVF, which was not significantly different. The intralipid group had a livebirth rate of 35.7%. Apart from flushing, which was experienced by one individual, there were no adverse events associated with intralipid use. As a prelude to definitive evidence of benefit, we did not identify a safety concern or reduced pregnancy rates in intralipid users compared to controls. Indeed, these outcomes were better than expected in a poor prognosis group. This data supports an argument for large, randomised controlled trials to determine the benefit of intralipid in the treatment of recurrent implantation failure or miscarriage.

Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization

2010 ◽  
Vol 93 (2) ◽  
pp. 437-441 ◽  
Author(s):  
Erika B. Johnston-MacAnanny ◽  
Janice Hartnett ◽  
Lawrence L. Engmann ◽  
John C. Nulsen ◽  
M. Melinda Sanders ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Chronic Endometritis ◽  
Vitro Fertilization ◽  
Frequent Finding

scholarly journals Analysis of Vaginal and Endometrial Microbiota Communities in Infertile Women With a History of Repeated Implantation Failure

2020 ◽  
Author(s):  
Takuhiko Ichiyama ◽  
Keiji Kuroda ◽  
Yoko Nagai ◽  
Daichi Urushiyama ◽  
Motoharu Ono ◽  
...  
Keyword(s):  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Implantation Failure ◽  
Repeated Implantation Failure ◽  
Infertile Women ◽  
Healthy Women ◽  
History Of ◽  
Rrna Gene Sequencing ◽  
Clinical Trials Registry

Abstract Background: Repeated implantation failure (RIF) is estimated to occur in 15%–20% of infertile women undergoing in vitro fertilization-embryo transfer (IVF-ET). Molecular identification recently confirmed that the uterine microbiota may have implications for reproductive and obstetrical outcomes. One hundred forty-five women who had been diagnosed with RIF were enrolled in the study. Twenty-one healthy women were also enrolled as controls. We investigated their vaginal and endometrial microbiotas using 16S rRNA gene sequencing and compared the microbiota profiles in the patients with RIF and controls.Results: The endometrial microbiotas had higher α-diversities than did the vaginal microbiotas (p<0.001 in both patients with RIF and healthy women). The microbiota profiles showed that vaginal and endometrial samples in patients with RIF had significantly higher levels of 5 and 14 bacterial genera, respectively, than those in healthy women. These genera included Atopobium, Gardnerella, Prevotella and Megasphaera. Vaginal Lactobacillus rates in patients with RIF were significantly lower at 76.4 ± 38.9% compared with those of the controls at 91.8 ± 22.7% (p=0.018), but endometrial Lactobacillus rates did not significantly differ between the RIF patients and controls (56.2 ± 36.4% and 58.8 ± 37.0%, respectively, p=0.79) Conclusions: Impaired microbiota communities containing specific bacteria in both the endometrium and vagina were associated with implantation failure. The Lactobacillus rate in the vagina, but not the endometrium, may be a biomarker for RIF.Trial registration: UMIN Clinical Trials Registry, UMIN000031731, Registered 15 March 2018; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000036121

scholarly journals Increased expression of HMGB1 in the implantation phase endometrium is related to recurrent implantation failure

2021 ◽  
Author(s):  
Mi Han ◽  
Yi Cao ◽  
Wenjie Zhou ◽  
Mingjuan Zhou ◽  
Xiaowei Zhou ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Underlying Mechanism ◽  
Endometrial Receptivity ◽  
In Vitro Assays ◽  
Control Group ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Tubal Infertility ◽  
Endometrial Stromal Cells

Abstract Impaired endometrial receptivity is the main cause of recurrent implantation failure (RIF), however, its underlying mechanism is unclear. In this study, we found that HMGB1 expression was significantly decreased in the implantation phase endometrium in the control group (patients with tubal infertility who successfully achieved conception after the first embryo transfer) (P = 0.006). However, the expression levels of HMGB1 mRNA and protein were significantly upregulated during the implantation phase in endometrial tissues obtained from patients with RIF compared to those in the control group (P = 0.001), consistent with the results of genome-wide expression profiling. Moreover, in vitro assays showed that increased expression of HMGB1 in human endometrial epithelial cells cause marked deficiency in supporting blastocysts and human embryonic JAR cell adhesion, mimicking the process of embryo adhesion. However, overexpression of HMGB1 had no effect on cell proliferation and in-vitro decidualization in a human endometrial stromal cell line (T-HESCs) and in primary human endometrial stromal cells (HESCs). These findings indicate that increased HMGB1 levels suppressed the adhesion capability of epithelial cells, contributing to impaired endometrial receptivity in patients with recurrent implantation failure. This characteristic can be used as a target for detecting and treating recurrent implantation failure in clinical practice.

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