Implantation failure of endometrial origin: it is not pathology, but our failure to synchronize the developing embryo with a receptive endometrium

Valdés, Cecilia T.; Schutt, Amy K.; Simón, Carlos

doi:10.1016/j.fertnstert.2017.05.033

Cited by 119 publications

(76 citation statements)

References 41 publications

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“…Embryo implantation is a multifactorial event that depends on the interaction of the blastocyst with the receptive endometrium and consists of molecular signaling by the embryo, followed by apposition and attachment to the endometrium (5). Following the formation of the fetal-maternal interface, the essential second step involves the invasion of the embryo endometrium (6).…”

Section: Introductionmentioning

confidence: 99%

Association between vascular endothelial growth factor promoter polymorphisms and the risk of recurrent implantation failure

et al. 2017

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Abstract. The objective of the present study was to investigate the association between recurrent implantation failure (RIF) and vascular endothelial growth factor (VEGF) gene polymorphisms that are associated with various female infertility disorders. A total of 116 women diagnosed with RIF and 218 control subjects were genotyped for the VEGF -2578C>A, -1154G>A, -634C>G and 936C>T polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism assay. The VEGF -2578AA genotype was associated with an increased prevalence (≥4) of RIF [adjusted odds ratio (AOR)=2.77; 95% confidence interval (CI)=1.10-7.02; P=0.031], whereas the VEGF -634CG+GG genotype was associated with an increased incidence of total RIF (AOR=2.03; 95% CI=1.02-4.05; P=0.044) and ≥4 RIF (AOR=3.16; 95% CI=1.19-8.37; P=0.021). The results of the haplotype analysis indicated that -2578A/-1154A/-634G/936C (AOR=1.76; 95% CI=1.03-3.00; P=0.040 for total RIF and AOR=2.11; 95% CI=1.12-3.97; P=0.021 for ≥4 RIF) was associated with the occurrence of RIF. In addition, it was revealed that there was a significant difference in serum prolactin level associated with the VEGF -634C>G polymorphism (P=0.013). Therefore the findings of the present study indicate that the VEGF -2578AA genotype, -634G allele and -2578A/-1154A/-634G/936C haplotype may be genetic markers for susceptibility to RIF. However, further studies on VEGF promoter polymorphisms that include an independent randomized-controlled population are required to confirm these results.

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Section: Introductionmentioning

confidence: 99%

Association between vascular endothelial growth factor promoter polymorphisms and the risk of recurrent implantation failure

et al. 2017

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“…Infertility is a major issue in human reproduction, and in vitro fertilization is costly with a relatively low success rate, in general below 30% [3]. The inadequacy of uterine receptivity significantly contributes to failure during in vitro fertilization and embryo transplantation [50]. Increasing evidence indicates that sEVs miRNAs are potential biomarkers for the diagnosis and treatment of diseases [23,51,52].…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs in Small Extracellular Vesicles Indicate Successful Embryo Implantation during Early Pregnancy

Tan

Shi

Liang

et al. 2020

Cells

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Synchronous communication between the developing embryo and the receptive endometrium is crucial for embryo implantation. Thus, uterine receptivity evaluation is vital in managing recurrent implantation failure (RIF). The potential roles of small extracellular vesicle (sEV) miRNAs in pregnancy have been widely studied. However, the systematic study of sEVs derived from endometrium and its cargos during the implantation stage have not yet been reported. In this study, we isolated endometrium-derived sEVs from the mouse endometrium on D2 (pre-receptive phase), D4 (receptive phase), and D5 (implantation) of pregnancy. Herein, we reveal that multivesicular bodies (MVBs) in the endometrium increase in number during the window of implantation (WOI). Moreover, our findings indicate that CD63, a well-known sEV marker, is expressed in the luminal and glandular epithelium of mouse endometrium. The sEV miRNA expression profiles indicated that miR-34c-5p, miR-210, miR-369-5p, miR-30b, and miR-582-5p are enriched during WOI. Further, we integrated the RIF’s database analysis results and found out that miR-34c-5p regulates growth arrest specific 1 (GAS1) for normal embryo implantation. Notably, miR-34c-5p is downregulated during implantation but upregulated in sEVs. An implication of this is the possibility that sEVs miR-34c-5p could be used to evaluate uterine states. In conclusion, these findings suggest that the endometrium derived-sEV miRNAs are potential biomarkers in determining the appropriate period for embryo implantation. This study also has several important implications for future practice, including therapy of infertility.

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“…In a recent retrospective study of women with RIF after euploid ETs, pET performed according to the ERA test also improved outcome (90). Given these findings, the question has arisen of whether RIF of endometrial origin is a ''condition'' or simply the result of inadequate timing of embryo replacement (91). Future randomized controlled trials using donated ova in RIF and non-RIF recipients will hopefully determine the indications for molecular tests of endometrial receptivity.…”

Section: Window Of Implantation and The Endometrial Receptivity Assaymentioning

confidence: 99%

Innovations in assisted reproductive technologies: impact on contemporary donor egg practice and future advances

Christianson

Bellver²

2018

Fertility and Sterility

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Innovations in assisted reproductive technologies (ART) have driven progress in the donor egg field since the birth of the first baby derived from a donor egg in 1983. Over time, donor oocytes have become an increasingly used option for patients unable to conceive with autologous oocytes. In donor egg, the unique separation of the oocyte source and recipient uterus has created a model that has propelled advances in ART. Progressive ART innovations that have optimized the oocyte donor and resulting embryo include the following: evaluation of ovarian reserve, controlled ovarian hyperstimulation regimens that reduce the risk of ovarian hyperstimulation syndrome, blastocyst culture, oocyte cryopreservation, and preimplantation genetic testing. For donor egg recipients, methods to optimize the endometrium to maximize implantation include endometrial receptivity testing, immunologic donor-recipient matching, and increased understanding of the uterine microbiome. (Fertil Steril Ò 2018;110:994-1002. Ó2018 by American Society for Reproductive Medicine.

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Implantation failure of endometrial origin: it is not pathology, but our failure to synchronize the developing embryo with a receptive endometrium

Cited by 119 publications

References 41 publications

Association between vascular endothelial growth factor promoter polymorphisms and the risk of recurrent implantation failure

Association between vascular endothelial growth factor promoter polymorphisms and the risk of recurrent implantation failure

MicroRNAs in Small Extracellular Vesicles Indicate Successful Embryo Implantation during Early Pregnancy

Innovations in assisted reproductive technologies: impact on contemporary donor egg practice and future advances

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