Embryo implantation failure as a prognostic factor of ART outcomes: An evaluation of 3315 ART cycles

Author(s):  
Felipe Dieamant
2020 ◽  
Vol 26 (3) ◽  
pp. 154-166 ◽  
Author(s):  
Vanessa de Oliveira ◽  
Jennifer Schaefer ◽  
Basim Abu-Rafea ◽  
George A Vilos ◽  
Angelos G Vilos ◽  
...  

Abstract The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone (P4) on mouse uterine aquaporin gene/protein (Aqp/AQP) expression on Day 1 (D1) and D4 of pregnancy. The study also examined the effect of ovarian stimulation on uterine luminal closure and uterine receptivity on D4 of pregnancy and embryo implantation on D5 and D7 of pregnancy. These analyses revealed that the expression of Aqp3, Aqp4, Aqp5 and Aqp8 is induced by E2 while the expression of Aqp1 and Aqp11 is induced by P4. Additionally, P4 inhibits E2 induction of Aqp3 and Aqp4 expression while E2 inhibits Aqp1 and Aqp11 expression. Aqp9, however, is constitutively expressed. Ovarian stimulation disrupts Aqp3, Aqp5 and Aqp8 expression on D4 and AQP1, AQP3 and AQP5 spatial expression on both D1 and D4, strikingly so in the myometrium. Interestingly, while ovarian stimulation has no overt effect on luminal closure and uterine receptivity, it reduces implantation events, likely through a disruption in myometrial activity and embryo development. The wider implication of this study is that ovarian stimulation, which results in supraphysiological levels of E2 and P4 and changes (depending on the degree of stimulation) in the E2:P4 ratio, triggers abnormal expression of uterine AQP during pregnancy, and this is associated with implantation failure. These findings lead us to recognize that abnormal expression would also occur under any pathological state (such as endometriosis) that is associated with changes in the normal E2:P4 ratio. Thus, infertility among these patients might in part be linked to abnormal uterine AQP expression.


2016 ◽  
Vol 75 (3) ◽  
pp. 388-401 ◽  
Author(s):  
Nathalie Lédée ◽  
Marie Petitbarat ◽  
Lucie Chevrier ◽  
Dominique Vitoux ◽  
Katia Vezmar ◽  
...  

2014 ◽  
Vol 101-102 ◽  
pp. 54-55
Author(s):  
Marie Petitbarat ◽  
Katia Vezmar ◽  
Sylvie Dubanchet ◽  
Dominique Vitoux ◽  
Nathalie Lédée

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5466-5466
Author(s):  
Tyler Davi d Hutchinson ◽  
Yuhua Song ◽  
Kevin Trainor ◽  
Ghazala Hashmi

Abstract Background: Alloimmunization against Human Platelet Antigens (HPA) is associated with Neonatal Alloimmune Thrombocytopenia (NAIT), post-transfusion purpura and refractoriness for platelet transfusion. A flexible BeadChip™ design was developed to simultaneously detect 22 platelet antigens, including HPA-1, and used to assay over 1,000 random blood donors from across the United States. Methods: Samples from 19 labs/centers from across the country were assayed for 11 HPA loci (HPA-1 through 9, 11 and 15) using the BioArray Solutions HPA Assay. Each locus was independently assessed for Hardy-Weinberg Equilibrium. Results: Allele and genotype frequencies for each locus were reported. Platelet antigens HPA-2 through HPA-9, HPA-11 and HPA-15 were all found to be in Hardy-Weinberg Equilibrium with a Chi-Squared value of <3.84 (1 degree of freedom, 5% confidence interval). HPA-1, however, did not exhibit Hardy-Weinberg Equilibrium yielding a Chi-Squared value of 43.4. Conclusions: After reaffirming there was no sampling preference by inclusion of a second blinded random group, it was acknowledged that HPA-1 did not conform to a Mendelian distribution of alleles. The lower incidence of heterozygote HPA-1 individuals may lend credence to the recent finding by Ivanov et al (Akush Ginekol, 2007) linking the polymorphism in GPIIIa that is responsible for the HPA-1 antigen with embryo implantation failure. Further research may help elucidate the causes behind the HPA-1 disequilibrium and how much implantation failure impacts HPA-1 frequencies.


2005 ◽  
Vol 13 (3) ◽  
pp. 125-133 ◽  
Author(s):  
Kaushik Deb ◽  
Madan Mohan Chaturvedi ◽  
Yogesh Kumar Jaiswal

Genito-urinary tract or systemic infections of the gram-negative bacteria in pregnant women, causes abortions, preterm labor, and several other perinatal complications. LPS is the most potent antigenic component of the gram-negative bacterial cell wall and is known to modulate the expression of various proinflammatory cytokines. Here we investigate the role of the soluble form of IL-1 i.e., IL-1β in the ‘minimum dose’ of LPS induced pregnancy loss in mice. Uterine cross-sections on each day of the preimplantation period of pregnancy were examined histopathologically for finding out LPS induced changes in the uterine preparation for embryo implantation. The expression of IL-1β in the various stages of the preimplantation period of pregnancy was studied by RT-PCR in the embryos and the uterine horns of the LPS treated and normal pregnant mice. We found that LPS significantly alters the proliferation of the glandular epithelium, luminal epithelium and stroma during the preimplantation period. We also found large infiltration of macrophages into the uterine horns of the LPS treated animals. The level and pattern of IL-1β expression in the preimplantation embryos and uterine horns were also altered in LPS treated animals. These observations indicate that LPS can alter the uterine preparation for blastocyst implantation, which could be due to the change in the IL-1β expression in the uterine horns. However, a change in the expression pattern of IL-1β in the preimplantation embryos underlines the significance of this molecule in LPS induced pregnancy loss or implantation failure in mouse.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Pingping Xue ◽  
Wenbo Zhou ◽  
Wenqiang Fan ◽  
Jianya Jiang ◽  
Chengcai Kong ◽  
...  

Abstract Background Recurrent implantation failure (RIF) is a major limitation of assisted reproductive technology, which is associated with impaired endometrial receptivity. Although N6-methyladenosine (m6A) has been demonstrated to be involved in various biological processes, its potential role in the endometrium of women with RIF has been poorly studied. Methods Global m6A levels and major m6A methyltransferases/demethylases mRNA levels in mid-secretory endometrium from normal and RIF women were examined by colorimetric m6A quantification strategy and quantitative real-time PCR, respectively. The effects of METTL3-mediated m6A modification on embryo attachment were evaluated by an vitro model of a confluent monolayer of Ishikawa cells co-cultured with BeWo spheroids, and the expression levels of homeo box A10 (HOXA10, a well-characterized marker of endometrial receptivity) and its downstream targets were evaluated by quantitative real-time PCR and Western blotting in METTL3-overexpressing Ishikawa cells. The molecular mechanism for METTL3 regulating HOXA10 expression was determined by methylated RNA immunoprecipitation assay and transcription inhibition assay. Results Global m6A methylation and METTL3 expression were significantly increased in the endometrial tissues from women with RIF compared with the controls. Overexpression of METTL3 in Ishikawa cells significantly decreased the ration of BeWo spheroid attachment, and inhibited HOXA10 expression with downstream decreased β3-integrin and increased empty spiracles homeobox 2 expression. METTL3 catalyzed the m6A methylation of HOXA10 mRNA and contributed to its decay with shortened half-life. Enforced expression of HOXA10 in Ishikawa cells effectively rescued the impairment of METTL3 on the embryo attachment in vitro. Conclusion Increased METTL3-mediated m6A modification represents an adverse impact on embryo implantation by inhibiting HOXA10 expression, contributing to the pathogenesis of RIF.


2021 ◽  
Vol 12 ◽  
Author(s):  
Nan-Xing Jiang ◽  
Xue-Lian Li

As a rate-limiting step in pregnancy, embryo implantation is highly dependent on intercellular communication. Extracellular vesicles (EVs) are newly identified to be important in the course of intercellular communication. EVs have been isolated from a wide variety of biofluids and tissues, including plasma, liver, uterine, semen, embryo, etc. The present and future use of EVs not only as biomarkers, but also as targeting drug delivery system, is promisingly pave the way for advanced comprehension of implantation failure in reproductive diseases. However, as the precise mechanisms of EVs in embryo implantation has not been elucidated yet. Herein, we summarize the current knowledge on the diverse effects of EVs from various sources and their cargos such as microRNA, long non-coding RNA, protein, etc. on embryo implantation, and the potential mechanisms of EVs in reproductive diseases such as recurrent implantation failure, polycystic ovary syndrome and endometriosis. It is essential to note that many of the biologically plausible functions of EVs in embryo implantation discussed in present literatures still need further research in vivo.


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