Treg/Th17 balance in murine embryo implantation and pregnancy
Polese, Barbara ; Gridelet, Virginie ; Araklioti, Eleni et al
Poster (2015, March)Detailed reference viewed: 23 (10 ULg)
Treg/Th17 balance during murine embryo implantation and pregnancy
Polese, Barbara ; Gridelet, Virginie ; et al
Poster (2014, November)Detailed reference viewed: 37 (9 ULg)
The endocrine milieu and CD4 T-lymphocyte polarization during pregnancy
Polese, Barbara ; Gridelet, Virginie ; et al
in Frontiers in Endocrinology (2014), 5(Article 106), 1-11
Acceptance of the fetal semi-allograft by the mother’s immune system has become the focus of intensive research. CD4+ T cells are important actors in the establishment of pregnancy. Th1/Th2 paradigm has ... [more ▼]
Acceptance of the fetal semi-allograft by the mother’s immune system has become the focus of intensive research. CD4+ T cells are important actors in the establishment of pregnancy. Th1/Th2 paradigm has been expanded to include CD4+ regulatory T (Treg) and T helper 17 (Th17) cells. Pregnancy hormones exert very significant modulatory properties on the maternal immune system. In this review, we describe mechanisms by which the endocrine milieu modulates CD4 T cell polarization during pregnancy. We first focused on Treg and Th17 cells and on their importance for pregnancy. Secondly, we review the effects of pregnancy hormones [progesterone (P4) and estradiol (E2)] on immune cells previously described, with a particular attention to human chorionic gonadotropin (hCG). The importance of Treg cells for pregnancy is evidenced. They are recruited before implantation and are essential for pregnancy maintenance. Decreased number or less efficient Treg cells are implicated in fertility disorders. As for Th17 cells, the few available studies suggest that they have a negative impact on fertility. Th17 frequency is increased in infertile patients. With the combination of its pro-effects on Th2 and Treg cells and anti-effects on Th1 and Th17 cells, P4 contributes to establishment of a favorable environment for pregnancy. E2 effects are more dependent on the context but it seems that E2 promotes Treg and Th2 cells while it inhibits Th1 cells. hCG positively influences activities of Treg and uterine natural killer cells. This embryo signal is an essential actor for the success of pregnancy, both as the endocrine factor regulating P4 secretion by the ovarian corpus luteum, but also as a paracrine agent during implantation as well as an angiogenic and immunologic mediator during the course of gestation. Luteinizing hormone (LH) immune properties begin to be studied but its positive impact on Treg cells suggests that LH could be a considerable immunomodulator in the mouse. [less ▲]Detailed reference viewed: 20 (6 ULg)
Y a-t-il une place pour les SPRMs avant PMA?
BRICHANT, Géraldine ; ; PERRIER d'HAUTERIVE, Sophie et al
in Louvain Medical (2014), 133(9), 38-43
Myomas may account for infertility by modifying the uterine cavity’s anatomy and intra-uterine signalling pathways leading to a hostile environment for embryo implantation. In vitro fertilization (IVF ... [more ▼]
Myomas may account for infertility by modifying the uterine cavity’s anatomy and intra-uterine signalling pathways leading to a hostile environment for embryo implantation. In vitro fertilization (IVF) alone is not always sufficient to result in pregnancy. While surgery, if performed before IVF, can increase the pregnancy rate, selective progesterone receptor modulator such as ulipristal acetate can decrease smooth muscle cell proliferation and induce apoptosis. In addition, ulipristal acetate when used before surgery could reduce surgical complications and induce a decrease in the myoma size before performing IVF. [less ▲]Detailed reference viewed: 33 (5 ULg)
Isoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation
Labied, Soraya ; Delforge, Yves ; Munaut, Carine et al
in Transplantation (2013), 95(3), 426-433
Background: Cryopreservation of cortex ovarian tissue before anti-cancer therapy is a promising technique for fertility preservation mainly in children and young women. Ischemia in the early stage after ... [more ▼]
Background: Cryopreservation of cortex ovarian tissue before anti-cancer therapy is a promising technique for fertility preservation mainly in children and young women. Ischemia in the early stage after ovarian graft causes massive follicle loss by apoptosis. VEGF111 is a recently described VEGF isoform that does not bind to the extracellular matrix, diffuse extensively and is resistant to proteolysis. These properties confer a significantly higher angiogenic potential to VEGF111 in comparison to the other VEGF isoforms. Methods: We evaluated the morphology of cryopreserved sheep ovarian cortex, grafted in the presence or absence of VEGF111. Ovarian cortex biopsies were embedded in type I collagen with or without VEGF111 addition before transplantation to SCID mice ovaries. Transplants were retrieved 3 days or 3 weeks later. Follicular density, vasculature network, haemoglobin content and cell proliferation were analysed. Results: Addition of VEGF111 increased density of functional capillaries (p=0.01) 3 days after grafting. By double immunostaining of Ki-67 and von Willebrand Factor (vWF) we demonstrated that proliferating endothelial cells were found in 83% of the VEGF111 group when compared to 33% in the control group (p=0.001). This angio-stimulation was associated with a significant enhancement of haemoglobin content (p=0.03). Three weeks after transplantation, the number of primary follicles was significantly higher in VEGF111 grafts (p=0.02). Conclusion: VEGF111 accelerates blood vessels recruitment, functional angiogenesis and improves the viability of ovarian cortex by limiting ischemia and ovarian cortex damage. [less ▲]Detailed reference viewed: 51 (19 ULg)
Evidence for cross-talk between the LH receptor and LH during implantation in mice
Gridelet, Virginie ; ; et al
in Reproduction, Fertility and Development (2013), 25
The present study investigated the first interaction that occurs between the blastocyst and endometrium during implantation. Given the ethical objections to studying implantation in humans, a mouse model ... [more ▼]
The present study investigated the first interaction that occurs between the blastocyst and endometrium during implantation. Given the ethical objections to studying implantation in humans, a mouse model was used to study the dialogue between luteinising hormone (LH) and luteinising hormone receptor (LHCGR). Several studies performed on LHCGR-knockout mice have generated controversy regarding the importance of the dialogue between LH and LHCGR during implantation. There has been no demonstration of a bioactive LH-like signal produced by the murine blastocyst. The first aim of the present study was to examine and quantify, using radioimmunoassay, the generation of a bioactive LH signal by the murine blastocyst. We went on to examine and quantify endometrial Lhcgr expression to validate the mouse model. Expression of LHCGR in mouse uteri was demonstrated using immunohistochemistry and western blot analysis. To quantify the expression of Lh in the mouse blastocyst and Lhcgr in the endometrium, reverse transcription–polymerase chain reaction (RT-PCR) and real-time quantitative (q) RT-PCR were performed. The results demonstrate that Lhcgr expression in BALB/c mouse endometrial epithelium is increased at the time of implantation and indicate that LHCGR may contribute to the implantation process. In support of this hypothesis, we identified a bioactive LH signal at the time of murine blastocyst implantation. [less ▲]Detailed reference viewed: 33 (11 ULg)
Hysteroscopic resection of abnormally invasive placenta residuals.
Nisolle, Michelle ; DELBECQUE, Katty ; PERRIER d'HAUTERIVE, Sophie et al
in Acta Obstetricia et Gynecologica Scandinavica (2013), 92(4), 451-6
OBJECTIVE: To present our experience in hysteroscopic removal of abnormally invasive placenta (AIP) residuals using bipolar energy. DESIGN: Case series. SETTING: University hospital. POPULATION: Sixteen ... [more ▼]
OBJECTIVE: To present our experience in hysteroscopic removal of abnormally invasive placenta (AIP) residuals using bipolar energy. DESIGN: Case series. SETTING: University hospital. POPULATION: Sixteen patients with AIP residuals after 17 pregnancies. METHODS: Cases were identified by ultrasound, treated with hysteroscopic bipolar electrosurgery and oral contraceptives, and followed up by ultrasound or hysteroscopy. Nine subsequent pregnancies were described. MAIN OUTCOME MEASURES AND RESULTS: Complete removal of AIP residuals was achieved by hysteroscopic bipolar electrosurgery in all cases except one. No peroperative complications occurred. AIP residual recurred in one patient after a subsequent pregnancy and was successfully treated using the same procedure. CONCLUSIONS: AIP residual is a rare condition. Management by hysteroscopic resection using bipolar energy is save and feasible. [less ▲]Detailed reference viewed: 35 (2 ULg)
Hyperglycosylated human chorionic gonadotropin stimulates angiogenesis through TGF-beta receptor activation.
; Blacher, Silvia ; Munaut, Carine et al
in FASEB Journal (2013), 27(4), 1309-21
Embryo implantation requires extensive angiogenesis at the maternal-fetal interface. Hyperglycosylated human chorionic gonadotropin (hCG-H), a trophoblast invasive signal produced by extravillous ... [more ▼]
Embryo implantation requires extensive angiogenesis at the maternal-fetal interface. Hyperglycosylated human chorionic gonadotropin (hCG-H), a trophoblast invasive signal produced by extravillous cytotrophoblasts and by choriocarcinoma, was evaluated for its angiogenic role. hCG-H was purified by HPLC from choriocarcinoma supernatant, and the glycosylation pattern was determined by 2D gel analysis. Angiogenesis models used were aortic ring assay with wild-type and LHCGR-knockout mice, endothelial and mural cell proliferation, and migration assays. The TGF-beta signaling pathway was studied by coimmunoprecipitation, competitive binding, TGF-beta reporter gene assays, and Smad immunoblotting. hCG-H displayed a potent angiogenic effect [3.2-fold increase of number of vessel intersections in wild-type aortic rings (11.406 to 36.964)]. hCG-H-induced angiostimulation was independent of the classic hCG signaling pathway since it persisted in LHCGR-knockout mice [4.73-fold increase of number of vessel intersections (10.826 to 51.288)]. Using TGF-beta signaling inhibitors, Tbeta-RII was identified as the hCG-H receptor responsible for its angiogenic switch. hCG-H exposure enhanced phosphorylation of Smad 2 in endothelial and mural cells and genomic activation of Smad-responsive elements. Interaction between hCG-H and Tbeta-RII was demonstrated by coimmunoprecipitation and binding competition with (125)I-TGF-beta. This new paracrine interaction between trophoblast and endothelial cells through the hCG-H and the TGF-beta receptor complex plays a key role in angiogenesis associated with placental development and tumorigenesis. [less ▲]Detailed reference viewed: 54 (8 ULg)
Impact of follicular G-CSF quantification on subsequent embryo transfer decisions: a proof of concept study.
; Gridelet, Virginie ; RAVET, Stéphanie et al
in Human Reproduction (2013), 28(2), 406-13
BACKGROUND: Previous experiments have shown that granulocyte colony-stimulating factor (G-CSF), quantified in the follicular fluid (FF) of individual oocytes, correlates with the potential for an ongoing ... [more ▼]
BACKGROUND: Previous experiments have shown that granulocyte colony-stimulating factor (G-CSF), quantified in the follicular fluid (FF) of individual oocytes, correlates with the potential for an ongoing pregnancy of the corresponding fertilized oocytes among selected transferred embryos. Here we present a proof of concept study aimed at evaluating the impact of including FF G-CSF quantification in the embryo transfer decisions. METHODS: FF G-CSF was quantified with the Luminex XMap technology in 523 individual FF samples corresponding to 116 fresh transferred embryos, 275 frozen embryos and 131 destroyed embryos from 78 patients undergoing ICSI. RESULTS: Follicular G-CSF was highly predictive of subsequent implantation. The receiving operator characteristics curve methodology showed its higher discriminatory power to predict ongoing pregnancy in multivariate logistic regression analysis for FF G-CSF compared with embryo morphology [0.77 (0.69-0.83), P < 0.001 versus 0.66 (0.58-0.73), P = 0.01)]. Embryos were classified by their FF G-CSF concentration: Class I over 30 pg/ml (a highest positive predictive value for implantation), Class II from 30 to 18.4 pg/ml and Class III <18.4 pg/ml (a highest negative predictive value). Embryos derived from Class I follicles had a significantly higher implantation rate (IR) than those from Class II and III follicles (36 versus 16.6 and 6%, P < 0.001). Embryos derived from Class I follicles with an optimal morphology reached an IR of 54%. Frozen-thawed embryos transfer derived from Class I follicles had an IR of 37% significantly higher than those from Class II and III follicles, respectively, of 8 and 5% (P < 0.001). Thirty-five per cent of the frozen embryos but also 10% of the destroyed embryos were derived from G-CSF Class I follicles. Non-optimal embryos appear to have been transferred in 28% (22/78) of the women, and their pregnancy rate was significantly lower than that of women who received at least one optimal embryo (18 versus 36%, P = 0.04). CONCLUSIONS: Monitoring FF G-CSF for the selection of embryos with a better potential for pregnancy might improve the effectiveness of IVF by reducing the time and cost required for obtaining a pregnancy. [less ▲]Detailed reference viewed: 69 (8 ULg)
The actors of human implantation: gametes, embryo and endometrium
Gridelet, Virginie ; GASPARD, Olivier ; Polese, Barbara et al
in Violin Pereira, Luis Antonio (Ed.) Embryology - Updates and Highlights on Classic Topics (2012)Detailed reference viewed: 35 (7 ULg)
Isoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation
Labied, Soraya ; Delforge, Yves ; Blacher, Silvia et al
in Journal of Assisted Reproduction & Genetics (2012), 28(11), 1009Detailed reference viewed: 38 (15 ULg)
CERTOLIZUMAB PEGOL DID NOT RESULT IN A DECREASE IN SEMEN QUALITY IN HEALTHY VOLUNTEERS: RESULTS FROM A PHASE 1 STUDY
Perrier d'Hauterive, Sophie ; KESSELER, Sophie ; RUGGERI, Philippe et al
in EULAR 2012 (2012)Detailed reference viewed: 24 (3 ULg)
TGFbeta-receptor-dependent angiostimulation through the hyperglycosylated isoform of human chorionic gonadotropin.
; ; et al
in Placenta (2011), 32(9), 44Detailed reference viewed: 8 (0 ULg)
New pre-conception immune biomarkers for clinical practice: interleukin-18, interleukin-15 and TWEAK on the endometrial side, G-CSF on the follicular side.
; ; et al
in Journal of Reproductive Immunology (2011), 88(2), 118-123
dentification of biomarkers of optimal uterine receptivity to the implanting embryo as well as biomarkers of oocyte competence would undoubtedly improve the efficiency of assisted reproductive technology ... [more ▼]
dentification of biomarkers of optimal uterine receptivity to the implanting embryo as well as biomarkers of oocyte competence would undoubtedly improve the efficiency of assisted reproductive technology (ART). Expression of IL-15 and IL-18 has been shown to be different in patients with failed implantation after IVF/ICSI compared with fertile controls and both correlate with local uNK (CD56+) recruitment and angiogenesis. Tumor necrosis factor weak inducer of apoptosis (TWEAK) has been described in mice as a potent early immune regulator able to protect the conceptus. The results of our studies in human suggest that TWEAK modulates the IL-18 related cytotoxicity of uNK cells. Quantification of IL-18, TWEAK and IL-15 mRNA expression by real-time PCR in endometrial tissue collected in mid-luteal phase of non-conception cycles allowed documentation of physiological events that occur at the time of uterine receptivity. Such information may be useful for the physician especially in patients where embryos fail to implant. Cytokine quantification may assist in understanding the mechanisms leading to repeated IVF/ICSI failure: either depletion of cytokines necessary for the apposition-adhesion, or an excess of cytokines leading to local cytotoxicity, may impair the implantation of the embryo. Other new data suggest that a pre-conception dialogue mediated by the oocyte and the follicular fluid and the oocyte may contribute to later implantation success. Follicular concentration of G-CSF appears as a useful biomarker of oocyte competence before fertilization. Moreover both in human and animal models, evidence of a role of the endometrium as a biosensor of the embryo is emerging. [less ▲]Detailed reference viewed: 66 (15 ULg)
Human Chorionic Gonadotropin: a hormone with immunological and angiogenic properties.
; Gridelet, Virginie ; Berndt, Sarah et al
in Journal of Reproductive Immunology (2010), 85(1), 93-8
The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological ... [more ▼]
The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological tolerance which allows conceptus survival. A cascade of cytokines mediates this dialogue and is crucial in the cross-talk between the immune and endocrine systems. The first known human embryo-derived signal is chorionic gonadotropin (hCG) by which the embryo profoundly influences immunological tolerance and angiogenesis at the maternal–fetal interface. hCG levels coincide with the development of trophoblast tolerance. Indeed, it increases the number of uterine natural killer cells that play a key role in the establishment of pregnancy. hCG also intervenes in the development of local immune tolerance through the cellular system of apoptosis via Fas/Fas-Ligand. It modulates the Th1/Th2 balance and acts on complement C3 and C4A/B factors modulating decidual immunity. The transient tolerance evident during gestation is at least partially achieved via the presence of regulatory T cells which are attracted by hCG at the fetal–maternal interface. Finally, hCG treatment of activated dendritic cells results in an up-regulation of MHC class II, IL-10 and IDO expression, reducing the ability to stimulate T cell proliferation. Successful implantation requires an extensive endometrial angiogenesis in the implantation site. Recent data demonstrate angiogenic effects of hCG via its interaction with endometrial and endothelial LH/hCG receptors. Our review focuses on these functions of hCG, giving new insight into the endocrine–immune dialogue that exists between the conceptus and immune cells within the receptive endometrium at the time of implantation. [less ▲]Detailed reference viewed: 71 (19 ULg)
Performance evaluation of microbead and ELISA assays for follicular G-CSF: a non-invasive biomarker of oocyte developmental competence for embryo implantation.
; Munaut, Carine ; et al
in Journal of Reproductive Immunology (2010), 86(2), 126-32
G-CSF in individual follicular fluids correlates with the potential of the corresponding embryo to result in a live birth after transfer in IVF. To evaluate the requirements for routine follicular fluid G ... [more ▼]
G-CSF in individual follicular fluids correlates with the potential of the corresponding embryo to result in a live birth after transfer in IVF. To evaluate the requirements for routine follicular fluid G-CSF quantification, we compared follicular fluid G-CSF measurements made with two multiplexed microbead assays purchased from Bio-Rad Laboratories and R&D Systems, and a commercial G-CSF ELISA (R&D Systems). Individual follicular fluids (n=139) associated with transferred embryos were analysed to determine cytokine profile and the fate of each transferred embryo was recorded. The effect of multiplexing as well as comparison of the respective performances of the microbead assay with a flow cytometry assay was explored. Multivariable logistic regression analysis was performed and receiver operating characteristic (ROC) analysis was used to determine the performance and sensitivity/specificity of each method for individual follicular fluids. Covariate factors known to influence IVF outcome such as age, serum oestradiol and embryo score were systematically integrated in each analysis. The quantification of follicular fluid G-CSF using microbead assay methodologies, but not ELISA, yielded results showing the utility of follicular fluid G-CSF as a biomarker predictive of a successful delivery (Au(roc): 0.77 [0.68-0.84] (p=0.003) and 0.75 [0.66-0.82] (p=0.004) for Bio-Rad and R&D Systems microbead assays respectively), whereas follicular fluid G-CSF values quantified by ELISA were not predictive (Au(roc):0.61 [0.52-0.70] p=0.84). Microbead assay and flow cytometry appeared similarly efficient for quantifying follicular fluid G-CSF and multiplex versus single-plex assays did not influence the reliability of quantification. [less ▲]Detailed reference viewed: 52 (16 ULg)
Chorionic Gonadotropin Stimulation of Angiogenesis and Pericyte Recruitment
; Blacher, Silvia ; PERRIER d'HAUTERIVE, Sophie et al
in Journal of Clinical Endocrinology and Metabolism (2009), 94(11), 4567-74
During the periimplantation period, human chorionic gonadotropin (hCG) plays a key role by increasing the uterine blood flow through uterine vessel vasodilatation but also through angiogenesis. Indeed, we ... [more ▼]
During the periimplantation period, human chorionic gonadotropin (hCG) plays a key role by increasing the uterine blood flow through uterine vessel vasodilatation but also through angiogenesis. Indeed, we previously demonstrated that hCG contributes to endothelial cell recruitment and vessel formation. OBJECTIVE: In this study, hCG was proposed as an arteriogenic factor that could promote perivascular cell recruitment and vessel stabilization. DESIGN: The aortic ring assay, a three-dimensional ex vivo angiogenesis system mimicking all the steps of the angiogenesis process was used to study the impact of hCG on pericyte recruitment and vessel maturation. SETTING: The study was conducted at a university hospital laboratory. MAIN OUTCOME MEASURES: Perivascular cell proliferation, migration, and apposition were quantified by computerized image analysis. RESULTS: Physiological concentrations of hCG (10-400 IU/ml) significantly enhanced pericyte sprouting and migration and gave rise to the maturation and coverage of endothelial capillaries. In a three-dimensional coculture model of endothelial and perivascular cells, hCG enhanced vessel tube formation and endothelial/mural cell adhesion. In addition, hCG stimulated the proliferation of human umbilical vein endothelial cells and smooth muscle cells. The specificity of these effects was determined by using an anti-hCG blocking antibody. Signaling pathways implicated on this hCG effect is protein kinase A and phospholipase C/protein kinase C dependent for the proliferative effect but only phospholipase C/protein kinase C for the migrative process. CONCLUSIONS: Our findings highlight a novel paracrine role of this early embryonic signal in vessel maturation by stimulating perivascular cell recruitment, migration, and proliferation. [less ▲]Detailed reference viewed: 117 (23 ULg)
Effects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18-35 years old.
; PERRIER d'HAUTERIVE, Sophie ; Pintiaux, Axelle et al
in Contraception (2009), 80(2), 187-93
Background Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. Study design A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ... [more ▼]
Background Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. Study design A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ethinylestradiol and 3 mg drospirenone have been compared to a matched control group of 30 noncontraception users (NCU). Blood levels of antioxidants, trace elements and markers of lipid peroxidation were assessed by biochemical methods. A microarray analysis of whole blood mRNA levels of 200 genes involved in OS-dependant pathway was also performed. Results Levels of zinc, vitamin E and antibodies to oxidized low-density lipoproteins (LDLs) were not significantly different between the two groups. On the other hand, significant increases in the mean levels of lipid peroxides (+176%, p<.001), oxidized LDLs (+145%, p<.002), copper (+103%, p<.001), Cu/Zn ratio (+100%, p<.001) and a significant decrease in the mean level of β-carotene (−41%, p<.01) were observed in the OCU compared to NCU. There was a highly significant positive correlation between the lipid peroxide levels and the copper-to-zinc ratio. From the 200 genes tested by microarray, one coding for HSP70 was significantly up-regulated (log2 fold change=+ 0.45, p<.02) and one coding for inducible nitric oxide synthase significantly down-regulated (log2 fold change=−0.24, p<.05) in the OCU compared to the NCU. Conclusions The recently introduced combination of ethinylestradiol and drospirenone induced the heightening of lipid peroxidation correlated with high levels of copper, a situation that could be associated with increased cardiovascular risk. [less ▲]Detailed reference viewed: 100 (5 ULg)
Soluble HLA-G in IVF/ICSI embryo culture supernatants does not always predict implantation success: a multicentre study.
; PERRIER d'HAUTERIVE, Sophie ; Thonon, Fabienne et al
in Reproductive Biomedicine Online (2009), 18(3), 374-81
Several reports have described an association between the presence of soluble human leukocyte antigen G (sHLA-G) in human embryo culture supernatants (ES) and implantation success. However, not all ... [more ▼]
Several reports have described an association between the presence of soluble human leukocyte antigen G (sHLA-G) in human embryo culture supernatants (ES) and implantation success. However, not all studies agree with these findings. To further document this debate, a multicentre blinded study was performed to investigate, on a large number of IVF ES and ICSI ES, whether sHLA-G is a useful criterion for embryo selection before transfer. A total of 1405 ES from 355 patients were collected from three assisted reproductive technique (ART) centres and evaluated for their sHLA-G content in a single laboratory, using a chemiluminescence enzyme-linked immunosorbent assay. In only one centre was a significant association between sHLA-G-positive ES and successful implantation established (P = 0.0379), whereas no such association was observed in the other centres. It was found that the percentages and concentrations of sHLA-G-positive ES varied between centres, depending on culture media and ART conditions. The percentage of sHLA-G-positive ES was significantly higher in IVF ES than ICSI ES (P < 0.001 and P < 0.01 for two centres). These data demonstrate that substantial variations of sHLA-G content in ES occur between different ART centres, highlighting the influence of several technical parameters that differ from one centre to another. [less ▲]Detailed reference viewed: 85 (5 ULg)