Influence of early ICSI-derived embryo sHLA-G expression on pregnancy and implantation rates: a prospective study

Sher, Geoffrey; Keskintepe, Levent; Batzofin, Joel; Fisch, Jeffrey D; Acacio, Brian; Ahlering, Peter; Ginsburg, Michael

doi:10.1093/humrep/deh758

Cited by 49 publications

(41 citation statements)

References 25 publications

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“…In this respect, the only biochemical marker so far proposed for the selection of the most promising embryo obtained by IVF is represented by the release of in vitro cultured embryo (24-, 48-and 72-hours embryo) of soluble HLA-G (Histocompatibility Leukocyte Antigen-G) molecules. This has been consistently reported by several groups [2][3][4][5][6][7]. Using Enzyme-Linked Immunosorbent Assay (ELISA) and Bio-plex approaches, these groups reported that high expression of soluble HLA-G is associated with higher pregnancy and implantation rates.…”

Section: Introductionsupporting

confidence: 63%

Transcriptional Proling Reveals Barcode-Like Toxicogenomic Responses in the Zebrash Embryo

2011

Current Research in Embryology

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Background: During the last years, several studies have reported the significant relationship between the production of soluble HLA-G molecules (sHLA-G) by 48-72 hours early embryos and an increased implantation rate in IVF protocols. As consequence, the detection of HLA-G modulation was suggested as a marker to identify the best embryos to be transferred. On the opposite, no suitable markers are available for the oocyte selection.

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Section: Introductionsupporting

confidence: 63%

Transcriptional Proling Reveals Barcode-Like Toxicogenomic Responses in the Zebrash Embryo

2011

Current Research in Embryology

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“…It has also been reported that soluble HLA-G secretion was independent of embryo grade, but the cleavage rate of embryos secreting soluble HLA-G was significantly higher than that of those lacking it, as was the live birth rate (9). A prospective study, in which at least one embryo known to be producing soluble HLA-G was transferred to the mother, has also shown significantly improved implantation and pregnancy rates (10).…”

Section: Discussionmentioning

confidence: 95%

Differential Expression of Alternatively Spliced Transcripts of HLA-G in Human Preimplantation Embryos and Inner Cell Masses

Yao

Barlow

Sargent

2005

The Journal of Immunology

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It has been reported that preimplantation human embryos secrete HLA-G, and the levels may be predictive of their ability to implant. However, it is not known which of the membrane-bound (HLA-G 1–4) and soluble (HLA-G 5–6) alternatively spliced forms are present, nor the developmental stage at which they appear. Therefore, we have investigated HLA-G mRNA isoform expression on single embryos at the two-, four-, six-, and eight-cell, morula, and blastocyst stages. The percentage of embryos expressing each HLA-G isoform mRNA increased with developmental stage, but contrary to expectation, HLA-G5 mRNA was not detected in single two- to eight-cell embryos and was only expressed by 20% of morulae and blastocysts. Similarly, soluble HLA-G6 mRNA was not detected until the blastocyst stage and then in only one-third of embryos. In contrast, labeling with MEM G/9 Ab (specific for HLA-G1 and -G5) was observed in 15 of 20 two- to eight-cell embryos and 5 of 5 blastocysts. This disparity between mRNA and protein may be due to HLA-G protein remaining from maternal oocyte stores produced before embryonic genome activation and brings into question the measurement of soluble HLA-G for clinical evaluation of embryo quality. Although HLA-G is expressed in the preimplantation embryo, later it is primarily expressed in the invasive trophoblast of the placenta rather than the fetus. Therefore, we have investigated whether down-regulation of HLA-G first occurs in the inner cell mass (precursor fetal cells) of the blastocyst and, in support of this concept, have shown the absence HLA-G1 and -G5 protein and mRNA.

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“…Due to the low sHLA-G concentration in embryo cultures (EC), the HLA-G immunodetection method and sample treatment strongly determine the reliability of the sHLA-G measurement in embryo culture supernatants. Technical difficulties have led to very controversial results in the past [100,[104][105][106][107][108][109][110][111][112][113][114][115][116][117][118] but are being resolved. sHLA-G in embryo culture supernatants is mostly measured by sandwich ELISA or ALBIA (addressable laser bead immunoassay) techniques.…”

Section: Hla-g Expression In Preimplantation Embryos and Its Clinicalmentioning

confidence: 99%

The importance of HLA-G expression in embryos, trophoblast cells, and embryonic stem cells

Rizzo

Vercammen

Velde

et al. 2010

Cell. Mol. Life Sci.

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The nonclassical HLA-G molecule is a trophoblast-specific molecule present in almost every pregnancy. It differs from classical HLA class I molecules by the low degree of allelic variants and the high diversity of protein structures. HLA-G is reported to be a tolerogenic molecule that acts on cells of both innate and adaptive immunity. At the maternal-fetal interface HLA-G seems to be responsible largely for the reprogramming of local maternal immune response. This review will focus on the HLA-G gene expression profile in pregnancy, in preimplantation embryos, and in human embryonic stem cells with emphasis on the structural diversity of the HLA-G protein and its potential functional and diagnostic implications.

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Influence of early ICSI-derived embryo sHLA-G expression on pregnancy and implantation rates: a prospective study

Abstract: PR and IR increased with the addition of each sHLA-G+ embryo, regardless of age. While there are significant barriers to routine embryo sHLA-G testing, we believe that if implemented, this would provide a mechanism for optimizing IVF PR while minimizing the risk of multiple pregnancies.

Cited by 49 publications

References 25 publications

Transcriptional Proling Reveals Barcode-Like Toxicogenomic Responses in the Zebrash Embryo

Transcriptional Proling Reveals Barcode-Like Toxicogenomic Responses in the Zebrash Embryo

Differential Expression of Alternatively Spliced Transcripts of HLA-G in Human Preimplantation Embryos and Inner Cell Masses

The importance of HLA-G expression in embryos, trophoblast cells, and embryonic stem cells

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