Focus on the importance of soluble HLA-G as a marker for embryo selection in ART

8 10 2013

To the Editor:

We have read with interest the paper by Kotze et al. (1), reporting the retrospective analysis of 2,040 patients for the expression of soluble HLA-G (sHLA-G) by day-2 embryos after intracytoplasmic injection. The data represent further confirmation of the role of sHLA-G molecule quantification in embryo culture supernatants as a marker for embryo selection (2). In pregnancy several tolerance mechanisms have been demonstrated to counteract the maternal immune response. Among these, the expression of HLA-G by invasive cytotrophoblasts has been shown to play a fundamental role in creating a tolerogenic condition at the feto-maternal interface (2).

By now, more than 15,000 embryo culture supernatants have been evaluated for sHLA-G expression, with a positive correlation with embryo implantation rate and pregnancy outcome. However, further research is needed in HLA-G investigation in assisted reproductive technology (ART). Three aspects should be taken into consideration: 1) recognition of a common sHLA-G detection protocol; 2) necessity to identify a standardized range for positivity, as reported by Kotze et al. (1); 3) comprehension of the factors involved in the differential expression of sHLA-G between equal stage embryos originating from the same woman (3). Read the rest of this entry »

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Letter to the editor on “Trophectoderm grade predicts outcomes of single-blastocyst transfers”

23 07 2013

To the Editor:

Hill and colleagues (1) and others (2) found that trophectoderm morphology grading but not inner cell mass morphology grading significantly correlated with implantation and live birth after single-blastocyst transfer. This could reflect a positive embryonic condition in the interaction with the endometrium at the implantation site. In this respect our findings on the localization of prostaglandin H (PGH) synthase or cyclooxygenase, the key enzyme in prostaglandin synthesis, in the preimplantation mouse embryo might be of interest (2). Intracytoplasmic PGH synthase, localized in the endoplasmic reticulum, was found from the two-cell stage onward. In the blastocyst, PGH synthase was abundant in the trophectoderm, but only minimal background activity was observed in the inner cell mass. The involvement of prostaglandins in the interaction between embryo and endometrium at the time of human implantation has been established (3).

Robin M. F. van der Weiden, M.D., Ph.D.
Sint Franciscus Gasthuis, Department of Obstetrics and Gynecology, Rotterdam, The Netherlands

References

1. Hill MJ, Richter KS, Heitmann RJ, Graham JR, Tucker MJ, DeCherney AH, et al. Trophectoderm grade predicts outcomes of single-blastocyt transfers. Fertil Steril 2013;99:1283-9.

2. Ahlström A, Westin C, Reismer E, Wikland M, Hardarson T. Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer. Hum Reprod 2011;26:3289-96.

3. Van der Weiden RMF, Wisse LJ, Helmerhorst FM, Keirse MJNC, Poelmann RE. Immunohistochemical and ultrastructural localization of prostaglandin H synthase in the preimplantation mouse embryo. J Reprod Fert 1996;107:161-6.

4. Van der Weiden RMF, Helmerhorst FM, Keise MJNC. Influence of prostaglandins and platelet activating factor on implantation. Hum Reprod 1991;6:436-42.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.07.1986

The authors respond:

We read with interest the comments of Dr. van der Weiden in regard to our recent publication demonstrating that trophectoderm morphologic grading was significantly correlated with implantation and live birth in single-blastocyst transfers (1). We agree that favorable trophectoderm morphology likely reflects embryonic capacity to interact with the endometrium and thus results in improved implantation. It is known that the trophectoderm is actively involved in implantation and produces numerous compounds including hCG, progestamedins, inteferons, and, as Dr. van der Weiden suggests, prostaglandin synthesis, all of which modulate embryonic-endometrial communication (2). The trophectoderm morphology has also been correlated with aneuploidy, is the first occurring specialized tissue distinguished from the embryo mass, and may be a more static measure than the assessment of the inner cell mass (3). It remains to be determined whether trophectoderm morphology is more accurately assessing trophectoderm function or aneuploidy or both. While assessing the mechanisms of the interaction between the endometrium and the trophectoderm was not the focus of our work, it would be reasonable to speculate that favorable morphologic characteristics of the trophectoderm would reflect improved biochemical function of the trophectoderm, including the production of prostaglandin H synthase and the importance of prostaglandins in human implantation and thus result in improved pregnancy outcomes (4, 5).

Micah J. Hill, D.O.a
Ryan J. Heitmann, D.O.a
Eric D. Levens, M.D.b
a Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
b Shady Grove Fertility Reproductive Science Center, Rockville, Maryland

References

1. Hill MJ, Richter KS, Heitmann RJ, Graham JR, Tucker MJ, DeCherney AH, Browne PE, Levens ED. Trophectoderm grade predicts outcomes of single blastocyt transfers. Fertil Steril 2013; 99: 1283-9.

2. Bazer FW, Spencer TE, Johnson GA, Burghardt RC, Wu G. Comparative aspects of implantation. Reprod 2009;138:195-209.

3. Krupinski P, Chickarmane V, Peterson C. Simulating the mammalian blastocyst- molecular and mechanical interactions pattern the embryo. PLoS Comput Biol 2011;7: e1001128.

4. Van der Weiden RMF, Wisse LJ, Helmerhorst FM, Keirse MJNC, Poelmann RE. Immunohistochemical and ultrastructural localization of prostaglandin H synthase in the preimplantion mouse embryo. J Reprod Fert 1996; 107: 161-6.

5. Van der Weiden RMF, Helmerhorst FM, Keise MJNC. Influence of prostaglandins and platelet activating factor on implantation. Hum Reprod 1991; 6: 436-42.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.07.1989





Is universal application of blastocyst biopsy with comprehensive chromosome screening for embryo selection ready for prime time?

29 05 2013

To the Editor:

We read with great interest the article by Scott and colleagues, “Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases IVF implantation and delivery rates: a randomized controlled trial” (1). This is the highly anticipated third study of a planned three-phase initial strategy designed to validate the use of the authors’ rapid qPCR-based comprehensive chromosome screening (CCS) technology for embryo screening and selection.

In the first of the three studies, validation of the technology was confirmed using cell lines and discarded blastocysts of previously confirmed ploidy status (either aneuploid or euploid) (2). In the second study, the technology was shown to have a high negative predictive value (NPV, failure to deliver when aneuploid embryos were transferred) of 96% albeit the positive predictive value (PPV, delivery per euploid embryo transferred) was considerably lower at 41.4% (3). In this, the third, study comprising a randomized controlled trial (RCT) to assess clinical utility of CCS, results showed that use of CCS resulted in impressively high implantation and delivery rates (79.8% and 84.7%, respectively) which were, indeed, both significantly greater than those obtained from embryos transferred after morphological evaluation alone (63.2% and 67.5%).

We appreciate the forward-thinking approach of the investigators in their systematic approach to validate and then assess efficacy of the technology for embryo screening and selection. However, we would like to raise some queries regarding the results reported, as well as discuss several limitations of this study. Read the rest of this entry »





Re: Relevance of the site of assisted hatching in thawed human blastocysts

16 06 2010

To the Editor:

With interest we read the elegant paper of Miyata et al. (1) which reported the existence of polarity in the hatching process of warmed human blastocysts. In detail, artificial zona pellucida (ZP) opening close to the inner cell mass (ICM) resulted in improved rates of complete hatching, whereas assisted hatching at the abembryonic site caused trapping of the embryo within the ZP (1). Read the rest of this entry »