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
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
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