Expression of L-selectin ligand MECA-79 as a predictive marker of human uterine receptivity.

Problem Patients with repeated implantation failure (RIF) represent a subgroup of couples who suffer from unexplained infertility. Human blastocysts utilize L-selectin to initiate implantation by binding to endometrial ligands composed of oligosaccharide moieties on the surface glycoproteins. The absence of these ligands could lead to recurrent implantation failure (RIF) in some of these couples.

Twenty fertile women and 20 patients with RIF were tested for the presence of the L-selectin ligands by immunohistochemistry. Endometrial biopsies were obtained on the sixth day post ovulation. After fixation, they were dated according to Noyes. Immunolocalization was performed using the MECA-79 antibody which is directed against ligands of L-selectin.

The fertile group all showed the presence of the L-selectin ligand. Of those with RIF, five were negative for the ligand and never, despite an average of five successive embryo transfers, became pregnant. Fifteen RIF patients were positive for the L-selectin ligand, of whom ten subsequently conceived. As a screening test for RIF patients who lack the ligand, the predictive value was 100% with a sensitivity of 50% and specificity of 100%. The positive predictive value was 100% and negative predictive value is 87%.

L-selectin and its ligands play a vital role for early human implantation. Screening for the absence of the ligand may help many patients with RIF to avoid undergoing repeated failed treatment cycles. Similar content being viewed by others

Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. N Engl J Med 2001;342:1400–8. Alon R, Feigelson S. From rolling to arrest on blood vessels: leukocyte tap dancing on endothelial integrin ligands and chemokines at sub-second contacts. Semin Immunol 2002;14:93–104. McEver RP. Selectins: lectins that initiate cell adhesion under flow. Curr Opin Cell Biol 2002;14:581–6. Rosen SD. Ligands for L-selectin: homing, inflammation, and beyond. Annu Rev Immunol 2004;22:129–56. Prakobphol A, Thomsson KA, Hansson GC, Rosen SD, Singer MS, Phillips NJ, et al. Human low-molecular-weight salivary mucin expresses the sialyl Lewis x determinant and has L-selectin ligand activity. Biochemistry 1998;37:4916–27. Prakobphol A, Boren T, Ma W, Zhixiang P, Fisher SJ. Highly glycosylated human salivary molecules present oligosaccharides that mediate adhesion of leukocytes and Helicobacter pylori. Biochemistry 2005;44:2216–24. Genbacev OD, Prakobphol A, Foulk RA, Krtolica A, Ilic D, Singer MS, et al. Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface. Science 2003;299:405–8. Carson DD, Julian J, Lessey B, Prakobphol A, Fisher SJ. MUC1 is a scaffold for selectin ligands in the human uterus. Front Biosci 2006;11:2903–9. Veeck LL. An atlas of human gametes and conceptuses. New York: Parthenon; 1999. p. 46–51. Noyes W, Hertig AI, Rock J. Dating the endometrial biopsy. Fertil Steril 1950;1:3–25. Yeh JC, Hiraoka N, Petryniak B, Nakayama J, Ellies LG, Rabuka D, et al. Novel sulfated lymphocyte homing receptors and their control by a corel extension β1,3-N,acetylglucosaminyltransferase. Cell 2001;105:957–69. Navot D, Scott RT, Droesch K, Veeck LL, Liu HC, Rosenwaks Z. The window of embryo transfer and the efficiency of human conception in vitro. Fertil Steril 1991;55:114–8. Lai TH, Shih IM, Vlahos N, Ho CL, Wallach E, Zhao Y. Differential expression of L-selectin ligand in the endometrum during the menstrual cycle. Fertil Steril 2005;83:1297–302 Lai TH, Zhao Y, Shih IM, Ho CL, Bankowski B, Vlahos N. Expression of L-selectin ligands in human endometrium during the implantation window after controlled ovarian stimulation for oocyte donation. Fertil Steril 2006;85(3):761–3. Vlahos NF, Lipari CW, Bankowski B, Lai TH, King JA, Shih IM, et al. Effect of luteal-phase support on endometrial L-selectin ligand expression after recombinant follicle-stimulating hormone and ganirelix acetate for in vitro fertilization. Clin Endocrinol Metab 2006;91:4043–9. Khan S, Pisarska D, Kao LC. Hormonal regulation of N-acetylglucosamine-6-O-sulfotransferase (GlcNAc-6-OST), expression in a human endometrial cell model. ASRM/CFAS Sept. 2005;85 Suppl 1:S434 (Abstract). Lessey BA. Adhesion molecules and implantation. J Reprod Immunol 2002;55:101–12. Kao LC, Germeyer A, Tulac S. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology 2003;144:2870–81. Mak W, Khan S, Pisarska D. Androgen suppression of a target human implantation gene N-acetylglucosamine-6-O-sulfotransferase (GlcNAc-6-OST) in a human endometrial cell model. ASRM/CFAS 2005;85 Sept Suppl 1:S10 (Abstract). Shamonki MI, Kligman I, Shamonki JM, Schattman GL, Hyjek E, Spandorfer SD, et al. Immunohistochemical expression of endometrial L-selectin ligand is higher in donor egg recipients with embryonic implantation. Fertil Steril 2006;86:1365–75. Author information Authors and Affiliations Corresponding author Additional information Absence of the L-selectin ligand on the endometrium acts as a predictive marker for failed implantation. Rights and permissions About this article Cite this article Foulk, R.A., Zdravkovic, T., Genbacev, O. et al. Expression of L-selectin ligand MECA-79 as a predictive marker of human uterine receptivity. J Assist Reprod Genet 24, 316–321 (2007). https://doi.org/10.1007/s10815-007-9151-8 Published: Issue date: DOI: https://doi.org/10.1007/s10815-007-9151-8