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Periovulatory Increases in Tissue Homing Potential of Circulating CD56^bright Cells Are Associated with Fertile Menstrual Cycles

Departments of Pediatrics, University of Western Ontario (M.J.v.d.H.), London, Canada N6C 2V5; Departments of Mathematics and Statistics (J.H.) and Biomedical Sciences (K.H., S.Ba., S.Bu.), University of Guelph, Guelph, Ontario, Canada N1G 2W1; Department of Molecular Immunology, State University of New York (S.S.E.), Buffalo, New York 14263; Department of Anatomy and Cell Biology, Queen’s University (B.A.C.), Kingston, Canada K7L 3N6; and Department of Obstetrics and Gynecology, University of Western Ontario (F.R.T.), London, Canada N6A 1C9

Address all correspondence and requests for reprints to: Dr. Marianne J. van den Heuvel, Department of Pediatrics, Child Health Research Institute, 800 Commissioner’s Road East, University of Western Ontario, London, Ontario, Canada N6C 2V5. E-mail: mvandenh{at}uwo.ca.

CD56^bright lymphocytes appear in the uterus 3–5 d after ovulation coincident with the onset of stromal cell decidualization. Although the source of these uterine immune cells is not defined, a subset of blood CD56^bright cells exhibits enhanced capacity to adhere to decidual vascular endothelium during the periovulatory period of menstrual cycles. In this study, the effects of early pregnancy on the adhesive capacity of CD56^bright cells to bind uterine substrates were examined in a time-course study of 18 infertile women undergoing natural cycles before transfer of frozen/thawed embryos and 18 infertile women undergoing controlled ovarian stimulation. There were three pregnancies in the natural cycle group and seven in the hormone-stimulated cohort. Hormone levels, and number and quality of transferred embryos were similar between pregnant and nonpregnant cycles. However, the adhesive function of CD56^bright cells increased before ovulation in hormone-treated women who became pregnant and before embryo transfer in naturally cycling women who became pregnant. This pattern of incremental adhesion, which was less frequently observed in unsuccessful cycles, suggests a role for NK cells in implantation. These results support the idea that temporal control of NK cell homing to the uterine microenvironment is a prerequisite to pregnancy.

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