Successful implantation is associated with a transient increase in serum pro-inflammatory cytokine profile followed by a switch to anti-inflammatory cytokine profile prior to confirmation of pregnancy

Abstract

To compare the changing peripheral levels of inflammation-related cytokine profile during a 9-day period after blastocyst transfer between women who did and did not conceive. Prospective, observational, and longitudinal study. University-affiliated hospital. Forty-seven women with infertility who were undergoing single day-5 blastocyst transfer were recruited. This prospective observational and longitudinal study on 47 women with infertility was performed in an invitro fertilization unit from December 2018 to August 2019. The amounts of a range of cytokines was measured on serial blood samples obtained during a 9-day period after blastocyst transfer. Serial blood samples were obtained on the day of embryo transfer, and 3, 6, and 9 days afterward for measurement of serum interferon gamma (IFN-γ), tumor necrosis factor alpha, interleukin (IL)-2, IL-4, IL-10, IL-12, IL-13, IL-17, IL-18, and IL-22 using cytometric bead arrays; transforming growth factor beta 1 (TGF-β1) was measured using commercial enzyme-linked immunosorbent assay kits. The cytokine profile was similar between the women who conceived and those who did not on the day of blastocyst transfer. In women who conceived, IFN-γ and IL-17 (pro-inflammatory cytokines) exhibited a transient and significant increase on day 3 after blastocyst transfer, which decreased to the baseline levels by day 6. Meanwhile, IL-10 (anti-inflammatory cytokine) was increased significantly on days 6 and 9, and TGF-β1 (anti-inflammatory cytokine) was increased significantly on day 9 after blastocyst transfer. In women who did not conceive, there was a more pronounced increase in IFN-γ and IL-17 (pro-inflammatory cytokines) on day 3, which was sustained on days 6 and 9 without a switch to an anti-inflammatory cytokine profile. Among women who conceived after blastocyst embryo transfer, there was a transient and modest increase in serum pro-inflammatory cytokine profile (IFN-γ and IL-17) 3 days after blastocyst transfer, which was followed by a switch to anti-inflammatory cytokine profile (increase IL-10 and TGF-β1) by 6 days after blastocyst transfer and the latter increase was sustained 9 days after blastocyst transfer, when pregnancy was confirmed.