A prospective study comparing the inflammation-related cytokine and chemokine profile from the day of blastocyst transfer to 7 weeks of gestation between pregnancies that did or did not result in a miscarriage

Immunomodulation is thought to be important for the successful establishment of pregnancy to prevent the rejection of the implanting semi-allograft embryo (Challis et al., 2009, Arck and Hecher, 2013, Miko et al., 2019). It is achieved by a complex interaction between maternal and fetal immune modulators including various cytokines and chemokines and this has resulted in various cytokines and chemokines being examined as markers of immune dysregulation in early pregnancy loss (Plevyak et al., 2002, Lidstrom et al., 2003, Chang et al., 2019). Previously, our team has shown that successful implantation is characterized by a transient increase of pro-inflammatory cytokines followed by a switch to an anti-inflammatory state in the peripheral blood around 3-6 days after embryo transfer (ET) (Zhao et al. 2020). Our results suggested an elaborate and timely coordinated biphasic immune response occurring at the very early stage during the implantation process. Several previous studies have also shown that women who miscarried had increased levels of pro‐inflammatory cytokines in their blood when compared to women with normal pregnancies (Vassiliadis et al., 1998, Jenkins et al., 2000, Paradisi et al., 2003, Saito et al., 2010, Calleja-Agius et al., 2011, Zhang et al., 2016). However, the biological and clinical significance of these observed changes remains uncertain. Firstly, it is not clear if these observed changes preceded the onset of miscarriage or merely represented secondary changes consequent upon the miscarriage process (Raghupathy et al., 2000, Laird et al., 2003, Calleja-Agius et al., 2012). Secondly, the samples from earlier studies were obtained from different individuals at different gestational weeks which may not be directly comparable because it is well recognized that peripheral blood cytokine levels change substantially following implantation and throughout the first trimester of pregnancy. Therefore, the comparison of samples collected from different people and different gestational weeks could have introduced a potential source of variance to the results (Raghupathy et al., 2000, Ng et al., 2002, Calleja-Agius et al., 2011).

A recent study compared the changing trends of inflammation-related peripheral blood cytokine profiles between pregnancies that ended in miscarriage and those that resulted in a live birth. In that study, there appeared to be a significant increase in the pro-inflammatory cytokine TNF-α and a decrease in the anti-inflammatory cytokine IL-10 with consequently a lower ratio of IL-10 to TNF-α around 4 to 5 weeks in women who miscarried when compared to those with viable pregnancies (Kaislasuo et al. 2020). However, the study was limited by the blood samples being not precisely timed according to the arrival of the embryo into the uterine cavity and the baselines of cytokines before pregnancy were not measured. Moreover, the serial changes of other cytokines and chemokines around the period of embryo implantation have yet to be determined.

Based on current literature, it is suggested that implantation occurred 6 to 10 days after ovulation and consisted of three stages: apposition, attachment and invasion (Wilcox et al., 1999, Norwitz et al., 2001). Herein, this current study aimed to extend our previous longitudinal study on the comparison of the peripheral blood cytokine profile during peri-implantation period (0 to 9 days after ET) between women who did or did not conceive after ET (Zhao et al. 2020) to post-implantation period (up to 30 days after ET) on women who achieved clinical pregnancy and those who subsequently suffered pregnancy loss. We hypothesize that there are significant differences in the cytokine and chemokine profiles between the 2 groups prior to the confirmation of miscarriage. We utilized precisely timed serum samples obtained on the day of ET (ET+0) and 3, 6, 9, 16, 23 and 30 days after ET (ET+3, +6, +9, +16, +23 and +30) in women undergoing single blastocyst transfer and measured levels of numerous inflammation-related cytokines and chemokines in these samples and compared the results between women with different pregnancy outcomes.

留言 (0)

沒有登入
gif