Immunological status in patients undergoing in vitro fertilisation: responses to hormone treatment and relationship to outcome

Abstract

We aimed to prospectively investigate the paternal antigen-induced cytokine secretion by peripheral blood mononuclear cells (PBMC) in response to hormone treatment in women undergoing in vitro fertilization (IVF) and to examine the predictive value of the cytokine secretion in the outcome of IVF treatment in a pilot study. Twenty-five women were included and IVF treatment was successful for six and unsuccessful for 19 women. Blood samples were collected before IVF treatment, on four occasions during IVF and 4 weeks after embryo transfer. The numbers of Th1-, Th2-and Th17-associated cytokine secreting cells and cytokine levels in cell supernatants were analyzed by enzyme linked immunospot-forming (ELISpot), enzyme-linked immune-sorbent (ELISA) or Luminex assay. None of the cytokines (IFN-γ, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, TNF and GM-CSF) had any predictive value regarding IVF outcome. The majority of the cytokines reached their peak levels at ovum pickup, suggesting an enhancing influence of the hormonal stimulation. Pregnancy was associated with a high number of IL-4-, IL-5-and IL-13-secreting cells four weeks after ET. In conclusion, the results do not support our hypothesis of a more pronounced peripheral Th1 and Th17 deviation towards paternal antigens in infertile women with an unsuccessful IVF outcome, although this is based on a small number of observations. Thus, a larger study should be conducted to confirm this conclusion. Higher numbers of Th2-associated cytokinesecreting cells in pregnant women four weeks after ET do corroborate the hypothesis of a Th2 deviation during pregnancy.

Physiological and molecular determinants of embryo implantation

“…Interestingly, progesterone suppresses the development of Th17 cells via inhibiting STAT3 activation in response to IL-6 (Lee et al, 2011b). However, a recent study fails to observe a predominant Th1 and Th17 response in women with repeated IVF failure (Persson et al, 2012), suggesting a diversified etiology of gestation diseases. Overall, the hitherto useful Th1/Th2/Th17 and Treg paradigm can be expanded into a well-orchestrated cytokine network conducive for maternal immune tolerance during pregnancy recognition and adaption.…”

Cytokines in relation to hCG are significantly altered in asymptomatic women with miscarriage – a pilot study

“…We can’t exclude that these findings can be transmitted to patients who conceived spontaneously. However, as ART seems to influence cytokine profile, our findings can be specific for patients following in-vitro-fertilization [ 29 ].…”

Gonadotropin‐releasing hormone analogues lead to pro‐inflammatory changes in T lymphocytes

“…Such medications may affect immune effectors and cytokine/chemokine milieus in peripheral blood . During IVF cycles, the majority of the cytokines were reported to reach their peak levels at the time of ovum pick‐up . These immunological changes were reported to be related with IVF outcomes as well.…”

“…For COH, gonadotropins, GnRH‐a or GnRH‐ant, and human chorionic gonadotropin are often utilized. Such medications may affect immune effectors and cytokine/chemokine milieus in peripheral blood . During IVF cycles, the majority of the cytokines were reported to reach their peak levels at the time of ovum pick‐up .…”