Increased circulating Th1/Th2 ratios but not other lymphocyte subsets during controlled ovarian stimulation are linked to subsequent implantation failure after transfer of in vitro fertilized embryos

Abstract

Problem: To investigate alterations of circulating lymphocyte subsets in women undergoing controlled ovarian stimulation (COS) and survey their relations with pregnancy outcome.

Method of study: Fifty-one women were included in this study, of which 24 women were successfully pregnant in the index IVF cycle (the successful pregnancy group, sPG) and 27 women failed to get pregnant (the non-pregnancy group, nPG). Peripheral blood was collected at three time points during COS: on the day before the first GnRHa administration (GnRHa day), on the day before the first Gn administration (Gn day), and on the day before HCG administration (HCG day). The intracellular Th1(IFN-γ and TNF-α)/Th2(IL-10) ratios in circulating Th cells after in vitro phorbol-12-myristate-13-acetate stimulation, the NK cytotoxicity, and the percentage of T, B and NK cell subsets were assessed by flow cytometer. A third group consisting of patients with recurrent implantation failure (RIF group, n = 18) was also enrolled, and the intracellular Th1/Th2 ratios were assessed at HCG day.

Results: Intergroup comparison: The ratios of IFN-γ/IL-10 and TNF-α/IL-10 at HCG day were significantly higher (P < 0.05) in nPG than those in sPG, while no change at GnRHa day or Gn day. Higher (P < 0.05) ratios of IFN-γ/IL-10 and TNF-α/IL-10 at HCG day were also observed in RIF group compared to those in sPG. No significant change (P > 0.05) was found in other assessed lymphocyte subsets or in the concentrations of progesterone, estradiol, luteinizing hormone, or follicle-stimulating hormone between the sPG and nPG at the three time points. Intragroup comparison: The ratios of IFN-γ/IL-10 and TNF-α/IL-10 at HCG day were significantly (P < 0.05) lower than those at GnRHa day in sPG, but not in nPG. No significant (P > 0.05) difference was found in other assessed parameters or at other time points.

Conclusions: The ratios of Th1/Th2 were fluctuated during COS, and they might affect the pregnancy outcome of IVF. The circulating NK cytotoxicity and percentage of lymphocyte subsets were relatively stable during the COS.

Keywords: Controlled ovarian stimulation; NK cytotoxicity; Th1/Th2 ratio; in vitro fertilization; peripheral blood lymphocyte.