The role of T-helper cytokines in human reproduction

Objective: To explore the role of maternal periimplantation endometrial T-helper-1 (TH-1) and T-helper-2 (TH-2) cytokines in the success or failure of human reproduction and their relation to the endocrine system and subsequent pregnancy outcome. Design: Controlled, prospective study. Setting: A tertiary care hospital with a university-based reproductive medicine clinic. Patient(s): Healthy women and women with recurrent miscarriage who had no history of infertility or autoimmune disease. Intervention(s): Measurement of qualitative cytokine expression by RT-PCR and quantitative by ELISA, also hormone levels and pregnancy outcome. Main Outcome Measure(s): Expression of TH-I and TH-2 cytokines and correlation with hormone levels and subsequent pregnancy outcome. Result(s): Levels of TH-I cytokines were significantly greater and higher in women with recurrent miscarriage compared with controls, whereas levels of TH-2 cytokine interleukin-6 were significantly lower in women with recurrent miscarriage than in controls. There was no correlation between cytokine expression and serum hormone levels, and periimplantation cytokine levels were not predictive of subsequent pregnancy outcome in women with recurrent miscarriage. Conclusion(s): This study demonstrated in vivo that women with recurrent miscarriage exhibit primarily TH-1 cytokines, whereas healthy women exhibit decreased TH-I cytokines and increased TH-2 cytokines. This suggests a potential role for a dichotomous T-helper response in the mediation of subsequent reproductive events. This maternal T-helper response appears to operate independently of hormonal factors in influencing the success or failure of human reproduction, as no correlation was evident between serum hormone levels and cytokine levels. An attempt to use periimplantation TH-1 and TH-2 cytokine profiles as a predictor of subsequent pregnancy outcome Give birth or no live birth was limited by the small number of patients studied. Fertil Sterile 2000;73:136-42. (C)1999 by American Society for Reproductive Medicine.