The role of T-helper cytokines in human reproduction

Objective: To explore the role of maternal periimplantation endometrial T-h elper-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 subseque nt pregnancy outcome. Design: Controlled, prospective study. Setting: A tertiary care hospital with a university-based reproductive medi cine clinic. Patient(s): Healthy women and women with recurrent miscarriage who had no h istory of infertility or autoimmune disease. Intervention(s): Measurement of qualitative cytokine expression by RT-PCR a nd quantitative by ELISA, also hormone levels and pregnancy outcome. Main Outcome Measure(s): Expression of TH-I and TH-2 cytokines and correlat ion with hormone levels and subsequent pregnancy outcome. Result(s): Levels of TH-I cytokines were significantly greater and higher i n women with recurrent miscarriage compared with controls, whereas levels o f TH-2 cytokine interleukin-6 were significantly lower in women with recurr ent 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 mi scarriage exhibit primarily TH-1 cytokines, whereas healthy women exhibit d ecreased TH-I cytokines and increased TH-2 cytokines. This suggests a poten tial role for a dichotomous T-helper response in the mediation of subsequen t reproductive events. This maternal T-helper response appears to operate i ndependently of hormonal factors in influencing the success or failure of h uman reproduction, as no correlation was evident between serum hormone leve ls and cytokine levels. An attempt to use periimplantation TH-1 and TH-2 cy tokine profiles as a predictor of subsequent pregnancy outcome Give birth o r 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 Medic ine.