Effect of ovaric hyper-stimulation on blood lymphocyte subpopulations, cytokines, leptin and nitrite among patients with unexplained infertility.

Fornari MC, Sarto A, Berardi VE, Martinez MA, Rocha MG, Pasqualini S, Diez RA. Effect of ovaric hyper-stimulation on blood lymphocyte subpopulations, cytokines, leptin and nitrite among patients with unexplained infertility. AJRI 2002; 48:394–403 © Blackwell Munksgaard, 2002 PROBLEM: To determine the effect of ovarian stimulation on TH1, TH2 and natural killer (NK) lymphocytes, plasma cytokines, leptin and nitrite levels. METHODS: Women with reproductive failure were studied during the implantation window, at baseline (n=18) and under ovarian stimulation (gonadotropins + progesterone, n=6). Controls: eight fertile women. Lymphocyte subpopulations and NK function were determined by flow cytometry. Interleukin-2 (IL-2), IL-4, IL-10, IFN-γ, TNF-α, TGF-β1 and leptin were measured by enzyme immunoassay (EIA); nitrite by the Griess reaction. RESULTS: At baseline, patients had higher values of NK effectors, NK activity and plasma IFN-γ and IL-2 than controls. Conversely, TGF-β1 values were lower. Hormones induced leukocytosis. Under stimulation, TH1 CD4+ cells, NK effectors and function and plasma IFN-γ and IL-2 decreased, while transforming growth factor (TGF)-β1 increased. Other variables did not change. CONCLUSION: The abnormal distribution of leukocytes, high TH1 cytokines and a low TGF-β1 associated with reproductive failure, respond to ovarian stimulation, achieving total or partial normalization.