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Effect of Ovaric Hyper-stimulation on Blood Lymphocyte Subpopulations, Cytokines, Leptin and Nitrite Among Patients with Unexplained Infertility


Dr Roberto A. Diez Immunopharmacology Lab., Paraguay 2155, piso 16, (1121) Buenos Aires, Argentina. E-mail:


Fornari MC, Sarto A, Berardi VE, Martínez 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.