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Among commercially available urinary human menopausal gonadotrophin (HMG) material, gonadotrophins comprise <5% of the total protein content. Thus, during a typical ovarian stimulation cycle with HMG, several milligrams of non-relevant proteins are administered that may lead to unwanted side effects, including allergic or other hypersensitivity reactions. The effects of two recombinant and four urinary gonadotrophin preparations of different purity upon the function of T cells from healthy blood donors were studied. Only one of the HMG preparations significantly enhanced the spontaneous proliferation of peripheral blood mononuclear cells. Phytohaemagglutinin-induced proliferation was not modified by any preparation, while two preparations significantly increased proliferation in the mixed lymphocyte reaction. Three of the HMG preparations induced the release of interleukin (IL)-1. Highly purified FSH, either urinary or recombinant, showed no effect. None of the preparations induced detectable IL-2 production, whereas only one HMG preparation tended to decrease IL-2 secretion. No major changes in CD25 expression were induced by any of the gonadotrophins. Cytokine measurement by immunoassays detected only IL-1β in two commercially available preparations. The various effects exhibited by the crude urinary preparations were not a result of the gonadotrophin content and differed from product to product, suggesting that the contaminants present in these preparations are not identical. This could contribute to unpredictable clinical manifestations of allergic or other immune reactions. [ABSTRACT FROM PUBLISHER]

Local reactions have been frequently reported following repeated injections of human menopausal gonadotrophins (HMG) for the treatment of infertility. Also immunoglobulin (Ig) E-mediated systemic reactions have sporadically been observed. Since most HMG preparations contain significant amounts of non-hormonal urine-derived proteins, it was suggested that these contaminating proteins are responsible for the various allergic reactions. In order to verify this hypothesis, different human follicle stimulating hormone (HFSH) and HMG preparations (Metrodin and Pergonal from Ares-Serono, and Humegon from Organon), were compared with a highly purified preparation (Metrodin HP from Ares-Serono) for the frequency and severity of allergic reactions induced in laboratory animals. The occurrence of anaphylactic shock or related symptoms was studied in sensitized guinea-pigs. The production of specific IgE was evaluated in serum from mice sensitized with the test drugs by the induction of passive cutaneous anaphylaxis in rats. In both models, two different schedules of sensitization were used. Severe allergic reactions were found in 20 and 7% of the guinea-pigs receiving highly purified FSH (Metrodin HP) in the two schedules, respectively, compared to 90 and 88% with the other preparations. Similarly significantly lower IgE titres were induced by highly purified FSH in respect to the other preparations. It can be concluded that the elimination of contaminating proteins significantly reduces the allergenicity of urine-derived HFSH preparations. [ABSTRACT FROM PUBLISHER]