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Familial Mediterranean Fever (FMF), an autosomal recessive disorder, is characterised by recurrent attacks of fever and serositis, lasting 24-72 hours. Since 1972 colchicine has become the drug of choice for prophylaxis against FMF attacks and amyloidosis FMF-associated. Colchicine, an alkaloid neutral, is absorbed in the jejunum and ileum. It metabolised by liver and only small amounts are recovered unchanged in the urine. Really plasma half-life is prolonged in patients with liver or renal failure. Colchicine is able to prevent activation of neutrophils, binding β-tubulin and making β-tubulin-colchicine complexes; this way inhibits assembly of microtubules and mitotic spindle formation; moreover its mode of action includes modulation of chemokines, prostanoids production, inhibition of neutrophil and endothelial cell adhesion molecules. The minimal daily dose in adults is 1.0 mg / die, but in children there is not a definite dose. Since in vitro high dosages of colchicine stop mitosis, this drug might interfere with male and female fertility and with children growth, but, according to current guidelines and because of rare side effects of the drug, FMF patients are recommended to take colchicine. Since colchicine treatment is often complicated by frequent gastrointestinal side effects, by our experience, in order to improve colchicine tolerance we recommend: lactose-free diet and treatment of intestinal bacterial overgrowth and / or Hp-infection, assessed by breath tests. Since our data showed that 10-15% of FMF patients seem are non-responders or intolerant to colchicine, today we are working in the design of colchicine analogues which may have lesser toxicities and a larger therapeutic window.

This prospective, randomized, controlled study compared the effects of recombinant human FSH (r-hFSH) and highly purified urinary FSH (u-hFSH HP) on lipoprotein(a) [Lp(a)] concentrations in women undergoing ovarian stimulation. Fifty infertile women were randomly allocated into two equally sized treatment groups (n = 25 per group). Thirty normal ovulation women were recruited as controls. The infertile women received u-hFSH or r-hFSH 150 IU/day starting on cycle day 2. From cycle day 6 the dose was adjusted according to ovarian response. Human chorionic gonadotrophin 10 000 IU was administered once there was at least one follicle ≥18 mm in diameter. The luteal phase was supported with progesterone 50 mg/day for at least 15 days. Repeated measurements of Lp(a) concentrations were performed during both stimulated and natural cycles. A significant increase in luteal phase Lp(a) concentrations was detected in the stimulated cycles, whereas no significant changes in serum Lp(a) concentrations were observed during natural cycles. There were no significant differences between the urinary and recombinant FSH effects on serum Lp(a). The luteal Lp(a) increase was transitory because after 1 month Lp(a) concentrations returned to baseline values if pregnancy failed to occur; in pregnant women persistent increased Lp(a) concentrations were found at the 8th week. The percentage changes in serum Lp(a) were positively correlated with the luteal progesterone increase (r = 0.40, P < 0.05), but not with follicular or luteal oestradiol increase. The women with low baseline Lp(a) (≤5 mg/dl) had a greater increase of the Lp(a) concentrations at midluteal phase than women with baseline Lp(a) >5 mg/dl. In conclusion, the recombinant or urinary hFSH administration does not directly influence Lp(a) concentrations. The luteal Lp(a) increase in stimulated cycles is not related to gonadotrophin treatment per se, but appears to be related to the high luteal progesterone concentrations, physiologically or pharmacologically determined. Our results also suggest that the sensitivity to the progesterone changes could be related to apolipoprotein(a) phenotype.

This prospective, randomized, controlled study compared the effects of recombinant human FSH (r-hFSH) and highly purified urinary FSH (u-hFSH HP) on lipoprotein(a) [Lp(a)] concentrations in women undergoing ovarian stimulation. Fifty infertile women were randomly allocated into two equally sized treatment groups (n = 25 per group). Thirty normal ovulation women were recruited as controls. The infertile women received u-hFSH or r-hFSH 150 IU/day starting on cycle day 2. From cycle day 6 the dose was adjusted according to ovarian response. Human chorionic gonadotrophin 10,000 IU was administered once there was at least one follicle > or =18 mm in diameter. The luteal phase was supported with progesterone 50 mg/day for at least 15 days. Repeated measurements of Lp(a) concentrations were performed during both stimulated and natural cycles. A significant increase in luteal phase Lp(a) concentrations was detected in the stimulated cycles, whereas no significant changes in serum Lp(a) concentrations were observed during natural cycles. There were no significant differences between the urinary and recombinant FSH effects on serum Lp(a). The luteal Lp(a) increase was transitory because after 1 month Lp(a) concentrations returned to baseline values if pregnancy failed to occur; in pregnant women persistent increased Lp(a) concentrations were found at the 8th week. The percentage changes in serum Lp(a) were positively correlated with the luteal progesterone increase (r = 0.40, P < 0.05), but not with follicular or luteal oestradiol increase. The women with low baseline Lp(a) (< or =5 mg/dl) had a greater increase of the Lp(a) concentrations at midluteal phase than women with baseline Lp(a) >5 mg/dl. In conclusion, the recombinant or urinary hFSH administration does not directly influence Lp(a) concentrations. The luteal Lp(a) increase in stimulated cycles is not related to gonadotrophin treatment per se, but appears to be related to the high luteal progesterone concentrations, physiologically or pharmacologically determined. Our results also suggest that the sensitivity to the progesterone changes could be related to apolipoprotein(a) phenotype.