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BACKGROUND One of the most well-documented cytokines suspected as a hazard to male fertility is tumor necrosis factor-alpha (TNFalpha). Genetic factors such as single-nucleotide polymorphisms (SNPs) in the TNF gene cluster impact TNFalpha levels. Our objective was to establish the potential involvement of -308 TNF SNP in male infertility risk. METHODS In 684 infertile male patients undergoing an intracytoplasmic sperm injection procedure, we used allele-specific polymerase chain reaction (PCR) and PCR-RFLP to investigate the distribution of the guanine (G)-to-adenosine (A) substitution at position -308 in the promoter region of the TNFalpha gene. RESULTS An increased frequency of the -308 TNFalpha A allele was found in patients with low sperm count of testicular origin [P = 0.002; odds ratio (OR) = 2.93] or with normal production count but altered sperm motility (P = 0.003; OR = 2.32), compared with a patient group with normal sperm count and quality (morphology and motility). In patients with low sperm count exhibiting TNFalpha A allele, compared with those with G allele, an alteration in hormonal balance was observed with increased inhibin B levels and subsequent reduced FSH plasma levels, leading to an FSH/inhibin B ratio roughly half as high (from 0.07 +/- 0.01 in TNFA versus 0.13 +/- 0.02 in TNFG allele groups, P < 0.0001). CONCLUSION As the -308 TNFalpha A allele has been associated with an increased expression/production of TNFalpha, the potential use of therapies based on inhibition of TNFalpha activities could represent possible therapeutic opportunities for patients with low sperm count (i.e. primary testicular dysfunction) or with altered sperm motility.

BACKGROUND: Although intrauterine insemination (IUI) is one of the most common assisted reproductive technology methods in the world, the relative influence of various semen characteristics on the likelihood of a successful outcome is controversial. The aim of our study was to assess the results of IUI as a function of both the number of motile spermatozoa inseminated (NMSI) and the percentage of morphologically normal spermatozoa after preparation. METHODS: This was a retrospective study of 889 couples who underwent 2564 IUI cycles of ovarian stimulation with HMG or recombinant FSH in our centre between January 1991 and December 2000. RESULTS: A total of 331 clinical pregnancies were obtained, for a pregnancy rate/cycle of 12.91%. When the NMSI was