Treatment of erectile dysfunction due to C677T mutation of the MTHFR gene with vitamin B6 and folic acid in patients non responders to PDE5i.

INTRODUCTION: Epidemiological studies conducted on erectile dysfunction (ED) have demonstrated its close correlation with cardiovascular disease. Since hyperhomocysteinemia is considered an important cardiovascular risk factor, it could also be involved in the pathogenesis of ED. AIM: To study the role of the C677T MTHFR mutation with subsequent hyperhomocysteinemia in the determination of ED. METHODS: We studied 75 consecutive patients presenting with ED. Patients were interviewed using the International Index of Erectile Function. Blood samples were drawn for determination of MTHFR gene C677T mutation, homocysteine (Hcy) and folate levels. Penile color Doppler was also performed. MAIN OUTCOME METHODS: Patients were administered sildenafil citrate for 2 months. The nonresponders were treated with combination of sildenafil, vitamin B6, and folic acid for 6 weeks. Patients were split into three groups, A, B, and C on the basis on their MTHFR genotype, and in a further group defined as "sildenafil nonresponders" (NR). RESULTS: We found 20 patients homozygous for mutant MTHFR 677T, 36 heterozygous, and 19 wild type. Difference in baseline values for Hcy and folic acid was found between groups A and B, and A and C. The NR group (18 patients from group A and B), presented high levels of Hcy and low levels of folic acid. After combination treatment 16 of them (88.9%) revealed an improvement in the IIEF questionnaire. Moreover, it was measured a significant difference between the values of Hcy and folic acid at the baseline and at the end of the study for the nonresponders. CONCLUSIONS: Hyperhomocysteinemia in patients homozygotes for the C677T mutation may interfere with erection mechanisms and thus be responsible for ED. In case of hyperhomocysteinemia associated with low levels of folates, the administration of PDE5 inhibitors may fail if not preceded by the correction of the alterated levels of Hcy and folates.

Testicular tumors as a possible cause of antisperm autoimmune response.

OBJECTIVE: To evaluate the presence of antisperm antibodies in testicular cancer patients 1 month after orchiectomy and before radiotherapy or chemotherapy. DESIGN: Clinical study. SETTING: Department of andrology and seminology at a university hospital. PATIENT(S): One hundred ninety patients with testicular cancer. INTERVENTION(S): Determination of semen parameters and autoimmune reaction evaluated on the sperm surface and in blood serum. MAIN OUTCOME MEASURE(S): Autoimmune reaction on the sperm surface by the direct immunobead test (IBT), and in blood serum by the indirect IBT and the gelatin agglutination test (GAT), was evaluated 1 month after orchiectomy and before beginning chemotherapy or radiotherapy. RESULT(S): Of the 190 patients, 11 (5.8%) were positive for antisperm antibody by GAT. On indirect IBT, 3 of the 11 GAT-positive patients were positive to IgG class only, with values of 22%, 24%, and 40%. Of the 11 GAT-positive patients, 4 showed no antibody bound to the sperm surface, and 3 were positive to IgG class only (28%, 21%, and 38%), with binding exclusively on the tail. Direct IBT could not be performed in the remaining 4 patients. CONCLUSION(S): Our data support the hypothesis that testicular cancer might not be a possible cause of antisperm autoimmunization and infertility.

Human semen refrigeration at + 4 degrees C: bio-kinetic characteristics.

The aim of our study was to evaluate the bio-kinetic characteristics of human semen refrigerated for different periods and to compare the effects of refrigeration at +4 degrees C against cryopreservation of human sperm at -196 degrees C. Semen was obtained from 30 male partners of infertile couples (infertile subjects) with the following semen profile: sperm count >or=10 x 10(6)/ml; progressive motility >or=20%; atypical forms <70% and white blood cells <1.0 x 10(6)/ml. Fifteen normospermic subjects were also selected as controls (control subjects). The following tests were carried out on basal, refrigerated and cryopreserved sperm: a) sperm kinetic properties (by Superimposed Image Analysis System); b) the Hypoosmotic Viability Test (HVT) (combined Hypoosmotic Swelling and Viability Test). The results of the study showed that the percentage recovery of kinetic properties and of HVT were optimum for up to 48 h. After refrigeration for 72 h, a drastic decrease in straight motility recovery was observed. No significant differences were observed between cryopreservation and refrigeration at +4 degrees C for 48 h for motility or HVT recoveries in samples from control subjects. However, in infertile subjects, a significant decrease in straight progressive motility and HVT recoveries was observed in cryopreserved samples compared to those refrigerated for 48 h. Neither refrigeration nor cryopreservation led to the growth of pathogenic bacteria in any of the cases studied. Based on the above results, refrigeration could represent a useful alternative to the cryopreservation method.

Antisperm immunity in assisted reproduction.

Antisperm antibodies (ASA) can impair the fertilising capacity of human spermatozoa, acting negatively on sperm motility and cervical mucus penetration, and at the level of in vitro gamete interaction. Several methods attempt to improve the potentially deleterious effects of ASA-mediated infertility: by decreasing ASA production, by removing ASA already bound to sperm, artificial insemination (AIH) and fertilisation (IVF, ICSI). Only ICSI seems able to overcome the problem, with fertilisation and pregnancy rates of ASA-positive patients undergoing this technique in the same range as ASA-negative patients. As immunological infertility is relatively rare, literature in the field is quite scarce and more studies need to be conducted to confirm that embryo quality is not impaired.

Testicular cancer and Hodgkin's disease: evaluation of semen quality.

BACKGROUND: The aim of our study was to establish whether there is a difference in semen quality between patients with testicular cancer (TC) and Hodgkin's disease (HD). METHODS: We evaluated 342 patients affected by TC (n = 232) or HD (n = 110) who cryobanked sperm before initiating chemo- or radiotherapy. All TC patients were evaluated approximately 1 month after orchidectomy. RESULTS: A total of 14 patients were azoospermic or cryptozoospermic. In the TC group (n = 222) the mean of the semen parameters was normal according to the World Health Organization (1992). However, dividing the cases into total sperm count > or =40x10(6)/ejaculate and <40x10(6)/ejaculate, 35.5% of the patients showed an impaired semen quality. The quality of sperm parameters was higher in seminoma patients than for the other histological groups. A significant difference for all semen variables was observed between patients with serum betahCG levels classified as pathological (>5 mIU/ml) and those with normal serum betahCG. Comparison of semen parameters between TC stages I and II showed no significant differences. In the HD group (n = 106), we found that by and large they showed normal spermatogenesis, with only 24.5% having a total sperm count <40x10(6)/ejaculate. There was a significant decrease in semen quality in stages III and IV of HD. CONCLUSIONS: Better semen quality was observed in patients with HD than in those with TC. The semen quality observed in our TC and HD groups seems better than previous results reported in the literature.

Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial.

OBJECTIVE: To determine the efficacy of L-carnitine therapy in selected cases of male factor infertility. DESIGN: Placebo-controlled, double-blind, crossover trial. SETTING: University tertiary referral center. PATIENT(S): One hundred infertile patients (ages 20-40 years) with the following baseline sperm selection criteria: concentration, 10-20 x 10(6)/mL; total motility, 10%-30%; forward motility, <15%; atypical forms, <70%; velocity, 10-30 micro/s; linearity, <4. Eighty-six patients completed the study. INTERVENTION(S): Patients underwent L-carnitine therapy 2 g/day or placebo; the study design was 2 months of washout, 2 months of therapy/placebo, 2 months of washout, and 2 months placebo/therapy. MAIN OUTCOME MEASURE(S): Variation in sperm parameters used in the patients selection criteria, in particular, sperm motility. Excluding outliers, a statistically significant improvement in semen quality, greater than after the placebo cycle, was seen after the L-carnitine therapy for sperm concentration and total and forward sperm motility. The increase in forward sperm motility was more significant in those patients with lower initial values, i.e., <5 x 10(6) or <2 x 10(6) of forward motile sperm/ejaculate or sperm/mL. CONCLUSION(S): Based on a controlled study of efficacy, L-carnitine therapy was effective in increasing semen quality, especially in groups with lower baseline levels. However, these results need to be confirmed by larger clinical trials and in vitro studies.