F. Dondero

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.

Superoxide anion in human semen related to seminal parameters and clinical aspects

OBJECTIVE To study the possible presence of extracellular superoxide anion (O2-) in untreated semen of normal and pathological subjects and to determine the possible relationship between superoxide anion levels, number of seminal leukocytes (WBCs) and seminal parameters. PATIENTS Semen samples were analyzed from fertile normospermic subjects (n = 20) and patients (n = 132) attending the Outpatient Department of the 5th Medical Clinic. MAIN OUTCOME MEASURE We evaluated superoxide anion levels by monitoring the reduction of cytochrome c. RESULTS O2- was detected in 55.0% of fertile normospermic subjects. Both the percentage of subjects in whom O2- was detected and the mean values +/- SD of O2- were significantly higher in the male partners of infertile couples, in subjects with varicocele, and in subjects with positive sperm culture than normospermic subjects. No variations were seen in vasectomized subjects or in patients with past cryptorchidism. A high correlation was observed between O2- levels and WBCs (rs = 0.58), nonrapid, immotile sperm (rs = 0.64), percentage decrease of motility within a specified time frame (2 to 6 hours) (rs = 0.73), and sperm abnormalities (rs = 0.49). CONCLUSIONS Superoxide anion in untreated semen is produced by WBCs and atypical and nonrapid, immotile sperm. A significant increase of superoxide anion was detected in the male partners of infertile couples and in some selected andrological conditions. The toxic effect of superoxide anion on sperm cells is dependent on the time of exposure and superoxide anion concentration.

Fertility and semen quality of workers exposed to high temperatures in the ceramics industry

The objective of this study was to test the hypothesis that chronic occupational exposure to high temperatures may be detrimental to male reproduction. The study was based on 92 healthy ceramics oven operators with a long exposure to high temperatures, and 87 controls, recruited from the shipment department of the same industry. Interviews with all subjects provided data on sociodemographic characteristics, health status, and fertility problems. Semen analysis was carried out on 46 of the workers exposed to high temperatures, and 14 of the controls, and included evaluation of the sperm concentration, morphology, and motility, including computer-assisted sperm motion analysis (velocity, linearity, ALH, BCF). The results of the questionnaire showed that exposed individuals had a higher incidence of childlessness and of self-reported difficulty in conceiving than controls. The semen analysis showed no significant differences except in sperm velocity. Although differences in semen parameters, taken singly, were not statistically significant, the overall evaluation of the sperm parameters indicated a higher prevalence of pathologic sperm profiles among the exposed compared to the controls.

Polyunsaturated fatty acids of germ cell membranes, glutathione and blutathione-dependent enzyme-PHGPx: From basic to clinic

The lipid metabolism in sperm cells is important both for energy production and for cell structure. A special composition of membrane phospholipids, rich in polyunsaturated fatty acids (PUFA), and the different composition of sperm and immature germ cell membrane are described and discussed. Testis germ cells as well as epididymal maturing spermatozoa are endowed with enzymatic and non-enzymatic scavenger systems to prevent lipoperoxidative damage. Catalase, superoxide dismutase, and glutathione-dependent oxidoreductases are present in variable amounts in the different developmental stages. Phospholipid hydroperoxide glutathione peroxidase (PHGPx) activity and roles in caput and cauda epididymal sperm cells are discussed. Also seminal plasma has a highly specialized scavenger system that defends the sperm membrane against lipoperoxidation and the degree of PUFA insaturation acts to achieve the same goal. Systemic predisposition and a number of pathologies can lead to an anti-oxidant/pro-oxidant disequilibrium. Scavengers, such as glutathione can be used to treat these cases as they can restore the physiological constitution of PUFA in the cell membrane.

Sperm parameters after early left varicocele treatment

Abstract Objective: We evaluated whether early treatment for left varicocele can improve sperm parameters. Design: Patient follow-up and comparison with control groups. Setting: Surgical department of a Childrens Hospital and a university infertility-care center. Patient(s): Nineteen patients who underwent surgery for left varicocele as adolescents (mean ± SD, 14.11 ± 1.59 years) were followed up as adults (mean ± SD, 19.37 ± 1.16 years). Main Outcome Measure(s): A testicular examination was performed and varicocele staging was done at the time of surgery. Andrologic examination and semen analysis were done 2–8 years later. Semen results were compared with those of two age-matched control groups of 19 healthy, randomly selected subjects and 19 unoperated patients suffering from left varicocele of the same degree. Result(s): The mean values of sperm parameters in the patient study group were similar to those of the healthy controls except that the sperm concentration was significantly lower. However, sperm motility and morphology mean values in the patient study group were significantly higher than those of the unoperated patients. Conclusion(s): This study indicates that surgery in adolescence can be useful, possibly because the testis is still developing at that age. Large-scale, double-blind controlled trials on early treatment of left varicocele are needed to identify possible markers of disease severity.

GLUTATHIONE THERAPY FOR MALE INFERTILITY

Eleven infertile men were treated with glutathione (600 mg/day IM) for 2 months. The patients were suffering from dyspermia associated with various andrological pathologies. Standard semen and computer analyses of sperm motility were carried out before treatment and after 30 and 60 days of therapy. Glutathione exerted significant effect on sperm motility patterns. Glutathione appears to have a therapeutic effect on some andrological pathologies causing male infertility.

Improved human sperm recovery using superoxide dismutase and catalase supplementation in semen cryopreservation procedure.

The aim of this work was to evaluate the effects of ROS scavenger supplementation in human semen samples undergoing cryopreservation procedures.After screening out andrological pathologies, we selected 25 male partners of infertile couples with the following semen profile: volume ≥ 2.0 ml, normal viscosity, sperm count ≥20 × 106/ml, straight progressive motility (classes 1 and 2) ≥ 40% (Mazzilli, Rossi, Delfino and Nofroni (1999) Andrologia 31: 187–194), atypical forms ≤ 70%, WBCs < 1.0 times 106/ml.After liquefaction, standard semen analysis and the Hypoosmotic Viability Test (HVT) were carried out; the samples were then divided into 4 aliquots. The first was untreated as a control; 200 U/ml of superoxide dismutase (SOD) was added to the second, 200 U/ml of catalase to the third and both SOD (100 U/ml) and catalase (100 U/ml) were added to the fourth aliquot. Each aliquot was mixed (v/v) with TEST yolk buffer freezing medium (Irvine Scientific) and then frozen at −196°C. The percent recovery of progressive motile and swollen spermatozoa was evaluated after thawing.No significant variation in the recovery of progressive motility was seen in the aliquots with added SOD or catalase alone, compared to the control group. On the other hand, a significant improvement in sperm parameter recovery was seen in the aliquot with both SOD and catalase supplementation; perhaps because of their combined and simultaneous action on superoxide anion and hydrogen peroxide. These results suggest that, in some selected cases, SOD and catalase supplementation can contribute greatly to the prevention of sperm membrane lipid peroxidation by ROS and thus allow good sperm parameter recovery after freezing–thawing procedures.

Psychosocial factors and male seminal parameters.

The relationships between (a) alexithymia, (b) extroversion (E), neuroticism (N), psychoticism (P), (c) coping style towards stressors, and seminal parameters, were assessed in 132 males on their first seminal fluid examination by means of a multivariate approach. They were given the TAS-20, the EPQ, and the Coping Inventory for Stressful Situations (CISS). Seminal parameters were: (1) sperm concentration; (2) total sperm count; (3) forward motility; (4) atypical forms. Multiple regressions considering quantitative parameters of seminal status as criterion showed a negative relationship with P, difficulty describing feelings (DDF), while a positive relationship was found for N, and emotion-oriented coping. A discriminant analysis also showed that P, N and DDF distinguished between two groups of normozoospermic and oligozoospermic subjects with a high probability of correct classifications. Results confirm the hypothesis that biological and psychological variables are not completely independent or randomly related in people with an impaired seminal status, although the correlations between psychosocial and biological data are not very strong.

Antisperm antibody detection: 2. Clinical, biological, and statistical correlation between methods

PROBLEM: In clinical andrology, the detection of antisperm antibodies (ASA) is regarded as one of the most important steps in the study of male infertility. This practice is generally accepted even though there is still some disagreement about the true meaning of antisperm immunity, and there remains a good deal of controversy about the test regarded as the most suitable for the detection of antibodies directed against sperm antigens. International Workshops have tried to standardize universally accepted protocols. A panel of three or four methods is generally advised to provide a correct and complete screening of patients with antisperm immunity.

Chromosomal alterations and male infertility

Reduced male fertility can be caused by genetic factors affecting gamete formation or function; in particular, chromosome abnormalities are a possible cause of male subfertility as shown by their higher frequency in infertile men than in the general male population. Meiotic studies in a number of these males have shown spermatogenesis breakdown, often related to alterations in the process of chromosome synapsis. Indeed, any condition that can interfere with X-Y bivalent formation and X-chromosome inactivation is critical to the meiotic process; furthermore, asynapsed regions may themselves represent a signal for the meiotic checkpoint that eliminates spermatocytes with synaptic errors. We performed cytogenetic, hormonal and seminal studies in 333 infertile patients selected because azoospermic, severely oligozoospermic or normozoospermic with failure to fertilize the partner’s oocytes in an in vitro fertilization (IVF) program. Our findings: 1) confirm the high incidence of chromosomal anomalies among infertile males; 2) highlight the relevance in male infertility of quantitative/positional modifications of the constitutive heterochromatin; and 3) underline the relevance of cooperation between andrologists and cytogenetists prior to every kind of assisted reproduction, above all prior to intracytoplasmic sperm injection, in which selective hurdles eliminating abnormal germ cells are bypassed.