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Biomedical subjects

F Comhaire

Publications and source records attributed to F Comhaire.

At least 19 recordsLinked to original sources

Mechanisms of sperm deficiency in male accessory gland infection.

The presence of 2 million or more peroxidase-positive white blood cells per ml of semen, or the diagnosis of male accessory gland infection, is associated with important biochemical and biological changes in semen plasma and in the spermatozoa, reducing their fertilizing potential in vitro and in vivo (e.g., during intra-uterine insemination). In addition to the effects of reactive oxygen species, and its influence on the essential fatty acid composition of the sperm membrane, potentially unfavourable effects can occur through the intermediate of increased concentrations of certain cytokines, and decreased activity of enzymes such as alpha-glucosidase. In contrast, lower numbers of white blood cells may exert beneficial effects on spermatozoa thanks to the increased production of hepatocyte growth factor/scatter factor (a tissue repairing substance), and the stimulation of immuno-competent cells by particular cytokines (e.g., Interleukin-6).

Cytokines

Deterioration of sperm quality in young healthy Belgian men.

We have retrospectively analysed the sperm characteristics of 416 consecutive healthy young men who presented themselves in the past 19 years as candidate sperm donors. Ejaculate volume increased slightly (P = 0.067), and average sperm concentration decreased (P = 0.035) by 12.4 x 10(6)/ml over the observation period, so that sperm count per ejaculate remained unchanged (P = 0.91). In contrast, sperm morphology (r = - 0.23, P < 0.0001), rapid progressive motility (r = - 0.42, P < 0.0001) and total motility (r = - 0.33, P < 0.0001) presented an important and time-related decrease. When a quadratic model was used rather than a linear one to analyse the data on rapid progressive motility, there appeared to have been no further decline since 1990. The average proportion of spermatozoa with normal morphology decreased from 39.2% in the period 1977-1980 to 26.6% in 1990-1995 (P < 0.0001), and the mean percentage of spermatozoa with rapid progressive motility decreased from 52.7 to 31.7% (P < 0.0001). The percentage of candidate donors with sperm characteristics below the 5th percentile cut-off value of a normal fertile population increased from 13 to 54% during the observation period (P < 0.0001). Since the technique of semen analysis has remained essentially unchanged in-so-far as has been practically possible, as has the method of recruitment of candidate sperm donors, the observed deterioration of sperm characteristics is considered to reflect degeneration of sperm production among men aged between 20 and 40 years.

Adult

The possible meaning of transferrin and its soluble receptors in seminal plasma as markers of the seminiferous epithelium.

Transferrin (Tf) and soluble transferrin receptors (S-Tf-R) were measured by enzyme immunoassay in seminal plasma of 130 semen samples. The mean concentration of S-Tf-R in cases with normozoospermia was 10.4 IU/ml (95% confidence interval: 9.5-11.3) and it was significantly lower in patients with oligozoospermia (6.6, 95% CI: 5.8-7.5, P < 0.001), asthenozoospermia (8.5, 95% CI: 5.5-10.7, P < 0.05), azoospermia of primary testicular origin (7.9, 95% CI: 6.1-9.6, P<0.05) and post-vasectomy samples (5.9, 95% CI: 5.4-6.9, P < 0.001). The concentration of S-Tf-R in post-vasectomy samples was lower than that in patients with azoospermia of primary testicular origin (P < 0.05; positive likelihood ration = 7 at value of 8.3 IU/ ml). S-Tf-R was positively correlated with motile sperm concentration (r = 0.50, P < 0.0001), percentage motility (r = 0.38, P < 0.001), percentage of normal forms (r = 0.43, P < 0.001), sperm linear velocity (r = 0.42, P < 0.001), and ATP concentration (r = 0.67, P < 0.0001). Follicle stimulating hormone (FSH) was found to be negatively correlated with the concentrations of both Tf (r = -0.31, P < 0.05) and of S-Tf-R (r = -0.45, P < 0.01). The mean concentration of Tf in seminal plasma was 50.4 micrograms/ml (35.9-67.2) in samples with normozoospermia (n = 22), and the concentration was significantly lower in patients with oligozoospermia (P < 0.05), azoospermia of testicular origin (P < 0.001), and post-vasectomy samples (P < 0.001). Seminal Tf was correlated with motile sperm concentration (r = 0.36, P < 0.001), percentage of motile spermatozoa (r = 0.25, P < 0.05), linear velocity (r = 0.24, P < 0.05) and ATP concentration (r = p.44, P < 0.001). The concentration of Tf was positively correlated with that of S-Tf-R both in cases with spermatozoa present (r = 0.66, P < 0.001), and in cases with azoospermia of testicular origin (r = 0.51, P < 0.05) but not in vasectomy cases. It is concluded that S-Tf-R in seminal plasma is a marker of spermatogenesis and may give information on the presence or absence of spermatogenetic cells in cases with azoospermia. Further investigations are needed to assess its usefulness for clinical practice.

Biomarkers

Critical evaluation of the effectiveness of different modes of treatment of male infertility.

Among cohorts of couples treated for infertility due to a male factor it is the effective cumulative rate of successful deliveries and the cost per delivery that must be considered in assessing the value of different modes of treatment. The 'wait and see', timed coitus, or counselling approach has a low success rate (about 15% in 12 months), and a relatively high cost per delivery because of the cost of control visits and of tests for the prediction of ovulation. The high success rate of varicocele treatment (35% in 12 months, between 60 and 80% after 24 months), and the moderate cost of retrograde venography and embolisation results in a low cost per delivery. This cost is the lowest in anti-oestrogen treatment of idiopathic oligozoospermia, with a 20-30% effective cumulative pregnancy rate in 6 months. Three months of intra-uterine insemination (IUI) of Percoll gradient selected spermatozoa has a higher effective cumulative success rate than conventional in vitro fertilization (IVF) applied in cases with similar sperm characteristics, and the cost per successful delivery of the former is eight times lower than that of the latter. Intracytoplasmic sperm injection can successfully be applied in cases with more severe sperm deficiency; it has a higher success rate than conventional IVF, and is slightly more cost-efficient. However, the effective cumulative pregnancy rate remains relatively low (about 45% in 12 months) because of the high drop-out rate and long time interval between treatment cycles among unsuccessful couples.

Cohort Studies

Intrauterine insemination in male subfertility: a comparative study of sperm preparation using a commercial Percoll kit and conventional sperm wash.

In order to evaluate the possible benefit of sperm preparation using a commercially available, ready-to-use Percoll gradient kit (PerWash, FertiPro, Belgium) for intrauterine insemination (IUI), a two-centre study was performed comparing this method with conventional sperm preparation by means of centrifugation-resuspension. In the Percoll group, 25 couples out of 52 (48%) achieved pregnancy requiring 136 cycles of insemination, with a per cycle success rate of 18.4%. This result was significantly better (P < 0.01) than the per cycle pregnancy rate of 8.9%, which is 23 pregnancies out of 65 cases treated during 259 cycles of insemination with conventionally prepared semen. Also, the 10th percentile of sperm characteristics among successful cases was lower for sperm concentration, proportion and concentration of grade (a) motile spermatozoa in the Percoll group as compared to couples inseminated with conventionally prepared semen. In contrast, cases with elevated proportion of grade (a) motility (> 22%) were significantly less likely (P < 0.001) to obtain pregnancy with IUI, using either sperm preparation method. It is concluded that sperm preparation for intrauterine insemination using the Percoll gradient kit gives a better success rate and can be applied in cases with more severe sperm deficiency.

Adult

Comparison of different methods for the investigation of antisperm antibodies on spermatozoa, in seminal plasma and in serum.

Since there is no gold standard for the diagnosis of immunological infertility, comparison between different methods and of their results with biological tests for the detection of antisperm antibodies must be used in defining the most reliable and clinically relevant method. We have evaluated the results of direct (n = 100) and indirect tests in serum (n = 140) and seminal plasma (n = 100) using the SpermMAR and Immunobead (IB) techniques for the detection of sperm antibodies of the immunoglobulin (Ig) classes G, A and M, and we have compared the results with those of the tray agglutination test and the adenosine triphosphate release cytotoxicity test. Results indicate the higher specificity and sensitivity of the SpermMAR results for IgG and IgA, as compared to the outcome of the IB test. It appears that the IB test for IgA may detect non-specific antibodies in serum. Little information is obtained from the tray agglutination test in seminal plasma, and the indirect SpermMar test for IgG in seminal plasma was the only independent variable associated with the outcome of the former test. Since the SpermMAR tests for IgG and IgA are more accurate and biologically relevant, as well as easier to perform than the respective IB tests, the former must be considered the method of first choice.

Agglutination Tests

Evaluation of the role of reactive oxygen species in male infertility.

Reactive oxygen species (ROS) production from spermatozoa has been measured by chemiluminescence in the two fractions of a Percoll gradient column (47 and 90%). Chemiluminescent signals were recorded in each fraction after the addition of luminol and horse-radish peroxidase (basal state), and after stimulation with formyl-methionyl-leucyl-phenylalanine and phorbol ester (PMA). Oligozoospermic samples show a higher rate of ROS production than the normozoospermic samples in both fractions of Percoll. Also, ROS were generated at a higher rate by asthenozoospermic samples in the 90% Percoll fraction than by normal samples after stimulation with PMA. Our data confirm that fact that white blood cells play a major role in the production of ROS, even after purification on a Percoll gradient. Immunological cases were also found to be associated with an increased production of ROS, which may be caused by the same underlying pathological condition responsible for the production of the antibodies. Repeated centrifugation of the samples triggers a burst of ROS in excess of that produced after Percoll preparation. In addition, superoxide dismutase activity was found to be significantly increased in cases with an elevated production of ROS. It is concluded that measuring the ROS generation by semen may yield useful information on the functional capacity of spermatozoa, which may be used to improve the success of male infertility management.

Case-Control Studies

Human semen analysis.

Rapid developments have occurred in the management of couple infertility due to a male factor. These have stimulated renewed interest in semen analysis, which has become more correct, more reliable and more informative. The so-called basic semen analysis, which includes subjective estimation of sperm concentration, motility and morphology, has largely become obsolete. It has been replaced by several alternative techniques such as the home testing of semen by the man himself, the elaboration of methods and equipments for the exact assessment of conventional sperm characteristics, and the measurement of new parameters evaluating the functional state and capacity of spermatozoa, accessory sex glands and seminiferous epithelium. The present paper covers the following items: (i) conventional methods of semen analysis, (ii) the resazurin test and home fertility scoring, (iii) advanced methods for the objective assessment of conventional sperm characteristics and motility parameters.

Coloring Agents

Does treatment with testosterone undecanoate improve the in-vitro fertilizing capacity of spermatozoa in patients with idiopathic testicular failure? (results of a double blind study).

Seventy-seven couples in whom conventional in-vitro fertilization (IVF) had remained unsuccessful because of low fertilization rate and abnormal sperm characteristics were given either testosterone undecanoate 120 mg/day, or placebo during 3 months, after which a new IVF treatment was applied under identical technical conditions. There were no significant changes in sperm characteristics among the treated and placebo couples and the fertilization rate showed a similar increase after treatment in both groups. No significant difference in pregnancies occurred, with 32% pregnancies in the placebo controls and 17% among couples treated with testosterone undecanoate. It is concluded that testosterone undecanoate intake does not improve sperm characteristics, or the in-vitro fertilizing potential, or pregnancy rate over those observed in the placebo controls in cases with primary idiopathic testicular failure.

Adult

Evaluation of beta-endorphin and interleukin-6 in seminal plasma of patients with certain andrological diseases.

Human semen contains large amounts of opioid peptides and cytokines. We have measured the concentrations of interleukin (IL)-6 in 140 semen samples and of beta-endorphin in 77 semen samples. The median concentration of beta-endorphin in seminal plasma from normozoospermic men (n = 23) was 154.7 pg/ml (10th-90th percentiles, 42.0-774.6), and there was no significant difference in the beta-endorphin concentration among normozoospermic, oligozoospermic (n = 28), asthenozoospermic (n = 15), azoospermic (n = 4) and post-vasectomy (n = 7) samples. There was no correlation between beta-endorphin concentration and sperm characteristics, nor with blood hormones. beta-Endorphin concentration was lower in cases with immunological infertility, as revealed by a positive direct mixed antiglobulin reaction test (n = 12) (P < 0.01), than in matched controls. The median concentration of IL-6 in samples with normal sperm concentration, motility and morphology with or without white blood cells (n = 39) was 26.1 pg/ml (10th-90th percentiles, 7.3-172.3), and there was no significant difference in the IL-6 concentration among normozoospermic, oligozoospermic (n = 46), asthenozoospermic (n = 32), azoospermic (n = 13) and post-vasectomy (n = 10) samples. The IL-6 concentration was significantly higher in cases of varicocele (n = 22) without white blood cells in semen (P < 0.001) than in matched controls without varicocele (n = 23). In addition, the IL-6 concentration was elevated (P < 0.0001) in cases with accessory sex gland inflammation (n = 40). IL-6 concentration was positively correlated with white blood cells in semen (n = 60, r = 0.59, P < 0.0001), but there was no correlation with beta-endorphin concentration. The IL-6 concentration chosen to differentiate between cases with and without accessory gland inflammation was 45.3 pg/ml, with a specificity of 80.6% and a sensitivity of 92.5%. It is concluded that beta-endorphin in seminal plasma plays an immune suppressive role, and that increased IL-6 concentration may be related to testicular dysfunction in cases with varicocele. Furthermore, IL-6 is an accurate marker of accessory sex gland inflammation.

Case-Control Studies

Relationship between resazurin reduction test, reactive oxygen species generation, and gamma-glutamyltransferase.

The production of reactive oxygen species (ROS) from spermatozoa has been measured by chemiluminescence in the two fractions of a Percoll gradient column (47 and 90%). Chemiluminescent signals were recorded in each fraction after addition of luminol and horse-radish peroxidase (basal state), and after stimulation with formyl-methionyl-leucyl-phenyl-alanine (FMLP) and phorbol ester (PMA). We found an inverse correlation between the reducing capacity of the semen as estimated by the resazurin test, and the production of ROS by the spermatozoa, especially after stimulation with PMA (r = 0.51, P < 0.001). gamma-glutamyltransferase activity of seminal plasma was inversely correlated with ROS (r = -0.47, P < 0.01) and the resazurin test result (r = -0.43, P < 0.001) suggesting a possible role of prostatic secretions in the protection of spermatozoa against oxygen radicals. The resazurin test has a positive predictive value of 92.5% at a criterion value of colour scale 4 to discriminate between normal and excessive ROS production by spermatozoa, with sensitivity 79% and specificity 74%. In addition, at criterion value of colour scale 3, the resazurin test could distinguish between samples with normal or low activity of gamma-glutamyltransferase, with sensitivity 57% and specificity 93%. It is concluded that the result of the resazurin test can be influenced by the oxidative stress of spermatozoa and by prostatic function.

Horseradish Peroxidase