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Biomedical subjects

F H Comhaire

Publications and source records attributed to F H Comhaire.

At least 37 records · Page 2Linked to original sources

Inhibin and steroid responses to testicular stimulation in normal men.

Static measurements of immunoreactive inhibin have proved to be of little relevance in the diagnosis of testicular disorders. To explore whether a dynamic evaluation of inhibin secretion might yield a more useful parameter of testicular function we compared the responses of inhibin with steroids to i.v. injections of pure follicle-stimulating hormone (FSH; 300 IU) or human chorionic gonadotrophin (HCG; 1500 IU) and oral administration of the anti-oestrogen Tamoxifen (20 mg/day for 7 days) in four normal fertile men. Blood was aspirated between 1 and 72 h after the injections and daily during Tamoxifen intake. Four controls were injected with physiological saline solution. An additional four men were injected with pure FSH, and blood was taken after 24, 48 and 72 h. Injection of FSH was accompanied by nycthemeral variations of testosterone comparable with those observed in the controls. The concentration of inhibin showed similar nycthemeral variations but a significant increase was observed in all eight cases at 12 noon on days 2 and 3 after FSH injection. HCG injection resulted in the expected biphasic response of testosterone. Inhibin displayed a pronounced increase 18 h after injection but the delayed response after 48 and 72 h was not observed. Tamoxifen intake increased testosterone but not inhibin, and caused a moderate and temporary increase of luteinizing hormone and FSH. It was concluded that primary stimulation both of Leydig cells by HCG and Sertoli cells by FSH increase circulating inhibin.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Male contraception: hormonal, mechanical and other.

Methods of male contraception that have been developed so far have mainly focused on the inhibition of spermatogenesis through suppression of the hypothalamo-pituitary secretion of gonadotrophins, and simultaneous supplementation with androgens. These methods include the use of combinations of progestogens or luteinizing hormone-releasing hormone antagonists and testosterone derivatives, or high dose testosterone. Though effective contraception can be obtained, side-effects and/or the high cost of treatment limit the widespread use of these approaches. Inhibition of sperm maturation in the epididymis, or direct interference with spermatogenic cells or the cells of Sertoli by e.g. gossypol have been abandoned because of toxic side-effects. Voluntary sterilization by vasectomy is the most commonly used method of male contraception, but its surgical nature, problematic reversibility and suspected link with subsequent prostate cancer render the method far from ideal. Non-surgical vas occlusion may overcome some of these problems, but data on long-term side-effects and reversibility are lacking. New contraceptive developments should focus on interfering with highly specific aspects of spermatogenesis such as unique enzymatic processes and intercellular communication through cytokines, or application of antibodies against antigens of the epididymis or the spermatozoa. Only through better understanding of normal and pathological spermatogenesis will it be possible to develop an acceptable male contraceptive.

Contraception↗

Comparison of the resazurin test, adenosine triphosphate in semen, and various sperm parameters.

The results of the resazurin test (RES) and adenosine triphosphate (ATP) concentration in semen, measured by two methods, were compared for their ability to predict sperm parameters of semen samples from 42 subfertile men as assessed by a semi-computerized system. The highest correlation of RES grade was with sperm concentration (r = 0.70, P < 0.001), concentration of motile spermatozoa, concentration of motile spermatozoa with normal morphology and the ATP concentration using the reference LKB method (all r = 0.65, P < 0.001). The RES test has a positive predictive value of 93% for a progressive motile sperm concentration of 20 x 10(6)/ml or more, and a negative predictive power of 90% for the same variable at a criterion value of 10 x 10(6)/ml. The results of ATP measurement using the reference LKB and FireZyme methods presented a strong correlation (r = 0.74, P < 0.001). The correlations between ATP measurements from the FireZyme method and sperm characteristics were better than those obtained using the reference LKB method for ATP determination. It is concluded that the RES test can be performed with a relatively small volume of semen; it is easy to perform and requires not technical equipment. The accuracy and predictive value of this test are similar to more sophisticated ATP measurements. In addition, the RES may identify a subgroup of subfertile men with a decreased reducing capacity of semen.

Adenosine Triphosphate↗

Methods to evaluate reproductive health of the human male.

The proportion of men suffering from subfertility has increased and sperm quality of the general population has decreased rather dramatically during the last decades. Conventional methods to measure sperm concentration, motility, and morphology give a rough estimate of the fertilizing capacity of semen. Objective assessment of motility characteristics and morphometric image analysis may give more precise information, but technology still needs to be refined. Some aspects of the functional capacity of spermatozoa may be impaired before measurable changes occur in their number or morphology. A battery of tests is described to evaluate sperm migration and capacitation, acrosome reaction and acrosin activity, zona adhesion and binding, sperm oolemma fusion, sperm head decondensation, and chromatin make-up. Also methods are described to localize the possible site of impairment of the genital tract. Implementation of these methods may enhance our capability to detect minor effects of environmental hazards on male reproductive health.

Evaluation Studies as Topic↗

An approach to the management of male infertility.

Male factors are present in nearly half the couples consulting for infertility. The correct approach to the management of male infertility follows a logical and scientifically sound sequence of procedures. These include history taking, systematic physical examination for general and local causes of abnormal semen quality, complemented by contact-thermoscopy, echography and hormone assays if available. Conventional semen analysis can be replaced by more accurate advanced methods measuring sperm motility characteristics. Several tests of sperm functional capacity are also available. It is mandatory to detect and treat known and accepted causes of impaired sperm quality using adequate and reliable methods. Complementary methods to stimulate spermatogenesis, or to assist reproduction should be offered in well-defined cases. The overall success rate of male infertility treatment remains lower than that of female treatment, though recent technology has improved results remarkably.

Humans↗

Objective semen analysis: has the target been reached?

Objectivity in assessing critical sperm characteristics such as concentration, motility and morphology, has been the target of many systems and devices. Methods based on physical principles such as turbidimetry, spectrophotometry, laser Doppler technology, are too imprecise or technically too complicated to be applied routinely in the laboratory. Microscopic images providing photographical, cinematographical or video data acquisition followed by manual or computer-assisted image analysis (CASA) suffer from practical and/or device deficiencies, making them tedious and time-consuming, or unreliable because of confounding factors and uncontrolled artefacts. A single-step computer system using visual evaluation of the microscopic field and manual tracking of sperm movement yields more reliable results, but technician expertise remains essential for correct performance. The scientific basis of multiple errors in semen aspiration, chamber quality, data acquisition and analysis is given. Biased interpretations of results or incorrect handling of statistical data are criticised.

Humans↗

Determination of adenosine triphosphate in human semen to estimate the fertilizing potential and to quantify sperm antibodies.

The measurement of the ATP content of fresh semen is as accurate as the estimation of sperm motility by conventional methods in discriminating between semen of fertile versus subfertile men. The ATP content of frozen thawed donor semen is correlated with the probability of conception per cycle of insemination. Exact quantification of cytotoxic sperm antibodies in serum is possible with the adenosine-triphosphate-release-cytotoxicity test, since measurement is free of the bias of microscopic examination. The procedure has been simplified by testing only one serum dilution and calculating the 'sperm toxicity index'.

Adenosine Triphosphate↗

Concentrations of oestradiol and testosterone in peripheral and spermatic venous blood of dogs with unilateral cryptorchidism.

Plasma testosterone and oestradiol concentrations were measured in peripheral and spermatic venous blood of 13 dogs with unilateral inguinal cryptorchidism, 9 dogs with unilateral abdominal cryptorchidism, and in a control group of 36 mature normal dogs. The hormone concentrations were similar in the three groups, both in the peripheral and in the spermatic venous blood. The weight of the testes in the control group was correlated with the body weight and there was no significant difference between the weight of the right and the left testes. The weight of the abdominal testes was lower than that of the inguinal testes, and there was no compensatory enlargement of the contralateral scrotal testis. The cryptorchid testes showed little or no histological evidence of spermatogenesis, and spermatogenesis was usually normal in the scrotal testes.

Animals↗

Accuracy of sperm characteristics in predicting the in vitro fertilizing capacity of semen.

Based on the results of in vitro fertilization (IVF) in 56 couples, the power was assessed of traditional sperm characteristics of native semen to discriminate between in vitro fertile and in vitro infertile semen. The number per ejaculate of spermatozoa with regular oval heads was the best discriminant, followed by the concentration of progressively motile spermatozoa. This contrasts with the in vivo fertilizing capacity, which depends mostly on the proportion and concentration of spermatozoa with rapid linear progression. The lower limit of sperm characteristics was assessed as the fifth percentile of in vitro fertile semen and was compared with the lower limit of semen of fertile men and of subfertile men who achieved spontaneous or treatment-related conception in vivo. It appeared that the semen quality needed for in vitro fertilization is inferior to that of fertile men but not remarkably different from that of subfertile men who achieved spontaneous conception during 1-year follow-up after consultation. If conventional methods for semen preparation are used, there seems to be no major advantage in favor of IVF for the treatment of male infertility due to sperm deficiency. An increased success rate may, however, be attained, thanks to improved techniques of semen collection, semen preparation, and oocyte insemination.

Female↗

Practical guidelines for the treatment of infertility in hirsute women.

On the basis of retrospective investigation of 315 infertile hirsute women aged between 19 and 35 years, it was attempted to find selection criteria for infertility treatment. Cases with adrenal, ovarian and pituitary tumors, congenital adrenal hyperplasia and genetic disorders should be excluded by means of preliminary investigations. It is possible to select the optimal treatment for each individual patient using a flow-chart. Thanks to this approach, a pregnancy rate of 83% is achieved.

Adult↗

Evaluation of the direct and indirect mixed antiglobulin reaction with latex particles for the diagnosis of immunological infertility.

The direct Mixed Antiglobulin Reaction (MAR test) is a simple method for the detection of auto-antibodies attached to spermatozoa in fresh semen. The test was improved by using IgG-coated latex particles (SpermMAR) instead of coated red blood cells. A positive direct MAR test with adherence of latex particles to 40% or more of the motile spermatozoa was found in 16 out of 312 men (5%) consulting for infertility, but never in fertile controls. The percentage of motile spermatozoa reacting with the coated latex particles was correlated significantly with the serum titre of sperm agglutinins assessed by the tray agglutination test. The direct MAR test on semen was highly specific but rather insensitive, particularly if the serum titre of agglutinins was low. The same kit (SpermMAR) can be used to detect circulating sperm antibodies in serum of male or female patients with the indirect mixed antiglobulin reaction. The indirect MAR test discriminated clearly between serum with low (less than 1/32) or high (greater than 1/32) titres of circulating agglutinins assessed by the tray agglutination test. Considering their simplicity and accuracy, both the direct test on semen and the indirect spermMAR test on serum should be included in the routine evaluation of the infertile couple.

Antibodies, Anti-Idiotypic↗

Concentration of pefloxacine in split ejaculates of patients with chronic male accessory gland infection.

The concentrations of pefloxacine and its N-demethylated derivative were measured in split ejaculates of 12 patients with chronic male accessory gland infection during treatment with 400 mg. pefloxacine twice a day. The mean concentrations of pefloxacine and N-demethylated pefloxacine (mg. per l.) were 8.7 +/- 1.2 (standard error of the mean) and 4.2 +/- 0.7 in fraction 1, and 9.8 +/- 1.1 and 4.3 +/- 0.6 in fraction 2. The concentrations in both fractions were correlated strongly (r equals 0.97). The concentration of pefloxacine in the secretory fluids of the prostate and seminal vesicles are 30-fold the minimal inhibitory concentration 90 of Escherichia coli and Klebsiella species, 100-fold the minimal inhibitory concentration 90 of Proteus mirabilis and equal to the minimal inhibitory concentration 90 of Streptococcus faecalis. In three-fourths of the patients signs of infection resolved after 4 weeks of treatment.

Adult↗

Reassessment of the accuracy of traditional sperm characteristics and adenosine triphosphate (ATP) in estimating the fertilizing potential of human semen in vivo.

Receiver operating characteristic curves and accuracy parameters were computed for traditional sperm characteristics (concentration, motility, morphology) and the number of peroxidase negative cells, and the concentration of adenosine triphosphate (ATP) in semen from populations of fertile and infertile men, and men who achieved a pregnancy after varicocele treatment. The percentage and concentration per millilitre of spermatozoa with rapid linear progressive motility, and the ATP concentration, provided the best discrimination between fertile and treated fertile from infertile men. The misclassification rate was higher for sperm morphology, total progressive motility and viability, whereas sperm concentration and the total sperm count per ejaculate had the worst discriminating power. The number of peroxidase negative cells per 100 spermatozoa was highly specific in identifying men who achieved pregnancy after varicocele treatment. The lower limit of normality of sperm characteristics was remarkably different between fertile men and men achieving pregnancy after treatment or during infertility work-up.

Adenosine Triphosphate↗

Simple model and empirical method for the estimation of spontaneous pregnancies in couples consulting for infertility.

Based on simple theoretical models and on the analysis of data of over 12,000 couples, a simple formula is proposed to predict the probability of spontaneous (treatment-independent) pregnancies in couples consulting for infertility after at least 12 months of unprotected intercourse. For a duration of infertility of between 12 months and 48 months the probability of conception per cycle of exposure is 4 X 0.97n X (a) X (bm) X (bf), where n is the number of months of unsuccessful trial to conceive, a refers to the type of infertility (primary vs secondary), bm depends on the severity of impairment of semen parameters, and bf relates to the age and pathology of the female partner. Some tentative values for these factors are calculated.

Age Factors↗