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Biomedical subjects

F H Comhaire

Publications and source records attributed to F H Comhaire.

16 recordsLinked to original sources

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

The effect of doxycycline in infertile couples with male accessory gland infection: a double blind prospective study.

Male accessory gland infection (MAGI, epididymo-prostato-vesiculitis) with abnormal semen quality was rarely the only abnormality in infertile couples since it occurred in no more than 1.6% of 2871 couples evaluated in 7 centres during a 3-year period. Both partners of 33 infertile couples with no other demonstrable abnormality than abnormal semen and MAGI consented to participate in a double blind trial and were treated with either doxycycline, 100 mg/day for 1 month (20 couples) or placebo (13 couples). Follow-up during a total of 175 couple-months included semen analysis and the recording of pregnancy. Pregnancy occurred in 2 of the doxycycline-treated couples (10%) and in 1 of the placebo treated couples (8%), corresponding with conception rates per month of 1.9% and 1.5%, respectively. Sperm motility and, to a lesser extent, morphology showed improvement in both groups. Evidence of infection, namely increased numbers of white blood cells and positive sperm culture, disappeared in both the doxycycline-treated and placebo group. It is concluded that features of MAGI in semen may regress spontaneously and are not influenced by the doxycycline treatment. The concomitant improvement of sperm motility and morphology still does not seem to enhance the probability of conception.

Bacterial Infections

Testosterone concentration in the fluids of seminiferous tubules, the interstitium and the rete testis of the rat.

Testosterone was measured by radioimmunoassay in interstitial fluid, 'free-flow' seminiferous tubular fluid, obtained by micropuncture, and rete testis fluid from intact adult anaesthetized rats. Under non-stimulated conditions the concentration of testosterone in interstitial fluid was below the limit of detection in two rats and achieved a mean level of 150 +/- 27 (S.E.M.) ng/ml in the remaining 17 determinations. The testosterone concentration of the seminiferous tubular fluid was below the limit of detection in two rats, and had a mean level in the remaining 15 determinations of 91 +/- 14 ng/ml, which is significantly lower (P less than 0-02) than that in interstitial fluid. The mean ratio of seminiferous tubular:interstitial fluid testosterone concentration calculated in 14 rats was 0-94 +/- 0.24. This ratio was less than unity whenever the interstitial fluid testosterone concentration was more than 50 ng/ml, whereas in all animals with interstitial fluid testosterone of 50 ng/ml, or less, the ratio was greater than or equal to one. The mean testosterone concentration of rete testis fluid in 32 samples was 33 +/- 3 ng/ml. After HCG stimulation in 12 rats, testosterone concentration in interstitial fluid increased to a mean value of 660 +/- 83 ng/ml, and in seminiferous tubular fluid to 460 +/- 44 ng/ml; the difference between the two was significant (P less than 0-05). These results are discussed in relation to the presumed dilution of seminiferous tubular fluid in rete testis fluid and the role of androgen-binding proteins in the transport of steroids.

Animals

Study of the accuracy of physical and biochemical markers in semen to detect infectious dysfunction of the accessory sex glands.

Infection of the male accessory sex glands may result in impaired secretory function and alteration of the composition of seminal plasma. Using receiver operating characteristic curves and accuracy tests, the power of several biochemical and physical markers was evaluated for their ability to discriminate between semen of infected and noninfected infertile men. The total output of citric acid had the strongest discriminating power, followed by acid phosphatase and gamma-glutamyltranspeptidase. Measurement of the concentration of fructose was found to be nondiscriminatory.

Acid Phosphatase

Evaluation of the hypo-osmotic swelling test in relation with advanced methods of semen analysis.

The hypo-osmotic swelling test was claimed to assess an independent functional characteristic of human spermatozoa bearing relevance to their fertilizing capacity. To test this claim, we have studied the relationship between the result of the hypo-osmotic swelling test with that of conventional semen analysis and sperm motility patterns, the semen content of adenosine triphosphate, the staining pattern to acidified aniline blue, and the zona-free hamster oocyte test. The result of the HOS test is significantly correlated with all sperm characteristics except for the aniline blue stainability and the hamster oocyte test. The capacity of spermatozoa to react in a hypo-osmotic environment expresses the same functional information as the viability test using eosine staining. It is concluded that the hypo-osmotic swelling test does not add relevant information to that obtained by routine sperm analysis with regards to the fertilizing potential of semen.

Adenosine Triphosphate