Leuven: birthplace of modern skeletology, thanks to Andreas Vesalius, with the help of Gemma Frisius, his friend and fellow-physician.

The skeleton-making technique of Andreas Vesalius is described and is compared with that of others. An overview is added of the skeletons he constructed himself. The significance of his friend Gemma Frisius is discussed as well as the translations of the chapter of this technique in the De humani corporis fabrica.

Gregorius-Josephus Jacquelart, born in 1759, the first andrologist at the University of Leuven.

At the time of his death in 1776, most medical doctors in Paris challenged the views of Théophile de Bordeu on the "hormonal" action of internal secretions. At the University of Leuven, however, his concepts on the hormonal activity of semen had been positively approached in 1780 on the occasion of a public debate (disputatio), conducted by the medical student, Gregorius-Josephus Jacquelart. Therefore, we consider G.J. Jacquelart as being the first andrologist at the University of Leuven.

Intrauterine insemination after ovarian stimulation with clomiphene citrate: predictive potential of inseminating motile count and sperm morphology.

This retrospective study aimed to evaluate the prognostic value of the inseminating motile count (IMC) and sperm morphology (using strict criteria) on success rates after homologous intrauterine insemination (IUI) combined with clomiphene citrate (CC) stimulation. A total of 373 couples underwent 792 IUI cycles in a predominantly (87.4%) male subfertility group. The overall cycle fecundity (CF) and baby take-home rate (BTH) was 14.6 and 9.9% respectively. The cumulative CF and BTH (per couple) after three cycles were 30.6 and 21.1% respectively. Overall, sperm morphology and IMC were of no prognostic value using receiver operating characteristic (ROC) curve analysis, but after classifying the study population into different subgroups according to IMC, sperm morphology turned out to be a valuable prognostic parameter in subgroup 1, i.e. IMC <1 x 10(6). In this subgroup, no pregnancies were seen when the morphology score was <4% and the mean value of sperm morphology was significantly different in the pregnant (8.3%) versus non-pregnant group (5.0%; P <0.05). The cumulative CF and BTH after three IUI cycles were comparable for all couples with the exception of those cases in which the IMC was <1 x 10(6) with a morphology score of <4% normal forms. We recorded only two twin pregnancies (2.5%) and no moderate or severe ovarian hyperstimulation syndrome. We conclude that in a selected group of patients without CC resistance and normal ovarian response following CC stimulation [maximum of three follicles with a diameter of >16 mm at the time of administration of human chorionic gonadotrophin (HCG)], IUI combined with CC-HCG can be offered as a very safe and non-expensive first-line treatment, at least with an IMC of >1 x 10(6) spermatozoa. In cases with <1 x 10(6) spermatozoa, CC-IUI remains important as a first-choice therapy provided the morphology score is > or =4%.

Treatment of male infertility due to sperm surface antibodies: IUI or IVF?

This prospectively designed study was aimed at comparing the results of two different treatment protocols in 29 infertile couples with proven male immunological infertility, i.e. a positive (>50%) mixed antiglobulin reaction (MAR) test (IgG and/or IgA). In the first protocol (group I, n = 14) couples were treated with ovarian stimulation/ intrauterine insemination (IUI), followed by in-vitro fertilization (IVF) if no pregnancy occurred after three IUI cycles. In the second protocol (group II, n = 15), patients were treated with IVF as a first choice procedure. The decision to follow protocol 1 or 2 was made by the couples after information about financial costs and expected success rates (according to the literature) for both treatment options. In group I, nine patients (64.3%) conceived after a maximum of three IUI cycles whereas seven patients (46.6%) of group II became pregnant during the first IVF cycle. The take-home baby rate per started IUI or IVF cycle was 27.3% (9/33) and 44.4% (16/36) respectively with a take-home baby rate of 64.3% after three IUI cycles and 93.3% after three IVF attempts. To conclude, both IUI and IVF yielded unexpectedly high pregnancy rates in this selected group of patients with long-standing infertility due to sperm surface (predominantly IgG) antibodies. Since cost benefit analysis comparing superovulation IUI with IVF may favour a course of four IUI cycles, we advocate superovulation IUI as the first line therapy in male immunological infertility.

Semen parameters in a fertile versus subfertile population: a need for change in the interpretation of semen testing.

This prospectively designed study was conducted to compare a fertile and a subfertile population so as to define normal values for different semen parameters. Semen analyses were performed according to the World Health Organization (WHO) guidelines, except for sperm morphology (strict criteria). In the fertile population (n = 144), all patients had recently achieved pregnancy, within 12 months of unprotected coitus. As subfertile controls we examined semen samples from 143 consecutive men attending our infertility clinic during the same study period. Couples with tubal factor infertility and/or ovulatory disorders were excluded from our study. Using receiver operating characteristic (ROC) curve analysis we determined the diagnostic potential and cut-off values for single and combined sperm parameters. Sperm morphology scored best, with a value of 78% (area under the ROC curve). Summary statistics showed a shift towards abnormality for most semen parameters in the subfertile population. Using the 10th percentile of the fertile population as the cut-off value, the following results were obtained: 14.3 x 10(6)/ml for sperm concentration, 28% for progressive motility and 5% for sperm morphology. Using ROC analysis, cut-off values were 34 x 10(6)/ml, 45% and 10% respectively. Cut-off values for normality were different from those described in the WHO guidelines. Routine bacterial and non-bacterial cultures turned out to be of little prognostic value.

Sperm morphology assessment: diagnostic potential and comparative analysis of strict or WHO criteria in a fertile and a subfertile population.

This prospective study compared the diagnostic and predictive potential of sperm morphology assessments in a fertile vs. a subfertile population, evaluated in three different laboratories. The fertile population included 144 men who had recently fertilized their partners. As subfertile controls, 136 men with a history of subfertility for more than 12 months were used. All semen samples (280) were evaluated in three different centres in a blind fashion, without any patient information. The evaluation of sperm morphology was performed according to the criteria normally used in the different laboratories: WHO (1992) criteria for laboratory A, and Tygerberg strict criteria for laboratories B and C. Using ROC analysis, the predictive power of sperm morphology turned out to be different in the three laboratories (area under ROC curve: 69% for lab A, 72% for lab B and 78% for lab C). Using percentile 10 of the fertile population as the cut-off value for normality, we obtained the following results: 2, 1 and 5% for laboratories A, B and C, respectively. Using ROC analysis cut-off values with optimal specificity and sensitivity were 6, 1 and 10%, respectively. Although our data highlight a reasonable predictive power of sperm morphology in centres using different or the same criteria, cut-off values for normality were different, even when the same criteria were applied. These results stress the importance of standardization in sperm morphology evaluation and the need for examining a reference population in estimating the real threshold value in different laboratories.

Chronobiological fluctuations in semen parameters with a constant abstinence period.

This study examined the seasonal variation in three semen parameters (total sperm count, % grade a progressive motility and sperm morphology according to strict criteria) with an identical abstinence period of 24 h. A total of 340 spermiograms of 107 different men enrolled in an intrauterine insemination (IUI) program were examined. To reduce variation due to interindividual disparities in semen quality, differences of each test result from the mean value obtained for that individual were analyzed. Mean values resulted from at least 3 observations during different IUI cycles. Using ANOVA and spectral analysis, no differences in semen parameter results in function of the month of the year were observed. The lack of any significant periodicity may be explained by the large biological variation for individual semen parameters and/or the lack of significant differences regarding light exposure and temperature between summer and winter months in moderate climates.

Sperm morphology assessment: historical review in relation to fertility.

Careful analysis of sperm morphology has always been an important part of a routine semen examination. However, the usefulness of sperm morphology assessment as a predictor of a man's fertilizing potential has often been challenged due to different classification systems, various slide preparation techniques and inconsistency of analyses within and between laboratories. Automated sperm morphology analysis instruments may overcome the subjective nature of visual assessments of sperm morphology, but the technical problems are numerous and the validity of these instruments has still to be proven. Having reviewed the literature, it seems clear that there is general agreement concerning the clinical relevance and predictive value of this single semen parameter in vivo and in vitro. Nevertheless, even in cases of severe teratozoospermia, fertilization may be possible. Studies on the acrosome reaction are very promising for patients with severe sperm morphology abnormalities that do not have major effects on the fertilizing potential. Most promising is the development of intracytoplasmic sperm injection (ICSI) as the treatment of first choice in cases of severe teratozoospermia with failed fertilization in vitro. Normal fertilization and pregnancy rates can be obtained with ICSI in the presence of extreme teratozoospermia, suggesting that sperm morphology may be important in spermatozoa-zona binding, penetration and spermatozoon-oocyte fusion but fails to be of any predictive value once the spermatozoon reaches the cytoplasm of the oocyte. To conclude, accurate and strict sperm morphology assessment is very useful in evaluating a patient's fertilizing potential, with the main advantage that the methods used to examine this parameter are easy to learn on equipment found in most laboratories.

Exposure to ethylene glycol ethers and spermatogenic disorders in man: a case-control study.

A case-control study was conducted among first time patients at a clinic for reproductive disorders. The study group consisted of 1019 cases, defined as patients diagnosed infertile or subfertile on the basis of a spermiogram and 475 controls who were diagnosed as normally fertile by the same procedure. Possible exposure to ethylene glycol ethers was assessed by the presence of the urinary metabolites methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) respectively for 2-methoxyethanol and 2-ethoxyethanol or their acetates. In total, EAA was detected in 39 cases and six controls, with a highly significant odds ratio of 3.11 (p = 0.004). On the other hand, MAA was only found in one case and two controls. The presence of EAA in urine proved to be strongly associated with exposure to preparations containing solvents, especially paint products, and with some groups of occupations, the most important of which were also directly or possibly connected with paint products. The absence of a significant correlation between the concentration of urinary EAA and the various measures of sperm quality could be explained by the expected latent period between exposure and observed effects. Other temporal aspects of the relation between exposure as judged from the presence of urinary EAA and diagnosis are also discussed.

Intracavernosal injection of prostaglandin E1 as an alternative for papaverine in penile angiography.

Arteriography of the penile vasculature was performed after intracavernous injection of prostaglandin E1 in five patients. Penile tumescence was obtained in three patients with a dose of 10 micrograms and in the other two patients with a dose of 20 micrograms. Mean duration of penile tumescence was 1 h 36 min. Visualization of the penile vasculature was adequate in all patients. Local pain was a minor side effect in one patient. These preliminary results suggest that prostaglandin E1 might represent an alternative for papaverine in the angiographic study of male impotence.

High ejaculate volume: a distinct entity?

In this study clinical, andrological and endocrinological data of a group of 101 patients with ejaculate volume of at least 8.0 ml are compared with data of 100 consecutive patients attending our infertility clinic. Within both groups correlations between different parameters are observed. Between both groups a significant difference in total sperm output is noted suggesting a 'dilution oligozoospermia' in the high ejaculate volume group. We suggest that, in order to avoid a falsely unfavourable fertility prognosis for those patients, total sperm output should be considered rather than sperm density. From the point of view of nomenclature, the term 'relative oligozoospermia' seems justified in cases with very high ejaculate volumes.

On the familial occurrence of congenital bilateral absence of vas deferens.

In this report we present the familial occurrence of congenital bilateral absence of vas deferens (CBAVD) in a 29-year-old, healthy and phenotypically normal male and in his maternal uncle. The incidence and the familial occurrence of CBAVD are reviewed and discussed.

Clinical and physical evaluation of the infertile male: testicular measurement or orchidometry.

SUMMARY: For the quantitative determination of the testicular size or volume, two groups of apparatus are available: on the one hand, model testes, which are extremely valuable in longitudinal and cross-sectional studies during the period of pubescence, and on the other hand, measuring devices, with which the testicular dimensions can be specified. The latter instruments are helpful chiefly during the adolescent years and the diagnosis of problems surrounding fertility. The testicular volume can be calculated subsequently from the specific testicular measurements. The formula, for computing the volume of an ellipsoid, seems to be the most suitable for this purpose. Appliances also have been developed, which allow the largest (longitudinal) dimension (in mm) and the testicular volume (in cm3) to be read off simultaneously. A tonometer can be useful to quantitatively estimate the testicular consistency, which is a parameter of the testicular integrity at the level of tubular function (spermatozoa production).

Fertility in twins.

From the 474 twins born in 1950 in 100 Flemish cities and towns in Belgium, 85% reached the age of 20 yr, against 37% in Austria a hundred years ago. More female than male twins are married (P = 0.03), in particular nonidentical female twins (P = 0.02). Fertility seems to be lower in male, especially male-male twins (P less than 0.03), and most strikingly so in identical male twins (P = 0.05). There seems to be no influence of premature birth or low birthweight.

The increase in number of orchidopexies: rather cause than prevention of male infertility.

Because of the present tendency to operate early on undescended testes, the indication for orchidopexy amounts to six-to-seven times the justified number in the Netherlands and two-to-three times in Flanders! The tendency to operate early has surely caused more fertility damage than prevented it. This critical statement asks for consideration and urges everybody concerned to a more accurate and repeated physical examination of the genital region and to a conservative attitude regarding treatment.

Physostigmine as a treatment for anejaculation with paraplegic men.

In connection with a case-study we go further into the subject of a subcutaneous injection of fysostigmine as an alternative way to obtain an ejaculation with men suffering a cross-lesion but still wishing to have children.

Solitary or predominantly right-sided varicocele: a possible sign of situs inversus.

Among more than 850 patients undergoing outpatient sclerotherapy of the internal spermatic vein, only 1 unilateral and 1 predominantly right-sided varicocele were encountered. In both patients with this finding a total situs inversus was present, with inversion of normal anatomy, enlarged "right" internal spermatic vein draining into the renal vein, and the "left" internal spermatic vein entering the inferior vena cava directly. Total situs inversus should be considered whenever right-sided varicocele is solitary or predominant.