Fertilité de l’homme en fonction de l’âge

The aim of this work was to analyse the evolution of sperm characteristics according to age. To this end we analysed the spermogram of 2,126 men aged 20 to 64 who came for consultation for feminine indications for in vitro fertilization at the Clermont-Ferrand Human Reproduction Unit during the period 1980 to 1994. A search for a link between the age of the patient at the time of the spermogram and 10 sperm parameters, by studying a linear regression, did not reveal any evidence of a significant correlation between the age and the parameters studied. The mean values for volume, concentration of spermatozoa, percentage of mobile forms (normal, diminished), percentage of typical and mobile forms and percentage of abnormal forms were compared for age classes covering 5 years. These values showed no significant difference according to the age classes. Between 20 and 60 years the essential parameters of the spermogram seem generally to be independent of age, from which it can be deduced that ejaculate quality remains the same until 50 years of age. However a bias in the recruitment of the population studied and a very wide spread for the values for a given age mean that we may not have detected fluctuations in sperm characteristics linked with age.     

Gene SRY et anomalies de la determination genetique du sexe chez l’homme

Normal sexual development in man is the consequence of a complex process. This review focuses on the translation of genedal sex (XX or XY karyotype) into gonadal sex (testis or ovary). During the last three years attempts to identify and clone the testis determining factor (TDF) have exploited detailed maps of the Y chromosome established by geneticists over the last decade. A candidate gene, named SRY (sex determining region, Y) located at the tip of the short arm of the Y chromosome, shows many characteristics in common with TDF in that it is the sole element of the Y chromosome required for male development. The discovery of TDF led us to analyse sex-reversed individuals, i.e. XX males and XY females, with the aim of constructing a model for the processes regulating the development of an organ as complex as the testis. This SRY gene is now the subject of intense molecular biological effort by various groups, effort which we hope will elucidate the mechanism(s) of sex determination.     

Reactivite thermique de la peau scrotale chez l’homme

Although the existence of heat exchange between the testicular artery and the adjacent veins is well known, it may be insufficient to maintain the lower temperature of the testis. In order to investigate the role of the scrotum in testicular thermoregulation, the dynamics of scrotal and other skin temperatures was studied in relation to thermal stress. The results of this study revealed that the scrotal skin exhibited a greater thermal inertia than did other skin areas. This finding may be due to modifications in scrotal blood flow patterns as temperature increased, as well as changes in the scrotal surface area. Other possible thermoregulatory factors may include the evaporation of sweat from the scrotum. In conclusion, there seems to be a complex collection of mechanisms, rather than a single specific mechanism, regulating testicular temperature.     

Dosage de la testostérone plasmatique chez l’homme

The measurement of testosterone in plasma is the main tool to investigate the endocrine function of the testis. Radioimmunoassay of total testosterone using³H-testosterone as tracer, after steroid extraction and chromatography avoids the interactions of steroids and plasma proteins in the assay. It can be considered as a method of reference. Direct methods, without extraction and chromatography, and using non-radioactive tracers have been developped. They are easier and faster to perform but less accurate because of the aforementioned interactions. In the plasma, testosterone is mainly bound with a high affinity to SBP and with a low affinity to albumin. Non-SBP-bound testosterone is considered to represent the fraction of the testosterone available for target cells. Non-SBP-bound testosterone can be measured after precipitation of SBP by ammonium sulfate. This procedure is usefull to investigate androgenicity when plasma SBP concentrations are altered such as in hyperthyroidism, aging and severe exocrine testicular failure. Plasma free testosterone can be mesured by equilibrium dialysis, a procedure not suitable for routine assay or more easily but less accuratly by direct measurement in the plasma with methods using tracer analogs. The interpretation of testosterone measurement must take into account moment-to-moment and nycthemeral variations. The inter-subject variations of plasma testosterone concentrations are large, the decrease with aging is very progressive. Testosterone has a permisive effect on male sexual function with a threshold level above which no relationship between plasma testosterone concentration and sexual “performances” could be demonstrated. Because of the multifactorial control of human sexual function, the threshold value is difficult to determine for a given patient.     

Physiopathologie des troubles de l’érection chez l’homme paraplégique

Peripheral mechanisms responsible for penile erection are dependant upon a complex control by the nervous system, including peripheral nervous pathways, spinally mediated reflex loops and supraspinal nervous structures. Spinal cord injury is accompanied by a partial or a complete modification of these controls. In relation to the reflexogenic or psychogenic origin of penile erection, spinal cord injury does not cause the same effects. Reflexogenic erections sitll occur after spinal cord injury at a suprasacral level. After lesions at a level lower than the thoracolumbar spinal cord, tumescence following psychogenic stimulation has been observed. The hypotheses resulting from clinical and experimental observations and explaining the differences at the origin of these response are detailed. The recent developments in the neurophysiology of penile erection and the role of neurotransmitters allow a more analytical approach of the phenomenous and also bring new insights into possible compensatory pathways following spinal cord injury.     

Contraception thermique de l’homme

Several characteristics of spermatogenesis are heat-dependent in mammals. A similar process does exist in man in whom a qualitatively and quantitatively normal spermatozoa out put occurs for a mean testicular temperature ranging between 33 and 34.5°C. As in many animal species, an induced increase in the testis temperature results in a decreased spermatozoa out put and quality, decrease which is a function of both the intensity and the duration of the increase in temperature as well as the heated target (whole body, scrotum, testes). A daily increase of 1 to 2°C in the testis temperature for at least the waking hours induces on spermatogenesis an inhibitory effect strong enough to temporarily suppress the fecundity, i.e. to achieve a male contraception, withtout any major side-effects as reported for 37 couples during 411 cycles of exposure. Both spermatogenesis and fecundity recover initial values within one year after the heatng is stopped.     

Aspects cliniques, biologiques et thérapeutiques de la cryptorchidie diagnostiquée à l’âge adulte: analyse d’une série de 69 cas

Objective

To report the clinical, biological and therapeutic features of adult cryptorchidism and to determine whether orchidopexy at adulthood may improve male fertility.

Material and methods

We retrospectively studied the clinical pattern, biological and therapeutic features of 69 men aged of more than 18 years admitted for cryptorchidism at the urological department of Aristide-Le-Dantec teaching hospital between January 1999 and December 2007.

Results

The mean age of our patients was 31.04 ± 8.4 years. In the majority of cases, cryptorchidism was diagnosed in a context of infertility (38 cases), scrotum vacancy (21 cases) and testicular cancer (six cases). Cryptorchidism was unilateral in 69.5% and bilateral in 30.4% of cases. Semen analyses were done for 60 patients and showed azoospermia in 46.6%, oligozoospermia in 38.3% and a normal sperm count in 15% of cases. In all bilateral cryptorchidism cases, semen analyses showed azoospermia. At surgery, the undescended testis was found in 66 cases (95.6%) and orchidopexy was the most done surgical procedure. Seven patients (without testicular cancer) underwent unilateral orchiectomy and histology of specimens showed sertoli-cell-only syndrome with no spermatogenesis in all cases. The histological type of testicular cancer was seminoma (three cases) and embryonic carcinoma (three cases). In azoospermic men (28 cases) no induction of spermatogenesis was achieved after orchidopexy. In infertile patients, the improvement of sperm count was seen in three patients with unilateral cryptorchidism. Three patients with unilateral crytorchidism achieved pregnancy (pregnancy rate of 7.8%).

Conclusion

Orchidopexy for adult cryptorcidism had little impact in male fertility. Because of the risk of testicular cancer, orchidectomy was recommended as treatment of unilateral cryptorchidism. But with the recent development of TESE, orchidopexy appears as a reasonable treatment of adult cryptorchidism.     

Diagnostic, traitement et surveillance de l’hypogonadisme de survenue tardive chez l’homme: Recommandations officielles de l’International Society for the Study of the Aging Male (ISSAM) et commentaires

There is increasing interest in the subject of hormone changes in the aging male, which is likely to become particularly important with the expected growth in the population of men over 50. The main concerns at present are androgen decline in the aging male (ADAM), or partial androgen deficiency of the aging male (PADAM), commonly known as the andropause. Although progress has been made in our knowledge of androgen deficiency in the aging male, it is still incomplete and sometimes confusing, and some aspects of androgen replacement therapy remain controversial. The International Society for the Study of the Aging Male (ISSAM) therefore felt it was a good time to review the current situation by publishing a series of practical and official guidelines concerning the diagnosis, treatment and monitoring of late-onset hypogonadism in males. The aim of this study is to present and discuss the French translation of these recent international guidelines.     

Applications cliniques de l’imagerie hybride TEP-IRM

This paper reports the results of a preliminary study evaluating the feasibility and performance of a first whole body hybrid PET/MR scanner allowing sequential acquisition of co-registered MR and PET images. Sixty-two patients underwent whole body PET/MR imaging immediately after a clinical PET/CT. The hybrid device consists of a 3T MR and a time-of-flight PET scanner sharing a single bed allowing sequential acquisition of co-registered MR and PET images. Imaging protocols included a whole body MR used for attenuation correction of PET followed by high-resolution diagnostic MR. Image analysis included visual identification of radiotracer uptake in tumors and measurement of standardized uptake values (SUV) in tumoral lesions and in normal organs. PET images acquired in the PET/MR with a delay of 85 ± 22 minutes (range 49–120 minutes) showed perfect correlation and identical diagnostic quality compared to PET/CT. In 42 patients (68%), additional high-resolution MR sequences were acquired for clinical diagnosis showing excellent quality without any visually detectable artifacts. SUV measurements of tumor lesions obtained after correction with MR attenuation maps showed an excellent correlation with PET/CT (R² = 0.89 and R² = 0.95 for mean and maximum tissue uptake respectively). Due to the delay between the two studies, changes in tracer uptake biodistribution of normal tissue were observed. Our preliminary data show that whole body PET/MR is clinically applicable in oncologic patients yielding a comparable diagnostic performance as PET/CT with respect to lesion detection and localization.     

L’irradiation des spermatozoïdes au Laser HeNe à faible énergie chez la souris et chez l’homme

Introduction

The effects of low energy He?Ne 630 laser (LEL) irradiation on various aspects of cell metabolism, including proliferation, respiration, ATP synthesis and Ca²⁺ uptake, have been recently recognized in somatic cells, animal spermatozoa and embryonic cells.

Objectives

1- To analyze thein vitro effects of LEL irradiation on the mouse IVF model. 2- To assess the effects of experimental LEL irradiation on human spermatozoa in the sperm-zona free hamster egg penetration (SPA) model.

Material & Methods

1- In a mouse IVF model, pooled oocytes were incubated for 24 h. with LEL-irradiated and non-irradiated epididymal mouse spermatozoa. The percentage of fertilized eggs, intracellular Ca²⁺ and Ca²⁺ uptake as well as the effects of reactive oxygen scavengers were compared in the two groups. 2- In the enhanced SPA model, with overnight TEST-Yolk preincubation, LEL-irradiated and non-irradiated ejaculated spermatozoa from 43 infertile men were incubated for 3 h with fresh zona-free hamster eggs. The percentage of eggs penetrated (SPA%) by irradiated or control sperm was compared. Acrosome reaction (AR) and Hemizona Assay (HZA) were also performed on the same ejaculates.

Results

1- In mice, brief LEL irradiation enhanced intracellular Ca²⁺ influx and increased thein vitro fertilization capacity of spermatozoa. Mitochondrial Ca²⁺ transport mechanisms and H₂O₂ appeared to be involved in these LEL effects. 2- In the 43 male patients, AR and SPA were correlated, while SPA and HZA were poorly correlated. In the whole group, the mean SPA% of LEL-irradiated and control sperm were not significantly different: 49.8±39.9 and 51.0±34.9, respectively. No significant change was observed in 50% of cases. Following irradiation, SPA% increased in 25% of cases and decreased in 25% of cases. However, classifying all cases according to the SPA cut-off point of 30% as poor and good sperm in this enhanced SPA model, showed that LEL irradiation significantly increased SPA% only in the poor sperm subgroup (n=16) from 5.5.±8.9 to 23.1±25.2 (p<0.0001). This increase was observed in 50% of these patients. In the good sperm category (n=27), no improvement of SPA% was observed. On the contrary, LEL irradiation decreased SPA% from 76.1±24.4 to 67.6±28.

Conclusion

In a mouse IVF model, LEL irradiation of spermatozoa improved intracellular Ca²⁺influx and egg fertilization. H₂O₂ seems to participate in the biochemical cascade transforming light signals into a biological response. In man, using the SPA model, LEL sperm irradiation might improve the penetration capacity only in the case of poor quality sperm, by increasing sperm egg penetration in one half of cases, otherwise LEL is ineffective. Further studies are required to confirm these results, but LEL should not be considered for clinical use until its safety has been proven. (Supported by grants from the Chief Scientist Office, Ministry of Health)     

Génomique quantitative chez Caenorhabditis elegans : stratégies pour l’identification de nouvelles cibles thérapeutiques et de nouveaux mécanismes moléculaires chez l’homme

Because the entire genome of Caenorhabditis elegans (C. elegans) is available for exploration since 1998, several information have been retrieved about the global interest of this organism when it became apparent that the similarity of genes in this 1 mm length nematode and those in humans is remarkable, with approximately 67% of genes that are associated with human disease having homologues in the worm genome. C. elegans worms can be easily maintained on various food-sources and culture media allowing testing for molecules or treatments in combination with different genetic mutants backgrounds as well as RNA interference (RNAi). Because of regulatory pathways conservation between humans and worms, several interesting strategies can be developed to facilitate drugs screenings on specific targets as well as to decipher complex physiological programmed traits with potential identification of new therapeutic targets interesting for human health. By using specific examples, we propose to introduce how to use the already available C. elegans data-cross that can be used as a basis for developing new therapeutic targets identification strategies.     

Prevention de l’infertilite d’origine infectieuse chez l’adolescent

Some causes of infertility can be prevented, as is the case for infertility of infectious origin. Genital infections represent a major source of infertility. Prostato-epididymitis consecutive to an urinary infection can be prevented by identifying and treating prostatic localizations at an early stage of urinary infection. The prevention of sexually transmitted diseases (STD), which cause male and female infertility, is, at the moment, accomplished by the prevention of the sexual transmission of the HIV. Teenagers represent a target of choice for the educational campaigns promoting condom use. The role of physicians, especially when teenagers are asking for a contraception, must be complementary to the public health campaign to decrease the spread of HIV and other STDs.     

Etiologie des infertilités secondaires de l’homme

Introduction

Secondary infertility is defined as the inability to achieve a new pregnancy for a couple that has been able to procreate in the past.

Material and methods

Over a 16-year period, 49 patients consulted for male secondary infertility. Clinical, laboratory or ultrasound assessment demonstrated the cause of infertility.

Results

These patients had a mean age of 33.6 years (range: 26 to 44 years). These couples had an average of 1 living child per family, corresponding to a girl in two-thirds of cases and a boy in one-third. In these patients, infertility was due to the presence of varicocele in 15 patients (31% of cases), infection in 14 patients (29%), and varicocele associated with infection in 11 cases (22%).

Conclusion

This assessment revealed two main aetiologies, but some causes remain obvious, such as surgery with resection of the prostate or testicles, or certain cytotoxic therapies.     

L’image de l’ovaloïde dans les gravures rupestres de la Tunisie

Rock art engravings discovered in the central (Jebel Ousselat) and centro-southern Tunisia (Gafsa region), show ovaloids of various types and morphologies associated with wild and domestic animals mainly ornate rams. We examine here these cases of associations and propose some interpretations about.     

Prevention de l’infertilite d’origine infectieuse chez l’adolescent

Some causes of infertility can be prevented, as is the case for infertility of infectious origin. Genital infections represent a major source of infertility. Prostato-epididymitis consecutive to an urinary infection can be prevented by identifying and treating prostatic localizations at an early stage of urinary infection. The prevention of sexually transmitted diseases (STD), which cause male and female infertility, is, at the moment, accomplished by the prevention of the sexual transmission of the HIV. Teenagers represent a target of choice for the educational campaigns promoting condom use. The role of physicians, especially when teenagers are asking for a contraception, must be complementary to the public health campaign to decrease the spread of HIV and other STDs.     

Les récepteurs aux œstrogènes dans le testicule et l’appareil reproducteur du primate et de l’homme

The impact of oestrogens on the male reproductive system remains the subject of intensive research activity and debate. Oestrogen action is mediated via high affinity intracellular receptors expressed in target tissues. Two subtypes of oestrogen receptor known as REα (NR3A1) and ERß (NR3A2) have been cloned and hERß variant isoforms identified. In target cells these receptors can exist as homo- or heterodimers. We have used immunohistochemistry to examine the patterns of expression of ERs in human and non-human primates as a first step in determining the cellular targets for oestrogen action in the male. REα was detected in the epithelial cells of efferent ductules (ED) occasionally in epithelial and stromal cells within the epididymis but was undetectable in human or primate testes. Using a polyclonal antibody raised against the hinge domain of ERß, immunopositive staining was detected in multiple cell types within the testis and in epithelial and stromal cell nuclei throughout the male reproductive system (ED, epididymis, vas deferens, seminal vesicles, prostate) and in the bladder. We have also used monoclonal antibodies that distinguish between wild type, full-length ERß (ERß1), and a splice variant isoform called ERßcx/ERß2 that does not bind oestrogens. ERß1 and ERß2 proteins were both detected in human testis and have distinct but overlapping patterns of expression. ERß1 was also detected in ED, epididymis and vas. In conclusion, oestrogen receptors are widely expressed in the male urogenital system and with the exception of the ED there are more cells that express ERß than REα. In the adult human the testicular cells most likely to be targets for oestrogens are round spermatids in which levels of expression of full-length wild type receptor (ERß1) are high.     

Intérêt de la ponction épididymaire et de la biopsie testiculaire systématique dans la prise en charge de l’azoospermie obstructive

Introduction

In obstructive azoospermia (OA), even if spermatozoa recovery rate are high, pregnancy rates could be lower as expected. When almost surgeons stop if they could find motile spermatozoa in the epididymis after microsurgical epididymal sperm aspiration (MESA), in our center, we add systematically a testicular biopsy with testicular sperm extraction (TESE). What are our sperm extraction rates in MESA or TESE? Are pregnancy and miscarriage rates different regarding the sperm origin?

Material and methods

A retrospective study including 48 infertile couples with ICSI because of OA. Between 2003 and 2011, each patient had a complete aetiological exploration and a surgery with the association of MESA and TESE. ICSI were asynchronous. Each time it was possible, ICSI was realized first with epididymal spermatozoa.

Results

For 48 couples, 99 ICSI were realized. Fifteen couples had 24 ICSI-TESE because no spermatozoon was found in MESA. Eleven couples had 20 ICSI-TESE because of bad quality of sperm recovered with MESA. Twenty-two couples had 22 ICSI-MESA in first intention. If failed, 11 couples had continued with 12 ICSI-MESA and 10 with 20 ICSI-TESE. Although the number of injected oocytes (7,1±4,1 vs 6,9 ±3,6 P: 0,8) and embryos (4,5±3,0 vs 4,7±2,7; P: 0,7) were not significantly different in the two ICSI groups, the number of top quality embryos (2,4±1,9 vs 3,6±2,0 P: 0,005) and frozen embryos (0,9±1,8 vs 1,7±1,9 P: 0,04) were higher in the ICSI-TESE group. Pregnancy rate per punction (58,5% vs 26,5%, P: 0,002) was higher when testicular spermatozoa were used.

Conclusion

Our approach is original with the systematic association of MESA and TESE for each OA man, when others stop surgery when they can find spermatozoa with MESA. We found that more than the half of epididymal explorations were not useful because negative or of bad quality. Embryo quality and per punction pregnancy rate were better with testicular spermatozoa. Association of MESA and TESE could improve the management of these infertile men without exposing them to an over surgical risk.     

Syndrome de Klinefelter et AMP à l’aube de l’an 2000

Material and Methods

The patient is a 33 year old male, with a 47, XXY karyotype (cytogenetical investigation of 16 metaphases). Semen analysis revealed a severe oligozoospermia. (spermatozoa ?1×106/mL) and asthenozoospermia (60% of decreased motiliy), for an ejaculate volume of 1.8mL. Three-colourIn Situ Hybridization was performed on spermatozoa recovered from his cryopreserved semen, in order to simultaneously detect the chromosome X, Y and one with specific appropriate probes. Semen from two 23 year old men were also analyzed as controls.

Results

502 spermatozoa were analyzed from the patient and about 10,000 from the controls. There was an increase of about ten times of the percentage of hyperhaploïd (24XY) spermatozoa in the semen of the Klinefelter patient compared to the controls.

Discussion and conlustion

In a general view of IVF-ICSI practice in Klinefelter patients, we also discuss here several practical points such as (i) is there any morphological criteria which may prevent from injecting an aneuploid spermatozoa, (ii) is the risk of aneuploidy higher when using testicular spermatozoa than when using ejaculated spermatozoa, (iii) what do we know about the offspring obtained by IVF-ICSI in Klinefelter patients and (iv) when should prenatal and/or preimplantatory genetical diagnosisbe proposed in this particular context.