Reduced serum testosterone levels in infant boys conceived by intracytoplasmic sperm injection

CONTEXT: Concern has been raised for the health of the offspring conceived by assisted reproduction technologies. Basal reproductive hormones around 3 months of age reflect the pituitary-testicular axis, which is transiently active at this age. OBJECTIVES: We tested the hypothesis that transmission of impaired testicular function from father to son could be detected at 3 months of age in boys conceived by intracytoplasmic sperm injection (ICSI), which is predominantly used in the management of male infertility. DESIGN: We conducted a longitudinal prospective cohort study, including 125 boys conceived by ICSI, 124 boys conceived by in vitro fertilization (IVF), and 933 naturally conceived (NC) boys. INTERVENTION: Anthropometrical measurements were performed at birth and at 3 months of age; 58, 67, and 64% of ICSI, IVF, and NC boys, respectively, had a blood sample taken at 3 months. MAIN OUTCOME MEASURES: We measured serum levels of LH, FSH, SHBG, inhibin B, testosterone, as well as penile length. RESULTS: Serum testosterone levels were significantly lower in boys conceived by ICSI (2.4 nmol/liter; 0.2-4.9 nmol/liter) (median; 2.5th-97.5th percentiles) compared with NC boys (3.3 nmol/liter; 0.6-7.6 nmol/liter; P < 0.001), and the LH to testosterone ratio was increased (0.8; 0.2-7.9 vs. 0.5; 0.2-2.3, respectively; P = 0.001). Boys conceived by IVF because of female infertility factors had a normal serum testosterone and LH to testosterone ratio compared with controls. Adjusted analyses for confounders did not alter the results. CONCLUSIONS: Our results point toward a subtle impairment of Leydig cell function in boys conceived by ICSI, possibly inherited from their fathers. The clinical significance of our findings is uncertain. However, our findings should raise concern because ICSI is increasingly used to overcome male infertility.     

Intracytoplasmic sperm injection with cryopreserved testicular spermatozoa

To assess if testicular sperm cryopreservation is a valid alternative to repetition of testicular sperm retrieval techniques, results of a cryopreservation technique in pills have been retrospectively analyzed. Enough motile spermatozoa for ICSI were obtained in 172 from 190 (90.5%) frozen-thawed testicular sperm samples. Overall, 249 couples underwent 390 ICSI cycles, 156 using fresh and 234 using cryopreserved testicular sperm. Mean two-pronuclear fertilization rates per cycle were not significantly different after ICSI with fresh (62.0%) or with cryopreserved (63.2%) spermatozoa. Mean embryo cleavage rate per cycle was higher in the fresh (90.6%) than in the cryopreserved (84.6%) group (P = 0.016). However, clinical pregnancy rates per cycle (28.2% with fresh vs 27.8% with cryopreserved), implantation rates (12.2% vs 13.1%) and ongoing pregnancy rates per cycle (22.4% vs 21.8%) were not significantly different. Cryopreservation of testicular spermatozoa is an effective technique that can be used both in obstructive and in non-obstructive azoospermia.     

Faut-il modifier la prise en charge du syndrome de Klinefelter pour améliorer les chances de paternité ?

Until a few years ago, Klinefelter syndrome with a homogeneous 47.XXY karyotype was considered a model of absolute male sterility. In this review, we will discuss: (1) potential fertility following TEsticular Sperm Extraction-IntraCytoplasmic Sperm Injection (TESE-ICSI), (2) the physiopathology of spermatogenic failure and the origin of focal spermatogenesis and risk of aneuploidy in potential offspring, (3) the advantage of searching for and cryopreserving spermatozoa in adolescent instead of adult patients. In previous published series, TESE was successful in almost 50% of patients and pregnancy rate following ICSI was not obviously different from other causes of spermatogenic failure. The rate of positive sperm extraction seemed to be better for younger patients. During childhood, the survival rate of 47.XXY spermatogonia is low. However, a few spermatogonia are able to eliminate their extra X chromosome, giving rise to rare clones of 46.XY gonia which are the origin of rare foci of complete spermatogenesis after puberty. Several arguments suggest that this focal spermatogenesis decreases with age. This suggests there would be a benefit to patients if TESE were performed in adolescences and spermatozoa were cryopreserved. In addition, androgenotherapy is a common treatment of Klinfelter syndrome but carries a risk of decreasing focal spermatogenesis by lowering gonadotropins. Preservation of spermatozoa from adolescence by TESE would allow androgenotherapy to be prescribed with less concern for future reproductive capacity. Controlled studies should be done to determine the best age for TESE-ICSI in 47.XXY homogeneous Klinefelter syndrome patients.     

Fertility in men with cystic fibrosis: an update on current surgical practices and outcomes

BACKGROUND: Men with cystic fibrosis (CF) have bilateral absence of the vas deferens causing an obstructive azoospermia that is not amenable to surgical correction. Advances in the field of reproductive medicine allow for the procurement of viable sperm and facilitate fertilization and pregnancy in couples where the man has CF. OBJECTIVES: To describe patient anatomy and semen characteristics and to determine the pregnancy rates of couples in whom the male partner has CF and who have undergone microsurgical epididymal sperm aspiration coupled with in vitro technology, specifically intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective analysis. SETTING: Clinical department of urology and two reproductive medicine units. PATIENTS: Thirteen married men with CF who were referred for infertility. INTERVENTIONS: History, physical examination, semen analysis, transrectal and renal ultrasonography, CF mutation analysis, and microsurgical sperm aspiration coupled with ICSI. RESULTS: All 13 men had low-volume azoospermia, absent vasa, and aplasia/hypoplasia of the seminal vesicles. CF mutation analysis was carried out in 11 of 13 men, and 9 of 11 were DeltaF508 homozygous. Eight men underwent microsurgical sperm aspiration, and their partners underwent one or more cycles of ICSI. Five couples (62.5%) achieved a pregnancy, with four couples delivering (three sets of twins and one singleton). CONCLUSIONS: CF in men is accompanied by bilateral vasal aplasia. The resultant obstructive azoospermia can be treated quite successfully with a combination of sperm aspiration and ICSI. It is important for physicians involved in the care of men with CF to convey the message that prospects for fatherhood are excellent with current technology.     

Fertility in men with Klinefelter's syndrome

Patients with a Klinefelter syndrome (KS), defined by a 47 XXY karyotype, were long considered infertile. Testicular sperm extraction (TESE) now allows them to access fatherhood. We will present the data of studies since first experiment of TESE. Several factors influencing TESE outcome were proposed in these different studies. Among them, clinical and hormonal parameters have reported by few studies, age has been one of the most discussed prognostic factor of positive sperm retrieval rate. Data seems to show that TESE carried out before an age greater than 30 has a poorer prognosis for positive sperm retrieval. In few studies performed in younger patient, before 20 years, SRR was closed to result for 20 to 30 year old patients. Offering a TESE before 16 years old does not improve positive sperm extraction rate. In fact, the few studies carried out before the age of 16 were of poorer prognosis, most often linked to insufficient maturation of the residual gametes. In addition, androgen therapy, frequently prescribed in case of Klinefelter syndrome, did not seem to show any effect on sperm retrieval but only few studies were interested in the possible impact of this treatment. In conclusion, further studies are necessary to determine the interest of new markers to predict the chance of sperm retrieval, taking into account age, hormonal therapy.     

Azoospermia as a new feature of Fabry disease

This case report describes two cases of azoospermia in men suffering from Fabry disease. Testicular biopsies revealed characteristic aspects of trihexosid ceramid deposit in the Leydig cells by optic and electronic microscopic analysis. Using TESE and ICSI, sperm retrieval led to pregnancies and deliveries of healthy children. Azoospermia should be considered as a possible complication of Fabry disease and we recommend a routine sperm analysis in the follow up of young patients with Fabry disease. As we do not know the efficacy of the agalsidase therapy on the genital issue of the Fabry disease, consideration of sperm cryopreservation is suggested.     

ICSI outcomes of fresh or cryopreserved spermatozoa from micro-TESE in patients with nonobstructive azoospermia: CONSORT

The aim of this study was to evaluate intracytoplasmic sperm injection (ICSI) outcomes of fresh and cryopreserved sperm via microdissection testicular sperm extraction (micro-TESE) in patients with nonobstructive azoospermia (NOA).From March 2016 to February 2020, a total of 244 men with NOA underwent micro-TESE at the Center for Reproductive Medicine, First Hospital of Jilin University, P. R. China. These cases included 40 patients who underwent 40 ICSI cycles with fresh spermatozoa from micro-TESE (Group A) and 30 patients who underwent 30 ICSI cycles with cryopreserved spermatozoa from micro-TESE (Group B). The characteristics, embryonic development, and ICSI outcomes of patients were compared between groups A and B.Our sperm retrieval rate (SRR) by micro-TESE in patients with NOA was 35.25%. No statistical differences in the patient characteristics and fertilization or quality embryo rates were observed between Groups A and B. Higher miscarriage rates and lower live births were observed in Group B than in Group A (both P < .05).Fresh testicular spermatozoa seem to produce better ICSI outcomes than cryopreserved testicular spermatozoa from patients with NOA in the micro-TESE-ICSI cycle.     

Klinefelter syndrome

Klinefelter syndrome (KS) is the most common genetic form of male hypogonadism, but overt phenotype becomes evident only after puberty. During childhood, and even during early puberty, pituitary-gonadal function in 47,XXY subjects is relatively normal, but from midpuberty onwards, FSH and LH levels increase to hypergonadotropic levels, inhibin B decreases to undetectable levels, and testosterone levels after some increase plateau at low-normal levels for healthy adult men. Hence, most adult KS males display a clear hypergonadotropism with a varying degree of androgen deficiency; subsequently testosterone substitution therapy is widely used to prevent symptoms and sequels of androgen deficiency. Testicular biopsies of prepubertal KS boys have shown preservation of seminiferous tubules with reduced numbers of germ cells, but Sertoli and Leydig cells have appeared normal. The testes in the adult KS male are characterized by extensive fibrosis and hyalinization of the seminiferous tubules, and hyperplasia of the interstitium. However, the tubules may show residual foci of spermatogenesis. Introduction of testicular sperm extraction (TESE) in combination with intracytoplasmic sperm injection (ICSI) techniques has allowed non-mosaic KS males to father children.     

Feasibility of microsurgical reconstruction of the male reproductive tract after percutaneous epididymal sperm aspiration (PESA)

For obstructive azoospermia, surgical sperm retrieval from the epididymis for IVF/ICSI is an established management. However, various recent studies have established that surgical reconstruction with vasovasostomy or vasoepididymostomy remains a more cost-effective treatment option than upfront assisted reproduction. After epididymal sperm retrieval, fibrosis and scarring of the punctured epididymal tubule can lead to complete epididymal obstruction. The feasibility of surgical reconstruction after surgical epididymal sperm retrieval has not been established. We describe two cases of bilateral microsurgical vasoepididymostomy, using a new 2-suture longitudinal intussusception technique we previously described, after previous successful bilateral percutaneous epididymal sperm aspiration (PESA). In both cases, motile sperm were found in ejaculate in the first post-operative semen analysis at 6 weeks and 2 months. We conclude that even in men with previous epididymal sperm retrieval, surgical reconstruction remains a feasible management option for fertility.     

Cryopreservation of epididymal sperm

The advent of ICSI and the perfecting of freezing protocols for sperm samples that in the pre-ICSI era would not have been frozen, allows now routine cryopreservation of epididymal sperm regardless of their quality and quantity. There are two methods to retrieve epididymal sperm: microsurgical epididymal sperm aspiration (MESA) and percutaneous epididymal sperm aspiration (PESA). The majority of the literature has focused on the technique of MESA to obtain sperm on the claim that the amount of sperm retrieved with PESA might not be sufficient to allow cryopreservation. However, there are no data on cryopreservation and ICSI with epididymal sperm collected with PESA technique. In this study, a total of 68 consecutive cycles of PESA, of which 46 were performed with fresh epididymal sperm and 22 with frozen/thawed specimens were retrospectively analyzed. In the fresh epididymal group (n = 46), 446 eggs were injected and 207 cleaving embryos were obtained (fertilization rate of 46%). In the cryopreserved epididymal sperm group (n = 22), 216 eggs were injected and 115 cleaving embryos were obtained (fertilization rate of 53%, P = NS). There were 18 pregnancies (39%) with 17 (37%) delivered/ongoing in the fresh group, while there were 11 (50%) with 9 (41%) delivered/ongoing in the frozen group (P = NS). Epididymal sperm for cryopreservation was available in 44 of the 46 PESA cycles. Additionally, in the fresh group, 19 couples had excess embryos for cryopreservation while in the frozen group, ten couples had excess embryos for cryopreservation. A total of 17 frozen embryo transfer with epididymal sperm from PESA were analyzed. Of these, 12 FET were from embryos from the fresh epididymal group and three pregnancies with livebirths (25%) were recorded. Five FET were performed with extra embryos from frozen epididymal sperm and two (40%) pregnancies with livebirths were obtained. In summary, these data show that epididymal sperm obtained by PESA can be successfully cryopreserved in order to avoid future retrievals procedures and fertilization and pregnancy rates are similar between fresh and cryopreserved epididymal sperm. It is also reported for the first time that the transfer of frozen embryos obtained with either fresh or frozen thawed epididymal sperm leads to the same pregnancy'and delivery rate.     

Should we be offering fertility preservation by surgical sperm retrieval to men with Klinefelter syndrome?

Advances in surgical sperm retrieval have greatly increased the chances of men with Klinefelter syndrome achieving biological paternity. Despite this, the vast majority of attempts to achieve fertility by using extracted gametes to fertilize eggs in vitro do not result in viable pregnancies. A powerful obstacle to success lies with the natural history of seminiferous tubule and germ cell function in Klinefelter syndrome, which typically peak (and thereafter steeply decline) up to a decade before most individuals would be contemplating paternity. Herein we discuss, in relation to a real clinical case, both the exciting technical advances surgical sperm retrieval and the logistic and ethical factors that, in practice, may act to limit their successful application.     

Genetic abnormalities among severely oligospermic men who are candidates for intracytoplasmic sperm injection

Recent reports suggest that children born after intracytoplasmic sperm injection performed for male factor infertility are at increased risk of congenital malformations and chromosome aberrations. To explain these observations, we hypothesized that infertile men may be more likely than fertile men to have genetic abnormalities. We studied 750 severely oligozoospermic men (sperm count <5 million/ml) who were candidates for intracytoplasmic sperm injection, and 303 fertile men. We analyzed the peripheral blood karyotype, the Y chromosome long arm for detection of microdeletions in the azoospermia factors, and mutations in the cystic fibrosis gene and the androgen receptor gene. We also analyzed sperm for chromosome aneuploidies among the 421 men who subsequently entered the in vitro fertilization program. A total of 104 genetic abnormalities were diagnosed, corresponding to a frequency of 13.9% (104 of 750). Chromosomal aberrations were present in 5.6% (42 of 750) of infertile men and 0.3% of controls (one of 295), and they were in most cases alterations of the sex chromosomes. Y chromosome long-arm microdeletions were detected in 6.0% (45 of 750) of infertile men and most frequently included the azoospermia factor c, whereas no cases were found in controls (zero of 210). Mutations in the cystic fibrosis gene were diagnosed in 1.2% (nine of 750) of infertile men and 1.0% of controls (three of 303), and mutations in the androgen receptor gene were found in 1.1% (eight of 750) of infertile men and none of the 188 controls. Sperm sex chromosome aneuploidies were increased in men with karyotype anomalies and Y chromosome microdeletions as well as in subjects without constitutional genetic abnormalities. This study shows that the frequency of genetic alterations is increased among men with severe spermatogenic impairment. Genetic tests and genetic counseling should therefore be considered in oligozoospermic men who are candidates for intracytoplasmic sperm injection.     

Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido

GnRH antagonists suppress pituitary and gonadal function by competing with endogenous GnRH for binding to receptors on pituitary gonadotrophs. We studied the effects of GnRH antagonist administration to men in a protocol simulating a likely male contraceptive regimen combined with a low dose of testosterone. The GnRH antagonist Nal-Glu was given daily (10 mg, sc) for 20 weeks to eight normal men, and a low dose of testosterone enanthate (25 mg, sc) was given every week. Sperm counts started declining during week 4, and complete azoospermia was reached within 6-12 weeks in six of the eight subjects. Subjects 7 and 8, whose sperm counts and serum gonadotropin levels were not suppressed after 10 weeks, were given 20 mg Nal-Glu starting at week 10. One became azoospermic at week 16, while the other's total sperm counts continued declining and reached a nadir of 1.4 million by week 20. Sperm motility and viability in this subject were completely suppressed after week 14. Sperm counts returned to baseline levels 12-14 weeks after the end of Nal-Glu administration. The mean serum LH level of the first six subjects decreased from 3 +/- 03. U/L at baseline to less than 0.1 U/L until week 20, and then levels returned to baseline. FSH levels similarly decreased from a combined mean of 3.6 +/- 0.9 U/L at baseline to below 0.3 U/L after 4 weeks of Nal-Glu administration. Serum mean testosterone levels between weekly injections of testosterone enanthate ranged from 27.4 +/- 5.9 to 4.8 +/- 1.4 nmol/L, but remained in the hypogonadal range (less than 10 nmol/L) for 4 of the 7 days. None of the subjects, however, complained of decreased libido or potency, as assessed by a questionnaire. No systemic or significant local side-effects were observed, other than a minimal reaction at the injection site. These data suggest that complete sustained azoospermia can be achieved in man, without loss of libido, by chronic administration of a GnRH antagonist plus testosterone.     

Serum inhibin B in combination with serum follicle-stimulating hormone (FSH) is a more sensitive marker than serum FSH alone for impaired spermatogenesis in men, but cannot predict the presence of sperm in testicular tissue samples.

The measurement of serum FSH is useful in the diagnostic workup of the infertile male, but fails to predict the presence of sperm in testicular tissue. We investigated whether inhibin B reflects testicular morphology and the presence of sperm more accurately than FSH. Serum inhibin B and gonadotropin levels were determined in 91 infertile men undergoing diagnostic bilateral testicular biopsy. In 52 of the 91 patients multiple samples were taken for testicular sperm extraction (TESE). Inhibin B levels were (mean +/- SEM) 238+/-32 pg/mL in men with normal spermatogenesis (n = 9), 102+/-18 pg/mL in men with spermatogenetic arrest (n = 15), 98+/-16 pg/mL in hypospermatogenesis (n = 23), 41+/-6 pg/mL in focal Sertoli cell-only syndrome (SCO; n = 26), and 27+/-8 pg/mL in complete SCO (n = 18). The percentage of SCO tubuli was more strongly correlated to serum inhibin B (r = -0.58; P<0.01) than to FSH (r = 0.34; P<0.05). Similarly, the percentage of tubules with elongated spermatids was significantly (P<0.05) more strongly correlated to serum inhibin B (r = 0.65; P<0.01) than to FSH (r = -0.4; P<0.01). Thus, inhibin B is slightly more sensitive than FSH as an index of the spermatogenic status. Neither FSH nor inhibin B alone, however, could predict the type of spermatogenetic damage exactly. The combination of FSH and inhibin B had high diagnostic sensitivity (88%) and specificity (83%) for the presence of elongated spermatids in testicular biopsies. Sperm could be retrieved in 34 (65%) of the TESE patients. The combination of inhibin B and FSH measurement showed a sensitivity of 75% and a specificity of 73% when identifying patients in whom sperm could possibly be retrieved by TESE. We conclude that although the measurement of serum inhibin B improves the sensitivity of predictive tests for the presence of sperm in histology or for TESE, this parameter cannot accurately predict TESE outcome.     

Visceral and subcutaneous adipose tissue assessed by magnetic resonance imaging in relation to circulating androgens, sex hormone-binding globulin, and luteinizing hormone in young men

CONTEXT: No large studies of young men have examined circulating sex hormones in relation to visceral and sc adipose tissues. OBJECTIVE: The aim of this study was to investigate the role of visceral adipose tissue and sc adipose tissue on circulating sex hormones and the impact of obesity on sex hormone reference intervals. DESIGN, SETTING, AND PARTICIPANTS: Population-based study of 783 Danish 20- to 29-yr-old men was performed using dual-energy x-ray absorptiometry in all men and magnetic resonance imaging in 406 men. MAIN OUTCOME MEASURES: Total, bioavailable, and free testosterone, dihydrotestosterone (DHT), total and bioavailable estradiol, SHBG, and LH were measured. RESULTS: In multiple regressions, visceral adipose tissue was an independent, inverse correlate of bioavailable and free testosterone. Subcutaneous adipose tissue correlated negatively with SHBG and positively with bioavailable estradiol adjusted for total testosterone. Both visceral adipose tissue and sc adipose tissue correlated inversely with total testosterone and DHT. Adjusting for SHBG, only visceral adipose tissue remained significantly correlated. Low total testosterone in viscerally obese men was not accompanied by increased LH. The androgen reference intervals were significantly displaced toward lower limits in obese vs. nonobese men (total testosterone: 8.5-29.3 vs. 12.5-37.6 nmol/liter; bioavailable testosterone: 6.1-16.9 vs. 7.6-20.7 nmol/liter; free testosterone: 0.23-0.67 vs. 0.29-0.78 nmol/liter; and DHT: 0.63-2.5 vs. 0.85-3.2 nmol/liter), whereas total estradiol (36.5-166 pmol/liter) and bioavailable estradiol (23.4-120 pmol/liter) reference intervals were not. In obese men, 22.9% had total testosterone less than 12.5 nmol/liter. CONCLUSIONS: Visceral adipose tissues correlate independently with bioavailable and free testosterone in young men. The inverse relationship between total testosterone and sc adipose tissue seems to be accounted for by variations in SHBG. The reference intervals for total testosterone, bioavailable testosterone, free testosterone, and DHT are displaced toward lower limits in obese men.     

Approach to the infertile man

INTRODUCTION: Infertility is one of commonest disorders to afflict young men and women. The evaluation of infertility is initiated typically after 1 yr of failure to conceive. DIAGNOSTIC EVALUATION: The couple should be evaluated together to determine whether the problem resides in the male partner, the female partner, or both. The objectives of evaluation are to exclude treatable conditions--gonadotropin deficiency, obstruction, and coital disorders--and identify those who are candidates for assisted reproductive technologies, those who are sterile and should consider adoption or artificial insemination using donor sperm, and those who should undergo genetic screening. All infertile men should undergo several semen analyses according to the World Health Organization manual, as well as measurements of testosterone, LH, and FSH levels. Hormone measurements can help determine whether the patient has gonadotropin deficiency (low testosterone and low or inappropriately normal LH and FSH), primary testicular failure (low testosterone, elevated LH and FSH), spermatogenic failure (normal testosterone and LH, elevated FSH), or androgen resistance (high testosterone, elevated LH). A majority of infertile men have normal testosterone, LH, and FSH levels. Obstruction should be ruled out in azoospermic men with normal testosterone, LH, and FSH levels. GENETICS: Yq microdeletions are the most prevalent cause of spermatogenic failure in men with azoospermia or severe oligozoospermia. Infertile men with azoospermia or severe oligozoospermia should undergo karyotyping and testing for Yq microdeletions. Men with congenital absence of vas should be tested for cystic fibrosis transmembrane conductance regulator mutations. THERAPY: Gonadotropin therapy is highly effective in gonadotropin-deficient men. Intracytoplasmic sperm injection (ICSI) has emerged as the treatment of choice for idiopathic male factor infertility. However, ICSI is expensive and associated with a higher risk of multiple gestation, low birth weight, preterm delivery, perinatal complications, and chromosome aneuploidy than naturally conceived pregnancies. Men considering ICSI should be offered karyotyping, Yq microdeletion testing, and genetic counseling by counselors experienced in reproductive disorders.     

Testosterone increases in men after a low dose of alcohol

BACKGROUND: Heavy acute alcohol drinking decreases blood testosterone in men due to an effect on the testicular level. An acute increase in blood testosterone levels after a low alcohol dose has, however, recently been reported in women. The objective of this investigation was to study the effect of a low alcohol dose on testosterone in men and further elucidate the mechanism behind the effect by using 4-methylpyrazole, an inhibitor of alcohol metabolism. METHODS: A double-blind placebo-controlled interventional crossover trial in random order (n = 13). RESULTS: After intake of alcohol (0.5 g/kg, 10% w/v), an acute increase in plasma testosterone (from 13.5 +/- 1.2 nmol/liter to 16.0 +/- 1.6 nmol/liter, mean +/- SEM; p < 0.05), a decrease in androstenedione (from 5.1 +/- 0.4 nmol/liter to 4.0 +/- 0.3 nmol/liter; p < 0.05), and an increase in the testosterone:androstenedione ratio (from 2.8 +/- 0.3 to 4.2 +/- 0.4; p < 0.01) were observed. The effects were not observed during pretreatment with 4-methylpyrazole (10-15 mg/kg orally), which inhibited the ethanol elimination rate by 37 +/- 3%. CONCLUSIONS: Alcohol intake affects the androgen balance in men through an effect mediated by the alcohol-induced change in the redox state in the liver.     

Suppression of pituitary and testicular function in normal men by constant gonadotropin-releasing hormone agonist infusion

In a trial for male fertility control the effects of constant GnRH agonist (buserelin) infusion on pituitary and testicular function was investigated. The agonist was administered sc for 12 weeks to two groups of normal young men using extracorporeal osmotic minipumps. Seven men received 118 +/- 24 (SD) micrograms/day from pumps changed biweekly and four men received 230 +/- 27 micrograms/day from pumps changed weekly. After an initial rise serum LH, FSH, and testosterone decreased. The decrease occurred faster in the high dose group and these subjects had no LH response to acute GnRH stimulation after 4 weeks of treatment, whereas the response was drastically reduced in the group receiving the low dose. Androgen substitution with testosterone undecanoate (80-120 mg orally daily) was initiated when the subjects complained of decreased libido and/or potency or when serum testosterone fell below 10 nmol/liter on average in the fifth week. Sperm counts decreased significantly and below the lower normal limit of 20,000,000/ml. The nadir was reached in week 12 of treatment in the high dose group, and in week 4 post treatment in the low dose group. Despite desensitization of the pituitary and impaired testicular function azoospermia did not occur. A higher dose of agonist appears to be required to achieve this goal.     

Klinefelter syndrome and TESE-ICSI

Until few years ago, Klinefelter syndrome with a homogenous 47,XXY karyotype was considered a model of absolute male sterility. We will discuss first the potential fertility following Testicular Sperm Injection, then the physiopathology of spermatogenic failure and the origin of focal spermatogenesis and risk of aneuploidy in offspring, and third the advantage of searching spermatozoa earlier instead of adult age. The rate of positive sperm extraction seems to be better for younger patients. During childhood, there is a low rate of spermatogonia. The spermagonia, which completes the spermatogenesis, seems resulting from a rare clone of 46,XY gonia, having lost their extra X chromosome. Several arguments suggest that this focal spermatogenesis decreases with age. In addition, androgen treatment, frequently prescribed in case of Klinefelter syndrome, carries a risk of decreasing focal spermatogenesis by lowering gonadotropins. The question arises if it is necessary to expect the sperm cryopreservation before introducing androgen treatment. Further studies are necessary to determine the best age of sperm retrieval in case of Klinefelter syndrome.