Persistent organochlorines, sedentary occupation, obesity and human male subfertility

BACKGROUND: Studies have suggested that the quality of human semen has been declining over recent decades, presumably because of lifestyle or environmental factors. METHODS: Polychlorinated biphenyls and organochlorine pesticides were analysed in the plasma of 25 men with poor semen quality, 20 men with normal semen quality and idiopathic subfertility and 27 men with normal semen quality and female factor subfertility. Samples of seminal fluid were also analysed to assess the relationship between the levels in blood and semen. RESULTS: The results indicate no difference in the levels of organochlorines between the groups. The levels of organochlorines in seminal fluid were proportional to the levels in plasma, but approximately 40 times lower. Men with poor semen quality were three times more likely to be obese than men with normal semen quality. There was also a significant negative correlation between semen quality parameters and body mass index among men with normal semen quality. The prevalence of sedentary work was lowest among men with the best semen quality. CONCLUSIONS: Poor semen quality was found to be associated with sedentary work and obesity but not with plasma levels of persistent organochlorines. More research is needed to assess whether sedentary lifestyle and obesity are causal factors in the decline of semen quality.     

The high incidence of meiotic errors increases with decreased sperm count in severe male factor infertilities

BACKGROUND:The high frequency of aneuploidy sperm raises concerns that there may be an increased incidence of aneuploid offspring in ICSI programmes. In order to assess the role that chromosome complement plays in normal and abnormal fertility, detailed molecular cytogenetic studies must be done on sperm samples from men with normal and abnormal fertility. METHODS: To understand more clearly the cytogenetic make-up of sperm from oligoasthenoteratozoospermic (OAT) patients, multi-colour fluorescence in situ hybridization was used to determine numerical chromosome abnormalities. RESULTS: Increased aneuploidy frequencies for chromosomes 13, 18, 21, X and Y were detected in sperm from OAT patients. The frequencies of diploidy also increased. There were no differences in non-disjunction at meiosis I compared to meiosis II. Sperm count inversely correlated with the frequencies of diploidy, aneuploidies for chromosomes 13 and 21 in OAT patients. Twenty-two cycles of ICSI and 18 embryo transfers were performed in 20 couples. Only three cases achieved successful pregnancies. CONCLUSIONS: A higher incidence of meiotic errors and lower sperm counts was found in sperm from OAT patients.     

Varicocele--the most common cause of male factor infertility?

Varicocele is often cited as the most common cause of male factor infertility. Arguments in support of this statement include reports of increased prevalence of varicocele in populations of infertile men compared with fertile or otherwise unselected men, association of varicocele with abnormal semen parameters, and improvements in semen parameters and/or pregnancy rates after varicocele repair. Logically, there would appear to be three possibilities regarding the relationship between varicocele and fertility: (i) varicocele has no association with or effect on male fertility; (ii) varicocele may be associated with, but is not the cause of, male subfertility; and (iii) varicocele is a direct cause of male subfertility. In the following, we review evidence from the literature for and against these three possibilities: at the current time, available evidence appears inadequate to confirm or deny any of these three possibilities. Since the ultimate goal of infertile couples is to conceive, it seem logical that future varicocele research should focus primarily on adequately powered, controlled clinical trials in well-characterized infertile couples, randomized to intervention or appropriate controlled observation, with pregnancy as the primary outcome.     

Male contraception: hormonal, mechanical and other

Methods of male contraception that have been developed so farhave mainly focused on the inhibition of spermatogenesis throughsuppression of the hypothalamo- pituitary secretion of gonodotrophins,and simultaneous supplementation with androgens. These methodsinclude the use of combinations of progestogens or luteinizinghormone-releasing hormone antagonists and testosterone derivatives,or high dose testosterone. Though effective contraception canbe obtained, side-effects and/or the high cost of treatmentlimit the widespread use of these approaches. Inhibition ofsperm maturation in the epididymis, or direct interference withspermatogenic cells or the cells of Sertoli by e.g. gossypolhave been abandoned because of toxic side-effects. Voluntarysterilization by vasectomy is the most commonly used methodof male contraception, but its surgical nature, problematicreversibility and suspected link with subsequent prostate cancerrender the method far from ideal. Non-surgical vas occlusionmay overcome some of these problems, but data on long-term side-effectsand reversibility are lacking. New contraceptive developmentsshould focus on interfering with highly specific aspects ofspermatogenesis such as unique enzymatic processes and intercellularcommunication through cytokines, or application of antibodiesagainst antigens of the epididymis or the spermatozoa. Onlythrough better understanding of normal and pathological spermatogenesiswill it be possible to develop an acceptable male contraceptive.     

Developmental outcome at 2 years of age for children born after ICSI compared with children born after IVF

BACKGROUND: Since the introduction of ICSI in 1991, medical outcome studies on ICSI children have been performed, but few have addressed developmental outcome. Hence, this outcome was assessed by performing a standard developmental test on children born after ICSI as compared with children born after IVF, at the age of 2 years. METHODS: In a prospective study, the medical and developmental outcome of 439 children born after ICSI (378 singletons, 61 twins) were compared with those of 207 children born after IVF (138 singletons, 69 twins), at the age of 24-28 months. These children were part of a cohort of children followed since birth. Of children reaching the age of 24-28 months between May 1995 and March 2002, 44.3% (2375/5356) were examined by a paediatrician who was unaware of the type of treatment used for each couple. Of all the children born, 12.2% (439/3618) in the ICSI group and 11.9% (207/1738) in the IVF group underwent a formal developmental assessment using the Bayley Scale of Infant Development (mental scale) by a paediatrician blinded to the type of treatment. RESULTS: There was no significant difference in maternal educational level, maternal age, gestational age, parity, birthweight, neonatal complication rate or malformation rate at 2 years between ICSI and IVF singletons, or between ICSI and IVF twins. No significant difference was observed in the developmental outcome using the Bayley scale at the age of 24-28 months (raw scores or test age) between ICSI children or IVF children. A multivariate regression analysis for the singleton children indicated that parity, sex (boys had lower scores than girls) and age had a significant influence on the test result, but that the fertility procedure (ICSI versus IVF) did not influence the test result. ICSI children from fathers with low sperm concentration, low sperm motility or poor morphology had a similar developmental outcome to that of children from fathers with normal sperm parameters. There were no significant differences between the initial cohort and the group lost to follow-up, nor between the psychologically tested and the non-tested group for a number of variables such as maternal educational level, birthweight in singletons and neonatal malformation rate. Although only some of the cohort of ICSI children were evaluated, a representative sample of both ICSI and IVF children was compared. CONCLUSIONS: There is no indication that ICSI children have a lower psychomotor development than IVF children. Paternal risk factors associated with male-factor infertility were found not to play a role in developmental outcome.     

脑红蛋白在成年男性生殖系统的表达及意义

目的:探讨脑红蛋白(neuroglobin,Ngb)在成年男性生殖系统的表达及其意义。方法:用免疫组织化学SP法观测Ngb在成人男性生殖系统的表达、分布与定位。结果:Ngb在生殖系统内神经节细胞、睾丸间质细胞有较强表达,在睾丸支持细胞、生精细胞、附睾管腔上皮、前列腺腺上皮及精囊黏膜上皮呈弱阳性表达。结论:Ngb在男性生殖系统中分布广泛,其功能值得研究。     

Correlation between semen parameters and sperm aneuploidy rates investigated by fluorescence in-situ hybridization in infertile men

Spermatozoa from 32 infertile patients and 13 controls with normal semen parameters were analysed using dual and triple colour fluorescence in-situ hybridization (FISH) techniques, in order to investigate the rates of aneuploidy for chromosomes 13, 18, 21, X and Y. The patients were divided into three groups according to their karyotypes or the karyotypes of their offspring: 15 were infertile men with abnormal semen parameters and normal karyotypes (group 1), 13 were infertile men with abnormal karyotypes and normal or abnormal semen (group 2) and four were infertile men with abnormal semen and normal karyotypes but whose wives conceived a child (or a fetus) with a numerical chromosomal abnormality through an intracytoplasmic sperm injection cycle (group 3). Patients with abnormal semen parameters showed a significantly higher aneuploidy rate for the investigated chromosomes in their spermatozoa compared to controls (P < 0.005). Our data suggest the presence of a correlation between poor semen parameters and an increase in aneuploidy rate of chromosomes 13, 18, 21, X and Y in spermatozoa (r = -0.81071, P < 0.002); therefore the risk of a chromosomal aneuploidy in spermatozoa seems to be inversely correlated to sperm concentration and total progressive motility. Patients with abnormal karyotypes showed a higher incidence of diploidy and chromosomal aneuploidies compared to controls (P < 0.002). This strongly suggests the presence of an interchromosomal effect of the cytogenetic rearrangement. Men who fathered a child with an abnormal karyotype through intracytoplasmic sperm injection did not present a higher aneuploidy rate for the investigated chromosomes in spermatozoa compared to patients with infertility due to a similar male factor but showed higher incidence of chromosomal aneuploidy compared to normal controls.     

Effectiveness and limits of antimicrobial treatment on seminal leukocyte concentration and related reactive oxygen species production in patients with male accessory gland infection

To evaluate whether bacteriological cure, sperm outcome, spontaneous pregnancy rate and white blood cell (WBC)-related reactive oxygen species (ROS) production were related to the extent of the infection and to an intermittent and repetitive antimicrobial treatment, 122 patients with bacterial [>10(5) colony-forming units (CFU)/ml] male accessory gland infections (MAGI) were studied. According to ultrasound criteria, patients had prostatitis (PR, n = 52), prostatovesiculitis (PV, n = 32) or prostatovesiculoepididymitis (PVE, n = 38). Each group was further subdivided into two subsets: one subset (PR, n = 40; PV, n = 20; PVE, n = 25) was given ofloxacin or doxycycline for 14 consecutive days per month for 3 months; the other subset (PR, n = 12; PV, n = 12; PVE, n = 13) received no treatment. The female partners were also treated. All patients were evaluated before, during (1 and 3 months) and after (3 months) treatment. The bacteriological cure rate was the highest (92.5%) after the third antibiotic course in PR, followed by PV (70.4%), and the lowest in PVE (52.0%). At 3 months after therapy discontinuation, some sperm parameters, seminal WBC concentration and ROS generation (assessed in the 45% Percoll fraction) were ameliorated in PR and PV, whereas no improvement occurred in patients with PVE, except for the percentage of coiled tails. Antibiotic treatment in PR and PV patients led to positive effects on sperm output and spontaneous pregnancy rate (40%) by removing pro-oxidant noxae (microbial and/or WBC-related ROS production). The persistent infertility, dyspermia and sperm-derived ROS overproduction in PVE may relate to a significant percentage of antibiotic-independent re-infection and/or to low antioxidative epididymal properties, which persisted following antimicrobial treatment.     

Effect of a single administration of ketoconazole on total and physiologically free plasma testosterone and 17β-oestradiol levels in healthy male volunteers

Summary The effect of a single oral dose of 400 mg ketoconazole, given as an 80 mg/ml suspension, on total and physiologically free (i.e. non-sex hormonebound) testosterone and 17-oestradiol has been investigated in 6 healthy male volunteers. The two steroids fell to nadir levels of 18 and 60% of their respective initial concentrations 6 hours after drug intake, and then completely recovered. Although in vitro slight displacement of testosterone from the sex-hormone binding globulin, by high doses of ketoconazole was found, the physiologically free concentration of testosterone in vivo was closely correlated with that of the total hormone, suggesting that there is no direct interference with sex-hormone binding globulin in vivo. Plasma LH and FSH were not significantly modified by treatment. The effect of ketoconazole on plasma oestradiol levels was less pronounced and was not clearly related to a block of the aromatase system, as reported in vitro.This work was presented in part at the International Symposium on the Regulation of Androgen Actions, Montreal, 29th June–1st July 1984