Decreased human semen quality and organochlorine compounds in blood

BACKGROUND: Various studies have been performed in which potential effects of xenoestrogens on fertility or sperm parameters were investigated by comparing groups of subjects exposed to different levels of these chemicals. METHODS: In our study we used an alternative approach, as we selected one group of men with very poor semen quality and another group with normal semen quality and determined the blood organochlorine contents in order to determine whether a difference in these levels could be established. Organochlorine compounds, including polychlorinated biphenyls (PCB) and PCB metabolites, were detected using gas chromatography. The concentrations were compared between both groups, and related to semen parameters. RESULTS: A comparison of both groups did not reveal significant differences in organochlorine levels. Linear relationships were found when PCB and metabolite concentrations were related to the age of the volunteers. Focusing on the subgroup of men with normal semen quality showed that sperm count and sperm progressive motility were inversely related to the concentrations of PCB metabolites within this group. CONCLUSIONS: The finding of a significantly decreased sperm count in relation to an elevated PCB metabolite level within the subgroup of men with normal semen quality is important. This is the first time that a correlation between exposure to environmental pollutants with endocrine-disrupting capacity and human sperm quality has been observed.     

Effects of sildenafil (Viagra) administration on seminal parameters and post-ejaculatory refractory time in normal males

Sildenafil is a specific inhibitor of phosphodiesterase (PDE) type 5 and represents a powerful therapy for male erectile dysfunction (ED) of different aetiology. Recently, sildenafil has been shown to restore erections in temporary ED related to the need of semen collection for assisted reproductive techniques. In this study, we investigated whether sildenafil administration modifies seminal parameters and/or erectile function in normal healthy volunteers. In a double-blind, randomized, placebo-controlled, cross-over two period investigation we enrolled 20 healthy male volunteers (mean +/- SE age 32 +/- 0.5 years). Subjects were not using any medication for the 3 month period prior to the study and were engaged in a stable relationship with proven fertility. The effects of sildenafil (100 mg) on seminal parameters and erectile function after audiovisual sexual stimulation were evaluated by semen analysis and by colour-Duplex ultrasound (the Resistive Index) respectively. In all subjects, sildenafil caused no changes in seminal and erection parameters when compared to placebo. Interestingly, sildenafil administration led to a marked reduction of the post-ejaculatory refractory time (10.8 +/- 0.9 min versus 2.6 +/- 0.7 min for placebo and sildenafil respectively; P < 0.0001). These results indicate that in normal subjects acute sildenafil treatment does not modify semen characteristics and has a positive influence over the resumption of erections following ejaculation in the presence of a continuous erotic stimulus.     

An evaluation of semen analysis and in-vitro tests of sperm function in the prediction of the outcome of intrauterine AIH

Twenty-nine couples with an average of 5 years of infertilitywere selected for treatment by intrauterine insemination ofwashed semen (AIH). The criteria for selection were (i) thefemale partner showed no detectable fertility disorders by routinescreening; (ii) the male partner showed subnormal semen qualityon conventional semen analysis. Ovulation was stimulated uniformlywith clomiphene citrate and precipitated with human chorionicgonadotrophin (HCG). Inseminations were performed 31–32h post-HCG, with the day of HCG determined by ultrasound monitoringof follicular development. The fertilizing capacity of the malepartners‘ spermatozoa was tested in vitro using donatedhuman oocytes and/or the zona-free hamster oocyte penetrationassay. Up to eight cycles of AIH were alternated with cyclesof natural intercourse. While no pregnancies occurred in thegroup during normal coital cycles, the AIH pregnancy rate was17% per couple, but only 3% per insemination cycle. Four furtherpregnancies were achieved spontaneously in couples from thestudy group within 3 years of completion of the AIH therapyand four patients became pregnant following subsequent GIFTor IVF treatments. Neither of the in-vitro tests was helpfulin predicting the outcome of AIH, spontaneous pregnancy norof subsequent assisted conception procedures.     

CA 125 in seminal plasma: correlation with semen parameters

Ovarian cancer marker CA 125 was measured in human seminal plasma,and the concentrations ranged between 22 and 1149 U/ml, andbetween 39 and 4711 U/ejaculate. This very high patient-to-patientvariability was in contrast to a much lower within-patient variability,which was comparable to that of other semen parameters. No significantdifferences in CA 125 concentration were found in seminal plasmafrom normospermic patients, patients with male factors, vasectomizedmen, and in aliquots of samples which led to a pregnancy, viaartificial insemination or in-vitro fertilization. The seminalplasma CA 125 concentration was not correlated with sperm count,motility and morphology. In contrast, seminal plasma CA 125concentrations correlated with the age of the patient (P <0.001) and inversely with the volume of the ejaculate (P <0.001). These correlations were independent of each other. CA125 did not correlate with the prostatic marker zinc, but diddo so with the seminal vesicle marker fructose and the epididymalmarker carnitine.     

Evolution of semen quality in North-eastern Spain: a study in 22,759 infertile men over a 36 year period

A retrospective study was conducted in a large population to determine whether sperm quality has changed in Northeastern Spain between 1960 and 1996. From a total initial population of 22,759 men, two separate groups were studied: men with spermatozoa (n = 20,411) and those with azoospermia (n = 1364). After adjustment for age and sexual abstinence, multiple linear regression analyses were used to assess changes in semen parameters over time. A 0.2% decline was observed in semen volume in the spermatozoa group (P < 0.001). No significant increase (0.04%) in sperm count (x 10(6)/ml) was observed in the spermatozoa group. There was a 0.4% increase in motile spermatozoa in the spermatozoa group (P < 0.001). There was a statistically significant decline in normal spermatozoa (3.6%) in the spermatozoa group (P < 0.001). Of the total population, 1364 men had azoospermia (6.0%). The changes observed in the semen parameters analysed in this large population showed no evidence of a deteriorating sperm quality, although a statistically significant decline was observed in the percentage of normal spermatozoa.     

Persistence of free HBV DNA in body secretions and liver despite loss of serum HBV DNA after interferon-induced seroconversion

Following interferon therapy, a chronic hepatitis B (HBV) carrier lost all serum markers of active viral replication and became anti-HBe positive but remained positive for free and replicative HBV-DNA in semen, saliva, urine, and liver four months later. At 12 months, when he also developed anti-HBs, urine and saliva analysed for free HBV-DNA were positive. Despite histological remission and loss of HBV-DNA from serum, the potential for transmission of HBV and reactivation of disease remain.     

The relationship between fertility potential measurements on cryobanked semen and fecundity of sperm donors

Sperm penetration assay (SPA) scores obtained from cryobanked semen were correlated with therapeutic insemination (TI) fecundity in a group of established sperm donors, thereby evaluating the efficacy of the SPA in screening donors for sperm banking. While the SPA has been used to separate fertile from infertile males, we altered assay conditions to use frozen semen and to distinguish performance among fertile donors. Three frozen ejaculates from 11 pregnancy-proven donors were analysed. Of 905 TI cycles, 275 recipients achieved 95 pregnancies. There were no significant relationships between fecundity and donor semen, washed sperm parameters, sperm recoveries or recipient age. A significant relationship was revealed between mean SPA scores (range 8.7-66.6 penetrations/ovum) and donor fecundity (range 0.04-0.16, P < 0.03). Sperm concentration was varied in an effort to establish the most sensitive test condition. Using 0.25x10(6) motile spermatozoa/ml, a highly significant relationship was observed (P < 0.002). The four donors with the lowest SPA scores achieved the four lowest fecundities. It is concluded that a modified SPA can be used on frozen donor semen to estimate donor fertility potential. If applied routinely in donor semen banking, poor quality applicants could be excluded, thereby increasing pregnancy rates while decreasing donor screening costs.     

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.     

A paradoxical decline in semen parameters in men treated with clomiphene citrate: A systematic review

Clomiphene, a selective oestrogen receptor modulator, has been utilised in managing male sub-fertility since 1967. Numerous controlled and uncontrolled studies have been published regarding the efficacy of clomiphene citrate in male sub-fertility cohorts. Although the primary intention of treating men with clomiphene citrate is to improve sperm parameters and testosterone levels, some studies have reported paradoxical decline in semen parameters. The information available on decline in sperm parameters following treatment with clomiphene is sparse. We conducted a systemic review using PubMed, Embase, Cochrane Library and Scopus databases for original studies reporting adverse effects of clomiphene citrate therapy on sperm parameters. This systematic review includes 384 men from 11 different studies that reported adverse effects of clomiphene citrate therapy. Of the men included in these studies, 19%, 21%, 17% and 24% of clomiphene-treated men demonstrated a decrease in sperm count, concentration, motility and total motile sperm count respectively. In up to 17% of patients, deterioration of semen parameters did not recover following discontinuation of therapy. In the future, more studies should report on this aspect so the magnitude of this effect can be more clearly understood.     

Normal sperm parameters per se do not reliably account for fertility: A case–control study in the real-life setting

A proportion of men are infertile despite having normal medical history/physical examination and normal semen analysis. We aimed to assess whether normal sperm parameters per se account for male factor fertility. 1,957 infertile men were compared with 103 age-comparable fertile controls. Semen analysis was based on 2010 World Health Organization reference criteria. Of all, 12.1% of infertile men and 40.8% of fertile men presented with normal sperm parameters. Among fertile men, 36.9% had isolated sperm abnormalities and 22.3% men showed two or more concomitant sperm abnormalities. Serum total testosterone was higher in infertile men with normal sperm parameters compared to those with ≥2 sperm abnormalities or azoospermia, but similar to those with isolated sperm abnormalities (p ≤ .001). Circulating hormones were similar among sperm parameters groups in fertile men. At multivariable analyses, testicular volume (OR 1.12, p ≤ .001) and FSH (OR 0.8, p ≤ .001) were associated with normal sperm parameters. Overall, the longer the infertility period, the greater the number of sperm parameters abnormalities (p < .01). In conclusion, we found that 12% of infertile men and only 41% of fertile men present with normal sperm parameters. Normal sperm parameters per se do not reliably account for fertility in the real-life setting.