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Biomedical subjects

Elisabeth Carlsen

Publications and source records attributed to Elisabeth Carlsen.

17 recordsLinked to original sources

Primary testicular failure in Klinefelter's syndrome: the use of bivariate luteinizing hormone-testosterone reference charts.

BACKGROUND: The diagnosis of androgen deficiency is based on clinical features and confirmatory low serum testosterone levels. In early primary testicular failure, a rise in serum LH levels suggests inadequate androgen action for the individual's physiological requirements despite a serum testosterone level within the normal range. The combined evaluation of serum LH and testosterone levels in the evaluation of testicular failure has not been widely advocated. PATIENTS: Seven hundred and six healthy males and 39 patients with known primary hypogonadism due to Klinefelter's syndrome and SRY-positive 46,XX karyotypes were included in the study. DESIGN: Testosterone, oestradiol and LH serum concentrations were measured in all individuals. Based on the 706 healthy males two-dimensional bivariate LH-testosterone reference charts were constructed. RESULTS: Despite a median serum total and free testosterone and oestradiol levels being reduced (P < 0.001) and LH levels elevated (P < 0.001) in Klinefelter's syndrome and 46,XX-males, many subjects (69%) had total testosterone within the reference range. However, using the bivariate charts all subjects lay outside the 97.5 percentile. CONCLUSION: Bivariate LH and testosterone charts are useful in the evaluation of men with known primary testicular failure due to sex chromosomal aneuploidy in whom evaluation based on testosterone measurement in isolation underestimates the prevalence of hypogonadism. It is, however, important to emphasize that isolated use of the bivariate evaluation should not form the basis for androgen substitution therapy. Further studies are needed in order to evaluate the use of bivariate LH and testosterone charts in the assessment of any younger man with possible primary testicular failure.

Adult↗

Fertility treatment and reproductive health of male offspring: a study of 1,925 young men from the general population.

Little is known the about the reproductive health of offspring after fertility treatment. In 2001-2005, the authors approached young Danish men attending a compulsory physical examination to determine their fitness for military service. A total of 1,925 men volunteered, delivered a semen sample, had a physical examination performed and a blood sample drawn, and responded to a questionnaire. Their mothers were questioned about whether they had received fertility treatment in order to conceive their sons. Forty-seven mothers reported having received fertility treatment to conceive the index subject. After control for confounders, men whose mothers had received fertility treatment to conceive them had a 46% lower sperm concentration (95% confidence interval (CI): -63, -20) and a 45% lower total sperm count (95% CI: -64, -16). They had a smaller testis size (-0.9 ml, 95% CI: -2.2, 0.4), fewer motile sperm (-4.0%, 95% CI: -8.0, -0.1), and fewer morphologically normal spermatozoa (-2.0%, 95% CI: -4.1, 0.0). They also had a lower serum testosterone level and free androgen index (results not statistically significant). These findings should be viewed in light of the increasing use of fertility treatments. Although the cause of these findings is unknown, they raise concern about possible late effects of fertility treatment. Larger-scale studies of children born after fertility treatment should be performed.

Adult↗

Is human fecundity declining?

Summary The decreasing trends in fertility rates in many industrialized countries are now so dramatic that they deserve much more scientific attention. Although social and behavioural factors undoubtedly play a major role for these trends, it seems premature, and not based on solid information, to conclude that these trends can be ascribed to social and behavioural changes alone. There is evidence to suspect that changing lifestyle and increasing environmental exposures, e.g. to endocrine disrupters, are behind the trends in occurrence of male reproductive health problems, including testis cancer, undescended testis and poor semen quality. These biological factors may also contribute to the extremely low fertility rates. However, the necessary research is complex and requires non-traditional collaboration between demographers, epidemiologists, clinicians, biologists, wild life researchers, geneticists and molecular biologists. This research effort can hardly be carried out without major support from governments and granting agencies making it possible to fund collaborative projects within novel research networks of scientists.

Environmental Pollutants↗

Coordinated European investigations of semen quality: results from studies of Scandinavian young men is a matter of concern.

For many years it has been acknowledged that Danish and Norwegian men have one of the highest risks in the world for testicular cancer in sharp contrast to neighbouring Baltic men from Finland, Estonia and Lithuania. As an association between poor semen quality and testicular cancer has been established, it was suggested that men from high-risk testicular cancer areas would be more likely to have poor semen quality. However, previous studies were not able to elucidate this question due to their retrospective nature. In prospectively designed and strictly controlled studies of fertile men, the existence of regional differences in semen quality was confirmed. In addition, studies of men from the general populations were undertaken and a similar regional difference in semen quality was detected. Men from the eastern part of the Nordic-Baltic area had better semen quality than men from the western part. These findings parallel the incidence of testicular cancer in these regions. Approximately 20% of young men from Norway and Denmark had sperm concentrations below the World Health Organization reference level of 20 x 10(6) spermatozoa/mL, and approximately 40% had <40 x 10(6) spermatozoa/mL which, according to recent publications, may be the 'threshold' below which fecundity declines. In Denmark, the situation is of concern and a continued surveillance of semen quality in young men was established in 2001 by a government-supported programme.

Adult↗

Longitudinal changes in semen parameters in young Danish men from the Copenhagen area.

BACKGROUND: Several recent studies have reported low sperm concentration in young men recruited from the general population, but it is unknown whether the semen quality of these young men reflects that of more mature men or is reduced due to relative immaturity. We conducted a longitudinal follow-up study to address this question. METHODS: We followed 158 young men (median age = 19.1 years at entry) for up to 4 years and requested quarterly semen samples (total 1838 semen samples) and yearly genital examinations. We examined longitudinal changes in sperm concentration, semen volume, percentage of immotile sperm and percentage of morphologically normal sperm. We used general linear models in which each man served as his own control which also controlled for age, smoking, urogenital infections or disorders, fever and abstinence time. RESULTS: We found no evidence that sperm concentration, total sperm count or percentage of morphologically normal sperm changed appreciably during the 4 years of follow-up. Semen volume appeared to increase slightly with age, perhaps due to greater acceptance of the study protocol by participants. Sperm motility also improved somewhat, although this may, at least in part, reflect a trend in motility measurement. CONCLUSIONS: In this analysis of 1838 semen samples from 158 young men from the Copenhagen area, sperm concentration, total sperm count and sperm morphology did not change significantly during 4 years of follow-up, suggesting that previously reported low sperm concentration and poor sperm morphology among young Danish men are unlikely to be the result of immaturity.

Adolescent↗

Assisted reproduction in male cancer survivors: fertility treatment and outcome in 67 couples.

BACKGROUND: Many male cancer survivors experience fertility problems due to antineoplastic treatment. We report the fertility outcome in 67 couples referred to assisted reproduction treatment (ART) because of male factor infertility due to cancer. METHODS: This was a retrospective study assessing the following parameters: diagnosis, cancer treatment, type of fertility treatment and type of sperm used, number of pregnancies and pregnancy outcome. RESULTS: Testicular cancer and lymphomas were the most prevalent diagnoses. Adjuvant treatment with chemo- and/or radiation therapy had been given to 90% of the men. Semen was cryopreserved in 82% of the men prior to treatment. Following antineoplastic treatment, 43% of the men had motile spermatozoa in the ejaculate, but 57% were azoospermic. A total of 151 ART cycles were performed [55 intra-uterine insemination (IUI), 82 ICSI and 14 ICSI-frozen embryo replacement (FER)]. The clinical pregnancy rate per cycle was 14.8% after IUI, 38.6% after ICSI and 25% after ICSI-FER. The corresponding delivery rates were 11.1, 30.5 and 21%. Cryopreserved semen was used in 58% of the pregnancies. The delivery rate per cycle was similar after use of fresh or cryopreserved spermatozoa. CONCLUSIONS: Male cancer survivors have a good chance of fathering a child by using either fresh ejaculated sperm or cryopreserved sperm.

Adult↗

Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries.

Between 1996 and 1999, the authors invited all young men from five European countries who were undergoing compulsory medical examination for possible military service to participate in a study on male reproductive health. The participation rate was 19% in two cities in Denmark (n = 889), 17% in Oslo, Norway (n = 221), 13% in Turku, Finland (n = 313), 14% in Kaunas, Lithuania (n = 157), and 19% in Tartu, Estonia (n = 190). Each man provided a semen sample, was examined by a physician, and, in collaboration with his mother, completed a questionnaire about general and reproductive health, current smoking habits, and exposure to smoking in utero. After adjustment for confounding factors, men exposed to smoking in utero had a reduction in sperm concentration of 20.1% (95% confidence interval (CI): 6.8, 33.5) and a reduction in total sperm count of 24.5% (95% CI: 9.5, 39.5) in comparison with unexposed men. Percentages of motile and morphologically normal sperm cells were 1.85 (95% CI: 0.46, 3.23) and 0.64 (95% CI: -0.02, 1.30) percentage points lower, respectively, among men exposed in utero, and exposed men had a 1.15-ml (95% CI: 0.66, 1.64) smaller testis size. The associations were present when data from the study centers were analyzed separately (though not in Lithuania, where only 1% of mothers smoked during pregnancy), although the strength of the association varied. Maternal smoking may have long-term implications for the reproductive health of the offspring. This is another good reason to advise pregnant women to avoid smoking.

Adolescent↗

Effects of ejaculatory frequency and season on variations in semen quality.

OBJECTIVE: To describe the intraindividual variation in semen parameters. DESIGN: Prospective, longitudinal study. SETTING: Academic research environment. PATIENT(S): Twenty-seven healthy men, followed monthly for 16 months. INTERVENTION(S): Monthly semen samples were collected, as well as information regarding duration of abstinence, febrile episodes, and ejaculatory frequency. MAIN OUTCOME MEASURE(S): Sperm concentration, percentage immotile spermatozoa, and percentage morphologically normal spermatozoa. RESULT(S): There were no significant seasonal variations in sperm concentration, motility, or morphology. The ejaculatory frequency was significantly higher during spring compared with winter months. There was a significant difference in sperm concentration with respect to having one, two, or more than two ejaculations during a 7-day period before the abstinence period. Sperm motility and morphology were not affected by ejaculatory frequency. Duration of abstinence, ejaculatory frequency, and fever accounted only little for the high intraindividual variation in individual semen parameters. Three semen samples compared with two reduced the intraindividual variations as follows: sperm concentration from 41% to 33.5%, percentage normal spermatozoa from 6.9% to 5.7%, and percentage immotile spermatozoa from 19% to 15.5%. CONCLUSION(S): Ejaculatory frequency but not season significantly affected sperm concentration. Most of the intraindividual variations in semen parameters could not be explained by duration of abstinence, fever, or ejaculatory frequency.

Ejaculation↗

Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men.

OBJECTIVE: To examine the relationship between body mass index (BMI) and semen quality among young men from the general population. DESIGN: Cross-sectional study. SETTING: Danish young men were approached when they attended a compulsory physical examination to determine their fitness for military service. PATIENT(S): From 1996-1998, 1,558 (19%) young men (mean age 19 years) volunteered. MAIN OUTCOME MEASURE(S): Semen volume (in milliliters), sperm concentration (in million per milliliter), percentage of motile spermatozoa, percentage of spermatozoa with normal morphology, total sperm count (in million), and testis size (in milliliters). In addition, serum reproductive hormones were measured. RESULT(S): Serum T, sex hormone-binding globulin (SHBG), and inhibin B all decreased with increasing BMI, whereas free androgen index and E(2) increased with increasing BMI. Serum FSH was higher among slim men. After control for confounders, men with a BMI <20 kg/m(2) had a reduction in sperm concentration and total sperm count of 28.1% (95% confidence interval [CI] 8.3%-47.9%) and 36.4% (95% CI 14.6%-58.3%), respectively, and men with a BMI >25 kg/m(2) had a reduction in sperm concentration and total sperm count of 21.6% (95% CI 4.0%-39.4%) and 23.9% (95% CI 4.7%-43.2%), respectively, compared to men with BMI between 20-25 kg/m(2). Percentages of normal spermatozoa were reduced, although not significantly, among men with high or low BMI. Semen volume and percentage of motile spermatozoa were not affected by BMI. CONCLUSION(S): High or low BMI was associated with reduced semen quality. It remains to be seen whether the increasing occurrence of obesity in the Western world may contribute to an epidemic of poor semen quality registered in some of the same countries. If so, some cases of subfertility may be preventable.

Adolescent↗

Frequent polymorphism of the mitochondrial DNA polymerase gamma gene (POLG) in patients with normal spermiograms and unexplained subfertility.

BACKGROUND: Male fertility largely depends on the quality of sperm production, which may be affected by environmental and genetic factors. In this study, we explored a possible role of the polymerase gamma (POLG) gene polymorphism, recently reported to be associated with male infertility in some populations. METHODS: The polymorphic CAG repeat (usually 10 codons long) in the POLG gene was studied in 1298 male subjects: 429 patients with infertility/subfertility, and 869 controls (495 men from the general population with unknown fertility and 374 recent fathers). In all subjects, the POLG polymorphism was assessed in relation to their semen quality, and--in the fertile controls--with biological fecundity measured as waiting time-to-pregnancy (TTP) for the couples. In the patients lacking the common POLG allele, the outcome of the assisted reproductive techniques (ART) for the couples was evaluated. RESULTS: The absence of one (10/ not equal to 10) or both common POLG alleles (not equal to 10/not equal to 10) was more frequent among the subfertile patients than among fertile controls (P=0.021 and P=0.04 respectively). The estimated predictive value for infertility in a man homozygous for the POLG polymorphism was 15.5% (95% CI: 4.8-51%). There was a positive association with sperm concentration: 14.3% of the normospermic subfertile patients were homozygous for the absence of the common POLG allele (not equal to 10/not equal to 10), in comparison with 2.3% of unselected controls (P=0.001) and 0.9% of the fertile men (P=0.0001). No association with sperm motility, morphology and TTP was found. Spermatozoa of the three not equal to 10/not equal to 10 patients treated with IVF retained the ability to penetrate the egg, but the fertilization rate was low. Nine homozygous not equal to 10/ not equal to 10 patients were treated with ICSI, resulting in pregnancy in seven couples. CONCLUSIONS: The POLG gene polymorphism should be considered as a possible contributing factor in patients with unexplained subfertility and normal spermiograms. The oocyte penetration ability of sperm may be partially impaired in the not equal to 10/not equal to 10 patients but most of them can be successfully treated with ICSI.

Adult↗

History of febrile illness and variation in semen quality.

BACKGROUND: The purpose of this study was to analyse the effect of a history of febrile illness on semen quality. METHODS: Twenty-seven healthy men (median age 24.4 years) were followed with monthly semen samples and a daily record of the occurrence of experienced febrile episodes over a 16 month period between March 1998 and June 1999 in Copenhagen, Denmark. Semen samples were analysed for semen volume, sperm concentration, percentage immotile sperm and percentage morphologically normal sperm. RESULTS: Sperm concentration significantly decreased by 32.6% (95% confidence interval -49.9; -9.2) following fever during meiosis and by 35.0% (-50.5; -14.6) following fever during the postmeiotic period of spermatogenesis (spermiogenesis). The percentage of morphologically normal sperm was decreased by 7.4% (-11.6; -3.0) and the percentage of immotile sperm was increased by 20.4% (6.0; 36.8) by fever during spermiogenesis. The number of days the men experienced fever significantly affected their semen parameters. Thus fever during meiosis and spermiogenesis reduced sperm concentration with respectively 7.1% (-12.9; -0.9) and 8.5% (-13.6; -3.0) per day of fever. The percentage of morphologically normal sperm decreased 1.6% (-2.5; -0.6) and the percentage of immotile sperm increased 4.5% (1.7; 7.3) per day of fever during spermiogenesis. There was, however, a large variation in the individual response to fever. CONCLUSIONS: Sperm concentration, morphology and motility in a semen sample are adversely affected by a febrile episode during the postmeiotic period of spermatogenesis (spermiogenesis). Sperm concentration was also adversely affected by fever during the period of meiosis, whereas fever at other time points during spermatogenesis did not seem to significantly affect these sperm parameters. The adverse effect seemed to be dependent upon the number of days with fever.

Adult↗

Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period: possible effects of seasons.

To obtain information on the scale of the intraindividual variation in testicular hormone, blood samples for inhibin B determination were collected monthly in 27 healthy male volunteers during a 17-month period. In addition, the traditional reproductive hormones FSH, LH, testosterone, estradiol, and SHBG were measured. The intraindividual variation in inhibin B over the study period was, on the average, 10%, corresponding to the assay variation of the inhibin B assay, indicating that most of the observed day to day variation in inhibin B levels in men could be explained by assay variation. A seasonal variation was observed in LH and testosterone levels, but not in the levels of the other hormones. The seasonal variation in testosterone levels could be explained by the variation in LH levels. The seasonal variation in LH levels seemed to be related to the mean air temperature during the month before blood sampling, but not to the length of daylight or the hours of sunshine. In conclusion, our data showed that day to day levels of inhibin B are relatively constant in men and do not seem to be influenced by seasonal factors. In contrast, we found a seasonal variation in LH and testosterone levels in men. The peak levels of both LH and testosterone were observed during June-July, with minimum levels present during winter-early spring. Air temperature, rather than light exposure, seems to be a possible climatic variable explaining the seasonal variation in LH levels.

Adult↗

CAG repeat length in androgen-receptor gene and reproductive variables in fertile and infertile men.

Several reports implicated a relation between the trinucleotide (CAG) repeat length in the androgen-receptor gene and male infertility, whereas others failed to find an association. We investigated the CAG repeat length in relation to sperm production and reproductive hormones in 119 infertile men and 110 men with proven fertility. We found no difference in the distribution of CAG repeat lengths between the groups and no association with reproductive parameters. This finding suggests that, within the normal range of 14-33 repeats, there is no biological link between the CAG repeat length and fertility. This lack of association was comfirmed by an analysis of the data from all previously published European studies (in total 674 infertile men and 660 controls).

Adolescent↗

Poor semen quality may contribute to recent decline in fertility rates.

During past decades, we have witnessed a remarkable decline in fertility rates (number of births per 1000 women of reproductive age) in the industrialized world. It seems beyond doubt that the enormous social changes of our societies play the major role in this decline, but can it be attributed to changing social structures alone or is a reduced fecundity in the population also a factor? To address this we have focused on trends in teenage pregnancies (which to a large extent are unplanned). During the period in question fertility rates among 15-19 year old Danish women have been falling and the decline in fertility rate is not counterbalanced by an increase in the rate of induced abortion. When seen together with recent results from Denmark, which have shown that more than 30% of 19 year old men from the general population now have sperm counts in the subfertile range, we argue that this fall may not be attributable to social factors, changes in conception practices or diminished sexual activity alone. It seems reasonable also to consider widespread poor semen quality among men as a potential contributing factor to low fertility rates among teenagers. Due to the concern caused by the low sperm count among younger Danish men, the Danish Ministries of Health and Environment have launched a surveillance programme which includes an annual examination of the semen quality in 600 young Danes from the general population. We propose that researchers in other countries with low and falling fertility rates among young women should consider the possibility that semen quality of their younger male cohorts may also have deteriorated.

Adolescent↗

East-West gradient in semen quality in the Nordic-Baltic area: a study of men from the general population in Denmark, Norway, Estonia and Finland.

BACKGROUND: Denmark and Norway have a three-fold higher incidence of testicular cancer than Estonia and Finland. Groups of young men from Denmark, Norway, Finland and Estonia were investigated to elucidate whether semen parameters and other related parameters follow a gradient between these countries, as does the gradient in incidence of testicular cancer. METHODS: In total, 968 young men from the general population in these four countries were investigated according to the same protocol. Possible confounders were evaluated, and included in the statistical analysis when appropriate. Inter-laboratory differences in assessment of sperm concentrations were controlled by an external quality control programme and morphology assessment was centralized to one person. RESULTS: The Finnish and Estonian men had an adjusted median sperm concentration of 54 and 57 x 10(6)/ml, respectively and the Norwegian and Danish men 41 x 10(6)/ml. The corresponding total sperm counts were 185, 174, 133 and 144 x 10(6). The frequency of normal sperm in men from Finland was 8.9%, Estonia 9.2%, Norway 6.9% and Denmark 6.4%. Within all four groups of men, a relationship between increasing levels of inhibin-B and increasing sperm counts was observed. However, inhibin-B levels were not predictive of sperm count differences between countries. CONCLUSIONS: It is believed that the men examined were representative of the normal population of young men in all four countries as they were recruited from groups attending a compulsory medical examination, and not selected for known fertility or semen quality. Moreover, the majority of participants had no prior knowledge of their fertility potential. It appears that an east-west gradient exists in the Nordic-Baltic area with regard to semen parameters, this being in parallel with the incidences of testicular cancer. Further investigations are required to determine whether these findings are due to genetic differences, to different environments, or perhaps to a combination of both factors.

Adult↗

Inhibin B: a marker for the functional state of the seminiferous epithelium in patients with azoospermia factor C microdeletions.

Testicular production of inhibin B is believed to be dependent on the presence of germ cells within the seminiferous tubules. However, this association has recently been questioned in patients with deletions of azoospermia factor (AZF) on the Y chromosome. We have addressed this problem in 442 unselected infertile/subfertile patients (excluding obstructive and iatrogenic forms) who were analyzed for Yq microdeletions. AZFc microdeletions were found in 16 patients (3.8% of the total infertile group, but 9% of the subgroup with azoospermia or severe oligozoospermia with sperm concentration <1 x 10(6)/ml). The reproductive hormone profiles in patients with AZFc microdeletions were analyzed and compared with those in infertile patients without microdeletions and those in fertile control individuals. The mean serum inhibin B concentration in the patients with AZFc microdeletions (39.5 +/- 36.0 pg/ml) was significantly lower than that in the group of infertile patients without microdeletions (134.6 +/- 88.5 pg/ml). However, no significant difference was found compared with that in a matched group of infertile patients with comparably low sperm counts (72.6 +/- 75.5 pg/ml). Bilateral testicular biopsies in the AZFc-deleted patients revealed a variable histological pattern suggestive of a progressive depletion of seminiferous epithelium. An association between testicular pathology and the reproductive hormone profile was found; the more severe forms had lower inhibin B and higher FSH levels. Importantly, if Sertoli cell-only tubules were prevalent in the biopsy, inhibin B was invariably undetectable. In patients with bilateral spermatocytic arrest, inhibin B remained within the normal range, which is consistent with a role of spermatocytes in the maintenance of inhibin B secretion. Our data support the view that, in contrast to recently published data, in patients with AZF microdeletions the serum concentration of inhibin B is dependent upon the functional interaction between Sertoli cells and spermatocytes and/or spermatids.

Adult↗