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N Jørgensen

Publications and source records attributed to N Jørgensen.

At least 19 recordsLinked to original sources
PubMed2002

Time to pregnancy in relation to semen quality assessed by CASA before and after sperm separation.

BACKGROUND: In order to provide a reference for infertile men, we defined normal values of semen quality in a population of fertile men, using computer-assisted semen analysis (CASA) before and after sperm separation. Additionally, we investigated the relationship between semen quality and time to pregnancy (TTP). METHODS AND RESULTS: Semen samples were obtained from 315 proven fertile men. The median sperm concentration in fresh samples was 107 x 10(6)/ml (5-95 percentiles: 16-322 x 10(6)/ml), the median percentage of motile sperm cells was 65% (14-87%) and the median percentage of progressively motile cells was 37% (5-64%). After density gradient sperm separation, the median total sperm count was 46 x 10(6) (4-350 x 10(6)), the median percentage of motile sperm cells was 77% (16-95%) and the median percentage of progressively motile cells was 63% (11-84%). No significant associations were found between TTP and sperm counts or sperm motility, either before or after sperm separation. This may be due in part to the fact that the study comprised couples with proven fertility. CONCLUSION: We have defined semen parameters, including the results of density gradient separation, in a population of normal fertile men which may be of interest in the evaluation of semen samples from infertile men.

Adult↗
PubMed2002

Time to pregnancy and semen parameters: a cross-sectional study among fertile couples from four European cities.

BACKGROUND: In fertile populations, little is known about the association between semen parameters and time to pregnancy (TTP). METHODS: Pregnant women from Copenhagen, Edinburgh, Paris and Turku who conceived without medical intervention were asked for their TTP (942 couples), and their partners provided a semen sample. The proportion of morphologically normal sperm and the multiple anomalies index (MAI, ratio of the total number of anomalies to the number of abnormal sperm) were centrally estimated. We estimated rate ratios for the occurrence of a pregnancy by a discrete survival model, adjusted for sexual activity and female factors affecting fecundity. RESULTS: Increasing sperm concentration influenced TTP up to 55 x 10(6)/ml. The proportion of morphologically normal sperm influenced TTP up to 39% according to David's criteria, and this association held among the subjects with a sperm concentration >55 x 10(6)/ml. For strict criteria, the threshold value was 19% normal sperm. An increase of 0.5 in MAI was associated with an adjusted rate ratio for the occurrence of a pregnancy of 0.68 (95% confidence interval: 0.54-0.85). CONCLUSIONS: These results highlight the importance of sperm morphology parameters and indicate that the effect of proportion of normal sperm on TTP may be independent of sperm concentration.

Cross-Sectional Studies↗
PubMed2001

Identification of a Y chromosome haplogroup associated with reduced sperm counts.

In man, infertility is associated with microdeletions of specific regions of the long arm of the Y chromosome. This indicates that factors encoded by the Y chromosome are necessary for spermatogenesis. However, the majority of men with either idiopathic azoospermia or oligozoospermia have grossly intact Y chromosomes and the underlying causes of their infertility are unknown. We hypothesized that some of these individuals may carry other rearrangements or sequence variants on the non-recombining region of the Y chromosome that may be associated with reduced spermatogenesis. To test this hypothesis, we typed the Y chromosome in a group of Danish men with known sperm counts and compared the haplotype distribution with that of a group of unselected Danish males. We found that one class of Y chromosome, referred to as haplogroup 26+, was significantly overrepresented (27.9%; P < 0.001) in the group of men with either idiopathic oligozoospermia (defined as <20 x 10(6 )sperm/ml) or azoospermia compared to the control Danish male population (4.6%). This study defines, for the first time, a class of Y chromosome that is at risk for infertility in a European population. This observation suggests that selection may be indeed active on the Y chromosome, at least in the Danish population, raising the possibility that it could alter the pattern of Y chromosome haplotype distribution in the general population.

Alleles↗
PubMed2001

Regional differences in waiting time to pregnancy among fertile couples from four European cities.

BACKGROUND: A previous European study found a longer time to pregnancy (TTP) among fertile women from Paris compared with women from other Western European countries. A co-ordinated, cross-sectional study of pregnant couples from Denmark (Copenhagen), France (Paris), Scotland (Edinburgh) and Finland (Turku) was therefore undertaken to assess differences in waiting TTP among couples from these cities. METHODS: Pregnant women were invited to participate when they showed up for their first antenatal visit in one of the four centres. Inclusion criteria included that their partner was 20-45 years of age and born in the country in which he was currently living and that the pregnancy was achieved without fertility treatment. Both partners filled in a questionnaire and the man underwent a physical examination and delivered a semen sample (Turku: n = 237, Copenhagen: n = 302, Edinburgh: n = 212, Paris: n = 191). RESULTS: French couples had a decreased probability of conception compared with couples from the other three countries, although only after adjustment for confounders. No significant differences between couples from the three other countries were found. CONCLUSION: The observed geographical differences in TTP remain unexplained and were not due to differences in semen quality, but may be caused by varying exposures to environmental factors or psychological distress. In addition, selection bias due to the low participation rates cannot be ruled out. Future studies examining the causes for geographical differences in TTP are needed.

Adult↗
PubMed2001

Sperm morphological defects related to environment, lifestyle and medical history of 1001 male partners of pregnant women from four European cities.

BACKGROUND: Recently, differences in semen quality have been found among the partners of pregnant women from four European cities: Turku, Copenhagen, Edinburgh and Paris. METHODS: During this study, slides from the four centres were subjected to a centralized assessment of sperm morphology. The percentages of sperm defects were recorded using a multiple-entry classification enabling the calculation of the multiple anomalies index (MAI), which is the mean number of anomalies per abnormal sperm. The relationships between various sperm abnormalities and self-reported data on medical history, lifestyle and occupational factors were examined. RESULTS: Significant differences in the MAI and most of the sperm defects were found between the four cities, and more abnormalities were found in spring than in winter. An increase in some sperm abnormalities was related to medical treatment of the mother during pregnancy, higher birthweight and previous treatment for cryptorchidism. Significant variations of several sperm defects were related to stress, weekly working time, occupational posture and metal welding, suggesting directions for further exposure studies. CONCLUSION: The present study indicated that the detailed assessment of sperm abnormalities is a useful biomarker of the effect of various external factors which may qualitatively affect human spermatogenesis.

Adult↗
PubMed2001

Regional differences in semen quality in Europe.

Recent reports have indicated a decrease in semen quality of men in some countries, and suggested regional differences. A study was undertaken of semen samples from 1082 fertile men from four European cities (Copenhagen, Denmark; Paris, France; Edinburgh, Scotland; and Turku, Finland). Semen analysis was standardized, inter-laboratory differences in assessment of sperm concentration were evaluated, and morphology assessment centralized. Lowest sperm concentrations and total counts were detected for Danish men, followed by French and Scottish men. Finnish men had the highest sperm counts. Men from Edinburgh had the highest proportion of motile spermatozoa, followed by men from Turku, Copenhagen and Paris. Only the differences between Paris/Edinburgh and Paris/Turku were statistically significant (P < 0.003 and P < 0.002 respectively). No significant differences in morphology were detected. A general seasonal variation in sperm concentration (summer 70% of winter) and total sperm count (summer 72% of winter) was detected. Semen quality of a 'standardized' man (30 years old, fertile, ejaculation abstinence of 96 h) were estimated. Typically, sperm concentrations (x 10(6)/ml) for winter/summer were: Turku 132/93; Edinburgh 119/84; Paris 103/73; and Copenhagen 98/69. These differences in semen quality may indicate different environmental exposures or lifestyle changes in the four populations. However, it remains to be seen whether such changes can account for these differences. These data may also serve as a reference point for future studies on time trends in semen quality in Europe.

Adult↗
PubMed2000

Inter-observer variation in the results of the clinical andrological examination including estimation of testicular size.

Inter-observer variation in andrological examination by 10 clinical investigators from five Nordic and Baltic countries was investigated. In addition, information on intra-observer variation was obtained for six of the 10 investigators. Testicular size was measured using Prader's orchidometer and one of the investigators also performed an ultrasound estimate of testicular size. A highly significant difference (p < 0.001) between observers was found with an inter-observer error of 16% in estimating testicular size in 23 young men. The difference in the estimate tended to increase with increasing testicular size. There was no significant intra-observer difference in two measurements performed on consecutive days. Only differences in median testis size, which were greater than 31% between measurements by two investigators, were found to be significant at the 5% level. The ultrasound estimate of testicular size was significantly lower than the orchidometer estimate, with a mean difference of 3.6 mL for the left testis and 4.3 mL for the right testis. Tanner staging of genitalia and diagnosis of a varicocele was subject to great inter-observer variation, and for the diagnosis of varicocele only one-third of the investigators was able to reproduce their results on a second examination. In conclusion, it was found that the clinical andrological examination of young men is subject to great inter-observer variation. This should be kept in mind when results from different studies are compared as well as in daily clinical practice.

Adult↗
PubMed2000

High frequency of sub-optimal semen quality in an unselected population of young men.

Male reproductive function seems to have deteriorated considerably during the past 4-5 decades. However, studies of the reproductive function in unselected populations have not previously been reported. As the large majority of young men in Denmark are subjected to a compulsory medical examination for military service, this provided a unique opportunity to study the reproductive function in an unbiased population. Altogether 891 young men delivered a blood sample in which reproductive hormones were measured. From 708 of these men data were also obtained on semen quality and testis size. The median sperm concentration was 41 x 10(6)/ml (mean 57.4 x 10(6)/ml). Men with ejaculation abstinence above 48 h had slightly higher sperm concentrations (median 45 x10(6)/ml, mean 63.2 x 10(6)/ml), but even in this subgroup, 21 and 43% respectively had sperm counts below 20 x 10(6)/ml and 40 x 10(6)/ml. Among men with no history of reproductive diseases and a period of abstinence above 48 h, as many as 18 and 40% respectively had concentrations below 20 and 40 x 10(6)/ml. Sperm counts were positively correlated with testis size, percentage normal spermatozoa and inhibin B, and negatively correlated with percentage immotile spermatozoa and follicle stimulating hormone. Possible causes for this high frequency of young men with suboptimal semen quality are obscure and need to be explored. Whether these findings apply for young male populations of comparable countries remains to be seen.

Analysis of Variance↗
PubMed1999

Relationships between bone mineral density, serum vitamin D metabolites and calcium:phosphorus intake in healthy perimenopausal women.

OBJECTIVES: To determine the relationships between serum vitamin D metabolites, bone mass, and dietary calcium and phosphorus in a cohort of 510 healthy Danish perimenopausal women. DESIGN: A population-based cross-sectional study. SUBJECTS: A total of 510 healthy women aged 45-58 years, with amenorrhoea for 3-24 months. None of the women was using hormone replacement therapy. MEASUREMENTS: Measurements of total bone mineral content and regional bone mineral density were performed by dual-energy X-ray absorptiometry. Analyses of serum levels of 25-OHD and 1,25-(OH)2D, intact PTH, ionized calcium and phosphate, as well as biochemical markers of bone turnover in blood and urine. Assessment of calcium and phosphorus intake using dietary records. RESULTS: A consistent inverse relationship between serum 1,25-(OH)2D and bone mineral content/ density was found in whole-body mineral content (P = 0.001), spine (P = 0.005) and femoral neck (P<0.05). There was a positive relationship between levels of 1,25-(OH)2D and biochemical bone markers, indicating that high levels of 1,25-(OH)2D are accompanied by increased bone turnover. The dietary calcium:phosphorus ratio was inversely related to serum 1,25-(OH)2D (P = 0.04) and positively related to bone mineral density (P<0.0005). No relationships could be detected between levels of PTH, serum ionized calcium and phosphate, and serum vitamin D metabolites. CONCLUSION: Within normal physiological range, elevated levels of 1,25-(OH)2D were associated with decreased bone mineral density and content, reduced calcium:phosphorus ratio in the diet and increased bone turnover.

Absorptiometry, Photon↗
PubMed1999

Expression of anti-Müllerian hormone during normal and pathological gonadal development: association with differentiation of Sertoli and granulosa cells.

The ontogeny of expression of anti-Müllerian hormone (AMH) was examined by immunohistochemistry in 135 human gonadal tissue specimens of various developmental age, ranging from 6 weeks of fetal development to 38 yr of postnatal age. The series included specimens from normal testes and ovaries and from individuals either with pathological conditions affecting gonadal development or with idiopathic infertility manifested as azoospermia or severe oligozoospermia. AMH expression was found only in Sertoli and granulosa cells. A 6-week-old fetal testis at the indifferent gonad stage did not yet express AMH. The protein was first visible at 8.5 weeks of development, when sex cords have not yet been formed. Afterward, a majority of testicular specimens, including those from pathological conditions, strongly expressed AMH through fetal development and childhood until puberty. Markedly prolonged expression of AMH was observed in a 20-yr-old 46,XY female with androgen insensitivity syndrome, who retained prepubertal testicular morphology. In normal testes, the switch-off of AMH expression was usually associated with the appearance of primary spermatocytes, suggesting that their presence had an inhibitory effect on AMH. However, in adolescent boys lacking germ cells because of cancer treatment and in a majority of infertile adult men with idiopathic germ cell aplasia, AMH expression was also down-regulated despite the complete lack of spermatogenesis. The decrease in AMH expression thus reflects the terminal differentiation of Sertoli cells and is probably only partially dependent upon a regulatory factor associated with the onset of meiosis. In fetal ovaries, AMH was first detected at 36 weeks gestation in granulosa cells of preantral follicles. Thus, the onset of ovarian expression is at the end of fetal life and not in infancy as previously reported.

Adolescent↗
PubMed1998

Germ cell cancer and disorders of spermatogenesis: an environmental connection?

Why is there a small peak of germ cell tumours in the postnatal period and a major peak in young age, starting at puberty? And, paradoxically, small risk in old age, although spermatogenesis is a lifelong process? Why is this type of cancer more common in individuals with maldeveloped gonads, including undescended testis, gonadal dysgenesis and androgen insensitivity syndrome? Why has there, during the past 50 years, been a quite dramatic increase in testicular cancer in many developed countries? These are just a few of many questions concerning testicular cancer. However, the recent progress in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which is a neoplastic caricature of embryonic growth. We consider the possibility that CIS cells may loose their stem cell potential with ageing. Along these lines, a seminoma is regarded a gonocytoma where the single gonocytes have little or no stem cell potential. The Sertoli and Leydig cells, which are activated postnatally and during and after puberty, may play a crucial role for both the development of the CIS gonocyte and progression of the neoplasm to invasiveness. The reported increase in testicular cancer is not the only sign that male reproductive health is at risk. There are reports that undescended testis and hypospadias have become more common. Also semen quality has deteriorated, at least in some countries. The epidemiological evidence suggests that environmental factors may play a role. Are the environmental hormone disrupters (e.g. DDT, PCB, nonylphenol, bisphenol A) to be blamed for the apparently synchronised deterioration in these aspects of male reproductive health?

Adult↗
PubMed1998

Developmental arrest of germ cells in the pathogenesis of germ cell neoplasia.

Clinical observations and epidemiological evidence suggest that important aetiopathological events that cause neoplastic transformation of the male germ cell may occur in fetal life or early infancy. The incidence of germ cell neoplasia is high in individuals with various disorders of gonadal development and sexual differentiation, such as gonadal dysgenesis or androgen insensitivity syndrome. Increased risk has also been noted in individuals with trisomy 21, idiopathic infertility and low birth weight. Infertility is sometimes associated with small aberrations of sex chromosomes (e.g. low frequency mosaicism XY/XO) which can also be found in patients with testicular cancer. The variety of conditions that predispose to testicular neoplasia and the rise in its incidence in many countries speaks for the influence of environmental factors which may affect genetically predisposed individuals. We hypothesise that if the development of the testis is disturbed or delayed, primordial germ cells or gonocytes undergo maturation delay or differentiation arrest which may render them susceptible to neoplastic transformation. Morphologically homogenous premalignant carcinoma in situ (CIS) cells have the potential to differentiate into a variety of histological forms of overt testicular tumours. Analysis of cell surface antigens expressed by CIS cells found in the vicinity of pure and mixed tumours demonstrates that CIS cells are phenotypically heterogeneous. Comparison of the phenotypes of CIS cells, primordial germ cells, human embryonal carcinoma cells and closely related primate embryonal stem cells reveals various similarities but also differences. We speculate that phenotypical heterogeneity of CIS cells may be associated with their potential to give rise to different tumour types, and may be related to the developmental stage of the early germ cell which has undergone malignant transformation.

Adult↗
PubMed1997

Heterogeneity of gonadoblastoma germ cells: similarities with immature germ cells, spermatogonia and testicular carcinoma in situ cells.

Gonadoblastoma is defined as a neoplasm containing nests of germ cells and cells resembling Sertoli cells or granulosa cells. Gonadoblastomas arise almost exclusively in dysgenetic gonads. They are associated with an increased risk of developing germ cell tumours. Testicular germ cell tumours in adults are preceded by carcinoma in situ cells, which are characterized by their morphology, by their immunohistochemical expression of placental-like alkaline phosphatase, the proto oncogene c-kit and/or epitopes for the monoclonal antibodies M2A, 43-9F and TRA-1-60, and by their aneuploid DNA content. In order to elucidate if gonadoblastomas are in situ neoplasms from the beginning, showing similarities with carcinoma in situ cells in otherwise normal testes, we investigated the germ cells in gonadoblastomas for their expression of the immunohistochemical markers of carcinoma in situ cells from six patients aged 8 1/2 months to 20 years and 4 months. In addition, the DNA content of the germ cells from five of the six patients was also determined by densitometric measurement on Feulgen stained specimens. The germ cell populations were heterogeneous both within the same patient and between the patients. Expression of the testicular carcinoma in situ markers was detected in specimens from all the patients and germ cells with an aneuploid DNA distribution pattern in accordance with testicular carcinoma in situ cells were detected. However, apparently normal immature germ cells were also present in four of the patients of whom two also had germ cells with a morphology similar to normal spermatogonia. Thus, gonadoblastoma is most likely an in situ germ cell neoplasia from the beginning. It seems probable that the germ cell tumours associated with gonadoblastomas originate from the carcinoma in situ cells inside the gonadoblastoma. Our findings of carcinoma in situ cells in gonadoblastomas from children support the theory that the cells arose prenatally.

Adolescent↗
PubMed1997

Semen analysis performed by different laboratory teams: an intervariation study.

Some recent studies have indicated that sperm concentration has decreased during the last 50 years. However, comparisons between laboratories have revealed that geographical differences seem to exist and that any decrease may not be global. One point of criticism concerning comparison of results from different laboratories has been that some of the discrepancies detected could reflect the lack of standardized methods used in the different laboratories. Four teams, each consisting of one physician and one technician from groups which have recently published data on semen quality, met in order to evaluate the variability between their laboratories on semen analysis. Twenty-six fresh semen samples from unselected men were analysed. The groups analysed the samples according to the normal practice in their laboratories, using their own equipment. The variation between laboratories was estimated through a random effects model. For sperm concentration and semen volume assessment a remarkable consistency between laboratories was detected, in contrast to the very considerable inter-individual variation. For sperm motility and morphology assessments interlaboratory consistency was much poorer. In conclusion, evaluation of sperm motility and morphology characteristics requires further standardization in order to achieve comparable data from different laboratories. However, semen volume and sperm concentration are characteristics which can be compared reliably between laboratories, when similar methodologies are used.

Adolescent↗
PubMed1996

Prolonged expression of the c-kit receptor in germ cells of intersex fetal testes.

Stem cell factor (SCF) and its receptor Kit encoded by the c-kit proto-oncogene are crucial for the development and migration of primordial germ cells in rodents. The expression of Kit has been examined immunohistochemically in gonads obtained from five specimens of fetal tissues with intersex conditions which included 45,X/46,XY mosaicism; androgen insensitivity syndrome; and 46,XY/iso(p)Y mosaicism. Individuals with such disorders of sexual differentiation and Y-chromosome material carry a very high risk of developing testicular neoplasms. Fetal testicular germ cells of the intersex subjects expressed Kit at a later developmental age than controls, in which no Kit protein was detectable beyond the 15th week of gestation. This finding may indicate a disturbance of the chronology of germ cell development, or it may suggest a change of the regulation of c-kit expression in subjects with disorders of gonadal development.

Disorders of Sex Development↗
PubMed1995

Trends in incidence of testicular cancer in boys and adolescent men.

Several epidemiological studies have described increasing trends over time in the incidence of testicular cancer in adult men. Less attention has been given to the trends in young boys, adolescents and old men. This paper describes the incidence of testicular cancer in young boys (0-4 years) and adolescents (15-19 years) in Denmark, Norway and Sweden, and compares these trends with the corresponding data on adults. Although only small numbers were available, the data suggest that the incidence of testicular cancer in young boys has been constant, at a level around 0.5 per 100,000. This observation lends support to the idea that testicular cancer in young boys is aetiologically distinct from testicular cancer in adults. In all three populations we found a particularly high average annual increase in the incidence of testicular cancer in adolescents (around 6% per year). It is proposed that this increase is mainly caused by a secular trend towards earlier age at puberty.

Adolescent↗