[Treatment of male infertility].

Impaired male fertility contributes to at least 50% of cases of couple infertility. Azoospermia is found in 1-2% of the male population. In the diagnostic workup, genetic and endocrine as well as lifestyle factors may be considered. Spermatozoa can be retrieved surgically in many cases of azoospermia, aspermia and difficult cases of retrograde ejaculation. Such spermatozoa can be used for injection into the oocytes of the female partners by intracytoplasmic sperm injection. Treatment with follicle stimulating hormone is only indicated in hypogonadotrophic hypogonadism. This review is a summarisation of the current male infertility treatment modalities.

A history of cryptorchidism is associated with impaired testicular function in early adulthood: a cross-sectional study of 6376 men from the general population.

STUDY QUESTION: Is there a difference in testicular function in early adulthood between men born with cryptorchidism and men born with normally descended testes? SUMMARY ANSWER: In men from the general population, a history of cryptorchidism was associated with lower total testis volume and impaired semen quality as well as altered serum levels of reproductive hormones. WHAT IS KNOWN ALREADY: The association between cryptorchidism and testicular function is well documented in studies based on sub-fertile or infertile men recruited from a clinical setting. However, the association has not previously been investigated in men from the general population, who were unselected regarding fertility status. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional population-based study of 6376 young Danish men examined from 1996 to 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study is based on young men from the greater Copenhagen area, Denmark (median age of 19 years) who were unselected regarding fertility status and semen quality. The young men delivered a semen sample, had a blood sample drawn and underwent a physical examination including assessment of testis volume. Participants completed a questionnaire regarding cryptorchidism at birth, current lifestyle and their mother's pregnancy, after consulting their mother. The differences in markers of testicular function, including testis volume, semen parameters and reproductive hormones between men with and without a history of cryptorchidism were investigated with multiple linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The participation rate was 24% for the entire study period. Overall, a history of cryptorchidism was associated with reduced testicular function. In the adjusted models, a history of cryptorchidism was associated with a 3.5 ml lower total testis volume, determined by orchidometer (P < 0.001), 28% lower sperm concentration (95% CI: -37 to -20) and 26% lower inhibin B/FSH ratio (95% CI: -50 to -22) compared to men without a history of cryptorchidism, suggesting a reduced spermatogenetic capacity. Men with a history of cryptorchidism also had a slightly reduced Leydig cell function expressed as a 6% lower testosterone/LH ratio (95% CI: -12 to -0.7). The significant effect sizes and different markers of testicular function pointing in the same direction across the different models based on a large sample size support that the results are not chance findings. LIMITATIONS, REASONS FOR CAUTION: Information on cryptorchidism at birth and treatment modus was obtained by retrospective self-report, and each participant only delivered one semen sample. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that men with a history of cryptorchidism could be at increased risk of experiencing fertility problems. However, among these men there is a wide variation in semen quality and further research is needed in order to identify the subgroup of boys born with cryptorchidism who are at the greatest risk of impaired semen quality when reaching adulthood. STUDY FUNDING/COMPETING INTEREST(S): The study received financial support from the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603. FP7/2007-2013, DEER Grant agreement no. 212844); the Danish Ministry of Health; the Danish Environmental Protection Agency; A.P. Møller and wife Chastine McKinney Møllers Foundation; and Svend Andersens Foundation. None of the founders had any role in the study design, collection, analysis or interpretation of data, writing of the paper or publication decisions. The authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Selection of High-Quality Spermatozoa May Be Promoted by Activated Vitamin D in the Woman.

Context: The vitamin D receptor (VDR) and enzymes involved in activation (CYP2R1, CYP27B1) and inactivation (CYP24A1) of vitamin D are expressed in ovary, testes, and spermatozoa. Objective: Determine responsiveness to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in spermatozoa from normal and infertile men, and identify the site of exposure and how 1,25(OH)2D3 influences sperm function. Design: Spermatozoa expressing VDR, CYP2R1, CYP27B1, and CYP24A1 were analyzed in normal and infertile men. 25-Hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D3], and 1,25(OH)2D3 were measured in serum, seminal fluid, cervical secretions, and ovarian follicular fluid. 1,25(OH)2D3 was tested on human spermatozoa. Setting: Tertiary center for fertility. Participants: Protein expression in spermatozoa and semen quality were assessed in 230 infertile and 114 healthy men. Vitamin D metabolites were measured in fluids from 245 men and 13 women, while 74 oocytes and 17 semen donors were used for sperm-function tests. Main Outcome Measures: VDR and CYP24A1 expressions in spermatozoa, fluid concentrations of 25-OHD, 24,25(OH)2D3, and 1,25(OH)2D3, and 1,25(OH)2D3-induced effects on intracellular calcium concentration ([Ca2+]i) and sperm-oocyte binding in vitro. Results: VDR and CYP24A1 were expressed in a >2-fold higher fraction of spermatozoa from normal than infertile men (P < 0.01). Concentrations of 25-OHD, 24,25(OH)2D, and 1,25(OH)2D3 were undetectable in seminal fluid but high in ovarian follicular fluid. Follicular concentrations of 1,25(OH)2D3 induced a modest increase in [Ca2+]i and sperm-oocyte binding in vitro (P < 0.05). Conclusion: Presence of VDR and CYP24A1 mainly in spermatozoa of higher quality supports that 1,25(OH)2D3 available in the female reproductive tract may promote selection of the best gametes for fertilization.

Varicocele Is Associated with Impaired Semen Quality and Reproductive Hormone Levels: A Study of 7035 Healthy Young Men from Six European Countries.

BACKGROUND: Present knowledge on the impact of varicoceles on testicular function is largely based on studies of subfertile and infertile men, making it difficult to extrapolate the impact of varicocele on the general population. OBJECTIVE: To describe associations between varicocele and testicular function assessed by semen analysis and reproductive hormones in men from the general population. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional multicentre study of 7035 young men, median age 19 yr, from the general population in six European countries (Denmark, Finland, Germany, Estonia, Latvia, and Lithuania) were investigated from 1996 to 2010. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analysed results from physical examination, conventional semen variables, and serum reproductive hormones using multivariable regression analyses. RESULTS AND LIMITATIONS: A total of 1102 (15.7%) had grade 1-3 varicocele. Increasing varicocele grade was associated with poorer semen quality, even in grade 1 varicocele. In grade 3 varicocele, sperm concentration was less than half of that in men with no varicocele. Presence of varicocele was also associated with higher serum levels of follicle-stimulating hormone, lower inhibin B, and higher levels of luteinising hormone; testosterone and free testosterone were not significantly different between men with and without varicocele. This study cannot draw a conclusion on the progressiveness of varicocele or the effect of treatment. CONCLUSIONS: We demonstrated an adverse effect of increasing grade of varicocele on testicular function in men not selected due to fertility status. PATIENT SUMMARY: The presence and increasing grade of varicocele is adversely associated with semen quality and reproductive hormone levels in young men from the general population.

Fertilization failure after IVF in 304 couples--a case-control study on predictors and long-term prognosis.

OBJECTIVES: To identify predictors of total fertilization failure (TFF) and thereby optimize the primary allocation of patients with no well-defined male factor to either IVF or intracytoplasmatic sperm injection (ICSI). Further, to evaluate the long-term fertility prognosis of couples experiencing TFF. STUDY DESIGN: A retrospective case-control study including 304 couples with TFF and 304 controls with fertilization after IVF during a 10-year period from year 2000-2010. The controls were the patients with minimum one fertilized oocyte just prior to the cases. Multiple logistic regression analysis was used to evaluate the predictors of TFF. RESULTS: The multiple regression analysis identified the following independent predictors of TFF: female smoking, adjusted odds ratio (AOR) 1.7 (95% CI 1.1-2.3), non-tubal factor AOR 2.2 (95% CI 1.5-3.4), progressive motile spermatozoa after preparation × 10(6)/ml (Log2 scale) AOR 1.4 (95% CI 1.2-1.6). For every oocyte, decreasing from four to one oocytes, the risk of TFF increased with AOR 2.0 (95% CI: 1.5-2.9) and from seven to four oocytes with AOR 1.2 (95%CI: 1.0-1.3), respectively. In case of more than seven oocytes the risk of TFF did not vary significantly by the number of oocytes. Female age, BMI, duration of infertility, earlier natural or IUI conceptions were not predictors of TFF. After a minimum of 30 months of follow-up from the index cycle, 50% of the TFF patients succeeded in a live childbirth compared with 70% of the controls. Only thirty five percent of the total number of births in the TFF patients was after ICSI. CONCLUSION: The risk of TFF is associated with the number of available oocytes for fertilization, female smoking, non-tubal factor infertility and an apparently minor sperm factor. However, anticipated predictors like advanced female age, duration of infertility and earlier conceptions proved not to have any predictive value. Couples experiencing TFF have a significantly reduced overall long-term chance of live birth compared with controls.

[Male infertility]. / Mandlig infertilitet.

In recent years approximately 8% of the newborn Danes have been conceived by infertility treatment, and approximately half of the cases are due to male subfertility. Male infertility can be caused by several factors, and only in about half of the cases is it possible to disclose an aetiological explanation. It is important to elucidate possible reasons for male infertility as low semen quality might be a symptom of pituitary dysfunction, genetic disorders or testicular cancer.

Human semen quality in the new millennium: a prospective cross-sectional population-based study of 4867 men.

OBJECTIVES: Considerable interest and controversy over a possible decline in semen quality during the 20th century raised concern that semen quality could have reached a critically low level where it might affect human reproduction. The authors therefore initiated a study to assess reproductive health in men from the general population and to monitor changes in semen quality over time. DESIGN: Cross-sectional study of men from the general Danish population. Inclusion criteria were place of residence in the Copenhagen area, and both the man and his mother being born and raised in Denmark. Men with severe or chronic diseases were not included. SETTING: Danish one-centre study. PARTICIPANTS: 4867 men, median age 19 years, included from 1996 to 2010. OUTCOME MEASURES: Semen volume, sperm concentration, total sperm count, sperm motility and sperm morphology. RESULTS: Only 23% of participants had optimal sperm concentration and sperm morphology. Comparing with historic data of men attending a Copenhagen infertility clinic in the 1940s and men who recently became fathers, these two groups had significantly better semen quality than our study group from the general population. Over the 15 years, median sperm concentration increased from 43 to 48 million/ml (p=0.02) and total sperm count from 132 to 151 million (p=0.001). The median percentage of motile spermatozoa and abnormal spermatozoa were 68% and 93%, and did not change during the study period. CONCLUSIONS: This large prospective study of semen quality among young men of the general population showed an increasing trend in sperm concentration and total sperm count. However, only one in four men had optimal semen quality. In addition, one in four will most likely face a prolonged waiting time to pregnancy if they in the future want to father a child and another 15% are at risk of the need of fertility treatment. Thus, reduced semen quality seems so frequent that it may impair the fertility rates and further increase the demand for assisted reproduction.

Trends in the use of intracytoplasmatic sperm injection marked variability between countries.

BACKGROUND: ICSI is used increasingly often compared with standard IVF. The aim of the present study was to analyse the changes in the use of ICSI, and discuss possible causes and consequences. METHODS: Data from National and Regional registers were analysed for trends in the use of ICSI and indications for assisted reproductive technology (ART). RESULTS: The use of ICSI increased from 39.6% of ART cycles in 1997 to 58.9% in 2004 (USA 57.5%, Australia/New Zealand 58.6%, Europe 59.3%). The Nordic countries, the Netherlands and the UK used ICSI to a low extent (40.0-44.3%), whereas Austria, Belgium and Germany (68.5-72.9%) and the southern European countries like Greece, Italy and Spain used ICSI frequently (66.0-81.2%). The marked increase in the proportion of ICSI cycles seems primarily due to an increased use in couples classified as having mixed causes of infertility, unexplained infertility and advanced age together with a relative decline in tubal factor infertility. An absolute increase in the prevalence of couples with impairment in semen quality remains a possibility. CONCLUSIONS: ICSI is used increasingly, but huge differences exist between countries within Europe. It is not possible to determine specific factors that explain the differences. As ICSI does not give higher pregnancy rates than IVF in couples without male factors, and as it adds additional costs, infertile couples and society may benefit from a less frequent use of ICSI in some countries.

Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes.

OBJECTIVE: The regulation of normal sexual maturation and reproductive function is dependent on a precise hormonal regulation at hypothalamic, pituitary, and gonadal levels. The aim of this study was to investigate the neuroendocrine integrity of the pituitary-gonadal axis in patients with primary testicular failure due to supernumerary X chromosomes. DESIGN: Cross-sectional study. METHODS: In this study, 7 untreated patients with primary gonadal insufficiency due to SRY-positive 46,XX (n=4) and 46,XXY karyotypes (n=3) aged 18.8 years and 25 age-matched healthy controls participated. Reproductive hormones, testicular size, and overnight LH and FSH serum profiles and overnight urine LH and FSH excretion were determined. RESULTS: Basal LH and FSH secretion was elevated 6.3- and 25.4-fold respectively in the patients and the amount of LH and FSH secreted per burst were 2.0- and 6.6-fold elevated. We found significantly more LH but not FSH peaks per 24 h, as estimated by the Weibull lambda analysis. There was no difference between approximate entropy ratios or Weibull gamma analyses indicating comparable orderliness and regularity of LH and FSH secretion. Overnight urinary LH and FSH excretion was significantly elevated in patients compared with controls and correlated significantly with calculated total overnight LH and FSH secretion respectively, thus validating deconvolution. CONCLUSION: In this group of patients with severe hypergonadotropic hypogonadism due to a supernumerary X chromosome, higher basal, pulsatile, and total LH and FSH secretion were associated with significantly more LH peaks per 24 h in comparison with healthy controls. Thus, our data indicate that in patients with Klinefelter syndrome and XX male karyotypes the entire hypothalamic-pituitary-gonadal axis has undergone functional changes.

Current approaches for detection of carcinoma in situ testis.

Testicular germ cell tumours have a favourable prognosis if detected early, but are potentially lethal in a subset of patients. Multi-modality treatment is often necessary, thus the preferable time of diagnosis is at the pre-invasive, but unfortunately often asymptomatic precursor stage of carcinoma in situ (CIS). This review describes current possible approaches for the detection of CIS. At present, an open testicular biopsy is the only definitive way of establishing the presence of CIS. The tissue section should be of an adequate size, be properly fixed, and evaluation be supported by at least one solid immunohistochemical marker, for example PLAP, OCT-3/4 or AP-2gamma. Determination of who should be offered testicular biopsies is based on clinical and ultrasonic examination along with the evaluation of risk factors. A surgical biopsy is an invasive procedure with potential complications, although rare. Therefore, a noninvasive and equally reliable method is needed. Testicular ultrasound is risk-free, painless and at present the only noninvasive method of aid for andrologists when CIS is suspected. The presence of testicular microlithiasis is, in some cases, indicative of pre-malignant changes, especially in males with additional risk factors. Promising results have recently been obtained with a novel noninvasive detection method based on immunocytological AP-2gamma-staining of CIS cells in semen. This method could be a supporting method in andrology centres where careful follow-up is possible. In conclusion, one difficulty is to determine in which males CIS should be suspected; secondly, there does not as yet exist an optimal noninvasive method of diagnosis that is more acceptable than an open surgical biopsy.

Fertility treatment in male cancer survivors.

The present study reviews the use of assisted reproductive technology in male cancer survivors and their partners. As antineoplastic treatment with chemotherapy or radiation therapy, has the potential of inducing impairment of spermatogenesis through damage of the germinal epithelium, many male cancer survivors experience difficulties in impregnating their partners after treatment. The impairment can be temporary or permanent. While many cancer survivors regain spermatogenesis months to years after treatment, some become infertile with a-, oligo- or azoospermia. An option to secure the fertility potential of young cancer patients is to cryopreserve semen before cancer treatment for later use. A desired pregnancy may be obtained in couples where the husband has a history of cancer, using assisted reproductive technology with either fresh or cryopreserved/thawed semen. Successful outcomes have been obtained with intrauterine insemination (IUI) as well as in vitro fertilization (IVF) with or without the use of intracytoplasmic sperm injection (ICSI). In conclusion, male cancer survivors and their partners who have failed to obtain a pregnancy naturally within a reasonable time frame after end of treatment should be referred to a fertility clinic.

Self-rated health and semen quality among 3,457 young Danish men.

OBJECTIVE: To study the relationship between self-rated health (SRH) and semen quality. DESIGN: Cross-sectional study of men attending a compulsory physical examination to determine their fitness for military service from 1996 to 2005. SETTING: Young men were approached when they were summoned for a compulsory physical examination to determine their fitness for military service in two major Danish cities. PATIENT(S): A total of 3,457 Danish young men delivered a semen sample, had a physical examination performed, and responded to a questionnaire including a question about SRH. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen quality and testis size. RESULT(S): After control for confounders, men with good and poor SRH had, respectively, 0.5 mL (95% CI: -0.8, -0.1) and 0.8 mL (95% CI: -2.4, 0.8) smaller testes size compared to men with very good SRH, the trend was statistically significant. Men with good and poor SRH had, respectively, 12.2% (95% CI: -21.2%, -2.2%) and 26.9% (95% CI: -55.7%, 20.8%) lower total sperm count compared to men with very good SRH, the trend was statistically significant, and had +0.4% (-1.4%, 2.2%) and 1.4% (-3.5%, 0.7%) fewer morphologically normal sperms (trend statistically significant). Percentages of motile spermatozoa and semen volume were not significantly associated with SRH. CONCLUSION(S): We found significant associations between SRH and semen quality and testicular size. Given the cross-sectional study design, we cannot establish a causal relationship but argue that SRH may be associated with semen quality. Our findings need to be validated and confirmed with other study designs (preferably prospective) and in populations of different age structure and fertility status.

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.

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.

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.

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.

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.

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.