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Declining sperm counts in the United States? A critical review.

PURPOSE: Recent reports suggest declining sperm counts in the United States. These reports did not include all available data and did not account for geographic variations noted in prior studies. We examined all available data on U.S. sperm counts and evaluated whether geographic variations account for the decline suggested. MATERIALS AND METHODS: We reviewed all 29 U.S. studies from 1938 to 1996 reporting manually counted semen analyses of 9,612 fertile or presumably fertile men. We determined mean sperm concentrations by geographic location with weighted analysis of variance, and assessed any changes with time by linear regression analysis. RESULTS: Mean sperm concentrations from New York were significantly higher than from all other U.S. cities (98.6 versus 71.6 x 10(6) sperm per cc, respectively, p = 0.006). There has been no statistically significant change with time for mean sperm concentrations reported from New York (p = 0.49) or from U.S. cities other than New York (p = 0.62). Analysis without separating by location revealed a decline (p = 0.047). CONCLUSIONS: Sperm concentrations are highest in New York compared to other U.S. cities. When accounting for this geographic difference and examining all available data, there appears to be no significant change in sperm counts in the U.S. during the last 60 years. Further studies addressing the causes of geographic variations are needed.

Humans↗

[Application of distilled water in sperm counting and hypoosmotic swelling test].

OBJECTIVE: To evaluate the application of distilled water in sperm-counting and hypoosmotic swelling test. METHODS: Thirty-seven semen samples were collected and each was diluted by distilled water and sodium acid carbonate-formaldehyde solution, respectively. Then the hemacytometer was used for sperm counting. Meanwhile, the percentage of swelled sperm diluted by distilled water was compared with the result of hypoosmotic swelling test recommended by WHO. Another 26 semen samples were diluted by distilled water and hypoosmotic swelling solution respectively, and the percentages of the swelled sperm were compared. RESULTS: There was no significant difference either between the sperm concentrations obtained by distilled water and sodium acid carbonate-formaldehyde solution (P > 0.05) or between the percentages of the swelled sperm diluted by distilled water and hypoosmotic swelling solution. CONCLUSION: Distilled water can not only replace sodium acid carbonate-formaldehyde solution for sperm-counting dilution but also be used as a hypoosmotic swelling solution.

Adult↗

Effect of zinc administration on plasma testosterone, dihydrotestosterone, and sperm count.

The effects of zinc therapy on plasma testosterone (T), dihydrotestosterone (DHT), and sperm count were studied in 37 patients with idiopathic infertility of more than five years duration. In the first group (T less than 4.8 ng/ml; 22 patients), T and DHT rose significantly after oral administration of zinc, as did the sperm count. Nine wives became pregnant, six within 3 months and three within 2 months of a second trial. In the second group (T greater than or equal to 4.8 ng/ml; 15 patients), T and sperm count were unaffected by zinc, while DHT increased significantly. There was no conception observed. The rationale of this treatment and the significance of the results are discussed.

Adult↗

Does smoking during pregnancy affect sons' sperm counts?

BACKGROUND: There has been an apparent decline in sperm density during the last 5 decades in Denmark, a country in which women have among the highest rates of smoking in Europe. We examined semen quality and sex hormones in men in relation to their mothers' tobacco smoking during pregnancy. METHODS: Male participants were selected from the population-based Danish Twin Registry and the Danish Civil Registration System as part of a study on hereditary and environmental determinants of semen quality. From November 1999 to May 2000 we collected one fresh semen and blood sample from each of 316 men. Data on prenatal tobacco exposure were obtained for 265 of these men from a questionnaire filled in by their mothers. RESULTS: Adjusting for age, current smoking status and other factors, sperm density was 48% lower(95% confidence interval = -69% to -11) among sons of mothers who smoked more than 10 cigarettes per day during pregnancy. Total sperm counts and levels of inhibin-B were also reduced among this group, whereas follicular stimulating hormone levels were somewhat higher (16% increase; 95% confidence interval = -13% to 54%). These effects were not seen in the lower smoking category (1-10 cigarettes per day). CONCLUSIONS: High levels of smoking (> 10 cigarettes per day) during pregnancy may be a partial explanation for the apparent secular decline and the geographic differences in sperm counts.

Adult↗

Effect of overdose zinc on mouse testis and its relation with sperm count and motility.

The purpose of this study was to investigate the effects of excessive zinc intake on the testes and on sperm count and motility in mice. Thirty Balb c mice were divided randomly into 3 groups of 10 animals in each. Group I acted as controls; group II was supplied with drinking water containing 1.5 g/100 mL Zn, and group III was supplied with drinking water containing 2.5 g/100 mL Zn. The animals were sacrificed after 3 wk supplementation and the epididymis and testis were quickly excised. A negative correlation between Zn dose and sperm count and motility was found. The sperm count in group III was significantly lower than in groups II and I (p<0.05). The sperm motility in group III was significantly lower than in the controls (p<0.05). Degenerative changes, including spermatic arrest, degeneration of seminiferous tubules, and fibrosis in interstitial tissue, were observed in group III animals. These results show that high doses of zinc significantly alter sperm motility.

Animals↗

Sperm count, morphology and fluorescent body frequency in autopsy service workers exposed to formaldehyde.

A battery of monitoring tests that could indicate genetic damage was used to investigate occupational formaldehyde exposure in a population of a hospital autopsy service workers. 11 exposed individuals and 11 matched controls were evaluated for sperm count, abnormal sperm morphology and 2F-body frequency. Subjects were matched for sex, age and customary use of alcohol, tobacco and marijuana. Additional information was collected on health, medications and other exposures to toxins. 10 subjects were employed for 4.3 months (range 1-11 months) prior to the first sample and 1 was employed for several years. Formaldehyde exposures were episodic but with a time weighed average between 0.61 and 1.32 ppm (weekly exposure range 3-40 ppm X h). Exposed and control subjects were sampled 3 times at 2-3 month intervals. Sperm morphology was also evaluated in B6C3F1 mice after 5 daily oral doses of 100 mg/kg formalin. No increase in abnormal morphology was detected in the treated animals. In humans, no statistically significant differences were observed between the exposed and control groups for the observed variables. Reduced sperm count correlated with increased abnormal morphology and 2F-body frequency in the exposed group but not in the control group. Evaluation of the impact of incidental exposures suggests a reduced count with marijuana use and increased abnormal morphology with medications used by controls. No effects on sperm were seen from formaldehyde or its metabolites in this population after occupational exposure, nor in mice following a high acute exposure. It is possible that minor effects might have occurred. The lack of an effect in this study may be due to a lack of statistical power to detect effects at this exposure level.

Air Pollutants, Occupational↗

Pachytene pairing and sperm counts in mice with single Robertsonian translocations and monobrachial compounds.

Data on testis weights, sperm counts, and synaptonemal complexes are presented for mice carrying the following Robertsonian translocations: Rb(6.15)lAld; Rb(4.6)2Bnr; Rb(4.15)4Rma; Rb(6.15)lAld/Rb(4.6))2Bnr, which is male-sterile; and Rb(6.15)lAld/Rb(4.15)4Rma, which is male-fertile. In RblAld/Rb2Bnr sperm were absent or sparse, whereas the sperm count in RblAld/Rb4Rma was just over 50% of the parental value. The translocated chromosomes appeared as fully paired bivalents in homozygotes, as trivalents in single heterozygotes, and as quadrivalents in compounds. About 20-40% of trivalents had unsynapsed ends. The proportion of quadrivalents with unsynapsed ends was about 85% in the male-sterile compound, compared with 75% in the male-fertile compound. The proportion of quadrivalents associated with XY was about 70% in both. Testis weights, but not sperm counts, were found to differ in two of three reciprocal crosses. It is concluded that, in addition to pairing failure and autosome/XY association, the effect of translocations on spermatogenesis is affected by other factors, including genetic background, inbreeding, and perhaps environmental factors. It remains to be elucidated whether pairing failure and XY association are primary or secondary effects.

Animals↗

The concentrations of transferrin, beta 2-microglobulin, and albumin in seminal plasma in relation to sperm count.

A number of studies have shown a relationship between transferrin levels in seminal plasma and sperm count. In the present study, the levels of transferrin, beta 2-microglobulin and albumin were measured in 171 samples of seminal plasma (50 subjects with normal sperm count; 32 with azoospermia; 49 with oligozoospermia; 10 with polyzoospermia; and 31 vasectomized). All three proteins were related to sperm count. It is concluded that there is a general relationship between seminal plasma proteins and sperm numbers and that some products of the sperm themselves must control the entry of plasma proteins into seminal plasma.

Humans↗

[Fibronectin and hyaluronic acid in seminal fluid: relationship with sperm count and percentage of typical forms].

Two components of the extra cellular matrix, hyaluronic acid (HA) and fibronectin (Fbn), were assessed in the seminal fluids of 29 patients submitted for diagnosis of infertility. The concentrations of HA and Fbn were elevated in seminal plasma in comparison to their ranges of concentration in normal sera. No correlations were found between seminal Fbn and sperm count per ml and/or ejaculate, normal sperm cytology and multiple anomaly index (MAI). The concentrations of HA were negatively correlated with sperm count per ml (p < 0.01, r = -0.5) and ejaculate (p < 0.005, r = -0.5), and also with sperm cytology (p < 0.001, r = -0.6). A positive correlation was found between seminal concentrations of HA and MAI (p < 0.001, r = +0.7). It seems that high seminal HA concentrations were in relation with the bad results of sperm count and sperm cytology. These data suggest that spermatozoon could be implicated, in part, in the seminal HA metabolism.

Fibronectins↗

Postulated human sperm count decline may involve historic elimination of juvenile iodine deficiency: a new hypothesis with experimental evidence in the rat.

Human sperm count studies, historic dietary iodination, and an animal model where neonatal goitrogen administration causes unprecedented testis enlargement, together suggest an hypothesis relevant to the postulated fall in human sperm counts. We present the hypothesis with a supporting study extending the model to include iodine deficiency. In a one-generation rat reproduction study, dams were fed an iodine sufficient (control, 200 ppb I) or deficient (low iodine diet [LID], <20 ppb I) diet from prebreeding through weaning, when male offspring were divided into three groups: 1) controls from iodine sufficient dams, 2) neonatal LID (NLID) from the LID dams, fed control diet postweaning, and 3) chronic LID (CLID) from LID dams, fed a moderate LID (40 ppb I) postweaning. F1 males were euthanized on postnatal day (PND) 133+/-1. Each of the three diet groups comprised two subgroups in which testicular parameters were evaluated: 1) daily sperm production (DSP), sperm motility, morphology, and histopathology, and 2) Sertoli cell and round spermatid morphometry. In the first subgroup, NLID and CLID testes weights were 8.5% and 14.0% heavier than their unusually heavy controls (3.921 g; historical control mean approximately 3.5 g), with proportional DSP increases. Sperm motility, morphology, and testis histopathology were unaffected. In the morphometry subgroup, respective increases in NLID and CLID rats included testes weights (+28.6% and +20.3%), Sertoli cells (+24.8% and +23.9%), and round spermatids (+20.4% and +15.8%). The results indicate that neonatal iodine deficiency can significantly increase spermatogenic function in rats, and support our hypothesis concerning human sperm counts.

Animals↗

Effects of time of insemination relative to ovulation, as determined by ultrasonography, on fertilization rate and accessory sperm count in sows.

The effects of the timing of insemination relative to ovulation on fertilization rate, accessory sperm count and early embryo development were studied in sows. Oestrus detection was performed at intervals of 8 h. Sows were artificially inseminated once with 3 x 10(9) spermatozoa. Transrectal ultrasonography was performed at intervals of 4 h to determine when ovulation occurred and sows were killed at 120 +/- 6 h after ovulation. For each insemination-ovulation interval of 8 h, fertilization rates were as follows: > 48 h, 35% (n = 1); 48-40 h, 51 +/- 36% (n = 6); 40-32 h, 54 +/- 36% (n = 14); 32-24 h, 79 +/- 32% (n = 19); 24-16 h, 94 +/- 11% (n = 24); 16-8 h, 92 +/- 21% (n = 24); 8-0 h, 95 +/- 22% (n = 21) and for the sows that were inseminated after ovulation: 0 to -8 h, 75 +/- 38% (n = 26); -8 to -16 h, 74 +/- 43% (n = 15) and < -16 h, 0% (n = 1). The median accessory sperm count differed among the groups from 1 (insemination 40-48 h before ovulation) to 126 (insemination 0-8 h after ovulation) (P = 0.0001). Within each 8 h time interval, the normal embryos from sows with less than 90% normal embryos were less developed and had a lower sperm count than did the normal embryos from sows with more than 90% normal embryos (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Proliferating cell nuclear antigen in testes of infertile men with varicocele--preliminary results of interrelationship with sperm count before and after varicocelectomy.

OBJECTIVE: This study was conducted to assess germ cell kinetics and correlate them with sperm counts before and after varicocelectomy. MATERIAL AND METHODS: Forty-three testicular biopsy specimens were obtained from 47 patients with varicocele during varicocelectomy. Similar specimens were obtained from 8 fertile volunteers. All specimens were immunostained using anti-proliferating cell nuclear antigen (anti-PCNA) antibody. PCNA expression was evaluated by assessing its staining intensity (SI) and labeling index (LI). RESULTS: The varicocele specimens revealed significantly lower SI and LI than the controls. There was a significant correlation between initial sperm concentration and LI but not SI. Coexistence of LI > or = 31 and preoperative sperm count > 1 million/ml correlated with a significant rise in the postoperative sperm count. CONCLUSIONS: PCNA is a useful molecular marker for assessing germ cell kinetics in varicocele patients. The decline in DNA synthesis, as suggested by the lower PCNA SI and LI in varicocele specimens, could be a reason for the disordered spermatogenesis in these patients. PCNA LI may also be considered as a beneficial clinical marker and may help to predict the surgical outcome after varicocele repair.

Adult↗

Effect of low-dose testicular irradiation on sperm count and fertility in patients with testicular seminoma.

The treatment of seminoma with radiation therapy risks transient infertility. We have prospectively followed eight patients with stage I seminoma of the testicle. All patients underwent radical orchiectomy of the affected testis. The mean age of the patients was 32.9 years (range 24-40). Each patient was treated with megavoltage radiation with a 10- or 18-MV linear accelerator. The remaining testicle was shielded using a standard lead enclosure, and the mean testicular dose was 44 cGy (range 20.8-78.2). Semen specimens were delivered to the lab within 30 minutes of ejaculation. All specimens were analyzed using a computer-assisted sperm analyzer. Pretreatment parameters were within normal limits for all but one patient; one patient presented with a borderline normal sperm count at 18 and 22 x 10(6)/ml. Following treatment, there was a decrease in sperm count, detected at 3 months, to < 10 x 10(6)/ml (range 4.4- 8.6 x 10(6)) in all patients except one, who presented with an initial pretreatment count of 189 x 10(6)/ml, which decreased to 58 x 10(6)/ml at 3 months, 32 x 10(6)/ml at 6 months, and rose to 325 x 10(6)/ml by 12 months following treatment. Although the sperm count for this patient (D.L.) was within the normal range, the post-radiation sperm count was less than 20% of the pretreatment count. There was no difference in the motility at 3 months, the mean of which was 51.3%. One patient's (F.C.) wife conceived at 9 months following treatment, one at 12 months (J.R.), and one (J.S.) at 14 months, and all have delivered normal infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sperm counts and serum follicle-stimulating hormone levels before and after radiotherapy and chemotherapy in men with testicular germ cell cancer.

Sperm counts were low (median, 15 X 10(6) per ejaculate) and serum follicle-stimulating hormone (FSH) levels were moderately elevated (median, 31 IU/l) after unilateral orchiectomy and immediately before radiotherapy and chemotherapy in 34 patients with seminomas and 20 patients with nonseminomatous germ cell tumors. The scattered radiation (0.2 to 1.3 Gray [Gy]) reaching the remaining testicle during radiotherapy caused azoospermia in more than two thirds of the patients. A median of 540 days elapsed after the end of treatment before spermatozoa were again found in semen samples, while a median of 1250 days passed before the pretreatment sperm count was reached. One to 5 years after treatment, sperm counts were still low (median, 6 X 10(6) per ejaculate) and serum FSH was elevated (median, 61 IU/l). The adjuvant chemotherapy given to the 20 patients with nonseminomatous tumors did not appear to affect restitution appreciably.

Adult↗

Relationship of seminal plasma testosterone and dihydrotestosterone to sperm count and motility in man.

A radioimmunoassay previously described for serum T and DHT was adapted for use in the measurement of these hormones in seminal plasma. The seminal plasmas of 273 semen specimens were assayed for T and DHT concentration. Mean levels of these hormones for various sperm count and sperm motility categories were determined. We found that: (1) the DHT level of the azoospermic group was significantly lower than all other groups; (2) the T level of the group whose mean sperm count exceeded 40 x 10(6)/ml was higher than that of all other groups; (3) the DHT level of the group with absent sperm motility was lower than the level of all other groups; and (4) changes in sperm motility were not accompanied by changes in T levels. We concluded that idiopathic male subfertility as evidenced by oligospermia, azoospermia, and decreased sperm motility may be related to insufficient androgen production due to a primary intratesticular defect.

Cell Count↗

Improvement of sperm count and motility after ligation of varicoceles detected with colour Doppler ultrasonography.

The debate regarding the efficacy of varicocele ligation for improvement of semen parameters and pregnancy rates is ongoing. In addition, no consensus exists as to the benefit of treatment of subclinical varicoceles. The aim of this study was to investigate, retrospectively, the effect of high ligation of both subclinical and clinical varicoceles on sperm count and motility. The value of several factors from history-taking and physical examination for the prediction of successful varicocelectomy was analysed. A total of 139 patients, operated on for a unilateral varicocele on the left side, were studied. Varicoceles were subclinical in 73 patients, based on colour Doppler ultrasonography, and 66 varicoceles were clinical, based on palpation in addition to ultrasonography. Comparison of semen parameters before and after surgery revealed a significant improvement. The median sperm count increased from 10.0 to 14.7, and from 18.2 to 28.6 million/ejaculate, in patients with subclinical and clinical varicoceles, respectively (p < 0.001). The percentage improvement in median sperm count in subclinical varicoceles was not statistically different from the improvement in clinical varicoceles. Mean progressive motility improved significantly after ligation (p < 0.001). The improvement in motility in subclinical varicoceles, from 16 to 23%, was significantly larger than the 24 to 27% improvement in clinical varicoceles. The increase in sperm count was related positively to testicular volume before surgery (p < 0.05). The increase in sperm motility was significantly lower in patients with a history of cryptorchidism (n = 22, p < 0.05). The present data show that ligation of varicoceles detected using Doppler ultrasonography, whether palpable or not, results in an increase in sperm concentration and motility.

Adult↗

Effect of the total motile sperm count on the efficacy and cost-effectiveness of intrauterine insemination and in vitro fertilization.

OBJECTIVE: To determine prognostic factors for achieving a pregnancy with intrauterine insemination (IUI) and IVF. To compare the effectiveness and cost-effectiveness of IUI and IVF based on semen analysis results. DESIGN: Retrospective cohort study. SETTING: Academic university hospital-based infertility center. PATIENT(S): One thousand thirty-nine infertile couples undergoing 3,479 IUI cycles. Four hundred twenty-four infertile couples undergoing 551 IVF cycles. INTERVENTION(S): IUI and IVF treatment. MAIN OUTCOME MEASURE(S): Multiple logistic regression analysis was used to assess the significance of prognostic factors including a woman's age, gravidity, duration of infertility, diagnoses, use of ovulation induction, and sperm parameters for predicting the outcomes of clinical pregnancy and live birth rate after the first cycle of IUI and IVF. The relative effectiveness and cost-effectiveness of these treatments were then determined based on sperm count results. RESULT(S): Female age, gravidity, and use of ovulation induction were all independent factors in predicting pregnancy after IUI. The average total motile sperm count in the ejaculate was also an important factor, with a threshold value of 10 million. For IVF, only female age was an important predictor for both clinical and ongoing pregnancy. When the average total motile sperm count was under 10 million, IVF with ICSI was more cost-effective than IUI in our clinic. CONCLUSION(S): An average total motile sperm count of 10 million may be a useful threshold value for decisions about treating a couple with IUI or IVF.

Adult↗