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Declining sperm count and fertility in males: an epidemiological controversy.

There have been several suggestions from different populations that sperm count has decreased in the past 20 years. Concerns have, however, been raised in the interpretation of these findings, particularly with regards to subject selection mechanisms and data-analysis. Furthermore, these findings are inconsistent with the reports that male infertility rates have remained constant during the past 3 decades. The increased number of men seeking consultation on infertility may only be the result of the tendency of couples to delay pregnancy and the increased availability of treatment. Moreover, sperm concentration is not always in itself the determinant of male fertility, so the use of sperm count as an indicator of male infertility in epidemiological studies should be considered with caution.

Humans↗

Sperm count and motility influence the results of human fertilization in vitro.

In order to select sperm characteristics that can predict the outcome of in-vitro fertilization-embryo transfer (IVF-ET), semen samples delivered in conjunction with this treatment were studied carefully. We have analysed these data retrospectively in relation to the outcome of treatment. Ninety-one couples were treated for tubal infertility by IVF-ET. Fifteen women became pregnant. Sperm were isolated from semen using a swim-up technique and in most cases 40-80 x 10(3) (range 20-120 x 10(3)) motile sperm per ovum were used for insemination. The couples were divided into three groups: group A who achieved pregnancies, group B who achieved cleaved ova but no pregnancies, and group C who achieved no ova that were cleaved 48 h after oocyte recovery. Comparisons between these groups showed that some characteristics of the native semen samples and the swim-up preparations were significantly different: the sperm concentration (P = 0.001) and total sperm count (P = 0.003) in the native sample, the number of sperm recovered during 30 min of swim-up (P = 0.001), and the specific progressive motility of sperm in the swim-up preparation, both at the time of insemination and on each day, up to 5 days thereafter (P = 0.002-0.028). No pregnancy was achieved with a sperm concentration below 26 x 10(6) ml-1 in the native sample. Some of the sperm characteristics studied in this paper may be of value in the pretreatment evaluation for IVF treatment.

Adult↗

The correlation between sperm count and testicular biopsy using a new scoring system.

Biopsies of 320 testes were evaluated and a new scoring system for describing testicular biopsies was used. This scoring system uses four criteria in the evaluation of the biopsy: the diameter of the tubules (D), the thickness of the peritubular membrane (M), the population of cells within the tubules (P), and the spermatogenic maturation degree (S). The score of each biopsy was correlated to the sperm count of each patient. A typical correlation between the biopsy score and the sperm count was found in cases with sperm count between 0 and 12 million/cc. The clinical value of the new scoring system in describing typical clinical syndromes and in the evaluation of the prognosis of treatment was emphasized.

Adult↗

Sperm count suppression without endocrine dysfunction in lead-exposed men.

To determine if increased lead absorption was associated with sperm count suppression or perterbation of the hypothalamopituitary system, we compared battery workers (N = 18), who were exposed to high airborne lead levels, with cement workers (N = 18), who were exposed to ambient lead levels. Blood lead, urinary lead, semen lead, and zinc protoporphyrin concentrations were markedly elevated (p less than .001) in battery workers. Battery workers had a significantly shifted (p less than .025) frequency distribution of sperm count (median count, 45 vs. 73 X 10(6) cells/cc, respectively). There were no significant differences between the two groups in mean follicle-stimulating hormone, testosterone, prolactin, luteinizing hormone, or total neutral 17-ketosteroid levels. Potential confounding factors (alcohol, cigarette, and coffee consumption, frequency of intercourse, and days of abstinence prior to semen donation) were not significantly different between the two groups. These results suggest a direct toxic effect of increased lead absorption on sperm production or transport in man.

Alcohol Drinking↗

Sperm count suppression without endocrine dysfunction in lead-exposed men.

To determine if increased lead absorption was associated with sperm count suppression or perterbation of the hypothalamopituitary system, we compared battery workers (N = 18), who were exposed to high airborne lead levels, with cement workers (N = 18), who were exposed to ambient lead levels. Blood lead, urinary lead, semen lead, and zinc protoporphyrin concentrations were markedly elevated (p less than .001) in battery workers. Battery workers had a significantly shifted (p less than .025) frequency distribution of sperm count (median count, 45 vs. 73 X 10(6) cells/cc, respectively). There were no significant differences between the two groups in mean follicle-stimulating hormone, testosterone, prolactin, luteinizing hormone, or total neutral 17-ketosteroid levels. Potential confounding factors (alcohol, cigarette, and coffee consumption, frequency of intercourse, and days of abstinence prior to semen donation) were not significantly different between the two groups. These results suggest a direct toxic effect of increased lead absorption on sperm production or transport in man.

Adult↗

Improved accuracy of sperm motility assessment using a modified Micro-Cell sperm counting chamber.

OBJECTIVE: To assess the effect of modifications made in the Micro-Cell sperm counting chamber on the motility of washed human spermatozoa. DESIGN: In a 2 x 2 experimental design, human sperm samples were washed with or without protein supplementation, loaded into modified or unmodified Micro-Cell chambers, and assessed by automated semen analysis for changes associated with sperm adhesion to the glass chamber surfaces. PARTICIPANTS: Twenty-one men who were undergoing semen analysis and presented with > or = 50% motile sperm, or normal donors. MAIN OUTCOME MEASURES: Reduced motility and elevated lateral head displacement associated with sperm adhesion to glass surfaces were compared using a doubly repeated measures analysis of variance. RESULTS: Addition of protein to the sperm washing solution partially reversed the adhesion of spermatozoa to the glass of unmodified Micro-Cell chambers. Chambers manufactured to reduce cell adhesion to glass surfaces yielded the highest motility and lowest lateral head displacement, whether the sperm were washed in a solution supplemented with or without protein. CONCLUSION: These findings indicate that, as in raw semen, kinematics of washed sperm can be measured reliably in the modified Micro-Cell chamber.

Cell Adhesion↗

Superiority of reproductive histories to sperm counts in detecting infertility at a dibromochloropropane manufacturing plant.

Sperm count distributions among exposed and control groups at a dibromochloropropane (DBCP) manufacturing plant were remarkably similar. Yet reproductive histories from 60 exposed men obtained in conjunction with the semen analyses indicated that fertility had been reduced during exposure. Ratios of observed to expected births or standardized fertility ratios (SFRs) were computed for reproductive experience at parities of 1 or greater. The SFR for the period at risk from DBCP exposure (SFR = 0.63) was significantly lower than those derived from the entire not-at-risk period (SFR = 1.21) or the portion related to nonexposed employment at the plant preceding exposure (SFR = 1.33). Significant reductions would have been evident at least 18 years prior to the year in which the histories were obtained. The effect on fertility seems to have been greatest during the initial period of DBCP production. Most fertility reduction occurred after 3.5 years of exposure. Fertility returned to normal following cessation of exposure (SFR = 1.18), although it appeared to remain subnormal for about two years. Wherever there is concern about the potential for adverse reproductive effects in the workplace, data suitable for fertility analyses should be collected during annual medical examinations.

Adolescent↗

Motility, vitality and percentages of morphologically abnormal forms of human spermatozoa in relation to sperm counts.

The present work was designed to study the proportions of motile and vital sperms as well as of various types of morphologically defective spermatozoa in both normozoospermic and oligozoospermic human semens, aiming at examining whether with the decrease in sperm counts there is a predilection of certain pathologies of these cells. It was found that, generally, the percentages of non-motile and non-vital spermatozoa and of all abnormal forms examined increase with the degree of oligozoospermia. However, no predilection of particular forms could be observed. It is suggested that morphological abnormalities of spermatozoa could be only a partial expression of pathological processes involved in fertility disorders and that the number of biologically defective spermatozoa may be higher than that assessed by routine laboratory techniques.

Adult↗

Sperm count depression in pesticide applicators exposed to dibromochloropropane.

Male pesticide applicators who worked with the nematocide dibromochloropropane (DBCP) were examined to determine the possible testicular toxicity from this exposure. Infertility and azoospermia which were first noted among factory workers exposed to DBCP were not observed among the applicators. Sperm count depression, however, was associated with the duration of exposure in the current year but not with exposure in past years. The extent of exposure to DBCP in the current year was also associated with an elevation of serum follicle stimulating hormone (FSH) but not of luteinizing hormone (LH). Sperm count depression was limited to applicators involved in irrigation setup work and in the calibration of equipment. These results suggest that the testicular toxicity of DBCP for men may occur in a shorter period than was previously reported, that the effect may be reversible in men with mild sperm count depression, and that public health measures might be directed at controlling specific application techniques.

Antinematodal Agents↗

Accuracy of computer-assisted semen analysis in prefreeze and post-thaw specimens with high and low sperm counts and motility.

OBJECTIVES: We evaluated the accuracy and precision of computer-assisted semen analysis (CASAs) to determine whether variations in the CASA results were related to the type of analyzer or to the type of specimens analyzed. METHODS: Semen specimens were analyzed manually and by CASA before freezing and after thawing. Multiple ejaculates (220 semen specimens) from normal healthy donors (n = 8) and 131 semen specimens from 57 patients with cancer were assessed. RESULTS: The differences between CASA and manual sperm counts and percent motility were higher in prefreeze and post-thaw specimens at sperm concentrations of less than 20 x 10(6)/mL. The differences between CASA and manual results were significant for cancer patients, compared with normal donors (P <0.01). CONCLUSIONS: CASA results are unreliable at sperm counts of less than 20 x 10(6)/mL and post-thaw motility is generally underestimated by CASAs.

Cryopreservation↗

Intrauterine insemination: evaluation of the results according to the woman's age, sperm quality, total sperm count per insemination and life table analysis.

We report on 332 infertile couples who underwent 1115 cycles of intrauterine insemination (IUI) with washed husband's semen. The indication for IUI was an abnormal post-coital test due to either a male or cervical infertility factor. The mean number of IUI cycles per patients was 3.4, the overall pregnancy rate 18.7%, and the pregnancy rate per cycle 5.6%. The cumulative pregnancy rate calculated by life table analysis showed that 16.0% of pregnancies occurred in the first three treatment cycles, while the cumulative pregnancy rate was 26.9% by the sixth cycle. The outcome of the therapy was adversely affected if the woman's age was > 39 years and/or total motile sperm count per insemination was < 1 x 10(6). No pregnancy occurred in women older than 44 years or in cases with a total motile sperm count before semen preparation of < 1 x 10(6).

Adult↗

Improved sperm counts in mink males (Mustela vison) treated with clomiphene citrate.

A group of 12 sterile, azoospermic mink males were treated with clomiphene citrate (10 mg/kg/day) for 10 days during the mating season; 50% of the males showed improved sperm counts already after 2 days of treatment and the maximum effect was seen 4-6 days after the start of the treatment. The other half of the group did not respond to the treatment and their sperm counts remained near zero during the whole experiment.

Animals↗

Within-subject variability and the importance of abstinence period for sperm count, semen volume and pre-freeze and post-thaw motility.

The within-subject variability of semen sperm count (n), volume (v), total number of spermatozoa (N) and pre-freeze (mo) and post-thaw (m1) motility was studied on 564 ejaculates from 98 normal subjects after an abstinence ranging from 1 to 5 days. After logarithmic transformation of n, v and N, the within-subject variances for each variable were found to be similar for all subjects; the within-subject centered distributions were nearly normal and 95% confidence intervals were calculated. These three variables appeared to increase linearly with the length of abstinence. For both mo and m1, the within-subject variances were also similar for all subjects and this without logarithmic transformation. Their respective within-subject centered distributions were normal; mo and m1 were not influenced by the length of abstinence during the period studied.

Humans↗

Relationship between the coagulation-liquefaction property of human ejaculates and their volume, sperm count and motility.

In ejaculates from selected infertile couples, the degree of coagulation revealed significant positive correlations with liquefaction time, sperm count and motility, but negative correlation with semen volume. Comparison of presumptively fertile and infertile ejaculates also showed significant variations in their amount of coagulum and liquefaction time. The study suggested a possible relationship between the coagulation-liquefaction property of human ejaculates and their semen quality.

Adult↗

Quantitative analysis of testicle biopsy: determination of partial obstruction and prediction of sperm count after surgery for obstruction.

Twenty-one male patients without ductal obstruction were studied prospectively by a simplified method of quantitative testicle biopsy. The mean number of mature spermatids per tubule in the testicle biopsy correlated closely with the sperm count in all 21 cases. Patients with less than 10,000,000 sperm/ml always had less than 20 mature spermatids per seminiferous tubule. Patients with more than 10,000,000 sperm/ml always had more than 20 mature spermatids per tubule. In azoospermic patients with epididymal obstruction, the sperm count after vasoepididymostomy could be predicted correctly by testicle biopsy. In severely oligospermic patients (less than 10,000,000 sperm/ml) the presence of more than 20 mature spermatids per tubule indicated partial epididymal obstruction.

Biopsy↗

Use of the total motile sperm count to predict total fertilization failure in in vitro fertilization.

OBJECTIVE: To evaluate the capacity of baseline characteristics and total motile sperm count (TMC) to predict total fertilization failure (TFF) in patients undergoing IVF. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): Eight hundred ninety-two couples with a total of 1,569 consecutive IVF cycles. INTERVENTION(S): Prewash and postwash TMC during fertility workup and at the time of ovum pickup (OPU). MAIN OUTCOME MEASURE(S): Analysis of logistic regression and the receiver operating characteristic curve were used to determine which variables could be used to predict TFF. RESULT(S): The area under the curve (AUC) for prewash TMC during fertility workup was 0.72, similar to a combination of pre- and postwash TMC. At the time of OPU, both pre- and postwash TMC had an AUC of 0.73. A model based on selected baseline characteristics (male age, number of IVF cycles, indication for IVF, and prewash TMC during fertility workup) had an AUC of 0.75. A model at the time of OPU, including the number of oocytes, had an AUC of 0.80. CONCLUSION(S): The use of both models, one before start of the IVF cycle and one at the time of OPU, allows an accurate prediction of the chance of TFF and is useful in counseling patients on whether to opt for IVF or ICSI.

Adult↗

Secular trend in reported sperm counts.

Claims that there has been a recent secular decline in splerm counts have been disputed. Protaglonists on both sides of the discussion have based their arguments on data from a few large samples at different times and (mostly) in different places. It is not disputed that the differences between the mean counts in the various samples are statistically significant: what is a tissue is whether a secular decline is responsible. The present not adops a different approach to the problem: an attempt has been made to locate representative data on mean sperm counts of unselected men over the last 45 years. Twenty-nine such means are cited here. There can be no reasonable doubt that these reported mean sperm counts show a decline with time of publication, at least since 1960. It is not easy to see what artifact - other than a real secular trend - might responsible. Accordingly it is concluded that - at least in some places - it seems likely that a secular decline has occurred.

Fertility↗

Estrogen receptor alpha promoter polymorphism: stronger estrogen action is coupled with lower sperm count.

BACKGROUND: Although the importance of estrogens in male reproduction is indisputable, little attention has been paid to the role of estrogen receptor (ER) gene mutations in male infertility. Significant correlation between (TA)n repeat allelic variants and lumbar bone mineral density was previously observed in the promoter region of the ERalpha gene, indicating that allelic combinations with higher number of (TA)n repeats are functionally more active genetic variants. METHODS: We studied the (TA)n repeat polymorphism situated in the promoter region of the ERalpha gene in a large group of infertile and normospermic men (n = 347). RESULTS: Although the (TA)n polymorphism failed to show a significant association with male infertility, we found a significant effect of this polymorphism on sperm count. In the group of infertile men, the mean TA repeat number and sperm concentration (P = 0.022) and total sperm number (P = 0.043) were inversely correlated, showing an association between higher TA repeat number (genotype A) and lower sperm production. In line with this observation, normospermic subjects with genotype A had a significantly lower mean sperm concentration with respect to men bearing genotype B with shorter TA alleles (P < 0.05) and a lower total sperm count (P < 0.01). CONCLUSIONS: Our data indicate that specific allelic combinations of the ERalpha, which confer a stronger estrogen effect, may negatively influence human spermatogenesis.

Alleles↗