OBJECTIVE--To investigate whether semen quality has changed during the past 50 years. DESIGN--Review of publications on semen quality in men without a history of infertility selected by means of Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991). SUBJECTS--14,947 men included in a total of 61 papers published between 1938 and 1991. MAIN OUTCOME MEASURES--Mean sperm density and mean seminal volume. RESULTS--Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density. CONCLUSIONS--There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.

https://www.bmj.com/content/bmj/305/6854/609.full.pdf

Evidence for decreasing quality of semen during past 50 years.

The sperm chromatin structure assay (SCSA) was used to measure over 500 human semen samples from two independent studies: Study I, 402 samples from 165 presumably fertile couples wishing to achieve pregnancy over 12 menstrual cycles; Study II, samples from 115 patients seeking fertility counselling. The SCSA measures susceptibility to DNA denaturation in situ in spermatozoa exposed to acid for 30 s, followed by acridine orange staining. SCSA data from the male partners of 73 couples (group 1) achieving pregnancy during months 1‐3 of Study I were used as the standard of ‘sperm chromatin compatible with high fertility’ and were significantly different from those of 40 couples (group 3) achieving pregnancy in months 4‐12 (P < 0.01) and those of male partners of 31 couples (group 4) not achieving pregnancy (P < 0.001). Group 2 contained couples who had a miscarriage. SCSA values for Study II were almost twice that of the Study I fertility standards. Within-couple repeatability tended to be less for group 3 than for groups 1, 2 or 4. Based on logistic regression, spermatozoa with denatured DNA (cells outside the main population, COMPa t) were the best predictor for whether a couple would not achieve pregnancy. Some 84% of males in group 1 had COMPat <15%, while no couples achieved pregnancy in group 1 with ‡30% COMPat, a threshold level considered not compatible with good fertility. Using selected cut-off values for chromatin integrity, the SCSA data predicted seven of 18 miscarriages (39%).

Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic

/pdf/evidence-for-decreasing-quality-of-semen-during-past-50-vlioqbfqzo.pdf

Evidence for Decreasing Quality of Semen During Past 50 Years

The predictive value of sperm chromatin integrity for pregnancy outcome following in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) was studied in 24 men attending a university-based assisted reproductive techniques laboratory using the flow cytometric sperm chromatin structure assay (SCSA). The SCSA is a measure of the susceptibility of sperm DNA to low pH-induced denaturation in situ. The mean percentage of spermatozoa in the neat sample demonstrating DNA denaturation was significantly lower in the seven men that initiated a pregnancy (15.4 +/- 4.6, P = 0.01) than in the 14 men who did not initiate a pregnancy (31.1 +/- 3.2). No pregnancies resulted if > or =27% of the spermatozoa in the neat semen sample showed DNA denaturation. These data demonstrate that SCSA parameters are independent of conventional semen parameters. Furthermore, the SCSA may allow physicians to identify male patients for whom IVF and ICSI will be unlikely to result in pregnancy initiation.

Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques

Recent reports have suggested that the incidence of genitourinary abnormalities in human males has increased during the past 50 years, including congenital abnormalities such as cryptorchidism and ...

Evidence for increasing incidence of abnormalities of the human testis: a review.

Semen samples from husbands with a history of unexplained infertility (n = 33), of women with habitual abortion (n = 36), or normal fertile donors (n = 20) were subjected to conventional semen analysis (SA), Acridine orange test (AOT), and zona-free hamster egg penetration test (HEPT). The three tests operate independently. The most discriminatory test was AOT (p = 0.0001) followed by HEPT (p = 0.019). The frequency of sperm chromatin heterogeneity as detected by AOT red fluorescence was highest in habitual abortion (39.4%), followed by unexplained infertility (16.4%), and, last, donors (9.4%). However the percentage of penetration was highest in habitual abortion (50.7%), followed by donors (43.1%), and least in unexplained infertility (33.9%). Conventional semen parameters (sperm density, motility, abnormality, and vitality) were the least to discriminate between the three groups. The presence of abnormal sperm chromatin may lead to infertility as a result of early pregnancy loss.

https://www.tandfonline.com/doi/pdf/10.3109/01485018808986723

Sperm chromatin heterogeneity as an infertility factor.

Acridine orange fluorescence, semen analysis, and zona-free hamster egg penetration tests were performed on 100 consecutive semen samples. No significant correlation was detected between sperm motility and red fluorescence. However, abnormal sperm morphology correlated significantly with red fluorescence (p ± 0.001) and fluorescence index (p ± 0.001). Presence of a high percentage of red fluorescing sperm did not prevent their penetration of zona-free hamster egg, indicating that the presence of abnormal DNA had no effect on the sperm fertility. The significance of acridine orange fluorescence male fertility test requires further elucidation.

https://www.tandfonline.com/doi/pdf/10.3109/01485018808987062

Acridine Orange Fluorescence as Male Fertility Test

Semen samples from two infertile men showed normal numbers of cells, but the majority of the spermatozoa were abnormal in shape and had very poor motility. The majority of the spermatozoa showed red fluorescence when stained with acridine orange, indicating the presence of single-stranded DNA. At the ultrastructural level the chromatin was decondensed to various degrees. The acrosomes were either lacking or highly abnormal in appearance. Abnormal tail elements were liberally scattered all over in the abnormal cells. Based on these findings and previous reports, it is suggested that certain infections and exposure to various toxic substances can result in such changes.

Ultrastructure of Spermatozoa With Abnormal Morphology and Predominantly Single-Stranded DNA

The efficacy of the zona-free hamster egg sperm penetration assay (SPA) as a predictor of in vitro fertilization (IVF) is studied. Indications for IVF were tubal factors in 35 couples and male factors in 24 couples. The diagnostic characteristics of SPA in reference to IVF for the whole group (n = 59) were reasonably reliable. Sensitivity was 74%, specificity was 84%, and diagnostic accuracy was 81%. However in patients with male factors, SPA was less reliable in terms of sensitivity (70%), specificity (57%), and diagnostic accuracy (63%), than in patients with tubal factors where the indicators were 80%, 97%, and 94%, respectively. Semen from patients with male infertility shared notable variations in terms of sperm density and motility which may account for the low SPA predictivity. SPA seems to be a useful screening test for prediction of IVF outcome. However other semen variables should be considered before interpretation, especially in male infertility where the diagnostic accuracy is low.

H. Pedersen

Papers

Sperm chromatin heterogeneity as an infertility factor.

Acridine Orange Fluorescence as Male Fertility Test

Ultrastructure of Spermatozoa With Abnormal Morphology and Predominantly Single-Stranded DNA

Efficacy of zona-free hamster egg sperm penetration assay as a predictor of in vitro fertilization.