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Study question Can a standardized assessment of abnormal human sperm morphology provide additional useful information by identifying men with more severe disturbances in different types of abnormalities? Summary answer Definition-based categorization of sperm head, midpiece and tail defects has shown how differently these abnormalities are distributed in fertile men and other groups of men, thus providing high and low thresholds, a starting point for diagnosis or research purposes. What is known already Several recent studies have reported indisputable genetic origins for various sperm defects. A few studies have also identified associations between environmental factors and low percentages of morphologically normal spermatozoa. Nevertheless, with the exception of rare situations in which the vast majority of spermatozoa have specific, easily characterized defects, such as 'globozoospermia', little attention has been paid to the description and precise quantification of human sperm abnormalities. The lack of standardization in the phenotyping of sperm morphological defects by conventional microscopy is a limiting factor for diagnosis and for intra- or inter-observer or centre consistency in studies investigating the causal factors and possible functional consequences of the abnormalities detected. There are currently no baseline data for abnormalities of sperm morphology based on a standardized classification, in the general population, among fertile or other groups of men. Study design, size, duration This study is based on detailed sperm abnormality datasets acquired by a standardized classification method, from several groups of men, over the same 5-year period. Participants/materials, setting, methods We studied cross-sectional data from fertile men (n = 926), male partners from infertile couples (n = 1747) and testicular cancer patients (n = 239). We used a standardized classification to analyse Shorr-stained slides, taking into account all the abnormalities encountered. Main results and the role of chance Most sperm defects were significantly more frequent in infertile than in fertile men, with 20-30% of infertile men having frequencies of abnormalities above the 95th percentile in fertile men for 9 out of the 15 categories of abnormalities. Interestingly, several head abnormalities were significantly more frequent in patients with testicular cancer than in infertile men, highlighting the particular impact of this condition on sperm morphogenesis. We used the 95th percentile in fertile men as the lower threshold and the 99th percentile in infertile men as an extreme upper threshold, for the classification of morphological abnormality frequencies into three levels: low, intermediate and high. The assessment of several semen samples, with or without a genetic background, for abnormal sperm morphology, based on the percentage of normal spermatozoa, a teratozoospermia index, and the detailed profile of abnormalities categorized according to the three levels proposed, has highlighted the value of detailed phenotyping for diagnosis and research purposes. Limitations, reasons for caution The thresholds proposed for the various categories of sperm abnormality should be considered relative rather than absolute, owing to the known sampling error related to the limited number of spermatozoa assessed per sample, or when studying the general population or populations from regions other than Western Europe. The standardized assessment of abnormal sperm morphology requires time and experience. We therefore suggest that this assessment is carried out during a first andrological check-up or for epidemiological or research studies, rather than in the routine management of infertile couples for assisted reproductive technologies. Wider implications of the findings The study design used for the fertile group of men was similar to that previously used for the WHO reference values, providing a rationale for considering the 95th percentile in fertile men as the level below which abnormalities may be considered to occur at a frequency representing random background variations of a normal spermiogenesis process. The crude frequencies obtained, and the three levels of abnormality frequency proposed for each standardized category of sperm defect, provide baseline data useful for diagnosis and a starting point for future studies aiming to identify associations with genetic or environmental factors. Study funding/competing interests Part of this study was supported by contract BMH4-CT96-0314 from the European Union. The authors have no competing interests to declare.

BACKGROUND: Poor sperm morphology is statistically associated with an increase in the incidence of chromosome abnormalities. Our aim was to examine the possible correlation between chromosomal aberrations and sperm morphology in the same cell. METHODS: 12349 spermatozoa from 7 teratozoospermic and one globozoospermic patients, and from 3 fertile donors were analyzed using a system which scans for cell morphology and chromosomal ploidy in the same cell using digital technology. RESULTS: Chromosomal aberrations were detected in 5.3% of teratozoospermic cases and in 6.7% in the globozoospermic patient compared with 1.6% in donors (P < 0.0001). Chromosomal aberrations were more common in abnormally formed sperm compared with normal spermatozoa: 4.5% vs 1.3% in the teratozoospermic group and 2.0% vs 0.3% in the control group (NS), especially frequent among sperm with two heads or two tails (52.1-77.2%) or extreme head deformations (10.6-11.1%) irrespective of grouping, and in mild amorphous heads in the globozoospermic patients (20.2%). The frequency of chromosomal aberrations in morphologically normal sperm was comparable whether derived from teratozoospermic or normospermic patients. CONCLUSIONS: The computerized cell-scanning system demonstrated the relationship between chromosomal aberrations and sperm morphology in the same spermatozoon. The incidence of chromosomal aberrations was positively linked to abnormal sperm morphology, the more severe the abnormality, the higher the incidence of aneuploidy.

Background We hypothesize that the potential relationship between abnormal sperm morphology and increased frequency of numerical chromosomal aberrations is based on two attributes of diminished sperm maturity: (i) cytoplasmic retention and consequential sperm shape abnormalities; and (ii) meiotic errors caused by low levels of the HspA2 chaperone, a component of the synaptonemal complex. Because sperm morphology and aneuploidies were assessed in semen, but not in the same spermatozoa, previous studies addressing this relationship were inconclusive. We recently demonstrated that sperm shape is preserved following fluorescence in situ hybridization (FISH). Thus, we examined the shape and chromosomal aberrations in the same sperm. Methods We performed phase contrast microscopy and FISH, using centromeric probes for chromosomes X, Y, 10, 11 and 17 in 15 men. The fluorescence and respective phase contrast images were digitized using the Metamorph program. We studied 1286 sperm (256 disomic, 130 diploid and 900 haploid sperm) by three criteria: head and tail dimensions, head shape and Kruger strict morphology. Furthermore, in each analysis, we considered whether disomic or diploid sperm may be distinguished from haploid sperm. Results There was an overall, but not discriminative, relationship between abnormal sperm dimensions or shape and increased frequencies of numerical chromosomal aberrations. However, approximately 68 of the 256 disomic, and four of 130 diploid sperm showed head and tail dimensions comparable with the most normal, lowest tertile of the 900 haploid spermatozoa. Considering all 1286 sperm, among those with the most regular, symmetrical shape (n = 367), there were 63 and five with disomic and diploid nuclei, respectively. In line with these findings, among the 256 disomic sperm, 10% were Kruger normal. Conclusions Sperm dimensions or shape are not reliable attributes in selection of haploid sperm for ICSI.

BACKGROUND: The number of (trinucleotide) CAG repeats within the androgen receptor (AR) gene is inversely correlated with transcriptional activity of testosterone-target genes. Although abnormally long CAG repeats are strongly associated with male infertility, it is unclear whether CAG repeat length polymorphism can affect androgen receptor activity and sperm parameters. To explore the previously suggested association between CAG repeats and male fertility, we conducted this prospective cohort study. METHODS: We enrolled 172 men attending the IVF unit in Shaare-Zedek Medical Center. Sperm concentration, motility and morphology and the number of CAG repeats in the AR gene were measured. RESULTS: Mean CAG repeat length was greater in teratozoospermia (

BACKGROUND: The aim of the present study was to define the effect of apoptosis on sperm quality and function. METHODS: The apoptotic features in sperm were assessed in 60 subfertile subjects, using Annexin-V staining for phosphatidylserine (PS) externalization and Tdt-mediated dUTP nick end labelling (TUNEL) assay for DNA fragmentation. RESULTS: On average, about 45% of the sperm were found to be apoptotic based on the results from Annexin-V staining, including both early (Annexin-V-positive, PI-negative) and late apoptosis (Annexin-Vpositive, PI-positive). TUNEL-positive cells (median value 15%) significantly correlated to late apoptosis but not early apoptosis, indicating that DNA fragmentation only occurs at the later stage of sperm apoptosis. TUNELpositive and late apoptotic cells (Annexin-V-positive, PI-positive) were found to be inversely correlated to sperm motility and vitality, and positively to abnormal sperm morphology. On the other hand, it is surprising to note that the apoptotic alterations in sperm positively correlated to sperm concentration or total sperm counts. CONCLUSIONS: Overall results from this study support the abortive apoptosis theory; apoptosis in mature sperm is initiated during spermatogenesis, after which some cells earmarked for elimination via apoptosis may escape the removal mechanism and contribute to poor sperm quality.

Selenium (Se) and glutathione peroxidase (GSH-Px) were determined from the seminal plasma samples and spermatozoa of human and four different animal species. The human sperm Se concentration was 1.8 +/- 0.8 micrograms/g dry weight, which was about half of that in the bull. Abnormal sperm morphology and motility correlated with low sperm Se content. The volume of sperm mitochondrial sheath in human, bull and stallion was measured using transmission electron microscopy. In these species the sperm Se content was highly correlated with the volume of mitochondria. Among the five species studied, the seminal plasma level of Se was lowest in human male and stallion, while the highest levels were encountered in the bull. No correlation was obtained between human semen quality and seminal plasma Se concentration. The seminal plasma GSH-Px activity was low in man and ram, absent in boar and stallion but very high in the bull. The amount of structural sperm Se as well as seminal plasma Se and GSH-Px activity appears to be highly variable in different species.