Another look at human sperm morphology. 2016

J Auger, and P Jouannet, and F Eustache
Service d'Histologie-Embryologie, Biologie de la Reproduction/CECOS, Hôpitaux Universitaires Paris Centre, Site Port-Royal, 53, Avenue de l'Observatoire, 75014 Paris, France INSERM U1016, Equipe "Génomique, Epigénétique et Physiologie de la Reproduction", Institut Cochin, Université Paris Descartes, Paris, France jacques.auger@aphp.fr.

OBJECTIVE 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? CONCLUSIONS 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. BACKGROUND 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. METHODS 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. 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. RESULTS 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. CONCLUSIONS 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. CONCLUSIONS 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. BACKGROUND Part of this study was supported by contract BMH4-CT96-0314 from the European Union. The authors have no competing interests to declare.

UI MeSH Term Description Entries
D007248 Infertility, Male The inability of the male to effect FERTILIZATION of an OVUM after a specified period of unprotected intercourse. Male sterility is permanent infertility. Sterility, Male,Sub-Fertility, Male,Subfertility, Male,Male Infertility,Male Sterility,Male Sub-Fertility,Male Subfertility,Sub Fertility, Male
D008297 Male Males
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D003430 Cross-Sectional Studies Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time. Disease Frequency Surveys,Prevalence Studies,Analysis, Cross-Sectional,Cross Sectional Analysis,Cross-Sectional Survey,Surveys, Disease Frequency,Analyses, Cross Sectional,Analyses, Cross-Sectional,Analysis, Cross Sectional,Cross Sectional Analyses,Cross Sectional Studies,Cross Sectional Survey,Cross-Sectional Analyses,Cross-Sectional Analysis,Cross-Sectional Study,Cross-Sectional Surveys,Disease Frequency Survey,Prevalence Study,Studies, Cross-Sectional,Studies, Prevalence,Study, Cross-Sectional,Study, Prevalence,Survey, Cross-Sectional,Survey, Disease Frequency,Surveys, Cross-Sectional
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D013077 Sperm Head The anterior portion of the spermatozoon (SPERMATOZOA) that contains mainly the nucleus with highly compact CHROMATIN material. Head, Sperm,Heads, Sperm,Sperm Heads
D013094 Spermatozoa Mature male germ cells derived from SPERMATIDS. As spermatids move toward the lumen of the SEMINIFEROUS TUBULES, they undergo extensive structural changes including the loss of cytoplasm, condensation of CHROMATIN into the SPERM HEAD, formation of the ACROSOME cap, the SPERM MIDPIECE and the SPERM TAIL that provides motility. Sperm,Spermatozoon,X-Bearing Sperm,X-Chromosome-Bearing Sperm,Y-Bearing Sperm,Y-Chromosome-Bearing Sperm,Sperm, X-Bearing,Sperm, X-Chromosome-Bearing,Sperm, Y-Bearing,Sperm, Y-Chromosome-Bearing,Sperms, X-Bearing,Sperms, X-Chromosome-Bearing,Sperms, Y-Bearing,Sperms, Y-Chromosome-Bearing,X Bearing Sperm,X Chromosome Bearing Sperm,X-Bearing Sperms,X-Chromosome-Bearing Sperms,Y Bearing Sperm,Y Chromosome Bearing Sperm,Y-Bearing Sperms,Y-Chromosome-Bearing Sperms
D013736 Testicular Neoplasms Tumors or cancer of the TESTIS. Germ cell tumors (GERMINOMA) of the testis constitute 95% of all testicular neoplasms. Cancer of Testis,Cancer of the Testes,Testicular Cancer,Testicular Neoplasm,Testicular Tumor,Testis Cancer,Cancer of the Testis,Neoplasms, Testicular,Neoplasms, Testis,Testicular Tumors,Testis Neoplasms,Tumor of Rete Testis,Cancer, Testicular,Cancer, Testis,Cancers, Testicular,Cancers, Testis,Neoplasm, Testicular,Neoplasm, Testis,Rete Testis Tumor,Rete Testis Tumors,Testicular Cancers,Testis Cancers,Testis Neoplasm,Testis Tumor, Rete,Testis Tumors, Rete,Tumor, Testicular,Tumors, Testicular
D055101 Semen Analysis The quality of SEMEN, an indicator of male fertility, can be determined by semen volume, pH, sperm concentration (SPERM COUNT), total sperm number, sperm viability, sperm vigor (SPERM MOTILITY), normal sperm morphology, ACROSOME integrity, and the concentration of WHITE BLOOD CELLS. Semen Quality,Semen Quality Analysis,Analyses, Semen Quality,Analysis, Semen Quality,Qualities, Semen,Quality Analyses, Semen,Quality, Semen,Semen Analyses,Semen Qualities,Semen Quality Analyses

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