Biomarker-Based Flow Cytometric Semen Analysis for Male Infertility Diagnostics and Clinical Decision Making in ART

  • Chapter
Screening the Single Euploid Embryo

Abstract

The influence of sperm phenotype and molecular makeup on fertilization and pregnancy after assisted reproductive therapy (ART) is now widely appreciated by the research and clinical medical communities, prompting the quest for objective clinical diagnostic techniques for unambiguous identification and treatment-relevant assessment of human male infertility. More accurate andrological evaluation may allow physicians to identify couples in which the sperm quality is sufficient to warrant single embryo transfer, thus reducing the incidence of unwanted multiple births after ART. This chapter reviews the emerging biomarker-based andrological approaches to automated semen analysis by high-throughput flow cytometry (FC). Such approaches are based on the flow cytometric quantification of spermatozoa with DNA fragmentation or acrosomal damage, immotile and apoptotic spermatozoa, spermatozoa lacking surface proteins relevant to sperm sustenance and function, and spermatozoa expressing redundant proteins as well as proteins associated with cell stress, death, or proteolysis. Simultaneously, FC can detect seminal white blood cells (WBC) and measure reactive oxygen species (ROS) produced by them. Flow cytometric outputs are easy to analyze statistically and results can be correlated with specific sperm phenotypes in addition to conventional semen parameters. Where applicable, these approaches are discussed in the context of clinical decision making and pregnancy outcomes in ART couples, particularly with regard to the possibility of single embryo transfer. Studies correlating semen FC with the incidence of multiple births after multi-embryo transfer or with recurrent or sporadic spontaneous abortion (SAB) are highlighted and discussed in the context of clinical decision making and treatment outcomes in ART couples. This review will be useful to andrologists considering addition of FC to their diagnostic arsenal as well as to current FC users, the early adopters interested in expanding their biomarker toolbox.

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Acknowledgments

We thank our past and present associates involved in research and clinical data collection concerned with human sperm quality. We are indebted to our collaborators Drs. Richard Oko, Antonio Miranda-Vizuete, Christophe Ozanon, Gary Clark, Russ Hauser, Hector Chemes, and Vanesa Rawe for their support and collegiality. Human male infertility research in the laboratory of PS has been funded by the F21C program of the University of Missouri and by grants from NIH-NICH and NIH-NIOSH.

Conflict of Interest The authors disclose no conflicts.

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Ahlering, P., Sutovsky, P. (2015). Biomarker-Based Flow Cytometric Semen Analysis for Male Infertility Diagnostics and Clinical Decision Making in ART. In: Sills, E. (eds) Screening the Single Euploid Embryo. Springer, Cham. https://doi.org/10.1007/978-3-319-16892-0_4

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