Advanced Diagnostic Approaches to Male Infertility

doi:10.1017/9781108937054.020

Chapter 18 - Advanced Diagnostic Approaches to Male Infertility

from Section 3 - Laboratory Diagnosis of Male Infertility

Published online by Cambridge University Press: 08 July 2023

Dolores J. Lamb

Edited by

Larry I. Lipshultz ,

Stuart S. Howards ,

Craig S. Niederberger and

Dolores J. Lamb

Show author details

Larry I. Lipshultz: Affiliation:
Baylor College of Medicine, Texas
Stuart S. Howards: Affiliation:
University of Virginia
Craig S. Niederberger: Affiliation:
University of Illinois, Chicago
Dolores J. Lamb: Affiliation:
Weill Cornell Medical College, New York

Book contents

Get access

Summary

Routine semen analysis remains the one laboratory diagnostic test that should be the cornerstone of evaluation of the infertile male. With visual assessment of semen characteristics, namely, color, volume (also may be defined by weight, as recommended by the World Health Organization (WHO) [1]), viscosity, and liquefaction, the analysis proceeds with a strictly defined series of steps using microscopic assessment of sperm agglutination, sperm aggregation, motility, morphology, and sperm concentration. The test provides a wealth of information about spermatogenesis (sperm morphology and count), function of the testis, and the genitourinary tract and glands – production of normal-appearing spermatozoa, acquisition of sperm motility during passage through the epididymis, functions of accessory organs (seminal vesicles and prostate impacting semen volume, liquefaction), including a reflection of androgen action in these tissues/organs, patency and health of the genital tract, and processes of emission and ejaculation. Yet, with few exceptions (no sperm in the ejaculate, complete globozoospermia, or asthenozoospermia), the test cannot be used to distinguish fertile from infertile men [2]. Even in the presence of severe idiopathic oligozoospermia, paternity has been documented without the use of assisted reproductive technology (ART) [3], and studies of large numbers of proven fertile men undergoing vasectomy revealed that about 11 percent of them were severely oligozoospermic who nevertheless fathered children without medical assistance (based upon WHO 3 and WHO 4 criteria; reviewed in [4]). Indeed, although increasing numbers of abnormal semen parameters are associated with a higher risk of infertility in men, for an individual male, it is impossible to predict with certainty whether or not he is infertile, based upon abnormal semen parameters.

Type: Chapter
Information: Infertility in the Male , pp. 348 - 362

DOI: https://doi.org/10.1017/9781108937054.020 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2023

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen, 5th ed. Geneva: World Health Organization, 2010.Google Scholar

Guzick, DS, Overstreet, JW, Factor-Litvak, P, et al. Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med 2001;345:1388–93.Google Scholar

Sokol, RZ, Sparkes, R. Demonstrated paternity in spite of severe idiopathic oligospermia. Fertil Steril 1987;47:356–8.Google Scholar

Silber, SJ. The relationship of abnormal semen parameters to male fertility. Hum Reprod 1989;4:947–53.Google Scholar

Puga Molina, LC, Luque, GM, Balestrini, PA, Marin-Briggiler, CI, Romarowski, A, Buffone, MG. Molecular sasis of human sperm capacitation. Front Cell Dev Biol 2018;6:72.CrossRef Google Scholar

World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction, 4th ed. Geneva: World Health Organization and Cambridge: Cambridge University Press 1999.Google Scholar

Muratori, M, Marchiani, S, Tamburrino, L, Baldi, E. Sperm DNA fragmentation: mechanisms of origin. Adv Exp Med Biol 2019;1166:75–85.Google Scholar

Muratori, M, Marchiani, S, Tamburrino, L, et al. DNA fragmentation in brighter sperm predicts male fertility independently from age and semen parameters. Fertil Steril 2015;104:582–90 e4.Google Scholar

Robinson, L, Gallos, ID, Conner, SJ, et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod 2012;27:2908–17.Google Scholar

Cissen, M, Wely, MV, Scholten, I, et al. Measuring sperm DNA fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta-analysis. PLoS ONE 2016;11:e0165125.Google Scholar

Simon, L, Zini, A, Dyachenko, A, Ciampi, A, Carrell, DT. A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome. Asian J Androl 2017;19:80–90.Google Scholar

Tan, J, Taskin, O, Albert, A, Bedaiwy, MA. Association between sperm DNA fragmentation and idiopathic recurrent pregnancy loss: a systematic review and meta-analysis. Reprod Biomed Online 2019;38:951–60.Google Scholar

Evgeni, E, Charalabopoulos, K, Asimakopoulos, B. Human sperm DNA fragmentation and its correlation with conventional semen parameters. J Reprod Infertil 2014;15:2–14.Google Scholar

Wang, BN, Nie, B, Tang, D, et al. Analysis of meiotic segregation patterns and interchromosomal effects in sperm from 13 Robertsonian translocations. Balkan J Med Genet 2017;20:43–50.CrossRef Google Scholar PubMed

Robbins, DJ, Coleman, MS. Initiator role of double stranded DNA in terminal transferase catalyzed polymerization reactions. Nucleic Acids Res 1988;16:2943–57.Google Scholar

Fernandez, JL, Cajigal, D, Lopez-Fernandez, C, Gosalvez, J. Assessing sperm DNA fragmentation with the sperm chromatin dispersion test. Methods Mol Biol 2011;682:291–301.Google Scholar

Fernandez, JL, Muriel, L, Goyanes, V, et al. Halosperm is an easy, available, and cost-effective alternative for determining sperm DNA fragmentation. Fertil Steril 2005;84:860.Google Scholar

Fernandez, JL, Muriel, L, Goyanes, V, et al. Simple determination of human sperm DNA fragmentation with an improved sperm chromatin dispersion test. Fertil Steril 2005;84:833–42.Google Scholar

Simon, L, Carrell, DT. Sperm DNA damage measured by comet assay. Methods Mol Biol 2013;927:137–46.Google Scholar

Collins, AR, Dobson, VL, Dusinska, M, Kennedy, G, Stetina, R. The comet assay: what can it really tell us? Mutat Res 1997;375:183–93.Google Scholar

Konca, K, Lankoff, A, Banasik, A, et al. A cross-platform public domain PC image-analysis program for the comet assay. Mutat Res 2003;534(1–2):15–20.Google Scholar

Gonzalez, JE, Romero, I, Barquinero, JF, Garcia, O. Automatic analysis of silver-stained comets by CellProfiler software. Mutat Res 2012;748(1–2):60–4.Google Scholar

Evenson, DP. Sperm chromatin structure assay (SCSA(R)). Methods Mol Biol 2013;927:147–64.Google Scholar

Evenson, DP, Jost, LK, Marshall, D, et al. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod 1999;14:1039–49.Google Scholar

Giwercman, A, Lindstedt, L, Larsson, M, et al. Sperm chromatin structure assay as an independent predictor of fertility in vivo: a case-control study. Int J Androl 2010;33:e221–7.Google Scholar

Hopps, CV, Mielnik, A, Goldstein, M, Palermo, GD, Rosenwaks, Z, Schlegel, PN. Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions. Hum Reprod 2003;18:1660–5.Google Scholar

Gekas, J, Thepot, F, Turleau, C, et al. Chromosomal factors of infertility in candidate couples for ICSI: an equal risk of constitutional aberrations in women and men. Hum Reprod 2001;16:82–90.Google Scholar

Kurinczuk, JJ, Bhattacharya, S. Assisted reproductive technologies: impact on fetal and neonatal outcomes. Semin Fetal Neonatal Med 2014;19:221.Google Scholar

Godo, A, Blanco, J, Vidal, F, Anton, E. Accumulation of numerical and structural chromosome imbalances in spermatozoa from reciprocal translocation carriers. Hum Reprod 2013;28:840–9.Google Scholar

Godo, A, Blanco, J, Vidal, F, Sandalinas, M, Garcia-Guixe, E, Anton, E. Altered segregation pattern and numerical chromosome abnormalities interrelate in spermatozoa from Robertsonian translocation carriers. Reprod Biomed Online 2015;31:79–88.Google Scholar

Morel, F, Douet-Guilbert, N, Le Bris, MJ, et al. Meiotic segregation of translocations during male gametogenesis. Int J Androl 2004;27:200–12.Google Scholar

Zhao, WW, Wu, M, Chen, F, et al. Robertsonian translocations: an overview of 872 Robertsonian translocations identified in a diagnostic laboratory in China. PLoS ONE 2015;10:e0122647.Google Scholar

Yatsenko, AN, Yatsenko, SA, Weedin, JW, et al. Comprehensive 5-year study of cytogenetic aberrations in 668 infertile men. J Urol 2010;183:1636–42.Google Scholar

Schlegel, PN, Sigman, M, Collura, B, et al. Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I. Fertil Steril 2021;115:54–61.Google Scholar

Schlegel, PN, Sigman, M, Collura, B, et al. Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II. Fertil Steril 2021;115:62–9.Google Scholar

Schlegel, PN, Sigman, M, Collura, B, et al. Diagnosis and treatment of infertility in men: AUA/ASRM Guideline PART II. J Urol 2021;205:44–51.Google Scholar

Schlegel, PN, Sigman, M, Collura, B, et al. Diagnosis and treatment of infertility in men: AUA/ASRM Guideline Part I. J Urol 2021;205:36–43.Google Scholar

Tiepolo, L, Zuffardi, O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet 1976;34:119–24.CrossRef Google Scholar PubMed

Saxena, R, Brown, LG, Hawkins, T, et al. The DAZ gene cluster on the human Y chromosome arose from an autosomal gene that was transposed, repeatedly amplified and pruned. Nat Genet 1996;14:292–9.Google Scholar

Reijo, R, Alagappan, RK, Patrizio, P, Page, DC. Severe oligozoospermia resulting from deletions of azoospermia factor gene on Y chromosome. Lancet 1996;347:1290–3.Google Scholar

Jorgez, CJ, Weedin, JW, Sahin, A, et al. Aberrations in pseudoautosomal regions (PARs) found in infertile men with Y-chromosome microdeletions. J Clin Endocrinol Metab 2011;96:E674–9.Google Scholar

Medina-Martinez, O, Haller, M, Rosenfeld, JA, O’Neill, MA, Lamb, DJ, Jamrich, M. The transcription factor Maz is essential for normal eye development. Dis Model Mech 2020;13:dmm044412.CrossRef Google Scholar PubMed

Haller, M, Au, J, O’Neill, M, Lamb, DJ. 16p11.2 transcription factor MAZ is a dosage-sensitive regulator of genitourinary development. Proc Natl Acad Sci U S A 2018;115:E1849–58.CrossRef Google Scholar PubMed

Haller, M, Mo, Q, Imamoto, A, Lamb, DJ. Murine model indicates 22q11.2 signaling adaptor CRKL is a dosage-sensitive regulator of genitourinary development. Proc Natl Acad Sci U S A 2017;114:4981–6.Google Scholar

Tannour-Louet, M, Han, S, Louet, JF, et al. Increased gene copy number of VAMP7 disrupts human male urogenital development through altered estrogen action. Nat Med 2014;20:715–24.Google Scholar

Yatsenko, AN, Georgiadis, AP, Ropke, A, et al. X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med 2015;372:2097–107.Google Scholar

Anguiano, A, Oates, RD, Amos, JA, et al. Congenital bilateral absence of the vas deferens. A primarily genital form of cystic fibrosis. JAMA 1992;267:1794–7.Google Scholar

Patat, O, Pagin, A, Siegfried, A, et al. Truncating mutations in the adhesion G protein-coupled receptor G2 gene ADGRG2 cause an X-linked congenital bilateral absence of vas deferens. Am J Hum Genet 2016;99:437–42.Google Scholar

Coutton, C, Escoffier, J, Martinez, G, Arnoult, C, Ray, PF. Teratozoospermia: spotlight on the main genetic actors in the human. Hum Reprod Update 2015;21:455–85.Google Scholar

Wang, WL, Tu, CF, Tan, YQ. Insight on multiple morphological abnormalities of sperm flagella in male infertility: what is new? Asian J Androl 2020;22:236–45.Google Scholar

Cooper, TG, Noonan, E, von Eckardstein, S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2010;16:231–45.Google Scholar

Enciso, M, Alfarawati, S, Wells, D. Increased numbers of DNA-damaged spermatozoa in samples presenting an elevated rate of numerical chromosome abnormalities. Hum Reprod 2013;28:1707–15.Google Scholar

Ramasamy, R, Scovell, JM, Kovac, JR, Cook, PJ, Lamb, DJ, Lipshultz, LI. Fluorescence in situ hybridization detects increased sperm aneuploidy in men with recurrent pregnancy loss. Fertil Steril 2015;103:906–9 e1.CrossRef Google Scholar PubMed

Ramasamy, R, Besada, S, Lamb, DJ. Fluorescent in situ hybridization of human sperm: diagnostics, indications, and therapeutic implications. Fertil Steril 2014;102:1534–9.Google Scholar