Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-669899f699-vbsjw Total loading time: 0 Render date: 2025-05-01T16:06:00.634Z Has data issue: false hasContentIssue false

Chapter 14 - Inheritance and Male Fertility

from Section 2 - Clinical Evaluation of the Infertile Male

Published online by Cambridge University Press:  08 July 2023

By
Cigdem Tanrikut  and
Robert D. Oates
Edited by
Larry I. Lipshultz ,
Stuart S. Howards ,
Craig S. Niederberger  and
Dolores J. Lamb
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
Get access

Summary

Infertility impacts approximately one in six couples attempting to conceive; male factor is at least contributory, if not the sole basis, in 50 percent of these couples [1, 2]. Evaluation of the infertile male starts with the history, followed by the physical examination, and is coupled with semen analysis. The synthesis of this information may suggest inherited conditions (usually autosomal recessive) or de novo abnormalities resulting in an aberrant clinical or spermatozoal phenotype [3, 4]. These may be recognized chromosomal abnormalities, specific gene mutations, or qualitative factors that affect spermatogenesis and fertility potential. Identification of a specific genetic mishap may be informative for the patient and his overall health, for the couple and their therapeutic strategies and results, for the patient’s siblings and first-order relatives, and for the offspring that might be conceived. Although these aberrations may limit natural conception, technical innovations, coupled with the evolution of assisted reproductive technology (ART), may allow previously infertile/sterile couples to parent their own biological children. Helping couples also involves informing them, as best we can, the reasons for the infertility – the etiologies of the sperm defect, the basis for vasal agenesis, and the genetic underpinnings of the abnormally shaped sperm. Although thorough clinical evaluation of the infertile male has always been appropriate, proper genetic analysis and counseling may be equally as important. Male reproductive medicine, surgery, and genetics are inextricably intertwined. This chapter reviews the forms of male infertility that have had an identified genetic basis, summarizes the laboratory tests employed for diagnosis, and briefly discusses more recent salient issues, including concerns regarding the impact of paternal age. Three general subdivisions will be employed: genetic disorders affecting sperm production (in essence, quantitative); genetic disorders affecting sperm function (in essence, qualitative); and genetic disorders affecting sperm transport. This is a paradigm that is unusual but helps to provide a visual way of conceptualizing and compartmentalizing the various conditions discussed. Epigenetics, as it relates to male fertility/infertility, will be discussed in Chapter 6.

Type
Chapter
Information
Infertility in the Male , pp. 237 - 252
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

Flannigan, R, Schlegel, PN. Genetic diagnostics of male infertility in clinical practice. Best Pract Res Clin Obstet Gynaecol 2017;44:26–37.Google Scholar
Harnisch, B, Oates, R. Genetic disorders related to male factor infertility and their adverse consequences. Semin Reprod Med 2012;30:105–15.Google Scholar
Tournaye, H, Krausz, C, Oates, RD. Novel concepts in the aetiology of male reproductive impairment. Lancet Diabetes Endocrinol 2017;5:544–53.Google Scholar
Tournaye, H, Krausz, C, Oates, RD. Concepts in diagnosis and therapy for male reproductive impairment. Lancet Diabetes Endocrinol 2017;5:554–64.Google Scholar
Kaprara, A, Huhtaniemi, IT. The hypothalamus-pituitary-gonad axis: tales of mice and men. Metabolism 2018;86:3–17.Google Scholar
Balasubramanian, R, Crowley, WF Jr. Isolated gonadotropin-releasing hormone (GnRH) deficiency. In: Adam, MP, Ardinger, HH, Pagon, RA, et al., eds. GeneReviews®. Seattle, WA: University of Washington, 2017.Google Scholar
de Castro, F, Seal, R, Maggi, R; Group of HGNC consultants for KAL1 nomenclature. ANOS1: a unified nomenclature for Kallmann syndrome 1 gene (KAL1) and anosmin-1. Brief Funct Genomics 2017;16:205–10.Google Scholar
Goncalves, CI, Fonseca, F, Borges, T, Cunha, F, Lemos, MC. Expanding the genetic spectrum of ANOS1 mutations in patients with congenital hypogonadotropic hypogonadism. Hum Reprod 2017;32:704–11.Google Scholar
Berges-Raso, I, Gimenez-Palop, O, Gabau, E, Capel, I, Caixas, A, Rigla, M. Kallmann syndrome and ichthyosis: a case of contiguous gene deletion syndrome. Endocrinol Diabetes Metab Case Rep 2017;2017:EDM170083.Google Scholar
Jarzabek, K, Wolczynski, S, Lesniewicz, R, Plessis, G, Kottler, ML. Evidence that FGFR1 loss-of-function mutations may cause variable skeletal malformations in patients with Kallmann syndrome. Adv Med Sci 2012;57:314–21.Google Scholar
Stamou, MI, Georgopoulos, NA. Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism. Metabolism 2018;86:124–34.Google Scholar
Men, M, Wu, J, Zhao, Y, et al. Genotypic and phenotypic spectra of FGFR1, FGF8, and FGF17 mutations in a Chinese cohort with idiopathic hypogonadotropic hypogonadism. Fertil Steril 2020;113:158–66.Google Scholar
Stamou, MI, Plummer, L, Galli-Tsinopoulou, A, Stergidou, D, Koika, V, Georgopoulos, NA. Unilateral renal agenesis as an early marker for genetic screening in Kallmann syndrome. Hormones (Athens) 2019;18:103–5.Google Scholar
Lanfranco, F, Kamischke, A, Zitzmann, M, Nieschlag, E. Klinefelter’s syndrome. Lancet 2004;364:273–83.Google Scholar
Oates, RD. The genetic basis of male reproductive failure. Urol Clin North Am 2008;35:257–70, ix.Google Scholar
Bearelly, P, Oates, R. Recent advances in managing and understanding Klinefelter syndrome. F1000Res 2019;8:F1000 Faculty Rev-112.Google Scholar
Kamischke, A, Baumgardt, A, Horst, J, Nieschlag, E. Clinical and diagnostic features of patients with suspected Klinefelter syndrome. J Androl 2003;24:41–18.Google Scholar
Abdelmoula, NB, Amouri, A, Portnoi, MF, et al. Cytogenetics and fluorescence in situ hybridization assessment of sex-chromosome mosaicism in Klinefelter’s syndrome. Ann Genet 2004;47:163–75.Google Scholar
Rajender, A, Oates, R. Evaluation and management of Klinefelter syndrome. AUA Update 2018. Available from: auau.auanet.org/content/update-series-2018-lesson-24-evaluation-and-management-klinefelter-syndrome#group-tabs-node-course-default1.Google Scholar
Gravholt, CH, Chang, S, Wallentin, M, Fedder, J, Moore, P, Skakkebaek, A. Klinefelter Syndrome: integrating genetics, neuropsychology, and endocrinology. Endocr Rev 2018;39:389–423.Google Scholar
Kanakis, GA, Nieschlag, E. Klinefelter syndrome: more than hypogonadism. Metabolism 2018;86:135–44.Google Scholar
Brinton, LA. Breast cancer risk among patients with Klinefelter syndrome. Acta Paediatr 2011;100:814–18.Google Scholar
Williams, LA, Pankratz, N, Lane, J, et al. Klinefelter syndrome in males with germ cell tumors: a report from the Children’s Oncology Group. Cancer 2018;124:3900–8.Google Scholar
Oates, RD. The natural history of endocrine function and spermatogenesis in Klinefelter syndrome: what the data show. Fertil Steril 2012;98:266–73.Google Scholar
Maiburg, M, Repping, S, Giltay, J. The genetic origin of Klinefelter syndrome and its effect on spermatogenesis. Fertil Steril 2012;98:253–60.Google Scholar
Boeri, L, Palmisano, F, Preto, M, et al. Sperm retrieval rates in non-mosaic Klinefelter patients undergoing testicular sperm extraction: what expectations do we have in the real-life setting? Andrology 2020;8:680–7.Google Scholar
Corona, G, Pizzocaro, A, Lanfranco, F, et al. Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis. Hum Reprod Update 2017;23:265–75.Google Scholar
Zitzmann, M, Bongers, R, Werler, S, et al. Gene expression patterns in relation to the clinical phenotype in Klinefelter syndrome. J Clin Endocrinol Metab 2015;100:E518–23.Google Scholar
Ghieh, F, Mitchell, V, Mandon-Pepin, B, Vialard, F. Genetic defects in human azoospermia. Basic Clin Androl 2019;29:4.Google Scholar
Jedidi, I, Ouchari, M, Yin, Q. Sex chromosomes-linked single-gene disorders involved in human infertility. Eur J Med Genet 2019;62:103560.Google Scholar
Vockel, M, Riera-Escamilla, A, Tuttelmann, F, Krausz, C. The X chromosome and male infertility. Hum Genet 2021;140:203–15.Google Scholar
Boroujeni, PB, Sabbaghian, M, Totonchi, M, et al. Expression analysis of genes encoding TEX11, TEX12, TEX14 and TEX15 in testis tissues of men with non-obstructive azoospermia. JBRA Assist Reprod 2018;22:185–92.Google Scholar
Sha, Y, Zheng, L, Ji, Z, et al. A novel TEX11 mutation induces azoospermia: a case report of infertile brothers and literature review. BMC Med Genet 2018;19:63.Google Scholar
Yang, F, Silber, S, Leu, NA, et al. TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse. EMBO Mol Med 2015;7:1198–210.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
Milunsky, A, Milunsky, JM, Dong, W, Hovhannisyan, H, Oates, RD. A contiguous microdeletion syndrome at Xp23.13 with non-obstructive azoospermia and congenital cataracts. J Assist Reprod Genet 2020;37:471–5.Google Scholar
Lubahn, DB, Joseph, DR, Sullivan, PM, Willard, HF, French, FS, Wilson, EM. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 1988;240:327–30.Google Scholar
Ferlin, A, Vinanzi, C, Garolla, A, et al. Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations. Clin Endocrinol (Oxf) 2006;65:606–10.Google Scholar
Abou Alchamat, G, Madania, A, Alhalabi M. Mild androgen insensitivity syndrome (MAIS): the identification of c.1783C>T mutation in two unrelated infertile men. BMJ Case Rep 2017;2017:bcr2017220361.Google Scholar
Goglia, U, Vinanzi, C, Zuccarello, D, et al. Identification of a novel mutation in exon 1 of androgen receptor gene in an azoospermic patient with mild androgen insensitivity syndrome: case report and literature review. Fertil Steril 2011;96:1165–9.Google Scholar
Yue, F, Zhang, H, Xi, Q, et al. Molecular cytogenetic analysis and genetic counseling: a case report of eight 46,XX males and a literature review. Mol Cytogenet 2019;12:44.Google Scholar
Terribile, M, Stizzo, M, Manfredi, C, et al. 46,XX testicular disorder of sex development (DSD): a case report and systematic review. Medicina (Kaunas) 2019;55:371.Google Scholar
Lahn, BT, Page, DC. Functional coherence of the human Y chromosome. Science 1997;278:675–80.Google Scholar
Kuroda-Kawaguchi, T, Skaletsky, H, Brown, LG, et al. The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat Genet 2001;29:279–86.Google Scholar
Colaco, S, Modi, D. Genetics of the human Y chromosome and its association with male infertility. Reprod Biol Endocrinol 2018;16:14.Google Scholar
Sun, C, Skaletsky, H, Rozen, S, et al. Deletion of azoospermia factor a (AZFa) region of human Y chromosome caused by recombination between HERV15 proviruses. Hum Mol Genet 2000;9:2291–6.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
Gueler, B, Sonne, SB, Zimmer, J, et al. AZFa protein DDX3Y is differentially expressed in human male germ cells during development and in testicular tumours: new evidence for phenotypic plasticity of germ cells. Hum Reprod 2012;27:1547–55.Google Scholar
Repping, S, Skaletsky, H, Lange, J, et al. Recombination between palindromes P5 and P1 on the human Y chromosome causes massive deletions and spermatogenic failure. Am J Hum Genet 2002;71:906–22.Google Scholar
Stouffs, K, Lissens, W, Verheyen, G, et al. Expression pattern of the Y-linked PRY gene suggests a function in apoptosis but not in spermatogenesis. Mol Hum Reprod 2004;10:15–21.Google Scholar
Rozen, SG, Marszalek, JD, Irenze, K, et al. AZFc deletions and spermatogenic failure: a population-based survey of 20,000 Y chromosomes. Am J Hum Genet 2012;91:890–6.Google Scholar
Sadeghi-Nejad, H, Oates, RD. The Y chromosome and male infertility. Curr Opin Urol 2008;18:628–32.Google Scholar
Oates, RD, Silber, S, Brown, LG, Page, DC. Clinical characterization of 42 oligospermic or azoospermic men with microdeletion of the AZFc region of the Y chromosome, and of 18 children conceived via ICSI. Hum Reprod 2002;17:2813–24.Google Scholar
Kalantari, H, Asia, S, Totonchi, M, et al. Delineating the association between isodicentric chromosome Y and infertility: a retrospective study. Fertil Steril 2014;101:1091–6.Google Scholar
Yang, Y, Hao, W. Clinical, cytogenetic, and molecular findings of isodicentric Y chromosomes. Mol Cytogenet 2019;12:55.Google Scholar
Zamani, AG, Tuncez, E, Yildirim, MS, Acar, A. Genetic evaluation of an infertile male with a ring Y chromosome and SHOX deletion. Genet Couns 2013;24:449–54.Google Scholar
Jiang, Y, Yue, F, Wang, R, et al. Molecular cytogenetic characterization of an isodicentric Yq and a neocentric isochromosome Yp in an azoospermic male. Mol Med Rep 2020;21:918–26.Google Scholar
Lange, J, Skaletsky, H, van Daalen, SK, et al. Isodicentric Y chromosomes and sex disorders as byproducts of homologous recombination that maintains palindromes. Cell 2009;138:855–69.Google Scholar
Wang, H, Jia, Z, Mao, A, et al. Analysis of balanced reciprocal translocations in patients with subfertility using single-molecule optical mapping. J Assist Reprod Genet 2020;39:509–16.Google Scholar
Zhang, H, Wang, R, Yu, Y, et al. Non-Robertsonian translocations involving chromosomes 13, 14, or 15 in male infertility: 28 cases and a review of the literature. Medicine (Baltimore) 2019;98:e14730.Google Scholar
Goutaki, M, Maurer, E, Halbeisen, FS, et al. The international primary ciliary dyskinesia cohort (iPCD Cohort): methods and first results. Eur Respir J 2017;49:1601181.Google Scholar
Leigh, MW, Pittman, JE, Carson, JL, et al. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Genet Med 2009;11:473–87.Google Scholar
Avellino, GJ, Oates, RD. Primary ciliary dyskinesia. In: Skinner, MK, ed. Encyclopedia of Reproduction, 2nd ed. Boston, MA: Academic Press, 2018; pp. 271–5.Google Scholar
Ji, ZY, Sha, YW, Ding, L, Li, P. Genetic factors contributing to human primary ciliary dyskinesia and male infertility. Asian J Androl 2017;19:515–20.Google Scholar
Knowles, MR, Daniels, LA, Davis, SD, Zariwala, MA, Leigh, MW. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med 2013;188:913–22.Google Scholar
Ebner, T, Maurer, M, Oppelt, P, et al. Healthy twin live-birth after ionophore treatment in a case of theophylline-resistant Kartagener syndrome. J Assist Reprod Genet 2015;32:873–7.Google Scholar
Kordus, RJ, Price, RL, Davis, JM, Whitman-Elia, GF. Successful twin birth following blastocyst culture of embryos derived from the immotile ejaculated spermatozoa from a patient with primary ciliary dyskinesia: a case report. J Assist Reprod Genet 2008;25:437–43.Google Scholar
Davila Garza, SA, Patrizio, P. Reproductive outcomes in patients with male infertility because of Klinefelter’s syndrome, Kartagener’s syndrome, round-head sperm, dysplasia fibrous sheath, and ‘stump’ tail sperm: an updated literature review. Curr Opin Obstet Gynecol 2013;25:229–46.Google Scholar
Hayden, RP, Wright, DL, Toth, TL, Tanrikut, C. Selective use of percutaneous testis biopsy to optimize IVF-ICSI outcomes: a case series. Fertil Res Pract 2016;2:7.Google Scholar
Paff, T, Loges, NT, Aprea, I, et al. Mutations in PIH1D3 cause X-linked primary ciliary dyskinesia with outer and inner dynein arm defects. Am J Hum Genet 2017;100:160–8.Google Scholar
Chemes, HE. Phenotypic varieties of sperm pathology: genetic abnormalities or environmental influences can result in different patterns of abnormal spermatozoa. Anim Reprod Sci 2018;194:41–56.Google Scholar
Sha, Y, Yang, X, Mei, L, et al. DNAH1 gene mutations and their potential association with dysplasia of the sperm fibrous sheath and infertility in the Han Chinese population. Fertil Steril 2017;107:1312–18.Google Scholar
Moretti, E, Gambera, L, Stendardi, A, Belmonte, G, Salvatici, MC, Collodel, G. Characterisation of three systematic sperm tail defects and their influence on ICSI outcome. Andrologia 2018;50:e13128.Google Scholar
Moretti, E, Pascarelli, NA, Belmonte, G, Renieri, T, Collodel, G. Sperm with fibrous sheath dysplasia and anomalies in head-neck junction: focus on centriole and centrin 1. Andrologia 2017;49(7).Google Scholar
Elkina, YL, Kuravsky, ML, Bragina, EE, et al. Detection of a mutation in the intron of sperm-specific glyceraldehyde-3-phosphate dehydrogenase gene in patients with fibrous sheath dysplasia of the sperm flagellum. Andrologia 2017;49(2).Google Scholar
Baccetti, B, Collodel, G, Estenoz, M, Manca, D, Moretti, E, Piomboni, P. Gene deletions in an infertile man with sperm fibrous sheath dysplasia. Hum Reprod 2005;20:2790–4.Google Scholar
Ghedir, H, Braham, A, Viville, S, Saad, A, Ibala-Romdhane, S. Comparison of sperm morphology and nuclear sperm quality in SPATA16- and DPY19L2-mutated globozoospermic patients. Andrologia 2019;51:e13277.Google Scholar
Guo, Y, Jiang, J, Zhang, H, et al. Proteomic analysis of Dpy19l2-deficient human globozoospermia reveals multiple molecular defects. Proteomics Clin Appl 2019;13:e1900007.Google Scholar
Oud, MS, Okutman, O, Hendricks, LAJ, et al. Exome sequencing reveals novel causes as well as new candidate genes for human globozoospermia. Hum Reprod 2020;35:240–52.Google Scholar
Ortega, V, Oyanedel, J, Fleck-Lavergne, D, Horta, F, Mercado-Campero, A, Palma-Ceppi, C. Macrozoospermia associated with mutations of AURKC gene: first case report in Latin America and literature review. Rev Int Androl 2020;18:159–63.Google Scholar
Eloualid, A, Rouba, H, Rhaissi, H, et al. Prevalence of the Aurora kinase C c.144delC mutation in infertile Moroccan men. Fertil Steril 2014;101:1086–90.Google Scholar
Dieterich, K, Soto Rifo, R, Faure, AK, et al. Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. Nat Genet 2007;39:661–5.Google Scholar
Dieterich, K, Zouari, R, Harbuz, R, et al. The Aurora Kinase C c.144delC mutation causes meiosis I arrest in men and is frequent in the North African population. Hum Mol Genet 2009;18:1301–9.Google Scholar
Ounis, L, Zoghmar, A, Coutton, C, et al. Mutations of the aurora kinase C gene causing macrozoospermia are the most frequent genetic cause of male infertility in Algerian men. Asian J Androl 2015;17:68–73.Google Scholar
Guthauser, B, Pollet-Villard, X, Boitrelle, F, Vialard, F. Is intracouple assisted reproductive technology an option for men with large-headed spermatozoa? A literature review and a decision guide proposal. Basic Clin Androl 2016;26:8.Google Scholar
Jequier, AM, Ansell, ID, Bullimore, NJ. Congenital absence of the vasa deferentia presenting with infertility. J Androl 1985;6:15–19.Google Scholar
Shaw, G, Renfree, MB. Wolffian duct development. Sex Dev 2014;8:273–80.Google Scholar
Arroteia, KF, Garcia, PV, Barbieri, MF, Justino, ML, Pereira, LAV. The epididymis: embryology, structure, function, and its role in fertilization and infertility. In: Pereira, LV, ed. Embryology - Updates and Highlights on Classic Topics. Croatia: In Tech, 2012; pp. 41–66.Google Scholar
de Mello, Santos T, Hinton, BT. We, the developing rete testis, efferent ducts, and Wolffian duct, all hereby agree that we need to connect. Andrology 2019;7:581–7.Google Scholar
Netter, FN. The Netter Collection of Medical Illustrations; Reproductive System. Philadelphia, PA: Elsevier Saunders, 2011.Google Scholar
Liou, TG, Rubenstein, RC. Carrier screening, incidence of cystic fibrosis, and difficult decisions. JAMA 2009;302:2595–6.Google Scholar
Buchwald, M, Tsui, LC, Riordan, JR. The search for the cystic fibrosis gene. Am J Physiol 1989;257:L47–52.Google Scholar
Riordan, JR, Rommens, JM, Kerem, B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 1989;245:1066–73.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
Dohle, GR, Veeze, HJ, Overbeek, SE, et al. The complex relationships between cystic fibrosis and congenital bilateral absence of the vas deferens: clinical, electrophysiological and genetic data. Hum Reprod 1999;14:371–4.Google Scholar
Yu, J, Chen, Z, Ni, Y, Li, Z. CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): a systemic review and meta-analysis. Hum Reprod 2012;27:25–35.Google Scholar
de Souza, DAS, Faucz, FR, Pereira-Ferrari, L, Sotomaior, VS, Raskin, S. Congenital bilateral absence of the vas deferens as an atypical form of cystic fibrosis: reproductive implications and genetic counseling. Andrology 2018;6:127–35.Google Scholar
Khan, MJ, Pollock, N, Jiang, H, et al. X-linked ADGRG2 mutation and obstructive azoospermia in a large Pakistani family. Sci Rep 2018;8:16280.Google Scholar
Pagin, A, Bergougnoux, A, Girodon, E, et al. Novel ADGRG2 truncating variants in patients with X-linked congenital absence of vas deferens. Andrology 2020;8:618–24.Google Scholar
Yuan, P, Liang, ZK, Liang, H, et al. Expanding the phenotypic and genetic spectrum of Chinese patients with congenital absence of vas deferens bearing CFTR and ADGRG2 alleles. Andrology 2019;7:329–40.Google Scholar
Wu, YN, Chen, KC, Wu, CC, Lin, YH, Chiang, HS. SLC9A3 affects vas deferens development and associates with Taiwanese congenital bilateral absence of the vas deferens. Biomed Res Int 2019;2019:3562719.Google Scholar
McCallum, T, Milunsky, J, Munarriz, R, Carson, R, Sadeghi-Nejad, H, Oates, R. Unilateral renal agenesis associated with congenital bilateral absence of the vas deferens: phenotypic findings and genetic considerations. Hum Reprod 2001;16:282–8.Google Scholar
Schlegel, PN, Sigman, M, Collura, B, et al. Diagnosis and treatment of infertility in men: AUA/ASRM Guideline Part 1. J Urol 2021;205:36–43.Google Scholar
Garcia-Mengual, E, Trivino, JC, Saez-Cuevas, A, Bataller, J, Ruiz-Jorro, M, Vendrell, X. Male infertility: establishing sperm aneuploidy thresholds in the laboratory. J Assist Reprod Genet 2019;36:371–81.Google Scholar
Hotaling, J, Carrell, DT. Clinical genetic testing for male factor infertility: current applications and future directions. Andrology 2014;2:339–50.Google Scholar
Franasiak, JM, Forman, EJ, Hong, KH, et al. The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril 2014;101:656–63 e1.Google Scholar
Nybo, AA, Wohlfahrt, J, Christens, P, Olsen, J, Melbye, M. Is maternal age an independent risk factor for fetal loss? West J Med 2000;173:331.Google Scholar
Brahem, S, Mehdi, M, Elghezal, H, Saad, A. The effects of male aging on semen quality, sperm DNA fragmentation and chromosomal abnormalities in an infertile population. J Assist Reprod Genet 2011;28:425–32.Google Scholar
Moskovtsev, SI, Willis, J, Mullen, JB. Age-related decline in sperm deoxyribonucleic acid integrity in patients evaluated for male infertility. Fertil Steril 2006;85:496–9.Google Scholar
D’Onofrio, BM, Rickert, ME, Frans, E, et al. Paternal age at childbearing and offspring psychiatric and academic morbidity. JAMA Psychiatry 2014;71:432–8.Google Scholar
Sharma, R, Agarwal, A, Rohra, VK, Assidi, M, Abu-Elmagd, M, Turki, RF. Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring. Reprod Biol Endocrinol 2015;13:35.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×