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Turgut NE, Basar MM. Case report: Comprehensive evaluation and management of male infertility with complete AZFC microdeletion and undescended testicle. Urol Case Rep 2025; 59:102934. [PMID: 39885845 PMCID: PMC11780711 DOI: 10.1016/j.eucr.2025.102934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 01/06/2025] [Indexed: 02/01/2025] Open
Abstract
This case report presents a 31-year-old male patient with primary infertility, a unilaterally undescended testicle, and a complete AZFc microdeletion. Despite failed attempts at testicular sperm extraction, the patient underwent successful microscopic testicular sperm extraction and subsequent viable sperm extraction, leading to successful fertilization through intracytoplasmic sperm injection (ICSI). The report underscores the potential for successful ICSI in male infertility cases with complex genetic and reproductive issues, highlighting the importance of comprehensive genetic evaluation and individualized reproductive techniques in managing male infertility associated with undescended testicle and genetic anomalies.
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Munoz-Lopez C, Wong A, Lewis K, Bole R, Vij SC, Lundy SD. The Evolving Landscape of Male Varicocele Pathophysiology in the Era of Multi-Omics: A Narrative Review of the Current Literature. BIOLOGY 2024; 13:80. [PMID: 38392299 PMCID: PMC10886418 DOI: 10.3390/biology13020080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 01/22/2024] [Accepted: 01/25/2024] [Indexed: 02/24/2024]
Abstract
Male-factor infertility is implicated in over half of the millions of cases of infertility worldwide, and varicoceles are the most common correctable cause of male-factor infertility. The pathophysiologic mechanism for varicoceles is complex and next-generation technologies offer promising insights into the molecular underpinnings of this condition. In this narrative review, we highlight historical and contemporary paradigms associated with varicoceles, with an emphasis on the biological underpinnings of this disease. Specifically, we review the literature describing the underlying causes of varicoceles, discuss the molecular and cellular mechanisms causing pathological changes in some (but not all) men, and highlight key articles regarding the next-generation analyses (e.g., transcriptome, epigenome, proteome, and microbiome) being applied to better understand the condition and its treatment. These data demonstrate an ongoing evolution of the knowledge of varicoceles and the potential for improved personalized care in the future for men with this condition.
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Affiliation(s)
- Carlos Munoz-Lopez
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA
- Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195, USA
| | - Anne Wong
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA
- Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195, USA
| | - Kieran Lewis
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA
- Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195, USA
| | - Raevti Bole
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Sarah C Vij
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Scott D Lundy
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA
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Lee TH, Song SH, Kim DK, Shim SH, Jeong D, Kim DS. An analysis of Y-chromosome microdeletion in infertile Korean men with severe oligozoospermia or azoospermia. Investig Clin Urol 2024; 65:77-83. [PMID: 38197754 PMCID: PMC10789543 DOI: 10.4111/icu.20230141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 08/19/2023] [Accepted: 10/16/2023] [Indexed: 01/11/2024] Open
Abstract
PURPOSE Infertility affects 10% to 15% of couples, and male factor accounts for 50% of the cases. The relevant male genetic factors, which account for at least 15% of male infertility, include Y-chromosome microdeletions. We investigated clinical data and patterns of Y-chromosome microdeletions in Korean infertile men. MATERIALS AND METHODS A total of 919 infertile men whose sperm concentration was ≤5 million/mL in two consecutive analyses were investigated for Y-chromosome microdeletion. Among them, 130 infertile men (14.1%) demonstrated Y-chromosome microdeletions. Medical records were retrospectively reviewed. RESULTS In 130 men with Y-chromosome microdeletions, 90 (69.2%) had azoospermia and 40 (30.8%) had severe oligozoospermia. The most frequent microdeletions were in the azoospermia factor (AZF) c region (77/130, 59.2%), followed by the AZFb+c (30/130, 23.1%), AZFa (8/130, 6.2%), AZFb (7/130, 5.4%), AZFa+b+c (7/130, 5.4%), and AZFa+c (1/130, 0.7%) regions. In men with oligozoospermia, 37 (92.5%) had AZFc microdeletion. Chromosomal abnormalities were detected in 30 patients (23.1%). Higher follicle-stimulating hormone level (23.2±13.5 IU/L vs. 15.1±9.0 IU/L, p<0.001), higher luteinizing hormone level (9.7±4.6 IU/L vs. 6.0±2.2 IU/L, p<0.001), and lower testis volume (10.6±4.8 mL vs. 13.3±3.8 mL, p<0.001) were observed in azoospermia patients compared to severe oligozoospermia patients. CONCLUSIONS Y-chromosome microdeletion is a common genetic cause of male infertility. Therefore, Y-chromosome microdeletion test is recommended for the accurate diagnosis of men with azoospermia or severe oligozoospermia. Appropriate genetic counseling is mandatory before the use of assisted reproduction technique in men with Y-chromosome microdeletion.
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Affiliation(s)
- Tae Ho Lee
- Department of Urology, Fertility Center, CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Seung-Hun Song
- Department of Urology, Fertility Center, CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Dae Keun Kim
- Department of Urology, CHA Fertility Center Seoul Station, CHA University, Seoul, Korea
| | - Sung Han Shim
- Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea
| | - Daeun Jeong
- Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea
| | - Dong Suk Kim
- Department of Urology, Fertility Center, CHA Gangnam Medical Center, CHA University, Seoul, Korea.
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Asanad K, Greenfeld E, Scherer SW, Yuen R, Marshall CR, Lo K, Mullen B, Lau S, Jarvi KA, Samplaski MK. Uncovering the Association Between Complete AZFc Microduplications and Spermatogenic Ability: The First Reported Series. Cureus 2023; 15:e51140. [PMID: 38283528 PMCID: PMC10811380 DOI: 10.7759/cureus.51140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/26/2023] [Indexed: 01/30/2024] Open
Abstract
Purpose This article aims to report the first series of men with complete AZFc microduplications and their clinical and reproductive characteristics. Methods We sampled 3000 men who presented for reproductive urology evaluation from 2012-2020, of which 104 men underwent high-resolution Y-chromosome microarray testing, and five men were identified to have complete AZFc microduplications. Medical, surgical, and reproductive histories were obtained. Semen and hormonal parameters as well as response to fertility therapies were recorded. Results Five men were identified as having complete AZFc microduplications. The mean age was 33.75 years, representing 0.2% (5/3000) of men presenting for fertility investigation, 4.8% (5/104) of men undergoing microarray testing, and 21% (5/24) of men with AZFc abnormalities. Two of the men had prior undescended testicles and one had several autoimmune processes. The mean follicle-stimulating hormone (FSH) was 5.5 IU/L, luteinizing hormone (LH) 3.6 IU/L, and testosterone 14.56 nmol/L. One man was azoospermic, one man alternated between severe oligospermia and rare non-motile sperm, one had variable parameters, with one semen analysis demonstrating azoospermia and a second demonstrating a total motile sperm count (TMSC) of 4 ×106, one man was persistently oligospermic with TMSCs ranging 3.96-12.6 ×106, and one man initially had severe oligospermia, with a mean TMSC of 1.5 ×106, which increased to 21.7 ×106 after intervention (varicocele embolization, clomiphene citrate). This last man then fathered a spontaneous pregnancy. Conclusion AZFc complete microduplications are a rare cause of spermatogenic failure but not an uncommon form of AZFc abnormality. Clinically, they represent a heterogeneous group, having a variable reproductive potential. Cases should be managed on an individual basis.
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Affiliation(s)
- Kian Asanad
- Institute of Urology, University of Southern California Keck School of Medicine, Los Agneles, USA
| | - Elena Greenfeld
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital Joseph and Wolf Lebovic Health Complex, Toronto, CAN
| | - Stephen W Scherer
- McLaughlin Center and Department of Molecular Genetics, Mount Sinai Hospital, Toronto, CAN
| | - Ryan Yuen
- McLaughlin Center and Department of Molecular Genetics, Mount Sinai Hospital, Toronto, CAN
| | - Christian R Marshall
- McLaughlin Center and Department of Molecular Genetics, Mount Sinai Hospital, Toronto, CAN
| | - Kirk Lo
- Division of Urology, Department of Surgery, Mount Sinai Hospital, Toronto, CAN
| | - Brendan Mullen
- Division of Urology, Department of Surgery, Mount Sinai Hospital, Toronto, CAN
| | - Susan Lau
- Division of Urology, Department of Surgery, Mount Sinai Hospital, Toronto, CAN
| | - Keith A Jarvi
- Division of Urology, Department of Surgery, Mount Sinai Hospital, Toronto, CAN
| | - Mary K Samplaski
- Institute of Urology, University of Southern California Keck School of Medicine, Los Angeles, USA
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Eisenberg ML, Esteves SC, Lamb DJ, Hotaling JM, Giwercman A, Hwang K, Cheng YS. Male infertility. Nat Rev Dis Primers 2023; 9:49. [PMID: 37709866 DOI: 10.1038/s41572-023-00459-w] [Citation(s) in RCA: 117] [Impact Index Per Article: 58.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/09/2023] [Indexed: 09/16/2023]
Abstract
Clinical infertility is the inability of a couple to conceive after 12 months of trying. Male factors are estimated to contribute to 30-50% of cases of infertility. Infertility or reduced fertility can result from testicular dysfunction, endocrinopathies, lifestyle factors (such as tobacco and obesity), congenital anatomical factors, gonadotoxic exposures and ageing, among others. The evaluation of male infertility includes detailed history taking, focused physical examination and selective laboratory testing, including semen analysis. Treatments include lifestyle optimization, empirical or targeted medical therapy as well as surgical therapies that lead to measurable improvement in fertility. Although male infertility is recognized as a disease with effects on quality of life for both members of the infertile couple, fewer data exist on specific quantification and impact compared with other health-related conditions.
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Affiliation(s)
- Michael L Eisenberg
- Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
- Department of Obstetrics & Gynecology, Stanford University School of Medicine, Stanford, CA, USA.
| | - Sandro C Esteves
- ANDROFERT Andrology and Human Reproduction Clinic, Campinas, Brazil
- Division of Urology, Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil
| | - Dolores J Lamb
- Center for Reproductive Genomics, Weill Cornell Medical College, New York, NY, USA
- Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, NY, USA
- Department of Urology, Weill Cornell Medical College, New York, NY, USA
| | - James M Hotaling
- Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA
| | | | - Kathleen Hwang
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Yu-Sheng Cheng
- Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance. Int J Mol Sci 2022; 24:ijms24010524. [PMID: 36613967 PMCID: PMC9820667 DOI: 10.3390/ijms24010524] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 12/21/2022] [Accepted: 12/24/2022] [Indexed: 12/30/2022] Open
Abstract
Deciphering the functional relationships of genes resulting from genome-wide screens for polymorphisms that are associated with phenotypic variations can be challenging. However, given the common association with certain phenotypes, a functional link should exist. We have tested this prediction in newly sequenced exomes of altogether 100 men representing different states of fertility. Fertile subjects presented with normal semen parameters and had naturally fathered offspring. In contrast, infertile probands were involuntarily childless and had reduced sperm quantity and quality. Genome-wide association study (GWAS) linked twelve non-synonymous single-nucleotide polymorphisms (SNPs) to fertility variation between both cohorts. The SNPs localized to nine genes for which previous evidence is in line with a role in male fertility maintenance: ANAPC1, CES1, FAM131C, HLA-DRB1, KMT2C, NOMO1, SAA1, SRGAP2, and SUSD2. Most of the SNPs residing in these genes imply amino acid exchanges that should only moderately affect protein functionality. In addition, proteins encoded by genes from present GWAS occupied peripheral positions in a protein-protein interaction network, the backbone of which consisted of genes listed in the Online Mendelian Inheritance in Man (OMIM) database for their implication in male infertility. Suggestive of an indirect impact on male fertility, the genes focused were indeed linked to each other, albeit mediated by other interactants. Thus, the chances of identifying a central player in male infertility by GWAS could be limited in general. Furthermore, the SNPs determined and the genes containing these might prove to have potential as biomarkers in the diagnosis of male fertility.
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Translational Bioinformatics for Human Reproductive Biology Research: Examples, Opportunities and Challenges for a Future Reproductive Medicine. Int J Mol Sci 2022; 24:ijms24010004. [PMID: 36613446 PMCID: PMC9819745 DOI: 10.3390/ijms24010004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/16/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Since 1978, with the first IVF (in vitro fertilization) baby birth in Manchester (England), more than eight million IVF babies have been born throughout the world, and many new techniques and discoveries have emerged in reproductive medicine. To summarize the modern technology and progress in reproductive medicine, all scientific papers related to reproductive medicine, especially papers related to reproductive translational medicine, were fully searched, manually curated and reviewed. Results indicated whether male reproductive medicine or female reproductive medicine all have made significant progress, and their markers have experienced the progress from karyotype analysis to single-cell omics. However, due to the lack of comprehensive databases, especially databases collecting risk exposures, disease markers and models, prevention drugs and effective treatment methods, the application of the latest precision medicine technologies and methods in reproductive medicine is limited.
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Arya D, Balasinor N, Singh D. Varicocele associated male infertility: cellular and molecular perspectives of pathophysiology. Andrology 2022; 10:1463-1483. [PMID: 36040837 DOI: 10.1111/andr.13278] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 08/18/2022] [Accepted: 08/18/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Varicocele is a common risk factor associated with reduced male fertility potential. The current understanding of varicocele pathophysiology does not completely explain the clinical manifestation of infertility. The present treatment options such as antioxidant supplementation and varicocelectomy only helps ∼35% of men to achieve spontaneous pregnancy. OBJECTIVE This review aims to summarize the available knowledge on cellular and molecular alterations implicated to varicocele associated male infertility and also highlights the new knowledge generated by 'Omics' technologies. MATERIALS AND METHODS PubMed, MEDLINE, Cochrane and Google Scholar databases are searched using different combinations of keywords (varicocele, infertile/fertile men with varicocele, cellular changes, molecular mechanisms, proteome, epigenome, transcriptome and metabolome). A total of 229 relevant human and animal studies published till 2021 were included in this review. RESULTS Current understanding advocates oxidative stress (OS) as a major contributory factor to the varicocele associated male infertility. Excessive OS causes alteration in testicular microenvironment and sperm DNA fragmentation which further contributes to infertility. Molecular and omics studies have identified several promising biomarkers such as AAMP, SPINT1, MKI67 (genetic markers), sperm quality and function related protein markers, global sperm DNA methylation level (epigenetic marker), Hspa2, Protamine, Gadd7, Dynlt1 and Beclin1 (mRNA markers), PRDX2, HSPA, APOA2, YKL40 (seminal protein markers), total choline and PHGDH (metabolic markers). DISCUSSION Mature spermatozoa harbours a plethora of molecular information in form of proteome, epigenome and transcriptome; which could provide very important clues regarding pathophysiology of varicocele associated infertility. Recent molecular and omics studies in infertile men with varicocele have identified several promising biomarkers. Upon further validation with larger and well-defined studies, some of these biomarkers could aid in varicocele management. CONCLUSION The present evidences suggest inclusion of OS and sperm DNA fragmentation tests could be useful to the diagnostic workup for men with varicocele. Furthermore, including precise molecular markers may assist in diagnostics and prognostics of varicocele associated male infertility. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Deepshikha Arya
- Department of Neuroendocrinology, ICMR- National Institute for Research in Reproductive and Child Health, Parel, Mumbai, 400012, India
| | - Nafisa Balasinor
- Department of Neuroendocrinology, ICMR- National Institute for Research in Reproductive and Child Health, Parel, Mumbai, 400012, India
| | - Dipty Singh
- Department of Neuroendocrinology, ICMR- National Institute for Research in Reproductive and Child Health, Parel, Mumbai, 400012, India
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Wang C, Mbizvo M, Festin MP, Björndahl L, Toskin I. Evolution of the WHO "Semen" processing manual from the first (1980) to the sixth edition (2021). Fertil Steril 2022; 117:237-245. [PMID: 34996596 PMCID: PMC8842884 DOI: 10.1016/j.fertnstert.2021.11.037] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 11/29/2021] [Accepted: 11/29/2021] [Indexed: 12/13/2022]
Abstract
As stated clearly in all editions of the WHO Laboratory Manual for the Examination and Processing of Human Semen, the goal of the manual is to meet the growing needs for the standardization of semen analysis procedures. With constant advances in andrology and reproductive medicine and the advent of sophisticated assisted reproductive technologies for the treatment of infertility, the manual has been continuously updated to meet the need for new, evidence-based, validated tests to not only measure semen and sperm variables but also to provide a functional assessment of spermatozoa. The sixth edition of the WHO manual, launched in 2021, can be freely downloaded from the WHO website, with the hope of gaining wide acceptance and utilization as the essential source of the latest, evidence-based information for laboratory procedures required for the assessment of male reproductive function and health.
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Affiliation(s)
- Christina Wang
- Clinical and Translational Science Institute, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California.
| | - Michael Mbizvo
- Reproductive Health Sciences, University of Zimbabwe and Country Director/Senior Associate, Population Council, Lusaka, Zambia
| | - Mario P Festin
- Department of Obstetrics and Gynecology and Department of Clinical Epidemiology, College of Medicine, University of the Philippines, Manila, Philippines
| | - Lars Björndahl
- ANOVA, Clinic for Endocrinology, Karolinska University Hospital and Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Igor Toskin
- Other Editorial Board Members and Contributors of the WHO Laboratory Manual for the Examination and Processing of Human Semen, 6th edition
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10
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Barratt CLR, Wang C, Baldi E, Toskin I, Kiarie J, Lamb DJ. What advances may the future bring to the diagnosis, treatment, and care of male sexual and reproductive health? Fertil Steril 2022; 117:258-267. [PMID: 35125173 PMCID: PMC8877074 DOI: 10.1016/j.fertnstert.2021.12.013] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 12/15/2021] [Accepted: 12/15/2021] [Indexed: 12/11/2022]
Abstract
Over the past 40 years, since the publication of the original WHO Laboratory Manual for the Examination and Processing of Human Semen, the laboratory methods used to evaluate semen markedly changed and benefited from improved precision and accuracy, as well as the development of new tests and improved, standardized methodologies. Herein, we present the impact of the changes put forth in the sixth edition together with our views of evolving technologies that may change the methods used for the routine semen analysis, up-and-coming areas for the development of new procedures, and diagnostic approaches that will help to extend the often-descriptive interpretations of several commonly performed semen tests that promise to provide etiologies for the abnormal semen parameters observed. As we look toward the publication of the seventh edition of the manual in approximately 10 years, we describe potential advances that could markedly impact the field of andrology in the future.
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Affiliation(s)
- Christopher L R Barratt
- Division of Systems Medicine, University of Dundee Medical School, Ninewells Hospital, Dundee, Scotland.
| | - Christina Wang
- Clinical and Translational Science Institute, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California
| | - Elisabetta Baldi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Igor Toskin
- Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland
| | - James Kiarie
- Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland
| | - Dolores J Lamb
- The James Buchanan Brady Foundation Department of Urology, Center for Reproductive Genomics and Englander Institute for Personalized Medicine, Weill Cornell Medical College, New York, New York
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11
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Golin AP, Yuen W, Flannigan R. The effects of Y chromosome microdeletions on in vitro fertilization outcomes, health abnormalities in offspring and recurrent pregnancy loss. Transl Androl Urol 2021; 10:1457-1466. [PMID: 33850780 PMCID: PMC8039589 DOI: 10.21037/tau-19-672] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Male factor infertility accounts for approximately 50% of all infertility evaluations. A common cause of severe oligozoospermia and azoospermia is Y chromosome microdeletions (YCMs). Men with these genetic microdeletions must typically undergo assisted reproductive technology (ART) procedures to obtain paternity. In this review, we performed a thorough and extensive search of the literature to summarize the effects of YCMs on in vitro fertilization (IVF) outcomes, health abnormalities in offspring and recurrent pregnancy loss (RPL). The PubMed database was searched using specific search terms and papers were identified using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Sperm retrieval amongst men with complete AZFa and/or AZFb deletions is extremely rare and thus data on ARTs is largely unavailable. In AZFc-deleted men undergoing assisted reproduction, the collective fertilization rate (FR) is 59.8%, the clinical pregnancy rate is 28.6% and the live birth rate is 23.4%. When successful, the YCM is always transmitted to the male offspring and the deletion size either remains unchanged or widens. YCMs generally result in decreased fertilization, clinical pregnancy and live birth rates compared to men with intact Y chromosomes during ART interventions. There is a minimal or absent association of YCMs with abnormalities in the offspring or RPL.
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Affiliation(s)
- Andrew P Golin
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
| | - Wallace Yuen
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
| | - Ryan Flannigan
- Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
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12
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Agarwal A, Baskaran S, Parekh N, Cho CL, Henkel R, Vij S, Arafa M, Panner Selvam MK, Shah R. Male infertility. Lancet 2021; 397:319-333. [PMID: 33308486 DOI: 10.1016/s0140-6736(20)32667-2] [Citation(s) in RCA: 530] [Impact Index Per Article: 132.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 08/13/2020] [Accepted: 08/19/2020] [Indexed: 02/06/2023]
Abstract
It is estimated that infertility affects 8-12% of couples globally, with a male factor being a primary or contributing cause in approximately 50% of couples. Causes of male subfertility vary highly, but can be related to congenital, acquired, or idiopathic factors that impair spermatogenesis. Many health conditions can affect male fertility, which underscores the need for a thorough evaluation of patients to identify treatable or reversible lifestyle factors or medical conditions. Although semen analysis remains the cornerstone for evaluating male infertility, advanced diagnostic tests to investigate sperm quality and function have been developed to improve diagnosis and management. The use of assisted reproductive techniques has also substantially improved the ability of couples with infertility to have biological children. This Seminar aims to provide a comprehensive overview of the assessment and management of men with infertility, along with current controversies and future endeavours.
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Affiliation(s)
- Ashok Agarwal
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA.
| | - Saradha Baskaran
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Neel Parekh
- Department of Urology, Cleveland Clinic, Cleveland, OH, USA
| | - Chak-Lam Cho
- SH Ho Urology Center, Department of Surgery, Chinese University of Hong Kong, Hong Kong
| | - Ralf Henkel
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA; Department of Medical Bioscience, University of Western Cape, Bellville, South Africa; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Sarah Vij
- Department of Urology, Cleveland Clinic, Cleveland, OH, USA
| | - Mohamed Arafa
- Male Infertility Unit, Urology Department, Hamad Medical Corporation, Doha, Qatar; Andrology Department, Cairo University, Cairo, Egypt
| | | | - Rupin Shah
- Department of Urology, Lilavati Hospital and Research Center, Mumbai, India
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13
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Nadă ES, Albu DF, Pătraşcu A, Albu ŞD, Gogănău AM, Albu CC. Current opportunities and new horizons into the genetic study of infertility. ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY = REVUE ROUMAINE DE MORPHOLOGIE ET EMBRYOLOGIE 2021; 62:191-200. [PMID: 34609421 PMCID: PMC8597361 DOI: 10.47162/rjme.62.1.18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 08/11/2021] [Indexed: 11/17/2022]
Abstract
INTRODUCTION An estimated 12.5% of couples experiencing fertility problems and almost 12% of reproductive age women have turned to health services at least once due to infertility. First trimester miscarriage is the most common clinical manifestation of infertility associated with a genetic cause. PATIENTS, MATERIALS AND METHODS The scientific research was conducted at A.S. Medical Center in Bucharest, Romania, between January 2016 and December 2018, on a representative group of 1264 Caucasian patients diagnosed with infertility, from which the study group was selected, consisting of 273 patients who were further genetically investigated. RESULTS Chromosomal instability, identified in 14% of patients, has been encountered most frequently in women (7%), and least often in fetuses (2%), unlike other chromosomal anomalies, identified in 55% of patients, which were more common in fetuses (27%) and least frequently in men (9%). Recurrent pregnancy loss due to genetic causes was identified in 53% of cases, being determined by chromosomal instability in 16% of cases and by other chromosomal anomalies in 37% of cases. Infertility due to a genetic cause was identified in 83% of cases, being determined by chromosomal instability in 17% of cases and by other chromosomal anomalies encountered in 66% of cases. In genetic risk pregnancies in evolution, fetal chromosomal anomalies were detected in 94% of cases, the most frequent being aneuploidy and polyploidy. Cytogenetic studies carried out on tissue fragments taken from aborted products of conception revealed the presence of a genetic cause in 57% of cases, an abnormal chromosome number being the most common (36%). The analysis of microdeletions of the long arm of the Y chromosome indicated that 5.5% of men with infertility are affected by this condition. CONCLUSIONS Although genetic tests are considered complex and expensive laboratory investigations, they are crucial in identifying the etiology of over 40% of infertility cases associated with genetic factors, as well as in the correct and effective management of infertility.
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Affiliation(s)
- Elena-Silvia Nadă
- Department of Obstetrics and Gynecology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Dinu-Florin Albu
- Department of Obstetrics and Gynecology, Prof. Dr. Panait Sîrbu Clinical Hospital of Obstetrics and Gynecology, Bucharest, Romania
| | - Anca Pătraşcu
- Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, Romania
| | - Ştefan-Dimitrie Albu
- Doctoral School, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | | | - Cristina-Crenguţa Albu
- Department of Genetics, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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14
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Huyghe E, Boitrelle F, Methorst C, Mieusset R, Ray PF, Akakpo W, Koscinski I, Chalas C, Rives N, Plotton I, Robin G, El Osta R, Hennebicq S, Eustache F, Marcelli F, Lejeune H. [AFU and SALF recommendations for the evaluation of male infertility]. Prog Urol 2020; 31:131-144. [PMID: 33309127 DOI: 10.1016/j.purol.2020.09.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 07/20/2020] [Accepted: 09/10/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND The aim of these Association Française d'Urologie (AFU) and Société d'Andrologie de Langue Française (SALF) common recommendations are to provide practice guidelines for the French Urological and Andrological community regarding the evaluation of infertile men. MATERIAL AND METHODS Literature search in PubMed using the keywords "male infertility", "diagnosis", "management" and "evaluation" limited to clinical articles in English and French prior to 1/01/2020. To inform the level of evidence, the HAS grading system (2013) was applied. RESULTS Concerning the evaluation of infertile men, the AFU and the SALF recommend : (1) a systematic interview exploring the family history, the fertility history of the man outside the couple, the patient's personal history that may have an impact on his fertility, lifestyle habits, treatments, symptoms and possible sexual difficulties of the couple; (2) a general physical examination to assess signs of hypogonadism and secondary sexual characters; (3) a scrotal physical examination performed by an urologist or andrologist to assess (i) the testes for volume and consistency, (ii) vas deferens and epididymes for total or partial absence or nodules, and (iii) presence of varicoceles; (4) Performing two semen analyses, according to World Health Organization guidelines, if the first one has at least one abnormaly; (5) a scrotal ultrasound as part of routine investigation, that can be completed with an endorectal pelvic ultrasound according to the clinic; (6) an endocrine evaluation with at least a Testosterone and FSH serum determination; (7) Karyotype analysis in infertile men with a sperm concentration ≤10 106/mL; (8) assessment of Yq microdeletions in infertile men with a sperm concentration ≤1 106/mL; (9) Cystic fibrosis transmembrane conductance regulator gene evaluation in case of suspicion for bilateral or unilateral congenital agenesis of vas deferens and seminal vesicles. The interest of tests analyzing DNA fragmentation (TUNEL, SCSA) is still under investigation. CONCLUSION These guidelines can be applied in routine clinical practice in all infertile men.
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Affiliation(s)
- Eric Huyghe
- Département d'Urologie, Transplantation Rénale et Andrologie, CHU de Toulouse, site de Rangueil, Toulouse, France; Médecine de la Reproduction, CHU de Toulouse, site de Paule de Viguier, Toulouse, France.
| | - Florence Boitrelle
- Service de gynécologie-obstétrique, CHI Poissy/Saint-Germain-en-Laye, Poissy, France
| | | | - Roger Mieusset
- Médecine de la Reproduction, CHU de Toulouse, site de Paule de Viguier, Toulouse, France
| | - Pierre F Ray
- Service de Biologie, Génétique de la reproduction, CHU de Grenoble, France
| | - William Akakpo
- Service d'Urologie, Hôpital universitaire de la Pitié Salpêtrière, APHP, Paris, France
| | | | - Céline Chalas
- Service d'Histologie, embryologie, cytologie, Hôpital Cochin, APHP, Paris, France
| | - Nathalie Rives
- Laboratoire de Biologie de la Reproduction, CECOS, CHU de Rouen, France
| | - Ingrid Plotton
- Service de médecine de la reproduction, Hôpital Femme Mère Enfant, HCL, Bron, France
| | - Geoffroy Robin
- Service de gynécologie, Médecine de la reproduction, Hôpital Jeanne de Flandres, CHRU de Lille, France
| | | | | | | | | | - Hervé Lejeune
- Service de médecine de la reproduction, Hôpital Femme Mère Enfant, HCL, Bron, France
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15
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Sharma A, Halder A, Kaushal S, Jain M. Intra-individual Genomic Variation Analysis in Tissues (Blood vs. Testis) Through SNP Microarray: A Case Report of Two Patients with Idiopathic Sertoli Cell Only Syndrome (SCOS). J Reprod Infertil 2020; 21:308-311. [PMID: 33209739 PMCID: PMC7648869 DOI: 10.18502/jri.v21i4.4325] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background: Inflammatory responses within the peritoneal cavity may result in endometrial dysfunction in women with endometriosis. The true causes of this disease remain poorly understood. It is hypothesized that downstream toll-like receptors (TLRs) inflammatory cytokines in response to pathogens may be associated with endometriosis. So, this study was aimed at evaluating the expression of TLRs signaling and endometriosis-associated inflammatory responses. Methods: Totally, 20 infertile endometriosis patients and 20 normal women undergoing controlled ovarian stimulation were enrolled. The cellular pellet and supernatant were obtained by centrifugation of follicular fluid (FF). Evaluation of TLRs and their signaling pathway gene expression was performed on cellular pellets using quantitative-PCR. The supernatant was used for determination of cytokine protein expression by ELISA. The results are expressed as mean±SEM and a p<0.05 was considered statistically significant. Results: Quantitative-PCR analysis suggested that TLR1, 5, 6, 7, 8, 10, MYD88, NF-ĸB, IL-10 and TGF-β genes expression significantly increased in patients compared to the control group (p<0.05). TLR3, 9, INF-β genes expression was significantly lower in endometriosis than control group (p<0.05). There was no significant difference in the expression of TLR2, TLR4, TIRAP, TRIF, TRAM, and IRF3 between two groups. Also, significant increase in the levels of IL-6, IL-8 and MIF protein in FF of endometriosis group was detected in comparison with normal women (p<0.05). Conclusion: The expression of TLR downstream signaling in the follicular cells can initiate inflammatory responses and changes in the FF cytokine profile which in turn may induce endometriosis and infertility disorder.
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Affiliation(s)
- Aiyush Sharma
- Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi, India
| | - Ashutosh Halder
- Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi, India
| | - Seema Kaushal
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Manish Jain
- Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi, India
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16
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Abstract
A male factor is a contributor in 50% of cases of infertility. Although assisted reproductive techniques can often bypass the need to improve semen parameters, the evaluation of the infertile man remains critical. Current methods for evaluating the infertile man are discussed, beginning with the basic workup that all suspected infertile men should undergo, followed by subsequent evaluation steps. Although the fundamental components of the evaluation have remained consistent, several new tools are available to assist in identifying the underlying etiology. As our understanding of male fertility expands, the technologies available to diagnose and ultimately treat it continue to evolve.
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Affiliation(s)
- Ujval Ishu Pathak
- Scott Department of Urology, Baylor College of Medicine, 6624 Fannin Street, Suite 1700, Houston, TX 77030, USA
| | - Joseph Scott Gabrielsen
- Department of Urology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 656, Rochester, NY 14642, USA
| | - Larry I Lipshultz
- Scott Department of Urology, Baylor College of Medicine, 6624 Fannin Street, Suite 1700, Houston, TX 77030, USA.
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17
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Al-Janabi AM, Rahim AI, Faris SA, Al-Khafaji SM, Jawad D. Prevalence of Y chromosome microdeletion in azoospermic infertile males of Iraqi population. J Genet 2020. [DOI: 10.1007/s12041-020-1181-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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18
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Babakhanzadeh E, Nazari M, Ghasemifar S, Khodadadian A. Some of the Factors Involved in Male Infertility: A Prospective Review. Int J Gen Med 2020; 13:29-41. [PMID: 32104049 PMCID: PMC7008178 DOI: 10.2147/ijgm.s241099] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 01/23/2020] [Indexed: 01/04/2023] Open
Abstract
Infertility is defined as the inability of couples to have a baby after one year of regular unprotected intercourse, affecting 10 to 15% of couples. According to the latest WHO statistics, approximately 50-80 million people worldwide sufer from infertility, and male factors are responsible for approximately 20-30% of all infertility cases. The diagnosis of infertility in men is mainly based on semen analysis. The main parameters of semen include: concentration, appearance and motility of sperm. Causes of infertility in men include a variety of things including hormonal disorders, physical problems, lifestyle problems, psychological issues, sex problems, chromosomal abnormalities and single-gene defects. Despite numerous efforts by researchers to identify the underlying causes of male infertility, about 70% of cases remain unknown. These statistics show a lack of understanding of the mechanisms involved in male infertility. This article focuses on the histology of testicular tissue samples, the male reproductive structure, factors affecting male infertility, strategies available to find genes involved in infertility, existing therapeutic methods for male infertility, and sperm recovery in infertile men.
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Affiliation(s)
- Emad Babakhanzadeh
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Majid Nazari
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Sina Ghasemifar
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Ali Khodadadian
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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19
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Wang Q, Yu Y, Liu Y, Wang L. Outcome of varicocelectomy on different degrees of total motile sperm count: A systematic review and meta-analysis. Syst Biol Reprod Med 2019; 65:430-436. [PMID: 31434522 DOI: 10.1080/19396368.2019.1655813] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- Qun Wang
- Department of Reproductive Medicine, Department of Prenatal Diagnosis, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yang Yu
- Department of Reproductive Medicine, Department of Prenatal Diagnosis, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yanhong Liu
- Department of Reproductive Medicine, Department of Prenatal Diagnosis, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Libo Wang
- Department of Pediatric Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin, China
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20
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Kohn TP, Kohn JR, Owen RC, Coward RM. The Prevalence of Y-chromosome Microdeletions in Oligozoospermic Men: A Systematic Review and Meta-analysis of European and North American Studies. Eur Urol 2019; 76:626-636. [PMID: 31400948 DOI: 10.1016/j.eururo.2019.07.033] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 07/16/2019] [Indexed: 10/26/2022]
Abstract
CONTEXT European and North American guidelines recommend Y-chromosome microdeletion (YCM) screening in azoospermic and oligozoospermic men with sperm concentrations of <5 million sperm/ml; however, numerous studies have suggested that YCMs are rare when sperm concentrations are >1 million sperm/ml. OBJECTIVE We systematically reviewed and meta-analyzed European and North American studies to determine the prevalence of a complete YCM in oligozoospermic men with sperm concentrations of >0-1, >1-5, and >5-20 million sperm/ml, and to determine whether 1 or 5 million sperm/ml is the most appropriate sperm concentration threshold for YCM screening. EVIDENCE ACQUISITION A systematic review of MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov was performed for studies assessing the prevalence of a complete YCM in oligozoospermic men in European and North American studies. EVIDENCE SYNTHESIS Thirty-seven studies were identified during a systematic review (n = 12 492 oligozoospermic men). All complete YCMs in oligozoospermic men were AZFc microdeletions. Eighteen studies contained data conducive to meta-analysis (n = 10 866 men). Comparing the pooled estimated prevalence by sperm concentration, complete YCMs were significantly more common in men with sperm concentrations of >0-1 million sperm/ml (5.0% [95% confidence interval {CI}: 3.6-6.8%]) versus >1-5 million sperm/ml (0.8% [95% CI: 0.5-1.3%], p < 0.001). YCMs were similar in men with sperm concentrations of >1-5 and >5-20 million sperm/ml (0.8% [95% CI: 0.5-1.3%] vs 0.5% [95% CI: 0.2-0.9%], p = 0.14). CONCLUSIONS In Europe and North America, the majority of YCMs occur in men with sperm concentrations of ≤1 million sperm/ml, with <1% identified in men with >1 million sperm/ml. Male infertility guidelines for North America and Europe should reconsider the sperm concentration screening thresholds to recommend testing for YCMs only for men with sperm concentrations of <1 million sperm/ml. PATIENT SUMMARY Complete Y-chromosome microdeletions (YCMs) are rare in men with >1 million sperm/ml. Routine screening for YCMs should occur only if sperm concentration is ≤1 million sperm/ml.
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Affiliation(s)
- Taylor P Kohn
- The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - Jaden R Kohn
- Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ryan C Owen
- Department of Urology, Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX, USA
| | - R Matthew Coward
- Department of Urology, University of North Caroline School of Medicine, Chapel Hill, NC, USA; UNC Fertility LLC, Raleigh, NC, USA
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21
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Zhou R, Cheng J, Ma D, Tan J, Wang Y, Hu P, Xu Z. Identifying Novel Copy Number Variants in Azoospermia Factor Regions and Evaluating Their Effects on Spermatogenic Impairment. Front Genet 2019; 10:427. [PMID: 31134133 PMCID: PMC6514098 DOI: 10.3389/fgene.2019.00427] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 04/18/2019] [Indexed: 01/02/2023] Open
Abstract
Microdeletions in Y-chromosomal azoospermia factor (AZF) regions have been regarded as the risk factor of spermatogenic failure (SF). However, AZF-linked duplications or complex copy number variants (CNVs) (deletion + duplication) were rarely studied. In this study, we performed multiplex ligation-dependent probe amplification (MLPA) analysis on 402 fertile healthy male controls and 423 idiopathic infertile SF patients (197 azoospermia and 226 oligozoospermia) in Han Chinese population. In total, twenty-four types of AZF-linked CNVs were identified in our study, including eleven novel CNVs (one deletion, seven duplications, and three complex CNVs). Our study revealed that AZFc-linked duplications and the instability of Y chromosome might be associated with spermatogenesis. Besides, the complex CNVs (b2/b3 deletion + DAZ1/2 duplication) were confirmed to increase genetic risks for SF in Han Chinese population. This study illustrated a spectrum of AZF-linked CNVs and presented valuable information for understanding the clinical significance of AZF-linked CNVs in male infertility.
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Affiliation(s)
- Ran Zhou
- State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China
| | - Jian Cheng
- State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China
| | - Dingyuan Ma
- State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China
| | - Jianxin Tan
- State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China
| | - Yuguo Wang
- State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China
| | - Ping Hu
- State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China
| | - Zhengfeng Xu
- State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China
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22
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Evaluation of the azoospermic male: a committee opinion. Fertil Steril 2018; 109:777-782. [PMID: 29778371 DOI: 10.1016/j.fertnstert.2018.01.043] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 01/25/2018] [Indexed: 11/28/2022]
Abstract
The purpose of this document is to review the current methods of diagnosis and evaluation for men with azoospermia.
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Affiliation(s)
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- American Society for Reproductive Medicine, Birmingham, Alabama
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23
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Kuroda S, Usui K, Mori K, Yasuda K, Asai T, Sanjo H, Yakanaka H, Takeshima T, Kawahara T, Hamanoue H, Kato Y, Miyoshi Y, Uemura H, Iwasaki A, Yumura Y. An infertile patient with Y chromosome b1/b3 deletion presenting with congenital bilateral absence of the vas deferens with normal spermatogenesis. Clin Exp Reprod Med 2018; 45:48-51. [PMID: 29662826 PMCID: PMC5897248 DOI: 10.5653/cerm.2018.45.1.48] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 01/15/2018] [Accepted: 02/07/2018] [Indexed: 11/29/2022] Open
Abstract
We report the case of a 46-year-old Chinese male patient who visited our clinic complaining of infertility. Semen analysis revealed azoospermia, and azoospermia factor c region partial deletion (b1/b3) was detected using Y chromosome microdeletion analysis. Testicular sperm extraction was performed after genetic counseling. The bilateral ductus deferens and a portion of the epididymis were absent, whereas the remaining epididymis was expanded. Motile intratesticular spermatozoa were successfully extracted from the seminiferous tubule. On histopathology, nearly complete spermatogenesis was confirmed in almost every seminiferous tubule. To our knowledge, this is the first case report of b1/b3 deletion with a congenital bilateral absence of the vas deferens and almost normal spermatogenesis.
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Affiliation(s)
- Shinnosuke Kuroda
- Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Kimitsugu Usui
- Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Kohei Mori
- Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Kengo Yasuda
- Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Takuo Asai
- Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Hiroyuki Sanjo
- Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Hiroyuki Yakanaka
- Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Teppei Takeshima
- Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Takashi Kawahara
- Department of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan
| | - Haruka Hamanoue
- Department of Genetics, Yokohama City University Hospital, Yokohama, Japan
| | - Yoshitake Kato
- Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Yasuhide Miyoshi
- Department of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan
| | - Hiroji Uemura
- Department of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan
| | - Akira Iwasaki
- Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Yasushi Yumura
- Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
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24
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Pan MM, Hockenberry MS, Kirby EW, Lipshultz LI. Male Infertility Diagnosis and Treatment in the Era of In Vitro Fertilization and Intracytoplasmic Sperm Injection. Med Clin North Am 2018; 102:337-347. [PMID: 29406062 DOI: 10.1016/j.mcna.2017.10.008] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
As assisted reproductive technologies use increases, the evaluation of male factor infertility has often become overlooked. However, male evaluation remains critically important, with benefits seen in overall health, as well as in natural and assisted pregnancy and birth rates. A comprehensive assessment of the male partner should be offered to all couples seeking infertility care.
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Affiliation(s)
- Michael M Pan
- Scott Department of Urology, Baylor College of Medicine, 6624 Fannin Street #1700, Houston, TX 77030, USA.
| | - Mark S Hockenberry
- Scott Department of Urology, Center for Reproductive Medicine and Surgery, Baylor College of Medicine, 6624 Fannin Street #1700, Houston, TX 77030, USA
| | - Edgar W Kirby
- Scott Department of Urology, Center for Reproductive Medicine and Surgery, Baylor College of Medicine, 6624 Fannin Street #1700, Houston, TX 77030, USA
| | - Larry I Lipshultz
- Scott Department of Urology, Center for Reproductive Medicine and Surgery, Baylor College of Medicine, 6624 Fannin Street #1700, Houston, TX 77030, USA
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25
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Bahrami Zadegan S, Dabbagh Bagheri S, Joudaki A, Samiee Aref MH, Saeidian AH, Abiri M, Zeinali S. Development and implementation of a novel panel consisting 20 markers for the detection of genetic causes of male infertility. Andrologia 2017; 50:e12946. [PMID: 29282760 DOI: 10.1111/and.12946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/24/2017] [Indexed: 11/28/2022] Open
Abstract
Azoospermia factor (AZF) genes are involved in spermatogenesis. Deletions in the region of these genes have been recognised as a major genetic cause of infertility due to defects in spermatogenesis. Klinefelter syndrome (KS) is the other main cause of male infertility. This study was performed to establish a novel method for the detection of genetic causes of infertility in males and also to investigate the prevalence, extent and position of Y chromosome microdeletions in Iranian infertile men. We developed a newly designed panel of fluorescent multiplex-PCR method to amplify 20 markers (15 sequence-tagged sites (STSs) markers which are placed in the Y chromosome AZF region, 2 short tandem repeats (STRs) and 3 segmental duplications (SDs)). This multifunctional method is for the simultaneous detection of Y chromosome microdeletions and KS. Among 149 studied infertile men, one was detected to suffer from KS and seven (4.7%) were detected with the presence of one or more deleted STS loci. The main cause of infertility for the remaining patients would be nongenetic factors. This strategy is represented as a fast and accurate method to determine the frequencies of different AZF microdeletions which are suitable for use in clinical purposes.
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Affiliation(s)
- S Bahrami Zadegan
- Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
- Dr. Zeinali's Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran
| | - S Dabbagh Bagheri
- Dr. Zeinali's Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran
| | - A Joudaki
- Dr. Zeinali's Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran
| | - M H Samiee Aref
- Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
- Dr. Zeinali's Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran
| | - A H Saeidian
- Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
| | - M Abiri
- Dr. Zeinali's Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran
- Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - S Zeinali
- Dr. Zeinali's Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran
- Department of Molecular Medicine, Pasteur Institute of Iran, Biotechnology Research Center, Tehran, Iran
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Gholami D, Jafari-Ghahfarokhi H, Nemati-Dehkordi M, Teimori H. Y chromosome microdeletions frequency in idiopathic azoospermia, oligoasthenozoospermia, and oligospermia. Int J Reprod Biomed 2017. [DOI: 10.29252/ijrm.15.11.703] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
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Ghirelli-Filho M, Marchi PLD, Mafra FA, Cavalcanti V, Christofolini DM, Barbosa CP, Bianco B, Glina S. Incidence of Y-chromosome microdeletions in children whose fathers underwent vasectomy reversal or in vitro fertilization with epididymal sperm aspiration: a case-control study. EINSTEIN-SAO PAULO 2017; 14:534-540. [PMID: 28076602 PMCID: PMC5221381 DOI: 10.1590/s1679-45082016ao3805] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 10/25/2016] [Indexed: 11/22/2022] Open
Abstract
Objective To evaluate the incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with sperm retrieval by epididymal aspiration (percutaneous epididymal sperm aspiration). Methods A case-control study comprising male children of couples in which the man had been previously vasectomized and chose vasectomy reversal (n=31) or in vitro fertilization with sperm retrieval by percutaneous epididymal sperm aspiration (n=30) to conceive new children, and a Control Group of male children of fertile men who had programmed vasectomies (n=60). Y-chromosome microdeletions research was performed by polymerase chain reaction on fathers and children, evaluating 20 regions of the chromosome. Results The results showed no Y-chromosome microdeletions in any of the studied subjects. The incidence of Y-chromosome microdeletions in individuals born from vasectomized fathers who underwent vasectomy reversal or in vitro fertilization with spermatozoa recovered by percutaneous epididymal sperm aspiration did not differ between the groups, and there was no difference between control subjects born from natural pregnancies or population incidence in fertile men. Conclusion We found no association considering microdeletions in the azoospermia factor region of the Y chromosome and assisted reproduction. We also found no correlation between these Y-chromosome microdeletions and vasectomies, which suggests that the assisted reproduction techniques do not increase the incidence of Y-chromosome microdeletions.
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Affiliation(s)
| | | | | | | | | | | | - Bianca Bianco
- Faculdade de Medicina do ABC, Santo André, SP, Brazil
| | - Sidney Glina
- Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
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Mozdarani H, Ghoraeian P, Mozdarani S, Fallahi P, Mohseni-Meybodi A. High frequency of de novo DAZ microdeletion in sperm nuclei of subfertile men: possible involvement of genome instability in idiopathic male infertility. HUM FERTIL 2017; 21:137-145. [PMID: 28521575 DOI: 10.1080/14647273.2017.1322718] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
The occurrence and diagnosis of Y-chromosome microdeletions, specifically deletions of the DAZ (Deleted in Azoospermia) genes are an important issue in male infertility. Screening Y chromosome microdeletion is mainly done using polymerase chain reaction (PCR) on blood leukocytes. However, there is some evidence indicating that presence of DAZ in somatic cells might not be indicative of its presence in the germ cell lineage. Therefore, a total of 130 men with poor semen quality were examined for presence of DAZ microdeletion in their leukocytes. From these, sperm from 40 randomly selected men with no DAZ microdeletions in their leukocytes (n = 10 oligozoospermia; n = 10 asthenozoospermia; n = 10 oligoasthenozoospermia; and n = 10 near-azoospermia) were were compared to sperm from men of normal semen quality (n = 10) using combined primed in situ labelling and fluorescent in situ hybridization (PRINS-FISH) technique as well as screening for sex chromosome aneuploidy. There was an increased frequency of DAZ microdeletion in blood samples from oligozoospermic (5%) (p < 0.05) and near azoospermic patients (14%) (p < 0.01). A high frequency of DAZ microdeletion was observed in the sperm of patients with no DAZ microdeletion in their leukocytes compared to control (p < 0.01). The frequency of sex chromosome aneuploidy also increased, correlating with the severity of infertility in the studied groups. A similar result was observed for sex chromosome aneuploidy. The results might be indicative of DAZ microdeletion induction during spermatogenesis.
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Affiliation(s)
- Hossein Mozdarani
- a Department of Medical Genetics, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran
| | - Pegah Ghoraeian
- a Department of Medical Genetics, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran
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Hong HH, Hu Y, Yu XQ, Zhou L, Lv MQ, Sun Y, Ren WJ, Zhou DX. Associations of C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene with male infertility risk: A meta-analysis. Eur J Obstet Gynecol Reprod Biol 2017; 212:101-109. [PMID: 28363185 DOI: 10.1016/j.ejogrb.2017.03.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 02/20/2017] [Accepted: 03/01/2017] [Indexed: 01/11/2023]
Abstract
PURPOSE Methylenetetrahydrofolate reductase is one of the key enzymes in folate metabolism. But the association between polymorphism and the risk of male infertility is still controversial. Therefore, this study used a meta-analysis on the collection of data to analyze MTHFR gene C677T polymorphism (known as c.665 C>T, rs1801133, p.Ala222Val). METHODS PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wan fang. Data were searched to identify eligible studies. We sifted the data collection by Hardy-Weinberg equilibrium calculator and used odds ratios (ORs) and 95% confidence intervals (95% CIs) to conduct data through RevMan5.0 and StataSE12.0 software. RESULTS A total of 15 studies have 3853 patients with infertility and 3613 healthy controls in this meta-analysis. Our results showed that T variant of MTHFR C677T gene polymorphism was significantly associated with an increased risk of male infertility (forT vs. C: OR=1.38, 95% CI=1.18-1.63; for TT vs. CC: OR=1.86, 95% CI=1.36-2.54; for CT vs. CC: OR=1.34, 95% CI=1.03-1.74; for TT vs. CT: OR=1.52, 95% CI=1.26-1.84; for TT vs. CT+CC: OR=1.42, 95% CI=1.19-1.70; for TT+CT versus CC: OR=1.46, 95%CI=1.05-2.04). In addition, the results indicated that T allele had the positive association which was driven by East-asian populations (random: OR=1.44, 95% CI=1.2-1.74; fixed: OR=1.39, 95% CI=1.20-1.61), Middle-eastern populations (random: OR=1.30, 95% CI=1.05-1.63; fixed: OR=1.30, 95% CI=1.05-1.63) and Mixed-race (random: OR=1.96, 95% CI=1.35-2.85; fixed: OR=1.31, 95% CI=1.20-1.43). CONCLUSION This meta-analysis suggests that MTHFR C677T polymorphism is associated with male infertility.
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Affiliation(s)
- Hui-Hui Hong
- Department of Pathology, Medical School, Xi'an Jiaotong University, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an 710061, China
| | - Yan Hu
- Department of Gynecology & Oncology , Shaanxi Provincial Tumor Hospital, Xi'an 710061, China
| | - Xiao-Qing Yu
- Department of Gynecology and Obstetrics, Kangfu Hospital of Shaanxi Province, Xi'an, China
| | - Liang Zhou
- Reproductive Medicine Center, North-West Maternal and child Hospital, Xi'an 710003, China
| | - Mo-Qi Lv
- Department of Pathology, Medical School, Xi'an Jiaotong University, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an 710061, China
| | - Ying Sun
- Department of Pathology, Medical School, Xi'an Jiaotong University, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an 710061, China
| | - Wen-Juan Ren
- Department of Pathology, Medical School, Xi'an Jiaotong University, Xi'an 710061, China; Reproductive Medicine Center, North-West Maternal and child Hospital, Xi'an 710003, China
| | - Dang-Xia Zhou
- Department of Pathology, Medical School, Xi'an Jiaotong University, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an 710061, China.
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He T, Zhang X, Deng H, Zhou W, Zhao X, Zhao H, Lu J, Zheng Y, Zhang C, Zhang L, Yin A. A novel Y chromosome microdeletion potentially associated with defective spermatogenesis identified by custom array comparative genome hybridization. Reprod Biomed Online 2017; 34:75-81. [DOI: 10.1016/j.rbmo.2016.09.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2016] [Revised: 09/20/2016] [Accepted: 09/22/2016] [Indexed: 10/20/2022]
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Cao J, Chen Y, Chen J, Yan H, Li M, Wang J. Fluoride exposure changed the structure and the expressions of Y chromosome related genes in testes of mice. CHEMOSPHERE 2016; 161:292-299. [PMID: 27441988 DOI: 10.1016/j.chemosphere.2016.06.106] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 06/24/2016] [Accepted: 06/27/2016] [Indexed: 06/06/2023]
Abstract
It is known that during spermatogenesis, pluripotent germ cells differentiate to become efficient delivery vehicles to the oocyte of paternal DNA, and the process is easily damaged by external poison. In this study, the effects of fluoride on the body weight, fluoride content in femur, testosterone levels in serum and testis, sperm quality, and the expressions of Y chromosome microdeletion genes and protein levels were examined in testes of Kunming male mice treated with different concentrations of 0, 25, 50, 100 mg/L of NaF in drinking water for 11 weeks, respectively. The results showed that compared with the control group, fluoride contents in three treatment groups were significantly increased and the structure of testes was seriously injured. The testosterone contents and the sperm count were decreased. Sperm malformation ratio was distinctly elevated. The expressions of Sly and HSF2 mRNA were markedly reduced in 100 mg/L NaF group and Ssty2 mRNA expression was dramatically decreased in 50 and 100 mg/L NaF groups. Meanwhile, the protein levels of Ssty2 and Sly were significantly reduced in 50 and 100 mg/L NaF groups and HSF2 protein levels were significantly decreased in 100 mg/L NaF group. These studies indicated that fluoride had toxic effects on male reproductive system by reducing the testosterone and sperm count, and increasing the sperm malformation ratio, supported by the damage of testicular structure, as a consequence of depressed HSF2 level, which resulted in the down-regulation of Ssty2 and Sly mRNA and protein.
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Affiliation(s)
- Jinling Cao
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, People's Republic of China
| | - Yan Chen
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, People's Republic of China
| | - Jianjie Chen
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, People's Republic of China
| | - Hanghang Yan
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, People's Republic of China
| | - Meiyan Li
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, People's Republic of China
| | - Jundong Wang
- Shanxi Key Laboratory of Ecological Animal Science and Environmental Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, People's Republic of China.
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Mascarenhas M, Thomas S, Kamath MS, Ramalingam R, Kongari AM, Yuvarani S, Srivastava VM, George K. Prevalence of chromosomal abnormalities and Y chromosome microdeletion among men with severe semen abnormalities and its correlation with successful sperm retrieval. J Hum Reprod Sci 2016; 9:187-193. [PMID: 27803587 PMCID: PMC5070401 DOI: 10.4103/0974-1208.192065] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 06/15/2016] [Accepted: 06/22/2016] [Indexed: 12/03/2022] Open
Abstract
AIM To estimate the prevalence of chromosomal abnormalities and Y chromosome microdeletion among men with azoospermia and severe oligozoospermia and its correlation with successful surgical sperm retrieval. SETTING AND DESIGN A prospective study in a tertiary level infertility unit. MATERIALS AND METHODS In a prospective observation study, men with azoospermia and severe oligozoospermia (concentration <5 million/ml) attending the infertility center underwent genetic screening. Peripheral blood karyotype was done by Giemsa banding. Y chromosome microdeletion study was performed by a multiplex polymerase chain reaction. RESULTS The study group consisted of 220 men, 133 of whom had azoospermia and 87 had severe oligozoospermia. Overall, 21/220 (9.5%) men had chromosomal abnormalities and 13/220 (5.9%) men had Y chromosome microdeletions. Chromosomal abnormalities were seen in 14.3% (19/133) of azoospermic men and Y chromosome microdeletions in 8.3% (11/133). Of the 87 men with severe oligozoospermia, chromosomal abnormalities and Y chromosome microdeletions were each seen in 2.3% (2/87). Testicular sperm aspiration was done in 13 men and was successful in only one, who had a deletion of azoospermia factor c. CONCLUSIONS Our study found a fairly high prevalence of genetic abnormality in men with severe semen abnormalities and a correlation of genetic abnormalities with surgical sperm retrieval outcomes. These findings support the need for genetic screening of these men prior to embarking on surgical sperm retrieval and assisted reproductive technology intracytoplasmic sperm injection.
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Affiliation(s)
- Mariano Mascarenhas
- Leeds Centre for Reproductive Medicine, Seacroft Hospital, Leeds, United Kingdom
| | - Sumi Thomas
- Reproductive Medicine Unit, Christian Medical College and Hospital, Vellore, India
| | - Mohan S. Kamath
- Reproductive Medicine Unit, Christian Medical College, Vellore, India
| | | | - Ann Marie Kongari
- Reproductive Medicine Unit, Bangalore Baptist Hospital, Bengaluru, Karnataka, India
| | - S Yuvarani
- Cytogenetics Unit, Christian Medical College, Vellore, India
| | - Vivi M. Srivastava
- Cytogenetics Unit, Christian Medical College and Hospital, Vellore, India
| | - Korula George
- Reproductive Medicine Unit, Bangalore Baptist Hospital, Bengaluru, Karnataka, India
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Bansal SK, Gupta G, Rajender S. Y chromosome b2/b3 deletions and male infertility: A comprehensive meta-analysis, trial sequential analysis and systematic review. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2016; 768:78-90. [PMID: 27234565 DOI: 10.1016/j.mrrev.2016.04.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Revised: 04/16/2016] [Accepted: 04/18/2016] [Indexed: 11/30/2022]
Abstract
The correlation of Y-chromosome b2/b3 partial deletions with spermatogenic failure remains dubious. We undertook a systematic review of the literature followed by meta-analyses and trial sequential analyses in order to compare the frequency of b2/b3 deletions between oligo/azoospermic infertile and normozoospermicmen. Out of twenty-four studies reviewed for meta-analysis, twenty reported no correlation between this deletion and male infertility and two studies each reported a direct and inverse correlation. In the collective analysis, 241 out of 8892 (2.71%) oligo/azoospermic individuals and 118 out of 5842 (2.02%) normozoospermic controls had a b2/b3 deletion, suggesting a relatively higher frequency of deletions in the cases. Eventually, meta-analysis showed a significant correlation between b2/b3 deletions and the risk of spermatogenic loss/infertility (Fixed model: OR=1.313, 95% CI=1.04-1.65, p=0.02; Random model: OR=1.315, 95% CI=1.02-1.70, p=0.037). Further meta-analysis on studies grouped by ethnicity and geographic regions showed that the b2/b3 deletions are significantly associated with spermatogenic loss/infertility in Mongolians, Nigro-Caucasians, East Asians and Africans, but not in Caucasians, Europeans, South Asians and Dravidians. In summary, the Y-chromosome b2/b3 deletions increase infertility risk; however, it may be significant only in the Mongolian populations and the East Asian region.
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Affiliation(s)
- Sandeep Kumar Bansal
- Central Drug Research Institute, Council of Scientific and Industrial Research (CSIR), Lucknow, India
| | - Gopal Gupta
- Central Drug Research Institute, Council of Scientific and Industrial Research (CSIR), Lucknow, India
| | - Singh Rajender
- Central Drug Research Institute, Council of Scientific and Industrial Research (CSIR), Lucknow, India.
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Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs). Sci Rep 2016; 6:21831. [PMID: 26907467 PMCID: PMC4764820 DOI: 10.1038/srep21831] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Accepted: 02/02/2016] [Indexed: 11/08/2022] Open
Abstract
Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome.
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Bansal SK, Jaiswal D, Gupta N, Singh K, Dada R, Sankhwar SN, Gupta G, Rajender S. Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses. Sci Rep 2016; 6:19798. [PMID: 26876364 PMCID: PMC4753437 DOI: 10.1038/srep19798] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Accepted: 12/18/2015] [Indexed: 11/25/2022] Open
Abstract
We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39–2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations.
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Affiliation(s)
| | - Deepika Jaiswal
- Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, UP, India
| | - Nishi Gupta
- Division of Endocrinology, Central Drug Research Institute, Lucknow, UP, India
| | - Kiran Singh
- Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, UP, India
| | - Rima Dada
- Lab for Molecular Reproduction and Genetics, All India Institute of Medical Sciences, New Delhi, India
| | | | - Gopal Gupta
- Division of Endocrinology, Central Drug Research Institute, Lucknow, UP, India
| | - Singh Rajender
- Division of Endocrinology, Central Drug Research Institute, Lucknow, UP, India
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Refaat AM. Pilot study for early prognosis of Azoospermia in relation to Y-STR Profiling. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2016. [DOI: 10.1016/j.ejmhg.2015.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Abstract
Precision medicine can greatly benefit men's health by helping to prevent, diagnose, and treat prostate cancer, benign prostatic hyperplasia, infertility, hypogonadism, and erectile dysfunction. For example, precision medicine can facilitate the selection of men at high risk for prostate cancer for targeted prostate-specific antigen screening and chemoprevention administration, as well as assist in identifying men who are resistant to medical therapy for prostatic hyperplasia, who may instead require surgery. Precision medicine-trained clinicians can also let couples know whether their specific cause of infertility should be bypassed by sperm extraction and in vitro fertilization to prevent abnormalities in their offspring. Though precision medicine's role in the management of hypogonadism has yet to be defined, it could be used to identify biomarkers associated with individual patients' responses to treatment so that appropriate therapy can be prescribed. Last, precision medicine can improve erectile dysfunction treatment by identifying genetic polymorphisms that regulate response to medical therapies and by aiding in the selection of patients for further cardiovascular disease screening.
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Zhu Y, Wu T, Li G, Yin B, Liu H, Wan C, Zhang H, Zeng Y. The sperm quality and clinical outcomes were not affected by sY152 deletion in Y chromosome for oligozoospermia or azoospermia men after ICSI treatment. Gene 2015; 573:233-8. [PMID: 26188156 DOI: 10.1016/j.gene.2015.07.051] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 06/25/2015] [Accepted: 07/14/2015] [Indexed: 11/26/2022]
Abstract
Azoospermia factor (AZF) microdeletion plays a key role in the genetic etiology of male infertility. The relationship between sY152 deletion in the AZFc region and clinical outcomes is still unclear. This study was to determine the effects of sY152 deletion on the sperm parameters and clinical outcomes of non-obstructive azoospermia or oligozoospermia men after intracytoplasmic sperm injection (ICSI) treatment. A total of 61 infertile men with AZFc microdeletion of the Y chromosome from January 2008 to December 2012 were recruited in the present study. They were divided into two groups, the sY152 group (n=12) and the AZFc group (n=49), based upon whether they have deleted single sY152 marker or all AZFc markers. Fifty azoospermia or oligozoospermia patients without Y chromosome microdeletion were included as the control group. The sperm quality and clinical data were compared among the three groups. Retrospective cohort-control study was performed. The sperm concentration and motility in sY152 group were better than AZFc group (P<0.05), and were comparable to the control group (P>0.05); the morphology, seminal zinc, seminal fructose and seminal carnitine were similar among the three groups (P>0.05). Patients in both sY152 and AZFc groups had lower fertilization rates (68.40% and 70.63%, respectively) than those in the control group (74.91%), and the differences were statistically significant (P<0.05). No significant differences were found in terms of MII oocyte, high-grade embryo rate, 2PN zygote, number of available embryos and transferred embryos, clinical pregnancy rate, implantation rate, miscarriage rate, multiple pregnancy rate, delivery rate, preterm rate and the male/female ratio among the three groups (P>0.05). Single sY152 deletion might cause a lower fertilization rate, but no adverse effects on sperm quality and clinical outcomes were found. Our study may provide more information for consultation in these patients.
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Affiliation(s)
- Yuanchang Zhu
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China; Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen 518045, PR China; Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China
| | - Tonghua Wu
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China; Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen 518045, PR China; Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China
| | - Guangui Li
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China; Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen 518045, PR China; Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China
| | - Biao Yin
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China; Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen 518045, PR China; Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China
| | - Hongjie Liu
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China; Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen 518045, PR China; Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China
| | - Caiyun Wan
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China; Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen 518045, PR China; Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China
| | - Hongzhan Zhang
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China; Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen 518045, PR China; Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China
| | - Yong Zeng
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China; Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen 518045, PR China; Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, PR China.
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Agarwal A, Hamada A, Esteves SC. Engaging practicing gynecologists in the management of infertile men. J Obstet Gynaecol India 2015; 65:75-87. [PMID: 25883438 PMCID: PMC4395576 DOI: 10.1007/s13224-014-0623-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Accepted: 09/16/2014] [Indexed: 12/01/2022] Open
Abstract
In the modern era, contemporary management of male infertility has undergone groundbreaking changes with the introduction of new concepts, advanced testing, and therapeutic interventions. As practicing gynecologists are often the first physicians who encounter an infertile couple, it is essential that these clinicians are continuously updated about the new pearls and pitfalls of male infertility management. Semen analysis is commonly ordered by gynecologists. In 2010, the WHO released new cutoff reference values for the semen parameters adopting novel methodology, which has incited much debate. Reference values have been lowered in comparison with previous standards, with a direct clinical implication in decision-making strategies. Specialized sperm-function tests, such as sperm oxidative stress and sperm chromatin integrity assessments, became clinically available, thus offering an opportunity to better understand sperm dysfunctions concealed during routine semen analysis. Furthermore, the initial counseling of azoospermic men by an andrologically well educated gynecologist may alleviate the misconception and distress surrounding the false belief of sterility, and will clarify the available options of percutaneous and microsurgical sperm-retrieval techniques and assisted conception outcome. Regarding varicocele, which is commonly seen in infertile males, it is now clear that the best treatment option for infertile men with clinical varicocele is the microsurgical vein ligation. Natural conception is significantly improved after varicocelectomy, and recent data suggest that such treatment optimizes reproductive outcome of couples undergoing ICSI or micro-TESE sperm retrieval. Lastly, new therapeutic interventions, including oral antioxidant therapy and lifestyle modifications, have gained increasing attention, as they aid in alleviating male infertility.
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Affiliation(s)
- Ashok Agarwal
- />Lerner College of Medicine, Andrology Center and Center for Reproductive Medicine, Cleveland Clinic, Mail Code X-11, 10681 Carnegie Avenue, Cleveland, OH 44195 USA
| | - Alaa Hamada
- />Department of Urology, Columbia University, New York, USA
| | - Sandro C. Esteves
- />Andrology and Human Reproduction Clinic, ANDROFERT, Av. Dr. Heitor Penteado, 1464, Campinas, SP 13075-460 Brazil
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41
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Ceylan GG, Ceylan C. Genetics and male infertility. World J Clin Urol 2015; 4:38-47. [DOI: 10.5410/wjcu.v4.i1.38] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 09/05/2014] [Accepted: 01/12/2015] [Indexed: 02/06/2023] Open
Abstract
The goal of this review is to explain the requirement for understanding the genetic structure of infertility arising from male factor and to discuss the essentials of these genetic elements (2). The majority of the population is affected by this disorder caused by male factor infertility (1); but the etiologies are still unknown. After the primary genetic structure in infertile phenotypes is searched, an evaluation can be made. Thus the reasons causing infertility can be discovered and patients can benefit from effective therapies (1). Publications about male infertility within the recent 10 years in the Pubmed database were discussed (1). There are some approachments for describing the function of specific genes, but no adequate study is present to be useful for diagnosing and treating male infertility (1). Male fertility and fertility in offspring of males are considerably affected by the exact transition of epigenetic information (1). When the genetic factors playing a role in male infertility were analysed, significant steps will be taken for treating patients and determining the reasons of idiopathic infertility (1). Developments in technology associated with the impact of genetics may enable to specify the etiology of male infertility by determining specific infertile phenotype marks (1).
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Li Z, Huang Y, Li H, Hu J, Liu X, Jiang T, Sun G, Tang A, Sun X, Qian W, Zeng Y, Xie J, Zhao W, Xu Y, He T, Dong C, Liu Q, Mou L, Lu J, Lin Z, Wu S, Gao S, Guo G, Feng Q, Li Y, Zhang X, Wang J, Yang H, Wang J, Xiong C, Cai Z, Gui Y. Excess of rare variants in genes that are key epigenetic regulators of spermatogenesis in the patients with non-obstructive azoospermia. Sci Rep 2015; 5:8785. [PMID: 25739334 PMCID: PMC4350091 DOI: 10.1038/srep08785] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Accepted: 02/04/2015] [Indexed: 01/08/2023] Open
Abstract
Non-obstructive azoospermia (NOA), a severe form of male infertility, is often suspected to be linked to currently undefined genetic abnormalities. To explore the genetic basis of this condition, we successfully sequenced ~650 infertility-related genes in 757 NOA patients and 709 fertile males. We evaluated the contributions of rare variants to the etiology of NOA by identifying individual genes showing nominal associations and testing the genetic burden of a given biological process as a whole. We found a significant excess of rare, non-silent variants in genes that are key epigenetic regulators of spermatogenesis, such as BRWD1, DNMT1, DNMT3B, RNF17, UBR2, USP1 and USP26, in NOA patients (P = 5.5 × 10(-7)), corresponding to a carrier frequency of 22.5% of patients and 13.7% of controls (P = 1.4 × 10(-5)). An accumulation of low-frequency variants was also identified in additional epigenetic genes (BRDT and MTHFR). Our study suggested the potential associations of genetic defects in genes that are epigenetic regulators with spermatogenic failure in human.
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Affiliation(s)
- Zesong Li
- 1] Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China [2] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [3] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
| | - Yi Huang
- 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
| | - Honggang Li
- Family Planning Research Institute/The Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | | | - Xiao Liu
- BGI-Shenzhen, Shenzhen 518083, China
| | - Tao Jiang
- BGI-Shenzhen, Shenzhen 518083, China
| | | | - Aifa Tang
- 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
| | - Xiaojuan Sun
- 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
| | - Weiping Qian
- The Center of Reproductive Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Yong Zeng
- Shenzhen Key Laboratory of Reproductive Immunology for Peri-implantation, Shenzhen Zhongshan Urology Hospital, Shenzhen 518045, China
| | - Jun Xie
- Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China
| | - Wei Zhao
- BGI-Shenzhen, Shenzhen 518083, China
| | - Yu Xu
- BGI-Shenzhen, Shenzhen 518083, China
| | | | | | - Qunlong Liu
- The Center of Reproductive Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Lisha Mou
- 1] Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China [2] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [3] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
| | - Jingxiao Lu
- 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
| | - Zheguang Lin
- Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China
| | - Song Wu
- 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
| | | | | | | | | | | | - Jun Wang
- BGI-Shenzhen, Shenzhen 518083, China
| | | | - Jian Wang
- BGI-Shenzhen, Shenzhen 518083, China
| | - Chengliang Xiong
- Family Planning Research Institute/The Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Zhiming Cai
- 1] Shenzhen Key Laboratory of Genitourinary Cancer, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China [2] National-Regional Engineering Laboratory for Clinical Application of Cancer Genomics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
| | - Yaoting Gui
- Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China
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Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril 2015; 103:e18-25. [PMID: 25597249 DOI: 10.1016/j.fertnstert.2014.12.103] [Citation(s) in RCA: 277] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Accepted: 12/05/2014] [Indexed: 02/07/2023]
Abstract
The purpose of this ASRM Practice Committee report is to provide clinicians with principles and strategies for the evaluation of couples with male infertility problems. This revised document replaces the document of the same name, last published in 2012 (Fertil Steril 2012;98:294-301).
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Decrease in fertilization and cleavage rates, but not in clinical outcomes for infertile men with AZF microdeletion of the Y chromosome. ZYGOTE 2014; 23:771-7. [PMID: 25315024 DOI: 10.1017/s096719941400046x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
This study aimed to explore whether the presence of a Y chromosome azoospermia factor (AZF) microdeletion confers any adverse effect on embryonic development and clinical outcomes after intracytoplasmic sperm injection (ICSI) treatment. Fifty-seven patients with AZF microdeletion were included in the present study and 114 oligozoospermia and azoospermia patients without AZF microdeletion were recruited as controls. Both AZF and control groups were further divided into subgroups based upon the methods of semen collection: the AZF-testicular sperm extraction subgroup (AZF-TESE, n = 14), the AZF-ejaculation subgroup (AZF-EJA, n = 43), the control-TESE subgroup (n = 28) and the control-EJA subgroup (n = 86). Clinical data were analyzed in the two groups and four subgroups respectively. A retrospective case-control study was performed. A significantly lower fertilization rate (69.27 versus 75.70%, P = 0.000) and cleavage rate (89.55 versus 94.39%, P = 0.000) was found in AZF group compared with the control group. Furthermore, in AZF-TESE subgroup, the fertilization rate (67.54 versus 74.25%, P = 0.037) and cleavage rate (88.96 versus 94.79%, P = 0.022) were significantly lower than in the control-TESE subgroup; similarly, the fertilization rate (69.85 versus 75.85%, P = 0.004) and cleavage rate (89.36 versus 94.26%, P = 0.002) in AZF-EJA subgroup were significantly lower than in the control-EJA subgroup; however, the fertilization rate and cleavage rate in AZF-TESE (control-TESE) subgroup was similar to that in the AZF-EJA (control-EJA) subgroup. The other clinical outcomes were comparable between four subgroups (P > 0.05). Therefore, sperm from patients with AZF microdeletion, obtained either by ejaculation or TESE, may have lower fertilization and cleavage rates, but seem to have comparable clinical outcomes to those from patients without AZF microdeletion.
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Yapijakis C, Serefoglou Z, Papadimitriou K, Makrinou E. High frequency of TTTY2-like gene-related deletions in patients with idiopathic oligozoospermia and azoospermia. Andrologia 2014; 47:536-44. [PMID: 24919818 DOI: 10.1111/and.12300] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/09/2014] [Indexed: 11/30/2022] Open
Abstract
Genes located on Y chromosome and expressed in testis are likely to be involved in spermatogenesis. TTTY2 is a Y-linked multicopy gene family of unknown function that includes TTTY2L2A and TTTY2L12A at Yq11 and Yp11 loci respectively. Using PCR amplification, we screened for TTTY2L2A- and TTTY2L12A-associated deletions, in 94 Greek men with fertility problems. Patients were divided into three groups as following: group A (n = 28) included men with idiopathic moderate oligozoospermia, group B (n = 34) with idiopathic severe oligozoospermia and azoospermia, and group C (n = 32) with oligo- and azoospermia of various known etiologies. No deletions were detected in group C patients and 50 fertile controls. However, two patients from group A had deletions in TTTY2L2A (7.1%) and six in TTTY2L12A (21.4%), whereas from group B, four patients had deletions in TTTY2L2A (11.8%) and 10 in TTTY2L12A (29.4%). In addition, five patients from both groups A and B (8%) appeared to have deletions in both studied TTTY2 genes, although these are located very far apart. These results indicate that the TTTY2 gene family may play a significant role in spermatogenesis and suggest a possible mechanism of nonhomologous recombinational events that may cause genomic instability and ultimately lead to male infertility.
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Affiliation(s)
- C Yapijakis
- Department of Neurology, University of Athens Medical School, Eginition Hospital, Athens, Greece; Department of Molecular Genetics, "Cephalogenetics" Diagnostic Center, Athens, Greece
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46
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Ray A, Tapadar A, Kar M, Kundu R, Nandy S. Microdeletions in the Y chromosome in cases of male infertility in a population of West Bengal. J ANAT SOC INDIA 2014. [DOI: 10.1016/j.jasi.2014.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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47
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Ye JJ, Ma L, Yang LJ, Wang JH, Wang YL, Guo H, Gong N, Nie WH, Zhao SH. Partial AZFc duplications not deletions are associated with male infertility in the Yi population of Yunnan Province, China. J Zhejiang Univ Sci B 2014; 14:807-15. [PMID: 24009201 DOI: 10.1631/jzus.b1200301] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE There are many reports on associations between spermatogenesis and partial azoospermia factor c (AZFc) deletions as well as duplications; however, results are conflicting, possibly due to differences in methodology and ethnic background. The purpose of this study is to investigate the association of AZFc polymorphisms and male infertility in the Yi ethnic population, residents within Yunnan Province, China. METHODS A total of 224 infertile patients and 153 fertile subjects were selected in the Yi ethnic population. The study was performed by sequence-tagged site plus/minus (STS+/-) analysis followed by gene dosage and gene copy definition analysis. Y haplotypes of 215 cases and 115 controls were defined by 12 binary markers using single nucleotide polymorphism on Y chromosome (Y-SNP) multiplex assays based on single base primer extension technology. RESULTS The distribution of Y haplotypes was not significantly different between the case and control groups. The frequencies of both gr/gr (7.6% vs. 8.5%) and b2/b3 (6.3% vs. 8.5%) deletions do not show significant differences. Similarly, single nucleotide variant (SNV) analysis shows no significant difference of gene copy definition between the cases and controls. However, the frequency of partial duplications in the infertile group (4.0%) is significantly higher than that in the control group (0.7%). Further, we found a case with sY1206 deletion which had two CDY1 copies but removed half of DAZ genes. CONCLUSIONS Our results show that male infertility is associated with partial AZFc duplications, but neither gr/gr nor b2/b3 deletions, suggesting that partial AZFc duplications rather than deletions are risk factors for male infertility in Chinese-Yi population.
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Affiliation(s)
- Jun-jie Ye
- State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Yunnan Key Laboratory of Fertility Regulation and Minority Eugenics, Yunnan Population and Family Planning Research Institute, Kunming 650021, China; Department of Urology, Kunming General Hospital of Chengdu Military Command, Kunming 650032, China; Haiyuan College, Kunming Medical University, Kunming 650021, China
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48
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Abstract
Male hypogonadism is a clinical syndrome that results from failure to produce physiological concentrations of testosterone, normal amounts of sperm, or both. Hypogonadism may arise from testicular disease (primary hypogonadism) or dysfunction of the hypothalamic-pituitary unit (secondary hypogonadism). Clinical presentations vary dependent on the time of onset of androgen deficiency, whether the defect is in testosterone production or spermatogenesis, associated genetic factors, or history of androgen therapy. The clinical diagnosis of hypogonadism is made on the basis of signs and symptoms consistent with androgen deficiency and low morning testosterone concentrations in serum on multiple occasions. Several testosterone-replacement therapies are approved for treatment and should be selected according to the patient's preference, cost, availability, and formulation-specific properties. Contraindications to testosterone-replacement therapy include prostate and breast cancers, uncontrolled congestive heart failure, severe lower-urinary-tract symptoms, and erythrocytosis. Treatment should be monitored for benefits and adverse effects.
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Affiliation(s)
- Shehzad Basaria
- Section on Men's Health, Aging and Metabolism, Division of Endocrinology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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49
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Abstract
Fertility rates have been declining in most Western nations over the past several decades, although it is not entirely clear if an increased rate of infertility substantially contributes to this. As compared to other species, the reproductive efficiency of humans is relatively low. Factors related to fertility include age, exposure to sexually transmitted diseases, frequency of intercourse, coital timing, as well as diet and lifestyle habits. Infertility is considered a disease due to its major disruption of major organ systems and life functions. An infertility evaluation is recommended after 12 months or more of regular, unprotected intercourse and may be considered after 6 months for those female patients over the age of 35 or with other known abnormalities. A proper infertility evaluation is a comprehensive examination of possibly identifiable infertility factors of both female and male partners, lending itself to the most appropriate and potentially effective treatment.
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50
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Liu XH, Yan LY, Lu CL, Li R, Zhu XH, Jin HY, Zhang Y, Zhang WX, Gao SH, Qiao J. ART do not increase the risk of Y-chromosome microdeletion in 19 candidate genes at AZF regions. Reprod Fertil Dev 2014; 26:778-86. [DOI: 10.1071/rd13092] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2013] [Accepted: 05/11/2013] [Indexed: 11/23/2022] Open
Abstract
Y-chromosome microdeletions (YCMs) have been found at a much higher rate in infertile men than fertile controls. A specific deletion in the azoospermia factor locus (AZF) at Yq11 is significantly associated with male infertility. Whether assisted reproductive technology (ART) increases the risk of YCM in ART-derived offspring remains unclear. In this study the occurrence of YCM in 199 fathers and their 228 sons (Chinese, Han ethnicity), including 85 offspring conceived by IVF, 73 by intra-cytoplasmic sperm injection (ICSI) and 70 by natural conception, was investigated. Nineteen candidate genes related to YCM were analysed by multiplex ligation-dependent probe amplification. We identified one de novo YCM from 70 naturally-conceived offspring and none from 158 ART-conceived offspring and found no statistical significance between these two groups. There was no statistically-significant difference in the detection rate of the father’s Y-chromosome microdeletion group: IVF 10.7% (8/75), ICSI 3.2% (2/63), natural conception 8.2% (5/61). These results suggest that ART does not increase the risk of YCM in male offspring.
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