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Chen GX, Sun Y, Yang R, Huang ZQ, Li HY, Zheng BH. Study on the influence of the sY1192 gene locus in the AZFb/c region on sperm quality and pregnancy outcome. Asian J Androl 2025; 27:231-238. [PMID: 39420567 DOI: 10.4103/aja202478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 08/01/2024] [Indexed: 10/19/2024] Open
Abstract
ABSTRACT Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
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Affiliation(s)
- Gang-Xin Chen
- Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China
| | - Yan Sun
- Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China
- Fujian Maternal-Fetal Clinical Medicine Research Center, Fuzhou 350001, China
| | - Rui Yang
- Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China
| | - Zhi-Qing Huang
- Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China
| | - Hai-Yan Li
- Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China
| | - Bei-Hong Zheng
- Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China
- Fujian Key Laboratory of Prenatal Diagnosis and Birth Defect, Fuzhou 350001, China
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Emre Bakircioglu M, Sahin KC, Ozcan C, Gultekin MH, Ozkara H. Clinical Predictors of Micro-Testicular Sperm Extraction Success in Nonobstructive Azoospermia With Complete Azoospermia Factor c Microdeletion. Urology 2025:S0090-4295(25)00116-5. [PMID: 39922233 DOI: 10.1016/j.urology.2025.01.066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 01/08/2025] [Accepted: 01/29/2025] [Indexed: 02/10/2025]
Abstract
OBJECTIVE To evaluate the clinical and histopathological parameters of sperm retrieval success using micro-testicular sperm extraction (micro-TESE) in nonobstructive azoospermia (NOA) with complete azoospermia factor c (AZFc) microdeletion, since there is limited data in the literature on the outcomes of this patient group and controversial results on the parameters affecting the success of micro-TESE in NOA patients. METHODS The data of 1308 patients with NOA who underwent micro-TESE surgery at two centers between 2014 and 2022 were retrospectively analyzed. Clinical and histopathological data were comparatively assessed in men with complete AZFc microdeletion according to sperm retrieval success. RESULTS Among the 1308 men, 54 (4.1%) were diagnosed with complete AZFc microdeletion. Micro-TESE was successful in retrieving sperm from 28 men with AZFc microdeletion (51.8%). The patient age, follicle-stimulating hormone and total testosterone levels, duration of infertility, and testicular volume did not statistically significantly differ between the sperm-positive and -negative groups (P>.05). The analysis revealed that parental consanguinity was significantly different between the two groups (P=.032). According to the testicular biopsy results in terms of sperm retrieval status, no statistically significant difference was observed in the distribution of histopathological patterns. CONCLUSION Parental consanguinity was found to be the only parameter that negatively affected the success of micro-TESE in patients with NOA who presented with AZFc microdeletion. Clinical parameters, including patient age, follicle-stimulating hormone and total testosterone levels, and testis volume, did not demonstrate predictive value for sperm retrieval success in micro-TESE in this patient population.
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Affiliation(s)
| | - Kadir Can Sahin
- Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Urology, Istanbul, Turkey
| | - Cenk Ozcan
- OTA & Jinemed Hospital IVF Center, Istanbul, Turkey
| | - Mehmet Hamza Gultekin
- Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Urology, Istanbul, Turkey
| | - Hamdi Ozkara
- Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Urology, Istanbul, Turkey
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Haghpanah A, Ayareh N, Akbarzadeh A, Irani D, Hosseini F, Moghadam FS, Gilani MAS, Shamohammadi I. Differentiating between obstructive and non-obstructive azoospermia: A machine learning-based approach. BJUI COMPASS 2025; 6:e493. [PMID: 39963581 PMCID: PMC11832300 DOI: 10.1002/bco2.493] [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: 11/22/2024] [Revised: 01/09/2025] [Accepted: 01/15/2025] [Indexed: 02/20/2025] Open
Abstract
Background Infertility is a major global concern, with azoospermia, being the most severe form of male infertility. Distinguishing between obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) is crucial due to their differing treatment approaches. This study aimed to develop a machine learning model to predict azoospermia subtypes using clinical, ultrasonographic, semen and hormonal analysis data. Methods This retrospective study included all subjects diagnosed with azoospermia. All patients were evaluated by at least one urologist, had their semen sample assessed on at least two different occasions for diagnosis and underwent a testicular biopsy to determine the type of azoospermia, categorized into OA and NOA. Clinical factors, hormonal levels, semen parameters and testicular features were compared between the OA and NOA groups. Three machine learning models, including logistic regression, support vector machine and random forest, were evaluated for their accuracy in differentiating the two subtypes. Results The study included a total of 427 patients with azoospermia, of which 326 had NOA and 101 had OA. The median age of the patients was 33.0 (IQR: 7.0) years. Our findings revealed that factors such as body mass index, testicular length, volume and longitudinal axis, semen parameters and hormonal levels differed significantly between the two groups. When these variables were input into the machine learning-based models, logistic regression achieved the highest F1-score and area under the curve value among the three models evaluated. Conclusions This study underscores the potential of machine learning to differentiate between azoospermia subtypes using readily available clinical data. However, further research is required to validate and refine the model before it can be applied clinically.
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Affiliation(s)
- Abdolreza Haghpanah
- Department of Urology, School of MedicineShiraz University of Medical SciencesShirazIran
| | - Nazanin Ayareh
- Student Research Committee, School of MedicineShiraz University of Medical SciencesShirazIran
| | - Ashkan Akbarzadeh
- Student Research Committee, School of MedicineShiraz University of Medical SciencesShirazIran
| | - Dariush Irani
- Department of Urology, School of MedicineShiraz University of Medical SciencesShirazIran
| | - Fatemeh Hosseini
- Student Research Committee, School of MedicineShiraz University of Medical SciencesShirazIran
| | - Farid Sabahi Moghadam
- Department of Compute Engineering, Faculty of Engineering, Mahshahr BranchAzad UniversityMahshahrIran
| | - Mohammad Ali Sadighi Gilani
- Department of Urology, Shariati Hospital, Faculty of MedicineTehran University of Medical SciencesTehranIran
- Department of Andrology, Reproductive Biomedicine Research CenterRoyan Institute for Reproductive BiomedicineTehranIran
| | - Iman Shamohammadi
- Department of Urology, School of MedicineShiraz University of Medical SciencesShirazIran
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Shamsi MB, Dada R, Balahmar RM, Zaytuni D, Alharbi G, Imam SN, Rajih E, Latif M, Ahmad S. Prevalence and clinical considerations of Y chromosome microdeletions in azoospermic and oligozoopsermic infertile men from Al Madinah Al Munawarah, Saudi Arabia. Saudi Med J 2025; 46:124-130. [PMID: 39933777 PMCID: PMC11822931 DOI: 10.15537/smj.2025.46.2.20240764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 12/26/2024] [Indexed: 02/13/2025] Open
Abstract
OBJECTIVES To characterize the potential role of Y-chromosome microdeletion (YCM) as a genetic cause for infertility in the Arab population from the Al Madinah Al Munawarah. METHODS We screened 97 infertile men from Al Madinah Al Munawarah, from February 2022 to March 2024. Genomic blood DNA was analyzed for 8 sequence tagged site (STS) markers of Y chromosome by multiplex polymerase chain reaction. RESULTS We found microdeletions in 3 infertile men, indicating a prevalence of 3.1%. The STS markers sY254 and sY255 corresponding to AZFc regions were deleted in these men. No deletion was observed in any other STS markers investigated in this study. CONCLUSION Our findings for prevalence in Arab population of Al Madinah Al Munawarah is comparable to other studies from Saudi Arabia. However, large variance in the prevalence of YCM in the Arab population of other Middle Eastern countries is reportedly observed. The YCM has significant prognostic value, since it indicates the spermatogenic profile, the success probability of assisted reproduction technique (ART) procedures as testicular sperm extraction and apprise of potential risk of vertical transmission of microdeletion from father to son in patients opting for ART. With these considerations, we re-emphasize the need for genetic screening of YCM in azoo- and oligozoospermic infertile men.
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Affiliation(s)
- Monis B. Shamsi
- From the Center for Genetics and Inherited Diseases (Shamsi, Balahmar, Zaytuni, Alharbi, Latif); from the Department of Basic Medical Sciences (Shamsi, Imam, Latif); from the Department of General and Specialized Surgery (Rajih), College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia, from the Department of Anatomy (Dada), Laboratory of Molecular Reproduction & Genetics, All India Institute of Medical Sciences, New Delhi, India, and from the Department of Translational Neuroscience (Ahmad), Barrow Neurological Institute, Phoenix, United States of America.
| | - Rima Dada
- From the Center for Genetics and Inherited Diseases (Shamsi, Balahmar, Zaytuni, Alharbi, Latif); from the Department of Basic Medical Sciences (Shamsi, Imam, Latif); from the Department of General and Specialized Surgery (Rajih), College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia, from the Department of Anatomy (Dada), Laboratory of Molecular Reproduction & Genetics, All India Institute of Medical Sciences, New Delhi, India, and from the Department of Translational Neuroscience (Ahmad), Barrow Neurological Institute, Phoenix, United States of America.
| | - Reham M. Balahmar
- From the Center for Genetics and Inherited Diseases (Shamsi, Balahmar, Zaytuni, Alharbi, Latif); from the Department of Basic Medical Sciences (Shamsi, Imam, Latif); from the Department of General and Specialized Surgery (Rajih), College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia, from the Department of Anatomy (Dada), Laboratory of Molecular Reproduction & Genetics, All India Institute of Medical Sciences, New Delhi, India, and from the Department of Translational Neuroscience (Ahmad), Barrow Neurological Institute, Phoenix, United States of America.
| | - Dimah Zaytuni
- From the Center for Genetics and Inherited Diseases (Shamsi, Balahmar, Zaytuni, Alharbi, Latif); from the Department of Basic Medical Sciences (Shamsi, Imam, Latif); from the Department of General and Specialized Surgery (Rajih), College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia, from the Department of Anatomy (Dada), Laboratory of Molecular Reproduction & Genetics, All India Institute of Medical Sciences, New Delhi, India, and from the Department of Translational Neuroscience (Ahmad), Barrow Neurological Institute, Phoenix, United States of America.
| | - Ghadeer Alharbi
- From the Center for Genetics and Inherited Diseases (Shamsi, Balahmar, Zaytuni, Alharbi, Latif); from the Department of Basic Medical Sciences (Shamsi, Imam, Latif); from the Department of General and Specialized Surgery (Rajih), College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia, from the Department of Anatomy (Dada), Laboratory of Molecular Reproduction & Genetics, All India Institute of Medical Sciences, New Delhi, India, and from the Department of Translational Neuroscience (Ahmad), Barrow Neurological Institute, Phoenix, United States of America.
| | - Syed N. Imam
- From the Center for Genetics and Inherited Diseases (Shamsi, Balahmar, Zaytuni, Alharbi, Latif); from the Department of Basic Medical Sciences (Shamsi, Imam, Latif); from the Department of General and Specialized Surgery (Rajih), College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia, from the Department of Anatomy (Dada), Laboratory of Molecular Reproduction & Genetics, All India Institute of Medical Sciences, New Delhi, India, and from the Department of Translational Neuroscience (Ahmad), Barrow Neurological Institute, Phoenix, United States of America.
| | - Emad Rajih
- From the Center for Genetics and Inherited Diseases (Shamsi, Balahmar, Zaytuni, Alharbi, Latif); from the Department of Basic Medical Sciences (Shamsi, Imam, Latif); from the Department of General and Specialized Surgery (Rajih), College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia, from the Department of Anatomy (Dada), Laboratory of Molecular Reproduction & Genetics, All India Institute of Medical Sciences, New Delhi, India, and from the Department of Translational Neuroscience (Ahmad), Barrow Neurological Institute, Phoenix, United States of America.
| | - Muhammad Latif
- From the Center for Genetics and Inherited Diseases (Shamsi, Balahmar, Zaytuni, Alharbi, Latif); from the Department of Basic Medical Sciences (Shamsi, Imam, Latif); from the Department of General and Specialized Surgery (Rajih), College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia, from the Department of Anatomy (Dada), Laboratory of Molecular Reproduction & Genetics, All India Institute of Medical Sciences, New Delhi, India, and from the Department of Translational Neuroscience (Ahmad), Barrow Neurological Institute, Phoenix, United States of America.
| | - Saif Ahmad
- From the Center for Genetics and Inherited Diseases (Shamsi, Balahmar, Zaytuni, Alharbi, Latif); from the Department of Basic Medical Sciences (Shamsi, Imam, Latif); from the Department of General and Specialized Surgery (Rajih), College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia, from the Department of Anatomy (Dada), Laboratory of Molecular Reproduction & Genetics, All India Institute of Medical Sciences, New Delhi, India, and from the Department of Translational Neuroscience (Ahmad), Barrow Neurological Institute, Phoenix, United States of America.
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Yi Zhou B, Ting Fu W, Gu H, Zhen Li M, Bin Zhong X, Tang J. A retrospective analysis of 1600 infertility patients with azoospermia and severe oligozoospermia. Clin Chim Acta 2025; 565:119973. [PMID: 39307333 DOI: 10.1016/j.cca.2024.119973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 09/06/2024] [Accepted: 09/18/2024] [Indexed: 09/27/2024]
Abstract
OBJECTIVE This study aimed to investigate the genetic etiology of male infertility patients. METHOD A total of 1600 male patients with infertility, including 1300 cases of azoospermia and 300 cases of severe oligozoospermia, underwent routine semen analysis, chromosomal karyotype analysis and sex hormone level testing. The Azoospermia factor (AZF) on the Y chromosome was detected using the multiple fluorescence quantitative PCR technique. Additionally, copy number variation (CNV) analysis was performed on patients with Sertoli-cell-only syndrome who had a normal karyotype and AZF. RESULT Chromosomal abnormalities were found in 334 cases (20.88 %) of the 1600 male infertility patients. The most common type of abnormality was sex chromosome abnormalities (18.94 %), with 47, XXY being the most frequent abnormal karyotype. The rates of chromosomal abnormalities were significantly different between the azoospermia group and the severe oligospermia group (23.69 % and 8.67 %, respectively; P<0.05). AZF microdeletions were detected in 155 cases (9.69 %), with various deletion types and AZFc region microdeletion being the most prevalent. The rates of AZF microdeletions were not significantly different between the azoospermia group and the severe oligospermia group (9.15 % and 12 %, respectively; P=0.133). In 92 patients with Sertoli-cell-only syndrome who had a normal karyotype and AZF, the detection rate of CNV was 16.3 %. Compared to the severe oligospermia group, the azoospermia group had higher levels of FSH and LH and lower levels of T and E2, and the differences were statistically significant (P<0.05). CONCLUSIONS Male infertility is a complex multifactorial disease, with chromosomal abnormalities and Y chromosome microdeletions being important genetic factors leading to the disease. Initial genetic testing of infertile men should include karyotyping and Y chromosome microdeletions. If necessary, CNV testing should be performed to establish a clinical diagnosis and provide individualized treatment for male infertility.
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Affiliation(s)
- Bing Yi Zhou
- NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou 510060, China
| | - Wen Ting Fu
- NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou 510060, China
| | - Heng Gu
- NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou 510060, China
| | - Ming Zhen Li
- NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou 510060, China
| | - Xiao Bin Zhong
- School of Medicine, Jinan University, Guangzhou 510632, China
| | - Jia Tang
- NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou 510060, China; School of Medicine, Jinan University, Guangzhou 510632, China.
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Zhao Y, Zhi W, Xiong D, Li N, Du X, Zeng J, Zhang G, Liu W. A family with normal sperm motility carrying a sY86 deletion in AZFa region and partial deletion in AZFc region. Front Genet 2025; 15:1519774. [PMID: 39850494 PMCID: PMC11754199 DOI: 10.3389/fgene.2024.1519774] [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: 10/30/2024] [Accepted: 12/05/2024] [Indexed: 01/25/2025] Open
Abstract
Introduction Usually, patients with sY84 or sY86 deficiency present with azoospermia, but recent studies have shown that some males with partial AZFa deletions, including sY84 or sY86, exhibit normal fertility. Here, we reported a rare case of AZF deletion in a family, where both father and son exhibited a deletion at the sY86 site in the AZFa region and a partial deletion in the AZFc region. Methods and Results Detection was performed using classical multiplex polymerase chain reaction and the "Male AZF Full-region Detection" Panel, revealing specific deletions in AZFa: Yq11.21 (14,607,372-14,637,973), 30.6 kb; AZFc: Yq11.223-11.23 (25,848,831-27,120,665), 1.3 M for the father; and Yq11.223-11.23 (25,505,378-27,120,665), 1.6 M for the son. Notably, although the son's sperm motility parameters showed no significant abnormalities, there was a history of failed pregnancies for twice, with sperm exhibiting a high rate of head defect. Discussion Given the complexities of the reproductive phenotype following AZF region deletions, additional extended genetic testing is necessary when partial deletions in the AZF region are detected, thus providing more accurate predictions of the spermatogenesis in patient. This study provides valuable insights and guidance for clinical decision-making and the implementation of assisted reproductive technologies in such cases.
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Affiliation(s)
- Yuhong Zhao
- The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, Sichuan Provincial Woman’s and Children’s Hospital, Chengdu, China
| | - Weiwei Zhi
- The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, Sichuan Provincial Woman’s and Children’s Hospital, Chengdu, China
- Reproductive Medicine Center, Sichuan Provincial Woman’s and Children’s Hospital, Chengdu, China
| | - Dongsheng Xiong
- The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, Sichuan Provincial Woman’s and Children’s Hospital, Chengdu, China
- Reproductive Medicine Center, Sichuan Provincial Woman’s and Children’s Hospital, Chengdu, China
| | - Ningjing Li
- School of Medicine and life sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xinrong Du
- School of Medicine and life sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Jiuzhi Zeng
- The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, Sichuan Provincial Woman’s and Children’s Hospital, Chengdu, China
- Reproductive Medicine Center, Sichuan Provincial Woman’s and Children’s Hospital, Chengdu, China
| | - Guohui Zhang
- The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, Sichuan Provincial Woman’s and Children’s Hospital, Chengdu, China
- Reproductive Medicine Center, Sichuan Provincial Woman’s and Children’s Hospital, Chengdu, China
| | - Weixin Liu
- The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, Sichuan Provincial Woman’s and Children’s Hospital, Chengdu, China
- Reproductive Medicine Center, Sichuan Provincial Woman’s and Children’s Hospital, Chengdu, China
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Deepika MLN, Srilekha A, Pavani CL, Gupta A, Nazneen R, Lakshmi BV. Prevalence and comparative analysis of Y chromosome microdeletions in recurrent pregnancy loss. J Appl Genet 2024:10.1007/s13353-024-00928-2. [PMID: 39673051 DOI: 10.1007/s13353-024-00928-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 11/18/2024] [Accepted: 11/23/2024] [Indexed: 12/15/2024]
Abstract
Recurrent pregnancy loss (RPL) is defined as the spontaneous loss of two or more pregnancies before reaching viability. Diagnosis for couples with RPL usually involves only the female partner. However, it is seen that male partners contribute equally to the occurrence of spontaneous abortions as the Y chromosome harbors several genes that control spermatogenesis and the quality of sperms. Three non-overlapping regions (AZFa, AZFb, AZFc) in the distal half of Y chromosome have been reported to be associated with spermatogenesis in males with normal karyotype. Microdeletions in these three regions have been identified in many male partners with repeated abortions. The STS regions of the Y chromosome are prone to self-recombination, making it susceptible to deletions, thereby leading to poor sperm quality and fetal implantation failure. The present study aimed to identify the frequency and type of microdeletions among male partners of RPL women. Analysis revealed nearly 76% of cases revealed microdeletions, whereas no deletions were observed among controls in Y chromosome, suggesting a strong link between RPL and microdeletion in the AZF regions of the Y chromosome in the male partner.
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Affiliation(s)
- M L N Deepika
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, India.
| | - Avvari Srilekha
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, India
| | - C Lalitha Pavani
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, India
| | - Aryan Gupta
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, India
| | - Ridah Nazneen
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, India
| | - B Vijaya Lakshmi
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, India
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Fang Y, Zhang Z, Cheng Y, Huang Z, Pan J, Xue Z, Chen Y, Chung VY, Zhang L, Hong K. Independent factors associated with intracytoplasmic sperm injection outcomes in patients with complete azoospermia factor c microdeletions. Hum Reprod Open 2024; 2024:hoae071. [PMID: 39697610 PMCID: PMC11652272 DOI: 10.1093/hropen/hoae071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 10/15/2024] [Indexed: 12/20/2024] Open
Abstract
STUDY QUESTION Which independent factors influence ICSI outcomes in patients with complete azoospermia factor c (AZFc) microdeletions? SUMMARY ANSWER In patients with complete AZFc microdeletions, the sperm source, male LH, the type of infertility in women, and maternal age are the independent factors associated with ICSI outcomes. WHAT IS KNOWN ALREADY AZF microdeletions are the second most prevalent factor contributing to infertility in men, with AZFc microdeletions being the most frequently affected locus, accounting for 60-70% of all cases. The primary clinical phenotypes are oligoasthenozoospermia and azoospermia in patients with complete AZFc microdeletions. These patients can achieve paternity through ICSI using either testicular (T-S) or ejaculated (E-S) spermatozoa. With aging in men with AZFc microdeletions, oligoasthenozoospermia or severe oligozoospermia may gradually progress to azoospermia. STUDY DESIGN SIZE DURATION In this retrospective cohort study, the independent factors associated with the outcomes of 634 ICSI cycles in 634 couples with the transfer of 1005 embryos between February 2015 and December 2023 were evaluated. The analysis included 398 ICSI cycles in 398 couples using E-S and 236 ICSI cycles in 236 couples using T-S; all men had complete AZFc microdeletions. PARTICIPANTS/MATERIALS SETTING METHODS The inclusion criteria were as follows: (i) men had complete AZFc microdeletions and (ii) the couple underwent ICSI treatment using T-S or E-S. The exclusion criteria were as follows: (i) cycles involving frozen-thawed oocytes; (ii) cycles in which all fresh embryos were frozen and not transferred; (iii) cycles lost to follow-up; and (iv) multiple ICSI cycles, apart from the first cycle for each couple. The primary outcome was the cumulative live birth rate per ICSI cycle, whereas the secondary outcomes were the clinical pregnancy rate per ICSI cycle, fertilization rate, and the no-embryo-suitable-for-transfer cycle rate (NESTR). Moreover, the maternal and neonatal outcomes were analyzed. Continuous variables showing non-normal distributions were expressed as median and interquartile range and were analyzed using the Kruskal-Wallis test. Categorical variables were expressed as percentages and were analyzed using the χ2 or Fisher's exact test. Linear and logistic regression models were constructed to assess the independent factors associated with ICSI outcomes. MAIN RESULTS AND THE ROLE OF CHANCE The T-S group exhibited inferior ICSI outcomes than the E-S group, marked by significantly reduced rates of cumulative live birth, clinical pregnancy, fertilization, high-quality embryos, blastocyst formation, and implantation, with higher NESTRs. However, the miscarriage rate and neonatal outcomes did not significantly differ between the groups. Multivariate linear regression analysis demonstrated that reduced fertilization rates were significantly associated with T-S use (adjusted β, -0.281; 95% CI, -0.332 to -0.229). Multivariate logistic regression demonstrated that increased NESTRs were significantly associated with T-S use (adjusted odds ratio (OR), 4.204; 95% CI, 2.340-7.691), along with uterine anomaly in women (adjusted OR, 2.853; 95% CI, 1.053-7.718), infertility in women with multiple etiologies (adjusted OR, 11.118; 95% CI, 2.034-66.508), and advanced maternal age (adjusted OR, 1.138; 95% CI, 1.029-1.263). The use of T-S (adjusted OR, 0.318; 95% CI, 0.188-0.528), uterine anomaly in women (adjusted OR, 0.263; 95% CI, 0.058-0.852), and increased maternal age (adjusted OR, 0.877; 95% CI, 0.801-0.958) were also associated with decreased clinical pregnancy rates per ICSI cycle. Likewise, lower cumulative live birth rates were associated with T-S use (adjusted OR, 0.273; 95% CI, 0.156-0.468), male LH levels (adjusted OR, 0.912; 95% CI, 0.837-0.990), uterine anomaly (adjusted OR, 0.101; 95% CI, 0.005-0.529), and increased maternal age (adjusted OR, 0.873; 95% CI, 0.795-0.958). No significant differences were observed in the maternal and neonatal outcomes between both groups. LIMITATIONS REASONS FOR CAUTION The study was based on a single-center, retrospective cohort design. The molecular diagnosis of AZFc microdeletions was reliant on loci sY254 and sY255 according to the European Academy of Andrology and European Molecular Genetics Quality Network guidelines. While our findings were based on the clinical phenotypes and laboratory parameters, the abnormalities in the genetic profiles of spermatogenesis and early embryonic development in patients between the T-S and E-S groups have not yet been elucidated. WIDER IMPLICATIONS OF THE FINDINGS Our results offer important insights into the independent factors that influence ICSI outcomes in patients with complete AZFc microdeletions. ICSI using E-S is a more favorable therapeutic option for younger patients with AZFc microdeletions and with sperm present in their ejaculate. This study highlights a new direction to investigate the molecular and phenotypic differences between the T-S and E-S groups, which may contribute to the diagnosis and treatment of complete AZFc microdeletions. STUDY FUNDING/COMPETING INTERESTS This study was supported by Capital's Funds for Health Improvement and Research (2022-2-4094), Beijing Natural Science Foundation (7232203, 7242164), National Key Research and Development Program (2021YFC2700200, 2023YFC2705600), National Natural Science Foundation of China (82301889), Peking University Third Hospital Innovation Transformation Fund (BYSYZHKC2023103), Peking University Third Hospital Clinical Cohort Construction Project (BYSYDL2023016), and Young Elite Scientists Sponsorship Program by CAST (2023QNRC001). None of the authors have any competing interests to declare. TRIAL REGISTRATION NUMBER N/A.
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Affiliation(s)
- Yangyi Fang
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Zhe Zhang
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Yinchu Cheng
- Department of Pharmacy, Peking University Third Hospital, Beijing, China
| | - Zhigao Huang
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Jiayuan Pan
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Zixuan Xue
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Yidong Chen
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- National Clinical Research Center for Obstetrics and Gynecology, Beijing, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China
| | - Vera Y Chung
- Department of Urology, Gleneagles Hong Kong Hospital, Hong Kong, China
| | - Li Zhang
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- National Clinical Research Center for Obstetrics and Gynecology, Beijing, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China
| | - Kai Hong
- Department of Urology, Peking University Third Hospital, Beijing, China
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9
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Çift A, Benlioğlu C, Özgür Yücel M, Özgür Çevik M, Kalyenci B, Gök A, Sever S, Sulhan H, Bağış H, Ayyıldız A. A New Sperm Concentration Threshold for Y Chromosome Microdeletion Analysis in Infertile Men: Could It Be Azoopermia? UROLOGY RESEARCH & PRACTICE 2024; 50:181-186. [PMID: 39498964 PMCID: PMC11562819 DOI: 10.5152/tud.2024.24061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 09/23/2024] [Indexed: 11/07/2024]
Abstract
Objective We aimed to assess the frequency of Y-chromosome microdeletions (YCMs) in a non-multiethnic urban population in our region, define predictive factors, and determine a new clinical threshold for YCMs in infertile men. Materials and Methods A total of 281 patients with a sperm concentration ≤5 million/mL were retrospectively evaluated. Oligozoospermic and/or azoospermic patients with a sperm concentration of ≤5 million/mL were screened for the YCM analysis. Results Y-chromosome microdeletion was detected in 9 (3.2%) of the 281 patients. All patients with YCM were azoospermic. The presence of azoospermia, a high folliclestimulating hormone level, and a high luteinizing hormone level were found to be important determinants for the identification of a microdeletion (P = .002, P = .002, and P=.021, respectively). If the presence of azoospermia and a sperm concentration threshold of <1 million/mL had been applied for the YCM test, the number of tests performed would have been reduced by 54.4% (153 tests) and 42.7% (120 tests), respectively, resulting in cost saving of approximately $11 474 and $9000, respectively. Conclusion We recommend that the threshold for sperm concentration for YCM analysis be set at <1 million in individuals in developed countries and only in patients with azoospermia in developing countries, in order to reduce costs and save labor by excluding unnecessary tests. These proposed thresholds (azoospermia and sperm counts less than <1 million/mL) provide cost-effectiveness by significantly reducing the number of genetic tests ordered without affecting the diagnosis rate.
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Affiliation(s)
- Ali Çift
- Department of Urology, Adıyaman University Faculty of Medicine, Adıyaman, Türkiye
| | - Can Benlioğlu
- Department of Urology, Adıyaman University Faculty of Medicine, Adıyaman, Türkiye
| | - Mehmet Özgür Yücel
- Department of Urology, Adıyaman University Faculty of Medicine, Adıyaman, Türkiye
| | - Muhammer Özgür Çevik
- Department of Medical Genetics, Adıyaman University Faculty of Medicine, Adıyaman, Türkiye
| | - Bedreddin Kalyenci
- Department of Urology, Adıyaman University Faculty of Medicine, Adıyaman, Türkiye
| | - Alper Gök
- Department of Urology, University of Health Sciences, Etlik City Hospital, Ankara, Türkiye
| | - Sait Sever
- Department of Urology, Adıyaman Education and Research Hospital, Adıyaman, Türkiye
| | - Hasan Sulhan
- Department of Urology, Adıyaman University Faculty of Medicine, Adıyaman, Türkiye
| | - Haydar Bağış
- Department of Medical Genetics, Adıyaman University Faculty of Medicine, Adıyaman, Türkiye
| | - Ali Ayyıldız
- Department of Urology, Adıyaman University Faculty of Medicine, Adıyaman, Türkiye
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10
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Dimitrovska M, Plaseska-Karanfilska D, Gogusev JK, Milenkovic T, Bozhinovski G, Dimitrovski C. Male Infertility associated with a Novel PRKAR1A Mutation in Carney Complex. Clin Med Insights Endocrinol Diabetes 2024; 17:11795514241293073. [PMID: 39445317 PMCID: PMC11497543 DOI: 10.1177/11795514241293073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 10/03/2024] [Indexed: 10/25/2024] Open
Abstract
Carney Complex (CNC) is a rare syndrome characterized by spotty skin pigmentation and multiple neoplasms, notably cardiac myxomas, schwannomas, and endocrine tumours. It is often inherited in an autosomal dominant manner with PRKAR1A gene mutations found in the majority of cases. Male infertility is established as part of the CNC phenotype and is largely associated with Large cell calcifying Sertoli cell tumours (LCCSCT). We describe a case of a 30-year-old male patient with Carney Complex, presenting with severe oligoasthenozoospermia and primary pigmented nodular adrenocortical disease (PPNAD). During follow-up consults, the severe oligozoospermia and impaired semen motility persisted and the patient was also diagnosed with a recurring cardiac myxoma and LCCSCT. Molecular testing identified a novel PRKAR1A mutation involving a deletion of exons 4 to 7. Our findings suggest this mutation causes PRKAR1A haploinsufficiency, which may be directly linked to male infertility, irrespective of the presence of testicular tumours. Accordingly, in male patients with CNC, detection of a PRKAR1A gene mutation may serve as a predictive marker for infertility. This case report illustrates the importance of early consideration and management of infertility in male patients diagnosed with CNC.
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Affiliation(s)
- Maja Dimitrovska
- University Clinic of Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre ‘Mother Teresa’, Skopje, North Macedonia
| | - Dijana Plaseska-Karanfilska
- Research Centre for Genetic Engineering and Biotechnology ‘Georgi D. Efremov’, Macedonian Academy of Science and Arts, Skopje, North Macedonia
| | - Jean K. Gogusev
- Department of Pathology, Hospital Necker-Enfants Malades, Paris, France
| | - Tatjana Milenkovic
- University Clinic of Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre ‘Mother Teresa’, Skopje, North Macedonia
| | - Gjorgji Bozhinovski
- Research Centre for Genetic Engineering and Biotechnology ‘Georgi D. Efremov’, Macedonian Academy of Science and Arts, Skopje, North Macedonia
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11
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Shi M, Ma S, Huang L, Huang C, Wang J, Qin X, Luo Y, Xiong Y, He N, Zeng J. Clinical Analysis of Y Chromosome Microdeletions and Chromosomal Aberrations in 1596 Male Infertility Patients of the Zhuang Ethnic Group in Guangxi. Reprod Sci 2024; 31:3074-3085. [PMID: 38836967 PMCID: PMC11438701 DOI: 10.1007/s43032-024-01568-x] [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: 02/01/2024] [Accepted: 04/18/2024] [Indexed: 06/06/2024]
Abstract
The long arm of the Y chromosome (Yq) contains many amplified and palindromic sequences that are prone to self-reorganization during spermatogenesis, and tiny submicroscopic segmental deletions in the proximal Yq are called Y chromosome microdeletions (YCM). A retrospective study was conducted on male infertility patients of Zhuang ethnicity who presented at Reproductive Medical Center of Nanning between January 2015 and May 2023. Seminal fluid was collected for standard examination. YCM were detected by using a combination of multiplex PCR and agarose gel electrophoresis. Preparation of peripheral blood chromosomes and karyotyping of chromosomes was performed. 147 cases (9.22%) of YCM were detected in 1596 male infertility patients of Zhuang ethnicity. Significant difference was found in the detection rate of YCM between the azoospermia group and the oligospermia group (P < 0.001). Of all types of YCM, the highest detection rate was AZFc (n = 83), followed by AZFb + c (n = 28). 264 cases (16.54%) of sex chromosomal aberrations were detected. The most prevalent karyotype was 47, XXY (n = 202). The detection rate of sex chromosomal aberrations in azoospermia group was higher than that in severe oligospermia group and oligospermia group, and the differences were significant (P < 0.001). 28 cases (1.57%) of autosomal aberrations and 105 cases (6.58%) of chromosomal polymorphism were identified. The current research has some limitations due to the lack of normal men as the control group but suggests that YCM and chromosomal aberrations represent key genetic factors influencing spermatogenesis in infertile males of Zhuang ethnicity in Guangxi.
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Affiliation(s)
- Mingfang Shi
- Department of Medical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/The Second Nanning People's Hospital, Nanning, 530031, Guangxi, China
- Guangxi Key Laboratory of Molecular Immunology Research, Nanning, 530031, Guangxi, China
| | - Shengjun Ma
- Department of Medical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/The Second Nanning People's Hospital, Nanning, 530031, Guangxi, China
- Guangxi Key Laboratory of Molecular Immunology Research, Nanning, 530031, Guangxi, China
| | - Li Huang
- Department of Medical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/The Second Nanning People's Hospital, Nanning, 530031, Guangxi, China
- Guangxi Key Laboratory of Molecular Immunology Research, Nanning, 530031, Guangxi, China
| | - Chaosheng Huang
- Department of Medical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/The Second Nanning People's Hospital, Nanning, 530031, Guangxi, China
- Guangxi Key Laboratory of Molecular Immunology Research, Nanning, 530031, Guangxi, China
| | - Jing Wang
- Department of Medical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/The Second Nanning People's Hospital, Nanning, 530031, Guangxi, China
- Guangxi Key Laboratory of Molecular Immunology Research, Nanning, 530031, Guangxi, China
| | - Xuemei Qin
- Department of Medical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/The Second Nanning People's Hospital, Nanning, 530031, Guangxi, China
- Guangxi Key Laboratory of Molecular Immunology Research, Nanning, 530031, Guangxi, China
| | - Yibing Luo
- Department of Medical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/The Second Nanning People's Hospital, Nanning, 530031, Guangxi, China
- Guangxi Key Laboratory of Molecular Immunology Research, Nanning, 530031, Guangxi, China
| | - Yu Xiong
- Department of Medical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/The Second Nanning People's Hospital, Nanning, 530031, Guangxi, China
- Guangxi Key Laboratory of Molecular Immunology Research, Nanning, 530031, Guangxi, China
| | - Ningyu He
- Department of Administrative Office, Nanning Maternity and Child Health Hospital/Nanning Women and Children's Hospital, Nanning, 530031, Guangxi, China.
- Department of Neurology, The Third Affiliated Hospital of Guangxi Medical University/The Second Nanning People's Hospital, Nanning, 530031, Guangxi, China.
| | - Jianghui Zeng
- Department of Medical Laboratory, The Third Affiliated Hospital of Guangxi Medical University/The Second Nanning People's Hospital, Nanning, 530031, Guangxi, China.
- Guangxi Key Laboratory of Molecular Immunology Research, Nanning, 530031, Guangxi, China.
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12
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Shah R, Rambhatla A, Atmoko W, Martinez M, Ziouziou I, Kothari P, Tadros N, Phuoc NHV, Kavoussi P, Harraz A, Salvio G, Gul M, Hamoda T, Toprak T, Birowo P, Ko E, Arafa M, Ghayda RA, Karthikeyan VS, Saleh R, Russo GI, Pinggera GM, Chung E, Savira M, Colpi GM, Zohdy W, Pescatori E, Park HJ, Fukuhara S, Tsujimura A, Rojas-Cruz C, Marino A, Mak SK, Amar E, Ibrahim W, Sindhwani P, Alhathal N, Busetto GM, Al Hashimi M, El-Sakka A, Ramazan A, Dimitriadis F, Timpano M, Jezek D, Altay B, Zylbersztejn DS, Wong MY, Moon DG, Wyns C, Gamidov S, Akhavizadegan H, Franceschelli A, Aydos K, Quang VN, Ashour S, Al Dayel A, Al-Marhoon MS, Micic S, Binsaleh S, Hussein A, Elbardisi H, Mostafa T, Taha E, Ramsay J, Zachariou A, Abdelrahman IFS, Rajmil O, Kalkanli A, Molina JMC, Bocu K, Duarsa GWK, Ceker G, Serefoglu EC, Bahar F, Gherabi N, Kuroda S, Bouzouita A, Gudeloglu A, Ceyhan E, Hasan MSM, Musa MU, Motawi A, Chak-Lam C, Taniguchi H, Ho CCK, Vazquez JFS, Mutambirwa S, Gungor ND, Bendayan M, Giulioni C, Baser A, Falcone M, Boeri L, Blecher G, Kheradmand A, Sethupathy T, Adriansjah R, Narimani N, Konstantinidis C, Nguyen TT, Japari A, Dolati P, Singh K, Ozer C, Sarikaya S, Sheibak N, Bosco NJ, Özkent MS, Le ST, Sokolakis I, Katz D, Smith R, Truong MN, Le TV, Huang Z, Deger MD, Arslan U, Calik G, Franco G, Rashed A, Kahraman O, Andreadakis S, Putra R, Balercia G, Khalafalla K, Cannarella R, Tuấn AĐ, El Meliegy A, Zilaitiene B, Ramirez MLZ, Giacone F, Calogero AE, Makarounis K, Jindal S, Hoai BN, Banthia R, Peña MR, Moorthy D, Adamyan A, Kulaksiz D, Kandil H, Sofikitis N, Salzano C, Jungwirth A, Banka SR, Mierzwa TC, Turunç T, Jain D, Avoyan A, Salacone P, Kadıoğlu A, Gupta C, Lin H, Shamohammadi I, Mogharabian N, Barrett T, Danacıoğlu YO, Crafa A, Daoud S, Malhotra V, Almardawi A, Selim OM, Moussa M, Haghdani S, Duran MB, Kunz Y, Preto M, Eugeni E, Nguyen T, Elshahid AR, Suyono SS, Parikesit D, Nada E, Orozco EG, Boitrelle F, Trang NTM, Jamali M, Nair R, Ruzaev M, Gadda F, Thomas C, Ferreira RH, Gul U, Maruccia S, Kanbur A, Kinzikeeva E, Abumelha S, Quang N, Kosgi R, Gokalp F, Soebadi MA, Paul GM, Sajadi H, Gupte D, Ambar RF, Sogutdelen E, Singla K, Basurkano A, Kim SHK, Gilani MAS, Nagao K, Brodjonegoro SR, Rezano A, Elkhouly M, Mazzilli R, Farsi HMA, Ba HN, Alali H, Kafetzis D, Long TQT, Alsaid S, Cuong HBN, Oleksandr K, Mustafa A, Acosta H, Pai H, Şahin B, Arianto E, Teo C, Jayaprakash SP, Rachman RI, Yenice MG, Sefrioui O, Paghdar S, Priyadarshi S, Tanic M, Alfatlawy NK, Rizaldi F, Vishwakarma RB, Kanakis G, Cherian DT, Lee J, Galstyan R, Keskin H, Wurzacher J, Seno DH, Noegroho BS, Margiana R, Javed Q, Castiglioni F, Tanwar R, Puigvert A, Kaya C, Purnomo M, Yazbeck C, Amir A, Borges E, Bellavia M, Deswanto IA, V VK, Liguori G, Minh DH, Siddiqi K, Colombo F, Zini A, Patel N, Çayan S, Al-Kawaz U, Ragab M, Hebrard GH, Hoffmann I, Efesoy O, Saylam B, Agarwal A. Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations. World J Mens Health 2024; 42:727-748. [PMID: 38606865 PMCID: PMC11439803 DOI: 10.5534/wjmh.230333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 11/27/2023] [Indexed: 04/13/2024] Open
Abstract
PURPOSE Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.
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Affiliation(s)
- Rupin Shah
- Division of Andrology, Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India
- Global Andrology Forum, Moreland Hills, OH, USA
| | - Amarnath Rambhatla
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Henry Ford Health System, Vattikuti Urology Institute, Detroit, MI, USA
| | - Widi Atmoko
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Marlon Martinez
- Global Andrology Forum, Moreland Hills, OH, USA
- Section of Urology, Department of Surgery, University of Santo Tomas Hospital, Manila, Philippines
| | - Imad Ziouziou
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, College of Medicine and Pharmacy, Ibn Zohr University, Agadir, Morocco
| | - Priyank Kothari
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, B.Y.L Nair Ch Hospital, Topiwala National Medical College, Mumbai, India
| | - Nicholas Tadros
- Global Andrology Forum, Moreland Hills, OH, USA
- Division of Urology, Southern Illinois University School of Medicine, Springfield, IL, USA
| | - Nguyen Ho Vinh Phuoc
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Binh Dan Hospital, Ho Chi Minh City, Vietnam
| | - Parviz Kavoussi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Reproductive Urology, Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA
| | - Ahmed Harraz
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Mansoura University Urology and Nephrology Center, Mansoura, Egypt
- Department of Surgery, Urology Unit, Farwaniya Hospital, Farwaniya, Kuwait
- Department of Urology, Sabah Al Ahmad Urology Center, Kuwait City, Kuwait
| | - Gianmaria Salvio
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy
| | - Murat Gul
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Selçuk University School of Medicine, Konya, Turkey
| | - Taha Hamoda
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Andrology, Faculty of Medicine, Assiut University, Asyut, Egypt
| | - Tuncay Toprak
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Ponco Birowo
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Edmund Ko
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Loma Linda University Health, Loma Linda, CA, USA
| | - Mohamed Arafa
- Global Andrology Forum, Moreland Hills, OH, USA
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
- Department of Urology, Hamad Medical Corporation, Doha, Qatar
- Department of Urology, Weill Cornell Medical-Qatar, Doha, Qatar
| | - Ramy Abou Ghayda
- Global Andrology Forum, Moreland Hills, OH, USA
- Urology Institute, University Hospitals, Case Western Reserve University, Cleveland, OH, USA
| | | | - Ramadan Saleh
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt
| | - Giorgio Ivan Russo
- Global Andrology Forum, Moreland Hills, OH, USA
- Urology Section, University of Catania, Catania, Italy
| | - Germar-Michael Pinggera
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, University Hospital Innsbruck, Innsbruck, Austria
| | - Eric Chung
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Princess Alexandra Hospital, University of Queensland, Brisbane, Australia
| | - Missy Savira
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, College of Medicine and Pharmacy, Ibn Zohr University, Agadir, Morocco
| | - Giovanni M Colpi
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology and IVF Center, Next Fertility Procrea, Lugano, Switzerland
| | - Wael Zohdy
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Sexology & STIs, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Edoardo Pescatori
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology and Reproductive Medicine Unit, Gynepro Medical, Bologna, Italy
| | - Hyun Jun Park
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Pusan National University School of Medicine, Busan, Korea
- Medical Research Institute of Pusan National University Hospital, Busan, Korea
| | - Shinichiro Fukuhara
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Akira Tsujimura
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Cesar Rojas-Cruz
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, University Hospital of Rostock, Rostock, Germany
| | - Angelo Marino
- Global Andrology Forum, Moreland Hills, OH, USA
- Reproductive Medicine Unit, ANDROS Day Surgery Clinic, Palermo, Italy
| | - Siu King Mak
- Global Andrology Forum, Moreland Hills, OH, USA
- Union Hospital, Hong Kong SAR, China
| | - Edouard Amar
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, American Hospital of Paris, Paris, France
| | - Wael Ibrahim
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Obstetrics Gynaecology and Reproductive Medicine, Fertility Care Center in Cairo, Cairo, Egypt
| | - Puneet Sindhwani
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, USA
| | - Naif Alhathal
- Global Andrology Forum, Moreland Hills, OH, USA
- King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Gian Maria Busetto
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy
| | - Manaf Al Hashimi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Burjeel Hospital, Abu Dhabi, UAE
- Department of Urology, Khalifa University College of Medicine and Health Science, Abu Dhabi, UAE
| | - Ahmed El-Sakka
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Asci Ramazan
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Fotios Dimitriadis
- Global Andrology Forum, Moreland Hills, OH, USA
- 1st Urology Department, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Massimiliano Timpano
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Molinette Hospital, A.O.U. Città della Salute e della Scienza, University of Turin, Torino, Italy
| | - Davor Jezek
- Global Andrology Forum, Moreland Hills, OH, USA
- Department for Transfusion Medicine and Transplantation Biology, Reproductive Tissue Bank, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Baris Altay
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Ege University Medical School, Bornova, Izmir, Turkey
| | - Daniel Suslik Zylbersztejn
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Fleury Group and Hospital Israelita Albert Einstein, São Paulo, Brazil
| | - Michael Yc Wong
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, International Urology, Fertility and Gynecology Centre, Mount Elizabeth Hospital, Singapore
| | - Du Geon Moon
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Korea University Guro Hospital, Seoul, Korea
| | - Christine Wyns
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Gynaecology-Andrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Safar Gamidov
- Global Andrology Forum, Moreland Hills, OH, USA
- V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia
| | - Hamed Akhavizadegan
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, School of Medicine, Hasheminejad Kidney Center, Iran University of Medical Science, Tehran, Iran
| | - Alessandro Franceschelli
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology Unit, University Hospital S. Orsola, Bologna, Italy
| | - Kaan Aydos
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Ankara University, Ankara, Turkey
| | - Vinh Nguyen Quang
- Global Andrology Forum, Moreland Hills, OH, USA
- Center for Andrology and Sexual Medicine, Viet Duc University Hospital, Hanoi, Vietnam
- Department of Urology, Can Tho University of Medicine and Pharmacy Hospital, Can Tho, Vietnam
| | - Shedeed Ashour
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Sexology & STIs, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Adel Al Dayel
- Global Andrology Forum, Moreland Hills, OH, USA
- Men's Health Clinic Dammam, Dammam, Saudi Arabia
| | - Mohamed S Al-Marhoon
- Global Andrology Forum, Moreland Hills, OH, USA
- Division of Urology, Department of Surgery, Sultan Qaboos University, Muscat, Oman
| | - Sava Micic
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Uromedica Polyclinic, Belgrade, Serbia
| | - Saleh Binsaleh
- Global Andrology Forum, Moreland Hills, OH, USA
- Division of Urology, Department of Surgery, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Alayman Hussein
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Faculty of Medicine, Assiut University, Asyut, Egypt
| | - Haitham Elbardisi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Hamad Medical Corporation, Doha, Qatar
- Department of Urology, Weill Cornell Medical-Qatar, Doha, Qatar
| | - Taymour Mostafa
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Sexology & STIs, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Emad Taha
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Andrology, Faculty of Medicine, Assiut University, Asyut, Egypt
| | - Jonathan Ramsay
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Hammersmith Hospital, London, UK
| | - Athanasios Zachariou
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Ioannina University School of Medicine, Ioannina, Greece
| | - Islam Fathy Soliman Abdelrahman
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Sexology & STIs, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Andrology, Armed Forces College of Medicine, Cairo, Egypt
| | - Osvaldo Rajmil
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Fundacio Puigvert, Barcelona, Spain
| | - Arif Kalkanli
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Taksim Education and Research Hospital, Istanbul, Turkey
| | - Juan Manuel Corral Molina
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Hospital Clínico de Barcelona, Barcelona, Spain
| | - Kadir Bocu
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Niğde Omer Halis Demir University Faculty of Medicine, Nigde, Turkey
| | - Gede Wirya Kusuma Duarsa
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Udayana University, Denpasar, Indonesia
| | - Gokhan Ceker
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey
| | - Ege Can Serefoglu
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Biruni University School of Medicine, Istanbul, Turkey
| | - Fahmi Bahar
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology Section, Siloam Sriwijaya Hospital, Palembang, Indonesia
| | - Nazim Gherabi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Medicine, University of Algiers 1, Algiers, Algeria
| | - Shinnosuke Kuroda
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Abderrazak Bouzouita
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Anatomy, Faculty of Medicine, Faculty Tunis Manar, Tunis, Tunisia
| | - Ahmet Gudeloglu
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Erman Ceyhan
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Mohamed Saeed Mohamed Hasan
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Muhammad Ujudud Musa
- Global Andrology Forum, Moreland Hills, OH, USA
- Urology Unit, Department of Surgery, Federal Medical Center, Katsina State, Nigeria
| | - Ahmad Motawi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Sexology & STIs, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Cho Chak-Lam
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Surgery, S. H. Ho Urology Centre, The Chinese University of Hong Kong, Hong Kong
| | - Hisanori Taniguchi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology and Andrology, Kansai Medical University, Osaka, Japan
| | - Christopher Chee Kong Ho
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Surgery, School of Medicine, Taylor's University, Selangor, Malaysia
| | | | - Shingai Mutambirwa
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Dr. George Mukhari Academic Hospital, Sefako Makgatho Health Science University, Medunsa, South Africa
| | - Nur Dokuzeylul Gungor
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Obstetrics and Gynecology, Reproductive Endocrinology and IVF Unit, School of Medicine, Bahcesehir University, Istanbul, Turkey
| | - Marion Bendayan
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France
- Department of Biology, Reproduction, Epigenetics, Environment and Development, Paris Saclay University, UVSQ, INRAE, BREED, Jouy-en-Josas, France
| | - Carlo Giulioni
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Polytechnic University of Marche, Ancona, Italy
| | - Aykut Baser
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Faculty of Medicine, Bandırma Onyedi Eylül University, Balıkesir, Turkey
| | - Marco Falcone
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Molinette Hospital, A.O.U. Città della Salute e della Scienza, University of Turin, Torino, Italy
| | - Luca Boeri
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Gideon Blecher
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Surgery, School of Clinical Sciences, Monash University, Melbourne, Australia
- Department of Urology, The Alfred Hospital, Melbourne, Australia
| | - Alireza Kheradmand
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Tamilselvi Sethupathy
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Obstetrics and Gynaecology, CK Medical Centre Hospital, Erode, India
| | - Ricky Adriansjah
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Hasan Sadikin General Hospital, Faculty of Medicine of Padjadjaran University, Bandung, Indonesia
| | - Nima Narimani
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, School of Medicine, Hasheminejad Kidney Center, Iran University of Medical Science, Tehran, Iran
| | - Charalampos Konstantinidis
- Global Andrology Forum, Moreland Hills, OH, USA
- Urology Department, General Hospital of Corinth, Corinth, Greece
| | - Tuan Thanh Nguyen
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, University of California, Irvine, CA, USA
- Department of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Department of Urology, Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | - Andrian Japari
- Global Andrology Forum, Moreland Hills, OH, USA
- Deparment of IVF, Fertility Clinic, Telogorejo Hospital, Semarang, Indonesia
| | - Parisa Dolati
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Animal Science, Faculty of Agriculture, University of Shiraz, Shiraz, Iran
| | - Keerti Singh
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Preclinical and Health Sciences, Faculty of Medical Sciences, The University of West Indies, Cave Hill Campus, Bridgetown, Barbados
- Windsor Medical Centre, Bridgetown, Barbados
| | - Cevahir Ozer
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - Selcuk Sarikaya
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Gulhane Research and Training Hospital, University of Health Sciences, Ankara, Turkey
| | - Nadia Sheibak
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Anatomical Sciences, Reproductive Sciences and Technology Research Center, Iran University of Medical Sciences, Tehran, Iran
- Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), Iran University of Medical Sciences, Tehran, Iran
| | - Ndagijimana Jean Bosco
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Dermatology, Venereology & Andrology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Mehmet Serkan Özkent
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Konya City Hospital, Konya, Turkey
| | - Sang Thanh Le
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Binh Dan Hospital, Ho Chi Minh City, Vietnam
- Deparment of IVF, Fertility Clinic, Telogorejo Hospital, Semarang, Indonesia
| | - Ioannis Sokolakis
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Martha-Maria Hospital Nuremberg, Nuremberg, Germany
| | - Darren Katz
- Global Andrology Forum, Moreland Hills, OH, USA
- Men's Health Melbourne, Victoria, Australia
- Department of Surgery, Western Precinct, University of Melbourne, Victoria, Australia
- Department of Urology, Western Health, Victoria, Australia
| | - Ryan Smith
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Manh Nguyen Truong
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | - Tan V Le
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Department of Urology and Andrology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | - Zhongwei Huang
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Obstetrics and Gynaecology, National University Health Systems, Singapore
| | - Muslim Dogan Deger
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Edirne Sultan 1st Murat State Hospital, Edirne, Turkey
| | - Umut Arslan
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Gokhan Calik
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Istanbul Medipol University, Istanbul, Turkey
| | - Giorgio Franco
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Ayman Rashed
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Faculty of Medicine, 6th of October University, Giza, Egypt
| | - Oguzhan Kahraman
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Ankara University, Ankara, Turkey
| | - Sotiris Andreadakis
- Global Andrology Forum, Moreland Hills, OH, USA
- Private Practice, Thessaloniki, Greece
| | - Rosadi Putra
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, RSUD Ciawi Regional General Hospital, West Java, Indonesia
| | - Giancarlo Balercia
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy
| | - Kareim Khalafalla
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Hamad Medical Corporation, Doha, Qatar
- Department of Urology, University of Illinois, Chicago, IL, USA
| | - Rossella Cannarella
- Global Andrology Forum, Moreland Hills, OH, USA
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Anh Đặng Tuấn
- Global Andrology Forum, Moreland Hills, OH, USA
- Tam Anh IVF Center, Tam Anh General Hospital, Hanoi, Vietnam
| | - Amr El Meliegy
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Sexology & STIs, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Birute Zilaitiene
- Global Andrology Forum, Moreland Hills, OH, USA
- Institute of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | | | - Filippo Giacone
- Global Andrology Forum, Moreland Hills, OH, USA
- HERA Center, Unit of Reproductive Medicine, Sant'Agata Li Battiati, Catania, Italy
| | - Aldo E Calogero
- Global Andrology Forum, Moreland Hills, OH, USA
- Urology Section, University of Catania, Catania, Italy
| | - Konstantinos Makarounis
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology and Andrology, Locus Medicus, Athens, Greece
| | - Sunil Jindal
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology & Reproductive Medicine, Jindal Hospital & Fertility Center, Meerut, India
| | - Bac Nguyen Hoai
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology and Sexual Medicine, Hanoi Medical University Hospital, Hanoi, Vietnam
| | - Ravi Banthia
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Western General Hospital, Edinburgh, UK
| | - Marcelo Rodriguez Peña
- Global Andrology Forum, Moreland Hills, OH, USA
- Instituto de Ginecología y Fertilidad (IFER), Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Dharani Moorthy
- Global Andrology Forum, Moreland Hills, OH, USA
- IVF Department, Swarupa fertility & IVF Centre, Vijayawada, India
| | - Aram Adamyan
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Astghik Medical Center, Yerevan, Armenia
| | - Deniz Kulaksiz
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Obstetrics and Gynecology, Kanuni Training and Research Hospital, University of Health Sciences, Trabzon, Turkey
| | - Hussein Kandil
- Global Andrology Forum, Moreland Hills, OH, USA
- Fakih IVF Fertility Center, Abu Dhabi, UAE
| | - Nikolaos Sofikitis
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Ioannina University School of Medicine, Ioannina, Greece
| | - Ciro Salzano
- Global Andrology Forum, Moreland Hills, OH, USA
- PO San Giovanni Bosco, ASL Napoli 1 Centro, Napoli, Italy
| | - Andreas Jungwirth
- Global Andrology Forum, Moreland Hills, OH, USA
- St. Barabara Private Clinic, Bad Vigaun, Austria
| | - Surendra Reddy Banka
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Androcare Institute of Andrology and Men's Health, Hyderabad, India
| | - Tiago Cesar Mierzwa
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Centro Universitario em Saude do ABC, Santo André, Brazil
| | - Tahsin Turunç
- Global Andrology Forum, Moreland Hills, OH, USA
- Urology Clinic, Iskenderun Gelisim Hospital, Iskenderun, Turkey
| | - Divyanu Jain
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Obstetrics and Gynecology, Jaipur Golden Hospital, New Delhi, India
| | - Armen Avoyan
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Astghik Medical Center, Yerevan, Armenia
| | - Pietro Salacone
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology and Pathophysiology of Reproduction Unit, Santa Maria Goretti Hospital, Latina, Italy
| | - Ateş Kadıoğlu
- Global Andrology Forum, Moreland Hills, OH, USA
- Section of Andrology, Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Chirag Gupta
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Jaipur National University, Jaipur, India
| | - Haocheng Lin
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Peking University Third Hospital, Peking University, Beijing, China
| | - Iman Shamohammadi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nasser Mogharabian
- Global Andrology Forum, Moreland Hills, OH, USA
- Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Trenton Barrett
- Global Andrology Forum, Moreland Hills, OH, USA
- Perth Urology Clinic, Perth, WA, Australia
| | - Yavuz Onur Danacıoğlu
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, University of Health Science Istanbul, Istanbul, Turkey
| | - Andrea Crafa
- Global Andrology Forum, Moreland Hills, OH, USA
- Urology Section, University of Catania, Catania, Italy
| | - Salima Daoud
- Global Andrology Forum, Moreland Hills, OH, USA
- Laboratory of Histo-Embryology and Reproductive Biology, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
| | - Vineet Malhotra
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology and Andrology, VNA Hospital, New Delhi, India
| | - Abdulmalik Almardawi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Osama Mohamed Selim
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Sexology & STIs, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamad Moussa
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Lebanese University, Beirut, Lebanon
- Department of Urology, Al Zahraa Hospital, UMC, Beirut, Lebanon
| | - Saeid Haghdani
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology Research Center, Yazd Reproductive Science Institute, Isfahan Fertility and Isfahan, Yazd, Iran
| | - Mesut Berkan Duran
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Pamukkale University School of Medicine, Denizli, Turkey
| | - Yannic Kunz
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, University Hospital Innsbruck, Innsbruck, Austria
| | - Mirko Preto
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Molinette Hospital, A.O.U. Città della Salute e della Scienza, University of Turin, Torino, Italy
| | - Elena Eugeni
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
- Department of Medicine and Medical Specialties, Division of Medical Andrology and Endocrinology of Reproduction, University of Terni, Terni, Italy
| | - Thang Nguyen
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology and Sexual Medicine, Hanoi Medical University Hospital, Hanoi, Vietnam
| | - Ahmed Rashad Elshahid
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Seso Sulijaya Suyono
- Global Andrology Forum, Moreland Hills, OH, USA
- Gladiool IVF, Magelang, Indonesia
| | - Dyandra Parikesit
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Universitas Indonesia Hospital, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia
| | - Essam Nada
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt
| | - Eduardo Gutiérrez Orozco
- Global Andrology Forum, Moreland Hills, OH, USA
- IVF Department, CITMER Reproductive Medicine, Nuevo Leon, Mexico
| | - Florence Boitrelle
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France
- Department of Biology, Reproduction, Epigenetics, Environment and Development, Paris Saclay University, UVSQ, INRAE, BREED, Jouy-en-Josas, France
| | - Nguyen Thi Minh Trang
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Mounir Jamali
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Military Teaching Hospital, Rabat, Morocco
| | - Raju Nair
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Reproductive Medicine, Mitera Hospital, Kottayam, India
| | - Mikhail Ruzaev
- Global Andrology Forum, Moreland Hills, OH, USA
- Urology Clinic, Moscow, Russia
| | - Franco Gadda
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Charalampos Thomas
- Global Andrology Forum, Moreland Hills, OH, USA
- Urology Department, General Hospital of Corinth, Corinth, Greece
| | - Raphael Henrique Ferreira
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Santa Casa de Ribeirão Preto, São Paulo, Brazil
| | - Umit Gul
- Global Andrology Forum, Moreland Hills, OH, USA
- Private EPC Hospital, Adana, Turkey
| | - Serena Maruccia
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, ASST Santi Paolo e Carlo, San Paolo Hospital, Milano, Italy
| | - Ajay Kanbur
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Kanbur Clinic, Thane, India
- Department of Urosurgery, Jupiter Hospital, Thane, India
| | - Ella Kinzikeeva
- Global Andrology Forum, Moreland Hills, OH, USA
- Zucchi Clinical Institutes, Monza, Italy
| | - Saad Abumelha
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Nguyen Quang
- Global Andrology Forum, Moreland Hills, OH, USA
- Center for Andrology and Sexual Medicine, Viet Duc University Hospital, Hanoi, Vietnam
- Department of Urology, Can Tho University of Medicine and Pharmacy Hospital, Can Tho, Vietnam
| | - Raghavender Kosgi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology and Andrology, AIG Hospitals, Hyderabad, India
| | - Fatih Gokalp
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Faculty of Medicine, Hatay Mu Stafa Kemal University, Antakya, Turkey
| | - Mohammad Ayodhia Soebadi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Faculty of Medicine, Universitas Airlangga, Soetomo Hospital, Surabaya, Indonesia
| | - Gustavo Marquesine Paul
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Hospital de Clínicas of the Federal University of Paraná, Curitiba, Brazil
| | - Hesamoddin Sajadi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Deepak Gupte
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Bombay Hospital and Medical Research Center, Mumbai, India
| | - Rafael F Ambar
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Fleury Group and Hospital Israelita Albert Einstein, São Paulo, Brazil
- Department of Urology, Centro Universitario em Saude do ABC, Santo André, Brazil
| | - Emrullah Sogutdelen
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Clarity Health, Chandigarh, India
| | - Karun Singla
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Dr. Dradjat Hospital, Serang, Indonesia
| | - Ari Basurkano
- Global Andrology Forum, Moreland Hills, OH, USA
- IVF Australia, Sydney, Australia
| | - Shannon Hee Kyung Kim
- Global Andrology Forum, Moreland Hills, OH, USA
- Macquarie School of Medicine, Macquaire University, Sydney, Australia
- Department of Urology, Imperial Healthcare NHS Trust, Charing Cross Hospital, London, UK
| | - Mohammad Ali Sadighi Gilani
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Koichi Nagao
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Toho University Faculty of Medicine, Tokyo, Japan
| | - Sakti Ronggowardhana Brodjonegoro
- Global Andrology Forum, Moreland Hills, OH, USA
- Division of Urology, Department of Surgery, Prof. Dr. Sardjito Hospital, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Andri Rezano
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology Study Program, Department of Biomedical Sciences, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang, Indonesia
| | - Mohamed Elkhouly
- Global Andrology Forum, Moreland Hills, OH, USA
- IVF Department, Bourn Hall Fertility Center, Dubai, UAE
| | - Rossella Mazzilli
- Global Andrology Forum, Moreland Hills, OH, USA
- Unit of Endocrinology, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Hasan M A Farsi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hung Nguyen Ba
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology Unit, ART Center, Vinmec Times City International Hospital, Hanoi, Vietnam
| | - Hamed Alali
- Global Andrology Forum, Moreland Hills, OH, USA
- King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Dimitrios Kafetzis
- Global Andrology Forum, Moreland Hills, OH, USA
- Orchid IVF Clinic, Dubai, UAE
| | - Tran Quang Tien Long
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Obstetrics and Gynecology, Hanoi Obstetric and Gynecology Hospital, Hanoi, Vietnam
| | - Sami Alsaid
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Hamad Medical Corporation, Doha, Qatar
| | - Hoang Bao Ngoc Cuong
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Surgery, Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam
| | - Knigavko Oleksandr
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Nephrology and Andrology, Kharkiv National Medical University, Kharkiv, Ukraine
| | - Akhmad Mustafa
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Hasan Sadikin General Hospital, Faculty of Medicine of Padjadjaran University, Bandung, Indonesia
| | - Herik Acosta
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Hrishikesh Pai
- Global Andrology Forum, Moreland Hills, OH, USA
- IVF Department, Bloom IVF Group, Mombai, India
| | - Bahadır Şahin
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, School of Medicine, Marmara University, İstanbul, Turkey
| | - Eko Arianto
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Prof R.D. Kandou Hospital, Manado, Indonesia
| | - Colin Teo
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Gleneagles Hospital, Singapore
| | - Sanjay Prakash Jayaprakash
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology Unit, Department of Urology, Apollo Hospitals, Greams Road, Chennai, India
| | - Rinaldo Indra Rachman
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Mustafa Gurkan Yenice
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, University of Health Science Istanbul, Istanbul, Turkey
| | - Omar Sefrioui
- Global Andrology Forum, Moreland Hills, OH, USA
- African Fertility Center, Casablanca, Morocco
| | - Smit Paghdar
- Global Andrology Forum, Moreland Hills, OH, USA
- UVA Urology Clinic in Charlottesville, UVA Specialty Care Clinic in Culpeper, Culpeper, VA, USA
| | - Shivam Priyadarshi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Sawai Man Singh Medical College and Hospital, Jaipur, Rajasthan, India
| | - Marko Tanic
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, General Hospital, Cuprija, Serbia
| | - Noor Kareem Alfatlawy
- Global Andrology Forum, Moreland Hills, OH, USA
- Fertility Center of Al-Najaf/Al-Sadr Medical City, Babylon Health Directorate, Iraqi Ministry of Health, Baghdad, Iraq
| | - Fikri Rizaldi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Faculty of Medicine, Universitas Airlangga, Soetomo Hospital, Surabaya, Indonesia
| | - Ranjit B Vishwakarma
- Division of Andrology, Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India
- Global Andrology Forum, Moreland Hills, OH, USA
| | - George Kanakis
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Endocrinology, Diabetes and Metabolism, Athens Naval & VA Hospital, Athens, Greece
| | - Dinesh Thomas Cherian
- Global Andrology Forum, Moreland Hills, OH, USA
- Urology Deparment, Aster Medcity, Kochi, India
| | - Joe Lee
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, National University Hospital, Singapore
| | - Raisa Galstyan
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Yerevan State Medical University, Yerevan, Armenia
| | - Hakan Keskin
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Jana Wurzacher
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, University Hospital Innsbruck, Innsbruck, Austria
| | - Doddy Hami Seno
- Global Andrology Forum, Moreland Hills, OH, USA
- Division of Urology, Department of Surgery, Persahabatan General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Bambang S Noegroho
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Hasan Sadikin General Hospital, Faculty of Medicine of Padjadjaran University, Bandung, Indonesia
| | - Ria Margiana
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Master's Programme Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Qaisar Javed
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Al-Ahlia Hospital, Abu Dhabi, UAE
| | - Fabrizio Castiglioni
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology Unit, ART Center - San Carlo Clinic, Milan, Italy
| | - Raman Tanwar
- Global Andrology Forum, Moreland Hills, OH, USA
- Urology Center, Jyoti Hospital, Gurugram, India
| | - Ana Puigvert
- Global Andrology Forum, Moreland Hills, OH, USA
- Institute of Andrology and Sexual Medicine (IANDROMS), Barcelona, Spain
| | - Coşkun Kaya
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Health Science University Eskisehir City HPRH, Eskisehir, Turkey
| | - Medianto Purnomo
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Brawijaya University, Malang, Indonesia
| | - Chadi Yazbeck
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Obstetrics Gynecology and Reproductive Medicine, Reprogynes Medical Institute, Paris, France
| | - Azwar Amir
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Dr Wahidin Sudirohusodo Hospital, Makassar, Indonesia
| | - Edson Borges
- Global Andrology Forum, Moreland Hills, OH, USA
- Fertility Assisted Fertilization Center, São Paulo, Brazil
| | - Marina Bellavia
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology and IVF Center, Next Fertility Procrea, Lugano, Switzerland
| | - Isaac Ardianson Deswanto
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, College of Medicine and Pharmacy, Ibn Zohr University, Agadir, Morocco
| | - Vinod K V
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Cure & SK Hospital, Trivandrum, India
| | - Giovanni Liguori
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, University of Trieste, Trieste, Italy
| | - Dang Hoang Minh
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Can Tho University of Medicine and Pharmacy Hospital, Can Tho, Vietnam
| | - Kashif Siddiqi
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Cleveland Clinic, Abu Dhabi, UAE
| | - Fulvio Colombo
- Global Andrology Forum, Moreland Hills, OH, USA
- Andrology and Reproductive Medicine Unit, Gynepro Medical, Bologna, Italy
| | - Armand Zini
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Surgery, McGill University, Montreal, QC, Canada
| | - Niket Patel
- Global Andrology Forum, Moreland Hills, OH, USA
- Akanksha Hospital and Research Institute, Anand, Gujarat, India
| | - Selahittin Çayan
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, University of Mersin School of Medicine, Mersin, Turkey
| | - Ula Al-Kawaz
- Global Andrology Forum, Moreland Hills, OH, USA
- High Institute for Infertility Diagnosis and Assisted Reproductive Technologies, Al-Nahrain University, Baghdad, Iraq
| | - Maged Ragab
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Tanta University, Tanta, Egypt
| | | | - Ivan Hoffmann
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Reproductive Medicine and Andrology, University Clinic Halle (Saale), Halle, Germany
- Reproductive Center Dr. Hoffmann, Berlin, Germany
| | - Ozan Efesoy
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Mersin City Training and Research Hospital, University of Health Sciences, Mersin, Turkey
| | - Barış Saylam
- Global Andrology Forum, Moreland Hills, OH, USA
- Department of Urology, Mersin City Training and Research Hospital, University of Health Sciences, Mersin, Turkey
| | - Ashok Agarwal
- Global Andrology Forum, Moreland Hills, OH, USA
- American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA.
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Japari A, El Ansari W. Varicocele repair for severe oligoasthenoteratozoospermia: Scoping review of published guidelines, and systematic review of the literature. Arab J Urol 2024; 23:33-52. [PMID: 39776560 PMCID: PMC11703451 DOI: 10.1080/20905998.2024.2400629] [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: 07/24/2024] [Accepted: 08/31/2024] [Indexed: 01/11/2025] Open
Abstract
Background The outcomes of varicocele repair (VR) for severe oligozooasthenoteratozoospermia (OAT) have not been widely examined. Methods Assessment of outcomes of VR after severe OAT, employing scoping review of published guidelines, and systematic review of literature. The Newcastle-Ottawa scale appraised the quality of included studies. Findings from both reviews were used to identify knowledge gaps and ways to enhance the evidence base. Results No published guidelines exist specifically on VR for severe OAT. Of 731 articles retrieved, 15 were included, indicating a scarcity of studies appraising the topic. Most included studies exhibited high risk of bias and low-level evidence. Studies focused on basic sperm parameters; fewer examined hormonal/testicular volume changes, or pregnancy/live births. Studies suggested some post-VR sperm parameters improvements but mostly no changes in hormone levels/testicular volume. We identified four knowledge gaps: methodological issues; narrow scope of research and measurement aspects; lack of genetic considerations; and scarce economic/cost-effectiveness appraisals. We propose some precautions, remedies, and research questions to enhance the thin evidence base. Conclusions VR for severe OAT has potential to improve sperm parameters. Scarcity of studies, high risk of bias, low-level evidence, and other limitations mitigate against drawing solid conclusions. Future research is required.
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Affiliation(s)
- Andrian Japari
- Fertility Clinic, Telogorejo Hospital, Semarang, Indonesia
| | - Walid El Ansari
- Department of Surgery, Hamad Medical Corporation, Doha, Qatar
- College of Medicine, Qatar University, Doha, Qatar
- Department of Clinical Population Health, Weill Cornell Medicine-Qatar, Doha, Qatar
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14
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Dutta S, Paladhi P, Pal S, Srimani S, Bose G, Ghosh P, Chattopadhyay R, Ghosh S. Screening of the Combined Risk of Genetics and Epidemiology on Infertility Among Indian Men: Synergistic Effect of AZFc Partial Deletions and Habits of Smokeless Chewing Tobacco. Am J Mens Health 2024; 18:15579883241279195. [PMID: 39311468 PMCID: PMC11437552 DOI: 10.1177/15579883241279195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/30/2024] Open
Abstract
The AZFc partial deletions of Y chromosome and lifestyle/epidemiological factors such as the use of smokeless chewing tobacco (SCT) exhibit intriguing variations in their association with male infertility across the population, ethnicity, and genetic background. Here, a pioneering attempt has been made to elucidate the interactions of such deletions with the habits of SCT consumption among the participating individuals, using their large epidemiological data. This screening program was conducted among Bengali-speaking men in West Bengal, India. We screened the prevalence and association of distinct partial deletions (gr/gr, b1/b3, and b2/b3) of the AZFc region using locus-specific sequence-tagged site (STS) markers among 728 case subjects and compared them with 264 ethnicity- and age-matched proven-fertile control men. The recorded epidemiological data of the study group and the outcome of partial deletion analysis were compiled to frame the plausible Gene × Epidemiological factor (G × E) interactions. The gr/gr deletion was reported to be significantly associated with azoospermic (p = .0015, odds ratio [OR] = 3.413) and oligozoospermic (p = .0382, OR = 3.012) case subgroups, and b1/b3 deletions were also detected among the infertile persons only. The G × E model revealed that men who carried microdeletions as well as were SCT users had an elevated risk of infertility (p = .002, OR = 6.38). The study highlights the fact that AZFc partial deletions and SCT, when co-occurred, synergistically increase the risk of infertility among men. This work helps to get more insight into the etiology of male infertility in the light of gene-environmental interaction.
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Affiliation(s)
- Saurav Dutta
- Cytogenetics and Genomics Research Unit, Department of Zoology, University of Calcutta, Kolkata, India
| | - Pranab Paladhi
- Cytogenetics and Genomics Research Unit, Department of Zoology, University of Calcutta, Kolkata, India
| | - Samudra Pal
- Cytogenetics and Genomics Research Unit, Department of Zoology, University of Calcutta, Kolkata, India
| | - Souvik Srimani
- Cytogenetics and Genomics Research Unit, Department of Zoology, University of Calcutta, Kolkata, India
| | - Gunja Bose
- Institute of Reproductive Medicine (IRM), Salt Lake City, Kolkata, India
| | - Papiya Ghosh
- Department of Zoology, Bijoy Krishna Girls' College (Affiliated to University of Calcutta), Howrah, India
| | | | - Sujay Ghosh
- Cytogenetics and Genomics Research Unit, Department of Zoology, University of Calcutta, Kolkata, India
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15
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Jiao ZY, Li MR, Zhuo L, Fang YY, Pan JY, Hong K. Sperm retrieval rate and patient factors in azoospermia factor c microdeletion azoospermia: a systematic review. BJU Int 2024; 134:6-12. [PMID: 37942695 DOI: 10.1111/bju.16205] [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] [Indexed: 11/10/2023]
Abstract
OBJECTIVE To reveal the overall sperm retrieval rate (SRR) and range in patients with azoospermia factor c (AZFc) microdeletion azoospermia by microdissection testicular sperm extraction (mTESE) and discuss the differences of preoperative patient factors among studies with various SRRs. PATIENTS AND METHODS We searched PubMed, Web of Science and Embase until February 2023. All studies reporting SRRs by mTESE and required parameters of patients with AZFc microdeletions were included. The primary outcome was the SRR and, if available, the pregnancy rate (PR) and live-birth rate (LBR) after intracytoplasmic sperm injection were also investigated as secondary outcomes. RESULTS Eventually 11 cohort studies were included in this review. A total number of 441 patients underwent mTESE and in 275 of them sperm was obtained, reaching an overall SRR of 62.4%. The SRRs among studies had a wide range from 25.0% to 85.7%. The studies reporting higher SRRs generally had older mean ages, and higher follicle-stimulating hormone and testosterone levels. Only four studies provided practical data on pregnancies and live-born children of patients with AZFc microdeletions, so the overall PR and LBR were unavailable. CONCLUSIONS The overall SRR of patients with AZFc microdeletion azoospermia was 62.4%. The effect of patient factors in SR needs further evidence in future work.
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Affiliation(s)
- Zhong-Yu Jiao
- Department of Urology, Peking University Third Hospital, Beijing, China
- Peking University Health Science Center, Beijing, China
| | - Mao-Ran Li
- Department of Urology, Peking University Third Hospital, Beijing, China
- Peking University Health Science Center, Beijing, China
| | - Lin Zhuo
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
| | - Yang-Yi Fang
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Jia-Yuan Pan
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Kai Hong
- Department of Urology, Peking University Third Hospital, Beijing, China
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China
- Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
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16
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He Q, Zhang Y, Song M, Zhou Y, Lin D, Ma Y, Sun F, Li Q. Detection of AZF microdeletions and analysis of reproductive hormonal profiles in Hainan men undergoing assisted reproductive technology. BMC Urol 2024; 24:123. [PMID: 38867229 PMCID: PMC11167749 DOI: 10.1186/s12894-024-01503-x] [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: 11/21/2023] [Accepted: 05/28/2024] [Indexed: 06/14/2024] Open
Abstract
BACKGROUND Male infertility has become a global health problem, and genetic factors are one of the essential causes. Y chromosome microdeletion is the leading genetic factor cause of male infertility. The objective of this study is to investigate the correlation between male infertility and Y chromosome microdeletions in Hainan, the sole tropical island province of China. METHODS We analyzed the semen of 897 infertile men from Hainan in this study. Semen analysis was measured according to WHO criteria by professionals at the Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, where samples were collected. Y chromosome AZF microdeletions were confirmed by detecting six STS markers using multiple polymerase chain reactions on peripheral blood DNA. The levels of reproductive hormones, including FSH, LH, PRL, T, and E2, were quantified using the enzyme-linked immunosorbent assay (ELISA). RESULTS The incidence of Y chromosome microdeletion in Hainan infertile men was 7.13%. The occurrence rate of Y chromosome microdeletion was 6.69% (34/508) in the oligozoospermia group and 7.71% (30/389) in the azoospermia group. The deletion of various types in the AZF subregion was observed in the group with azoospermia, whereas no AZFb deletion was detected in the oligozoospermia group. Among all patients with microdeletions, the deletion rate of the AZFc region was the higher at 68.75% (44 out of 64), followed by a deletion rate of 6.25% (4 out of 64) for the AZFa region and a deletion rate of 4.69% (3 out of 64) for the AZFb region. The deletion rate of the AZFa region was significantly higher in patients with azoospermia than in patients with oligozoospermia (0.51% vs. 0.39%, p < 0.001). In comparison, the deletion rate of the AZFc region was significantly higher in patients with oligozoospermia (3.08% vs. 6.30%, p < 0.001). Additionally, the AZFb + c subregion association deletion was observed in the highest proportion among all patients (0.89%, 8/897), followed by AZFa + b + c deletion (0.56%, 5/897), and exclusively occurred in patients with azoospermia. Hormone analysis revealed FSH (21.63 ± 2.01 U/L vs. 10.15 ± 0.96 U/L, p = 0.001), LH (8.96 ± 0.90 U/L vs. 4.58 ± 0.42 U/L, p < 0.001) and PRL (263.45 ± 21.84 mIU/L vs. 170.76 ± 17.10 mIU/L, p = 0.002) were significantly increased in azoospermia patients with microdeletions. Still, P and E2 levels were not significantly different between the two groups. CONCLUSIONS The incidence of AZF microdeletion can reach 7.13% in infertile men in Hainan province, and the deletion of the AZFc subregion is the highest. Although the Y chromosome microdeletion rate is distinct in different regions or populations, the regions mentioned above of the Y chromosome may serve an indispensable role in regulating spermatogenesis. The analysis of Y chromosome microdeletion plays a crucial role in the clinical assessment and diagnosis of male infertility.
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Affiliation(s)
- Qina He
- Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, the Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, 571101, China
- Haikou Key Laboratory for Preservation of Human Genetic Resource, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 571101, China
| | - Yongle Zhang
- Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, the Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, 571101, China
- Haikou Key Laboratory for Preservation of Human Genetic Resource, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 571101, China
| | - Mengyi Song
- Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, the Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, 571101, China
- Haikou Key Laboratory for Preservation of Human Genetic Resource, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 571101, China
| | - Yao Zhou
- Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, the Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, 571101, China
- Haikou Key Laboratory for Preservation of Human Genetic Resource, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 571101, China
| | - Dan Lin
- Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, the Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, 571101, China
- Haikou Key Laboratory for Preservation of Human Genetic Resource, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 571101, China
| | - Yanlin Ma
- Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, the Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, 571101, China.
- Haikou Key Laboratory for Preservation of Human Genetic Resource, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 571101, China.
| | - Fei Sun
- Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, the Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, 571101, China.
- Haikou Key Laboratory for Preservation of Human Genetic Resource, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 571101, China.
- Department of Obstetrics and Gynecology, Reproductive Medicine, Nanfang Hospital, Southern Medical University, Guangdong, 510515, China.
| | - Qi Li
- Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, the Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, 571101, China.
- Haikou Key Laboratory for Preservation of Human Genetic Resource, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 571101, China.
- Hainan Modern Women and Children's Hospital, Reproductive Medicine, Haikou, Hainan, 571101, China.
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Zhang G, Ye F, Yang Y, Xiong D, Zhi W, Wu Y, Sun Y, Zeng J, Liu W. Identification of a novel mutation in chibby family member 2 in a non-obstructive azoospermic patient. Reprod Biol 2024; 24:100891. [PMID: 38733656 DOI: 10.1016/j.repbio.2024.100891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 04/25/2024] [Accepted: 04/27/2024] [Indexed: 05/13/2024]
Abstract
Azoospermia constitutes a significant factor in male infertility, defined by the absence of spermatozoa in the ejaculate, afflicting 15% of infertile men. However, a subset of azoospermic cases remains unattributed to known genetic variants. Prior investigations have identified the chibby family member 2 (CBY2) as prominently and specifically expressed in the testes of both humans and mice, implicating its potential involvement in spermatogenesis. In this study, we conducted whole exome sequencing (WES) on an infertile family to uncover novel genetic factors contributing to azoospermia. Our analysis revealed a homozygous c .355 C>A variant of CBY2 in a non-obstructive azoospermic patient. This deleterious variant significantly diminished the protein expression of CBY2 both in vivo and in vitro, leading to a pronounced disruption of spermatogenesis at the early round spermatid stage post-meiosis. This disruption was characterized by a nearly complete loss of elongating and elongated spermatids. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation assays demonstrated the interaction between CBY2 and Piwi-like protein 1 (PIWIL1). Immunofluorescence staining further confirmed the co-localization of CBY2 and PIWIL1 in the testes during the spermatogenic process in both humans and mice. Additionally, diminished PIWIL1 expression was observed in the testicular tissue from the affected patient. Our findings suggest that the homozygous c .355 C>A variant of CBY2 compromises CBY2 function, contributing to defective spermatogenesis at the round spermiogenic stage and implicating its role in the pathogenesis of azoospermia.
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Affiliation(s)
- Guohui Zhang
- Key Laboratory of Reproductive Medicine, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu 610045, China; Reproductive Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu 610045, China
| | - Fei Ye
- Reproductive Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu 610045, China
| | - Yihong Yang
- Reproduction Medical Center of West China Second University Hospital, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu 610041, China
| | - Dongsheng Xiong
- Reproductive Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu 610045, China
| | - Weiwei Zhi
- Reproductive Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu 610045, China
| | - Yang Wu
- Reproductive Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu 610045, China
| | - Yongkang Sun
- Department of Obstetrics/Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
| | - Jiuzhi Zeng
- Reproductive Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu 610045, China.
| | - Weixin Liu
- Key Laboratory of Reproductive Medicine, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu 610045, China.
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18
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Dornbush J, Golan R, Gurayah AA, Kuchakulla M, Jhaveri H, Kresch E, Sathe A, Manda P, Campbell K, Ramasamy R. Top-cited articles in andrology journals from 2013-2022: a bibliometric analysis. Int J Impot Res 2024:10.1038/s41443-024-00908-4. [PMID: 38806629 DOI: 10.1038/s41443-024-00908-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 03/12/2024] [Accepted: 05/08/2024] [Indexed: 05/30/2024]
Abstract
Bibliometric analyses serve to identify influential articles that have shaped medical practice and fostered new research ideas. Over the past decade, research in andrology has witnessed exponential growth, with an increasing number of academic publications, collaborations, and research innovations. However, there is a lack of literature that has identified the top-cited andrology articles. We conducted a bibliometric analysis to identify the top 1000 citations in andrology journals, with a focus on the top funding agencies, authors, institutions, countries/regions, and journals. To perform this analysis, we identified the top-cited articles in andrology journals as indexed in the Web of Science Core Collection. From 2013 through 2022, we found a total of 9827 articles published in andrology journals. The top publishers included "Andrology," the "Asian Journal of Andrology," and "Andrologia." The top affiliations contributing to research include the Cleveland Clinic Foundation (269 publications), Egyptian Knowledge Bank (EKB) (265), and Shanghai Jiao Tong University (202). Funding was primarily provided by notable agencies such as the National Natural Science Foundation of China (905 grants), United States Department of Health Human Services (321), and National Institutes of Health (NIH USA) (317). The present bibliometric analysis highlights andrology research from 2013 through 2022, offering key insights into leading contributors, influential authors, prominent funding sources, and major trends in the field.
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Affiliation(s)
- James Dornbush
- Medical College of Georgia, AU/UGA Medical Partnership, Athens, GA, USA
| | - Roei Golan
- Florida State University College of Medicine, Tallahassee, FL, USA
| | - Aaron A Gurayah
- Department of Urology, Weill Cornell Medicine, New York, NY, USA
| | | | - Hasan Jhaveri
- Department of Urology, Duke University Medical Center, Durham, NC, USA
| | - Ely Kresch
- Department of Urology, University of Florida College of Medicine, Jacksonville, FL, USA
| | - Aditya Sathe
- Department of Urology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA
| | - Pranay Manda
- Department of Urology, Emory University School of Medicine, Atlanta, GA, USA
| | - Kevin Campbell
- Department of Urology, University of Florida College of Medicine, Gainesville, FL, USA
| | - Ranjith Ramasamy
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
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19
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Fontana L, Sirchia SM, Pesenti C, Colpi GM, Miozzo MR. Non-invasive biomarkers for sperm retrieval in non-obstructive patients: a comprehensive review. Front Endocrinol (Lausanne) 2024; 15:1349000. [PMID: 38689732 PMCID: PMC11058837 DOI: 10.3389/fendo.2024.1349000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 04/01/2024] [Indexed: 05/02/2024] Open
Abstract
Recent advancements in reproductive medicine have guided novel strategies for addressing male infertility, particularly in cases of non-obstructive azoospermia (NOA). Two prominent invasive interventions, namely testicular sperm extraction (TESE) and microdissection TESE (micro-TESE), have emerged as key techniques to retrieve gametes for assisted reproduction technologies (ART). Both heterogeneity and complexity of NOA pose a multifaceted challenge to clinicians, as the invasiveness of these procedures and their unpredictable success underscore the need for more precise guidance. Seminal plasma can be aptly regarded as a liquid biopsy of the male reproductive tract, encompassing secretions from the testes, epididymides, seminal vesicles, bulbourethral glands, and prostate. This fluid harbors a variety of cell-free nucleic acids, microvesicles, proteins, and metabolites intricately linked to gonadal activity. However, despite numerous investigations exploring potential biomarkers from seminal fluid, their widespread inclusion into the clinical practice remains limited. This could be partially due to the complex interplay of diverse clinical and genetic factors inherent to NOA that likely contributes to the absence of definitive biomarkers for residual spermatogenesis. It is conceivable that the integration of clinical data with biomarkers could increase the potential in predicting surgical procedure outcomes and their choice in NOA cases. This comprehensive review addresses the challenge of sperm retrieval in NOA through non-invasive biomarkers. Moreover, we delve into promising perspectives, elucidating innovative approaches grounded in multi-omics methodologies, including genomics, transcriptomics and proteomics. These cutting-edge techniques, combined with the clinical and genetics features of patients, could improve the use of biomarkers in personalized medical approaches, patient counseling, and the decision-making continuum. Finally, Artificial intelligence (AI) holds significant potential in the realm of combining biomarkers and clinical data, also in the context of identifying non-invasive biomarkers for sperm retrieval.
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Affiliation(s)
- Laura Fontana
- Medical Genetics Unit, Aziende Socio Sanitarie Territoriali (ASST) Santi Paolo e Carlo, Milan, Italy
- Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Silvia M. Sirchia
- Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Chiara Pesenti
- Medical Genetics Unit, Aziende Socio Sanitarie Territoriali (ASST) Santi Paolo e Carlo, Milan, Italy
| | - Giovanni Maria Colpi
- Next Fertility Procrea, International Center for Assisted Reproductive Technology, Lugano, Switzerland
| | - Monica R. Miozzo
- Medical Genetics Unit, Aziende Socio Sanitarie Territoriali (ASST) Santi Paolo e Carlo, Milan, Italy
- Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
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20
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Ng R, Stanar P, Louie K, Chow V, Ma S. Increased Y Chromosome Microdeletions in Cord Blood of Male Newborns From Assisted Reproductive Technology Compared to Natural Conception. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2024; 46:102342. [PMID: 38176679 DOI: 10.1016/j.jogc.2023.102342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 12/05/2023] [Accepted: 12/06/2023] [Indexed: 01/06/2024]
Abstract
OBJECTIVES To investigate the incidence of Y chromosome microdeletions in male newborns conceived by intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), and natural conception (NC). METHODS A total of 186 male newborns were recruited, including 35 conceived by ICSI, 37 conceived by IVF, and 114 conceived naturally. DNA was extracted from umbilical cord blood after birth. The Yq genetic status of the newborns was determined according to 18 Y-specific sequence tagging sites (STS) markers covering 3 azoospermia factor (AZF) sub-regions and internal control sequences. RESULTS Partial AZF microdeletions were identified in 8 of 35 (22.9%) ICSI newborns, 4 of 37 (10.8%) IVF newborns, and 1 of 114 (0.9%) NC newborns. There was a statistically significant difference in the proportion of newborns with partial Y chromosome microdeletions between the ICSI, IVF, and NC groups. When analyzed individually, only the SY114 and SY152 STS markers showed a statistically significant difference in incidence between the 3 cohorts. CONCLUSIONS Our study indicates that the population of male children conceived through assisted reproductive technologies (ART), particularly ICSI, is at an increased risk of genetic defect in the form of partial Y chromosome microdeletions. The growing population of ART-conceived children emphasizes the importance of studying the genetic repercussions of these procedures regarding the future fertility of males conceived in vitro.
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Affiliation(s)
- Richard Ng
- Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada
| | - Paloma Stanar
- Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada
| | - Kenny Louie
- Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada
| | - Victor Chow
- Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada
| | - Sai Ma
- Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada.
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21
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Adriano MRG, Bortolai A, Madia FAR, da Silva Carvalho GF, Nascimento AM, Zanardo EA, Wolff BM, Waisberg J, Bos-Mikich A, Kulikowski LD, Dias AT. Cytogenetics investigation in 151 Brazilian infertile male patients and genomic analysis in selected cases: experience of 14 years in a public genetic service. BMC Res Notes 2024; 17:67. [PMID: 38444014 PMCID: PMC10916190 DOI: 10.1186/s13104-024-06710-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 01/31/2024] [Indexed: 03/07/2024] Open
Abstract
OBJECTIVES Male infertility accounts for approximately 30% of cases of reproductive failure. The characterization of genetic variants using cytogenomic techniques is essential for the adequate clinical management of these patients. We aimed to conduct a cytogenetic investigation of numerical and structural rearrangements and a genomic study of Y chromosome microdeletions/microduplications in infertile men derived from a single centre with over 14 years of experience. RESULTS We evaluated 151 infertile men in a transversal study using peripheral blood karyotypes and 15 patients with normal karyotypes through genomic investigation by multiplex ligation-dependent probe amplification (MLPA) or polymerase chain reaction of sequence-tagged sites (PCR-STS) techniques. Out of the 151 patients evaluated by karyotype, 13 presented chromosomal abnormalities: two had numerical alterations, and 11 had structural chromosomal rearrangements. PCR-STS detected a BPY2 gene region and RBMY2DP pseudogene region microdeletion in one patient. MLPA analysis allowed the identification of one patient with CDY2B_1 and CDY2B_2 probe duplications (CDY2B and NLGN4Y genes) and one patient with BPY2_1, BPY2_2, and BPY2_4 probe duplications (PRY and RBMY1J genes).
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Affiliation(s)
- Márcia Regina Gimenes Adriano
- Laboratório de Citogenética, Serviço de Laboratório de Análises Clínicas, Instituto de Assistência Médica do Servidor Público do Estado de São Paulo (IAMSPE), São Paulo, SP, 04039-901, Brasil.
| | - Adriana Bortolai
- Laboratório de Citogenética, Serviço de Laboratório de Análises Clínicas, Instituto de Assistência Médica do Servidor Público do Estado de São Paulo (IAMSPE), São Paulo, SP, 04039-901, Brasil
| | - Fabricia Andreia Rosa Madia
- Laboratório de Citogenômica, Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, 05403-000, Brasil
| | - Gleyson Francisco da Silva Carvalho
- Laboratório de Citogenômica, Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, 05403-000, Brasil
| | - Amom Mendes Nascimento
- Laboratório de Citogenômica, Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, 05403-000, Brasil
| | - Evelin Aline Zanardo
- Laboratório de Citogenômica, Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, 05403-000, Brasil
| | - Beatriz Martins Wolff
- Laboratório de Citogenômica, Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, 05403-000, Brasil
| | - Jaques Waisberg
- Laboratório de Citogenética, Serviço de Laboratório de Análises Clínicas, Instituto de Assistência Médica do Servidor Público do Estado de São Paulo (IAMSPE), São Paulo, SP, 04039-901, Brasil
| | - Adriana Bos-Mikich
- Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, 90050-170, Brasil
| | - Leslie Domenici Kulikowski
- Laboratório de Citogenômica, Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, 05403-000, Brasil
| | - Alexandre Torchio Dias
- Laboratório de Citogenética, Serviço de Laboratório de Análises Clínicas, Instituto de Assistência Médica do Servidor Público do Estado de São Paulo (IAMSPE), São Paulo, SP, 04039-901, Brasil
- Laboratório de Citogenômica, Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, 05403-000, Brasil
- Universidade Paulista - UNIP - Instituto de Ciências da Saúde - Curso de Biomedicina, São Paulo, Brasil
- CITOGEM Biotecnologia, São Paulo, Brasil
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22
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Graziani A, Merico M, Grande G, Di Mambro A, Vinanzi C, Rocca MS, Selice R, Ferlin A. A cryptozoospermic infertile male with Y chromosome AZFc microdeletion and low FSH levels due to a simultaneous polymorphism in the FSHB gene: a case report. Hum Reprod 2024; 39:504-508. [PMID: 38224259 DOI: 10.1093/humrep/dead277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 12/13/2023] [Indexed: 01/16/2024] Open
Abstract
Genetic causes account for 10-15% of male factor infertility, making the genetic investigation an essential and useful tool, mainly in azoospermic and severely oligozoospermic men. In these patients, the most frequent findings are chromosomal abnormalities and Y chromosome long arm microdeletions, which cause a primary severe spermatogenic impairment with classically increased levels of FSH. On the other hand, polymorphisms in the FSH receptor (FSHR) and FSH beta chain (FSHB) genes have been associated with different FSH plasma levels, due to variations in the receptor sensitivity (FSHR) or in the production of FSH from the pituitary gland (FSHB). Here, we describe an unusual patient with a combined genetic alteration (classic AZFc deletion of the Y chromosome and TT homozygosity for the -211G>T polymorphism in the FSHB gene (rs10835638)), presenting with cryptozoospermia, severe hypospermatogenesis, and normal LH and testosterone plasma concentrations, but low FSH levels. The patient partially benefitted from treatment with FSH (150 IU three times/week for 6 months) which allowed him to cryopreserve enough motile spermatozoa to be used for intracytoplasmic sperm injection. According to our knowledge, this is the first report of an infertile man with AZFc microdeletion with low FSH plasma concentrations related to homozygosity for the -211G>T polymorphism in the FSHB gene.
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Affiliation(s)
| | - Maurizio Merico
- Department of Systems Medicine, Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
| | - Giuseppe Grande
- Department of Systems Medicine, Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
| | - Antonella Di Mambro
- Department of Systems Medicine, Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
| | - Cinzia Vinanzi
- Department of Systems Medicine, Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
| | - Maria Santa Rocca
- Department of Systems Medicine, Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
| | - Riccardo Selice
- Department of Systems Medicine, Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
| | - Alberto Ferlin
- Department of Medicine, University of Padova, Padova, Italy
- Department of Systems Medicine, Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
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23
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Krausz C, Navarro-Costa P, Wilke M, Tüttelmann F. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: State of the art 2023. Andrology 2024; 12:487-504. [PMID: 37674303 DOI: 10.1111/andr.13514] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 08/11/2023] [Indexed: 09/08/2023]
Abstract
Testing for AZoospermia Factor (AZF) deletions of the Y chromosome is a key component of the diagnostic workup of azoospermic and severely oligozoospermic men. This revision of the 2013 European Academy of Andrology (EAA) and EMQN CIC (previously known as the European Molecular Genetics Quality Network) laboratory guidelines summarizes recent clinically relevant advances and provides an update on the results of the external quality assessment program jointly offered by both organizations. A basic multiplex PCR reaction followed by a deletion extension analysis remains the gold-standard methodology to detect and correctly interpret AZF deletions. Recent data have led to an update of the sY84 reverse primer sequence, as well as to a refinement of what were previously considered as interchangeable border markers for AZFa and AZFb deletion breakpoints. More specifically, sY83 and sY143 are no longer recommended for the deletion extension analysis, leaving sY1064 and sY1192, respectively, as first-choice markers. Despite the transition, currently underway in several countries, toward a diagnosis based on certified kits, it should be noted that many of these commercial products are not recommended due to an unnecessarily high number of tested markers, and none of those currently available are, to the best of our knowledge, in accordance with the new first-choice markers for the deletion extension analysis. The gr/gr partial AZFc deletion remains a population-specific risk factor for impaired sperm production and a predisposing factor for testicular germ cell tumors. Testing for this deletion type is, as before, left at the discretion of the diagnostic labs and referring clinicians. Annual participation in an external quality control program is strongly encouraged, as the 22-year experience of the EMQN/EAA scheme clearly demonstrates a steep decline in diagnostic errors and an improvement in reporting practice.
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Affiliation(s)
- Csilla Krausz
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, University Hospital Careggi, Florence, Italy
| | - Paulo Navarro-Costa
- EvoReproMed Lab, Environmental Health Institute (ISAMB), Associate Laboratory TERRA, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
- Gulbenkian Science Institute, Oeiras, Portugal
| | - Martina Wilke
- Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
| | - Frank Tüttelmann
- Institute of Reproductive Genetics, University of Münster, Münster, Germany
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Li JP, Zhang FB, Li LJ, Chen WK, Wu JG, Tian YH, Liang ZY, Chen C, Jin F. Y chromosome polymorphisms contribute to an increased risk of non-obstructive azoospermia: a retrospective study of 32,055 Chinese men. J Assist Reprod Genet 2024; 41:757-765. [PMID: 38270748 PMCID: PMC10957810 DOI: 10.1007/s10815-024-03022-y] [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: 08/09/2023] [Accepted: 01/04/2024] [Indexed: 01/26/2024] Open
Abstract
PURPOSE To investigate the prevalence of Y chromosome polymorphisms in Chinese men and analyze their associations with male infertility and female adverse pregnancy outcomes. METHODS The clinical data of 32,055 Chinese men who underwent karyotype analysis from October 2014 to September 2019 were collected. Fisher's exact test, chi-square test, or Kruskal-Wallis test was used to analyze the effects of Y chromosome polymorphism on semen parameters, azoospermia factor (AZF) microdeletions, and female adverse pregnancy outcomes. RESULTS The incidence of Y chromosome polymorphic variants was 1.19% (381/32,055) in Chinese men. The incidence of non-obstructive azoospermia (NOA) was significantly higher in men with the Yqh- variant than that in men with normal karyotype and other Y chromosome polymorphic variants (p < 0.050). The incidence of AZF microdeletions was significantly different among the normal karyotype and different Y chromosome polymorphic variant groups (p < 0.001). The detection rate of AZF microdeletions was 28.92% (24/83) in the Yqh- group and 2.50% (3/120) in the Y ≤ 21 group. The AZFb + c region was the most common AZF microdeletion (78.57%, 22/28), followed by AZFc microdeletion (7.14%,2/28) in NOA patients with Yqh- variants. There was no significant difference in the distribution of female adverse pregnancy outcomes among the normal karyotype and different Y chromosome polymorphic variant groups (p = 0.528). CONCLUSIONS Patients with 46,XYqh- variant have a higher incidence of NOA and AZF microdeletions than patients with normal karyotype and other Y chromosome polymorphic variants. Y chromosome polymorphic variants do not affect female adverse pregnancy outcomes.
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Affiliation(s)
- Jing-Ping Li
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Feng-Bin Zhang
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Le-Jun Li
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Wei-Kang Chen
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Jing-Gen Wu
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Yong-Hong Tian
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Zhong-Yan Liang
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Chong Chen
- Department of Ultrasound, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Fan Jin
- Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
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Yi S, Wang W, Su L, Meng L, Li Y, Tan C, Liu Q, Zhang H, Fan L, Lu G, Hu L, Du J, Lin G, Tan YQ, Tu C, Zhang Q. Deleterious variants in X-linked RHOXF1 cause male infertility with oligo- and azoospermia. Mol Hum Reprod 2024; 30:gaae002. [PMID: 38258527 DOI: 10.1093/molehr/gaae002] [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: 06/08/2023] [Revised: 12/24/2023] [Indexed: 01/24/2024] Open
Abstract
Oligozoospermia and azoospermia are two common phenotypes of male infertility characterized by massive sperm defects owing to failure of spermatogenesis. The deleterious impact of candidate variants with male infertility is to be explored. In our study, we identified three hemizygous missense variants (c.388G>A: p.V130M, c.272C>T: p.A91V, and c.467C>T: p.A156V) and one hemizygous nonsense variant (c.478C>T: p.R160X) in the Rhox homeobox family member 1 gene (RHOXF1) in four unrelated cases from a cohort of 1201 infertile Chinese men with oligo- and azoospermia using whole-exome sequencing and Sanger sequencing. RHOXF1 was absent in the testicular biopsy of one patient (c.388G>A: p.V130M) whose histological analysis showed a phenotype of Sertoli cell-only syndrome. In vitro experiments indicated that RHOXF1 mutations significantly reduced the content of RHOXF1 protein in HEK293T cells. Specifically, the p.V130M, p.A156V, and p.R160X mutants of RHOXF1 also led to increased RHOXF1 accumulation in cytoplasmic particles. Luciferase assays revealed that p.V130M and p.R160X mutants may disrupt downstream spermatogenesis by perturbing the regulation of doublesex and mab-3 related transcription factor 1 (DMRT1) promoter activity. Furthermore, ICSI treatment could be beneficial in the context of oligozoospermia caused by RHOXF1 mutations. In conclusion, our findings collectively identified mutated RHOXF1 to be a disease-causing X-linked gene in human oligo- and azoospermia.
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Affiliation(s)
- Sibing Yi
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
| | - Weili Wang
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan, China
- Center for Biology Post-Doctoral studies, College of Life Science, Hunan Normal University, Changsha, China
| | - Lilan Su
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
| | - Lanlan Meng
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan, China
| | - Yong Li
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
| | - Chen Tan
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
| | - Qiang Liu
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Department of Hepatobiliary Surgery, Hunan Cancer Hospital and the Affiliated Cancer of Xiangya School of Medicine, Central South University, Changsha, China
| | - Huan Zhang
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan, China
| | - Liqing Fan
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan, China
- Key Laboratory of Stem Cell and Reproduction Engineering, Ministry of Health, Changsha, China
| | - Guangxiu Lu
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan, China
- Key Laboratory of Stem Cell and Reproduction Engineering, Ministry of Health, Changsha, China
| | - Liang Hu
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan, China
- Center for Biology Post-Doctoral studies, College of Life Science, Hunan Normal University, Changsha, China
- Key Laboratory of Stem Cell and Reproduction Engineering, Ministry of Health, Changsha, China
| | - Juan Du
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan, China
- Key Laboratory of Stem Cell and Reproduction Engineering, Ministry of Health, Changsha, China
| | - Ge Lin
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan, China
- Center for Biology Post-Doctoral studies, College of Life Science, Hunan Normal University, Changsha, China
- Key Laboratory of Stem Cell and Reproduction Engineering, Ministry of Health, Changsha, China
| | - Yue-Qiu Tan
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan, China
- Center for Biology Post-Doctoral studies, College of Life Science, Hunan Normal University, Changsha, China
- Key Laboratory of Stem Cell and Reproduction Engineering, Ministry of Health, Changsha, China
| | - Chaofeng Tu
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan, China
| | - Qianjun Zhang
- Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan, China
- Center for Biology Post-Doctoral studies, College of Life Science, Hunan Normal University, Changsha, China
- Key Laboratory of Stem Cell and Reproduction Engineering, Ministry of Health, Changsha, China
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Tai T, Miyamoto W, Fukuoka Y, Shibasaki S, Takahashi M, Okuyama N, Hattori H, Ishikawa I, Nagaura S, Yoshinaga K, Koizumi M, Hashimoto T, Toya M, Kumagai J, Igarashi H, Kyono K. Micromapping testicular sperm extraction: A new technique for microscopic testicular sperm extraction in nonobstructive azoospermia. Reprod Med Biol 2024; 23:e12566. [PMID: 38476958 PMCID: PMC10927935 DOI: 10.1002/rmb2.12566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 02/08/2024] [Accepted: 02/14/2024] [Indexed: 03/14/2024] Open
Abstract
Purpose In microscopic testicular sperm extraction (mTESE) for nonobstructive azoospermia (NOA), sperm can be recovered relatively easily in some cases, and mTESE may be retrospectively considered excessive. However, mTESE is routinely performed in the majority of NOA patients because of the difficulty in predicting tissue status. A minimally invasive and comprehensive sperm retrieval method that allows on-the-spot tissue assessment is needed. We have developed and evaluated a novel sperm retrieval technique for NOA called micromapping testicular sperm extraction (MMTSE). Methods MMTSE involves dividing the testis into four sections and making multiple small needle holes in the tunica albuginea to extract seminiferous tubules and retrieve sperm. The sperm-positive group by MMTSE (Group I) underwent additional tissue collection (ATC) via a small incision, whereas the sperm-negative group by MMTSE (Group 0) underwent mTESE. Results In total, 40 NOA participants underwent MMTSE. Group I included 15 patients and Group 0 included 25 patients. In Group 1, sperm were recovered from all patients by ATC. In Group 0, sperm were recovered in 4 of 25 cases using mTESE. Conclusions MMTSE shows promise as a simple method that comprehensively searches testicular tissue and retrieves sperm using an appropriate method while minimizing patient burden.
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Affiliation(s)
- Toshihiro Tai
- Kyono ART Clinic SendaiSendaiMiyagiJapan
- Kyono ART Clinic TakanawaTokyoJapan
| | - Wakaba Miyamoto
- Kyono ART Clinic SendaiSendaiMiyagiJapan
- Kyono ART Clinic Shinagawa/Human Ovarian‐tissue Preservation Enterprise (HOPE)TokyoJapan
| | - Yuriko Fukuoka
- Kyono ART Clinic TakanawaTokyoJapan
- Kyono ART Clinic Shinagawa/Human Ovarian‐tissue Preservation Enterprise (HOPE)TokyoJapan
| | - Sena Shibasaki
- Kyono ART Clinic SendaiSendaiMiyagiJapan
- Kyono ART Clinic Shinagawa/Human Ovarian‐tissue Preservation Enterprise (HOPE)TokyoJapan
| | | | - Noriyuki Okuyama
- Kyono ART Clinic TakanawaTokyoJapan
- Kyono ART Clinic Shinagawa/Human Ovarian‐tissue Preservation Enterprise (HOPE)TokyoJapan
| | - Hiromitsu Hattori
- Kyono ART Clinic SendaiSendaiMiyagiJapan
- Kyono ART Clinic TakanawaTokyoJapan
- Kyono ART Clinic Shinagawa/Human Ovarian‐tissue Preservation Enterprise (HOPE)TokyoJapan
- Kyono ART Clinic MoriokaIwateJapan
| | | | | | | | | | - Tomoko Hashimoto
- Kyono ART Clinic TakanawaTokyoJapan
- Kyono ART Clinic Shinagawa/Human Ovarian‐tissue Preservation Enterprise (HOPE)TokyoJapan
| | | | | | | | - Koichi Kyono
- Kyono ART Clinic SendaiSendaiMiyagiJapan
- Kyono ART Clinic TakanawaTokyoJapan
- Kyono ART Clinic Shinagawa/Human Ovarian‐tissue Preservation Enterprise (HOPE)TokyoJapan
- Kyono ART Clinic MoriokaIwateJapan
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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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Zhang H, Li H, Ma S, Zhang S, Li W, Gu Y, Zhang E, Hu L. Very severe oligozoospermia with AZFc microdeletion patients may affect intracytoplasmic sperm injection clinical outcomes: A propensity score matching analysis. Reprod Med Biol 2024; 23:e12596. [PMID: 38983692 PMCID: PMC11232045 DOI: 10.1002/rmb2.12596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 06/20/2024] [Indexed: 07/11/2024] Open
Abstract
Purpose To explore whether spermatozoa from AZFc microdeletion patients affect their outcomes of intracytoplasmic sperm injection (ICSI). Methods Eighty-five patients with AZFc microdeletion were recruited. A control group of one hundred and forty patients with severe oligozoospermia but without AZF microdeletion was selected using propensity score matching analysis with a 1:2 nearest neighbor algorithm ratio. The ICSI outcomes of the two groups were compared. Results AZFc microdeletion had lower rates of normal fertilization (73% vs. 80%, p = 0.17) and high-quality embryos (44% vs. 58%, p = 0.07) than the control group. There was no significant difference in the clinical pregnancy rate, miscarriage rate, and live birth rate between the two groups. When the sperm concentration was <1 million/mL, the AZFc microdeletion group exhibited lower rates of fertilization (71% vs. 80%, p = 0.03), high-quality embryo (44% vs. 58%, p = 0.02), clinical pregnancy (57% vs. 76%, p = 0.02), and live birth (49% vs. 72%, p = 0.01) than the control group. However, if sperm concentration was ≥1 million/mL, no significant differences were found. Conclusion If the sperm concentration is <1 million/mL, AZFc microdeletion do have a detrimental effect on most outcomes of ICSI.
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Affiliation(s)
- Huan Zhang
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical SciencesCentral South UniversityChangshaHunanChina
| | - Huanzhu Li
- School of MedicineHunan Normal UniversityChangshaHunanChina
| | - Shujuan Ma
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical SciencesCentral South UniversityChangshaHunanChina
- Clinical Research Center for Reproduction and Genetics in Hunan ProvinceReproductive and Genetic Hospital of CITIC‐XiangyaChangshaHunanChina
| | - Shuoping Zhang
- Clinical Research Center for Reproduction and Genetics in Hunan ProvinceReproductive and Genetic Hospital of CITIC‐XiangyaChangshaHunanChina
| | - Wen Li
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical SciencesCentral South UniversityChangshaHunanChina
- Clinical Research Center for Reproduction and Genetics in Hunan ProvinceReproductive and Genetic Hospital of CITIC‐XiangyaChangshaHunanChina
| | - Yifan Gu
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical SciencesCentral South UniversityChangshaHunanChina
- Clinical Research Center for Reproduction and Genetics in Hunan ProvinceReproductive and Genetic Hospital of CITIC‐XiangyaChangshaHunanChina
| | - Erchen Zhang
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical SciencesCentral South UniversityChangshaHunanChina
| | - Liang Hu
- NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical SciencesCentral South UniversityChangshaHunanChina
- School of MedicineHunan Normal UniversityChangshaHunanChina
- Clinical Research Center for Reproduction and Genetics in Hunan ProvinceReproductive and Genetic Hospital of CITIC‐XiangyaChangshaHunanChina
- National Engineering and Research Center of Human Stem CellsChangshaHunanChina
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Huang N, Zhou J, Lu W, Luo L, Yuan H, Pan L, Ding S, Yang B, Liu Y. Characteristics and clinical evaluation of X chromosome translocations. Mol Cytogenet 2023; 16:36. [PMID: 38129867 PMCID: PMC10740294 DOI: 10.1186/s13039-023-00669-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 12/05/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND Individuals with X chromosomal translocations, variable phenotypes, and a high risk of live birth defects are of interest for scientific study. These characteristics are related to differential breakpoints and various types of chromosomal abnormalities. To investigate the effects of X chromosome translocation on clinical phenotype, a retrospective analysis of clinical data for patients with X chromosome translocation was conducted. Karyotype analysis plus endocrine evaluation was utilized for all the patients. Additional semen analysis and Y chromosome microdeletions were assessed in male patients. RESULTS X chromosome translocations were detected in ten cases, including seven females and three males. Infantile uterus and no ovaries were detected in case 1 (FSH: 114 IU/L, LH: 30.90 mIU/mL, E2: < 5.00 pg/ml), and the karyotype was confirmed as 46,X,t(X;22)(q25;q11.2) in case 1. Infantile uterus and small ovaries were both visible in two cases (FSH: 34.80 IU/L, LH: 17.06 mIU/mL, E2: 15.37 pg/ml in case 2; FISH: 6.60 IU/L, LH: 1.69 mIU/mL, E2: 23.70 pg/ml in case 3). The karyotype was detected as 46,X,t(X;8)(q13;q11.2) in case 2 and 46,X,der(X)t(X;5)(q21;q31) in case 3. Normal reproductive hormone levels and fertility abilities were found for cases 4, 6 and 7. The karyotype were detected as 46,X,t(X;5)(p22.3;q22) in case 4 and 46,X,der(X)t(X;Y)(p22.3;q11.2) in cases 6 and 7. These patients exhibited unremarkable clinical manifestations but experienced a history of abnormal chromosomal pregnancy. Normal phenotype and a complex reciprocal translocation as 46,X,t(X;14;4)(q24;q22;q33) were observed in case 5 with a history of spontaneous abortions. In the three male patients, multiple semen analyses confirmed the absence of sperm. Y chromosome microdeletion and hormonal analyses were normal. The karyotypes were detected as 46,Y,t(X;8)(q26;q22), 46,Y,t(X;1)(q26;q23), 46,Y,t(X;3)(q26;p24), respectively. CONCLUSIONS Our study provides insights into individuals with X chromosome translocations. The clinical phenotypes are variable and unpredictable due to differences in breakpoints and X chromosome inactivation (XCI) patterns. Our results suggest that physicians should focus on the characteristics of the X chromosome translocations and provide personalized clinical evaluations in genetic counselling.
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Affiliation(s)
- Ning Huang
- Medical Genetics Center, Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, China
- Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, 330006, China
| | - Jihui Zhou
- Medical Genetics Center, Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, China
- Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, 330006, China
| | - Wan Lu
- Medical Genetics Center, Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, China
- Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, 330006, China
| | - Laipeng Luo
- Medical Genetics Center, Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, China
- Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, 330006, China
| | - Huizhen Yuan
- Medical Genetics Center, Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, China
- Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, 330006, China
| | - Lu Pan
- Medical Genetics Center, Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, China
- Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, 330006, China
| | - Shujun Ding
- Medical Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, China
| | - Bicheng Yang
- Medical Genetics Center, Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, China.
- Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, 330006, China.
| | - Yanqiu Liu
- Medical Genetics Center, Jiangxi Maternal and Child Health Hospital, Nanchang, 330006, China.
- Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, 330006, China.
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Fedder J, Fagerberg C, Jørgensen MW, Gravholt CH, Berglund A, Knudsen UB, Skakkebæk A. Complete or partial loss of the Y chromosome in an unselected cohort of 865 non-vasectomized, azoospermic men. Basic Clin Androl 2023; 33:37. [PMID: 38093178 PMCID: PMC10720143 DOI: 10.1186/s12610-023-00212-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 10/26/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND Structural abnormalities as well as minor variations of the Y chromosome may cause disorders of sex differentiation or, more frequently, azoospermia. This study aimed to determine the prevalence of loss of Y chromosome material within the spectrum ranging from small microdeletions in the azoospermia factor region (AZF) to complete loss of the Y chromosome in azoospermic men. RESULTS Eleven of 865 azoospermic men (1.3%) collected from 1997 to 2022 were found to have a karyotype including a 45,X cell line. Two had a pure 45,X karyotype and nine had a 45,X/46,XY mosaic karyotype. The AZF region, or part of it, was deleted in eight of the nine men with a structural abnormal Y-chromosome. Seven men had a karyotype with a structural abnormal Y chromosome in a non-mosaic form. In addition, Y chromosome microdeletions were found in 34 men with a structural normal Y chromosome. No congenital malformations were detected by echocardiography and ultrasonography of the kidneys of the 11 men with a 45,X mosaic or non-mosaic cell line. CONCLUSIONS In men with azoospermia, Y chromosome loss ranging from small microdeletions to complete loss of the Y chromosome was found in 6.1% (53/865). Partial AZFb microdeletions may give a milder testicular phenotype compared to complete AZFb microdeletions.
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Affiliation(s)
- J Fedder
- Centre of Andrology & Fertility Clinic, Odense University Hospital, Kløvervænget 23, DK-5000, Odense, Denmark.
- Department of Clinical Medicine, University of Southern Denmark, Odense, Denmark.
- Fertility Clinic, Horsens Hospital, Horsens, Denmark.
| | - C Fagerberg
- Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
| | - M W Jørgensen
- Department of Clinical Genetics, Lillebaelt Hospital, Vejle, Denmark
| | - C H Gravholt
- Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - A Berglund
- Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
- Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
| | - U B Knudsen
- Fertility Clinic, Horsens Hospital, Horsens, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - A Skakkebæk
- Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
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Chen D, Fan G, Zhu X, Chen Q, Chen X, Gao F, Guo Z, Luo P, Gao Y. Y chromosome microdeletions in Chinese men with infertility: prevalence, phenotypes, and intracytoplasmic sperm injection outcomes. Reprod Biol Endocrinol 2023; 21:116. [PMID: 38053137 DOI: 10.1186/s12958-023-01168-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 11/28/2023] [Indexed: 12/07/2023] Open
Abstract
BACKGROUND The incidence of Y chromosome microdeletions varies among men with infertility across regions and ethnicities worldwide. However, comprehensive epidemiological studies on Y chromosome microdeletions in Chinese men with infertility are lacking. We aimed to investigate Y chromosome microdeletions prevalence among Chinese men with infertility and its correlation with intracytoplasmic sperm injection (ICSI) outcomes. METHODS This single-center retrospective study included 4,714 men with infertility who were evaluated at the Reproductive Center of the First Affiliated Hospital of Sun Yat-sen University between May 2017 and January 2021. Semen analysis and Y-chromosome microdeletion via multiplex polymerase chain reaction were conducted on the men. The study compared outcomes of 36 ICSI cycles from couples with male azoospermia factor (AZF)cd deletions with those of a control group, which included 72 ICSI cycles from couples without male Y chromosome microdeletions, during the same period. Both groups underwent ICSI treatment using ejaculated sperm. RESULTS Among 4,714 Chinese men with infertility, 3.31% had Y chromosome microdeletions. The combined deletion of sY254 and sY255 in the AZFc region and sY152 in the AZFd region was the prevalent pattern of Y chromosome microdeletion, with 3.05% detection rate. The detection rates of AZF deletions in patients with normal total sperm count, mild oligozoospermia, severe oligozoospermia, cryptozoospermia, and azoospermia were 0.17%, 1.13%, 5.53%, 71.43%, and 7.54%, respectively. Compared with the control group, the AZFcd deletion group exhibited no significant difference in the laboratory results or pregnancy outcomes of ICSI cycles using ejaculated sperm. CONCLUSIONS This is the largest epidemiological study on Y chromosome microdeletions in Chinese men with infertility. The study results underline the necessity for detecting Y chromosome microdeletion in men with infertility and severe sperm count abnormalities, especially those with cryptozoospermia. The combined deletion of sY254 and sY255 in the AZFc region and sY152 in the AZFd region was the most prevalent Y chromosome microdeletion pattern. Among patients with AZFcd deletion and ejaculated sperm, ICSI treatment can result in pregnancy outcomes, similar to those without AZFcd deletion.
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Affiliation(s)
- Dongjia Chen
- Reproductive Medicine Center, Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong Provincial Clinical Research Center for obstetrical and gynecological diseases, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, China
| | - Guoqing Fan
- Reproductive Medicine Center, Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong Provincial Clinical Research Center for obstetrical and gynecological diseases, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, China
| | - Xianqing Zhu
- Reproductive Medicine Center, Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong Provincial Clinical Research Center for obstetrical and gynecological diseases, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, China
| | - Qinyun Chen
- Reproductive Medicine Center, Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong Provincial Clinical Research Center for obstetrical and gynecological diseases, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, China
| | - Xuren Chen
- Reproductive Medicine Center, Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong Provincial Clinical Research Center for obstetrical and gynecological diseases, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, China
| | - Feng Gao
- Reproductive Medicine Center, Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong Provincial Clinical Research Center for obstetrical and gynecological diseases, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, China
| | - Zexin Guo
- Reproductive Medicine Center, Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong Provincial Clinical Research Center for obstetrical and gynecological diseases, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, China
| | - Peng Luo
- Reproductive Medicine Center, Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong Provincial Clinical Research Center for obstetrical and gynecological diseases, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, China
| | - Yong Gao
- Reproductive Medicine Center, Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong Provincial Clinical Research Center for obstetrical and gynecological diseases, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, China.
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Verpoest W, Okutman Ö, Van Der Kelen A, Sermon K, Viville S. Genetics of infertility: a paradigm shift for medically assisted reproduction. Hum Reprod 2023; 38:2289-2295. [PMID: 37801292 DOI: 10.1093/humrep/dead199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 09/12/2023] [Indexed: 10/07/2023] Open
Abstract
The field of reproductive genetics has undergone significant advancements with the completion of the Human Genome Project and the development of high-throughput sequencing techniques. This has led to the identification of numerous genes involved in both male and female infertility, revolutionizing the diagnosis and management of infertility patients. Genetic investigations, including karyotyping, specific genetic tests, and high-throughput sequencing, have become essential in determining the genetic causes of infertility. Moreover, the integration of genetics into reproductive medicine has expanded the scope of care to include not only affected individuals or couples but also their family members. Genetic consultations and counselling play a crucial role in identifying potentially affected relatives and offering tailored therapy and the possibility of fertility preservation. Despite the current limited therapeutic options, an increasing understanding of genotype-phenotype correlations in infertility genes holds promise for improved treatment outcomes. The availability of genetic diagnostic tools has reduced the number of idiopathic infertility cases by providing accurate aetiological diagnoses. The transition from research to clinical practice in reproductive genetics requires the establishment of genetic consultations and data warehousing systems to provide up-to-date information on gene-disease relationships. Overall, the integration of genetics into reproductive medicine has brought about a paradigm shift, emphasizing the familial dimension of infertility and offering new possibilities for personalized care and family planning.
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Affiliation(s)
- Willem Verpoest
- Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, Research Group Genetics of Reproduction and Development, Brussels IVF Centre for Reproductive Medicine, Brussels, Belgium
| | - Özlem Okutman
- Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Hôpital Erasme, Service de Gynécologie-Obstetrique, Clinique de Fertilité, Route de Lennik, Bruxelles, Belgium
| | - Annelore Van Der Kelen
- Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, Research Group Genetics of Reproduction and Development, Centre for Medical Genetics, Brussels, Belgium
| | - Karen Sermon
- Vrije Universiteit Brussel (VUB), Faculty of Medicine and Pharmacy, Research Group Genetics of Reproduction and Development, Brussels, Belgium
| | - Stéphane Viville
- Laboratoire de Génétique Médicale LGM, Institut de Génétique Médicale d'Alsace IGMA, INSERM UMR 1112, Université de Strasbourg, Strasbourg, France
- Laboratoire de Diagnostic Génétique, Unité de Génétique de l'infertilité (UF3472), Hôpitaux Universitaires de Strasbourg, Strasbourg, France
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Eid MM, Eid OM, Abdelrahman AH, Abdelrahman IFS, Aboelkomsan EAF, AbdelKader RMA, Hassan M, Farid M, Ibrahim AA, Abd El-Fattah SN, Mahrous R. Detection of AZFc gene deletion in a cohort of Egyptian patients with idiopathic male infertility. J Genet Eng Biotechnol 2023; 21:111. [PMID: 37947911 PMCID: PMC10638347 DOI: 10.1186/s43141-023-00584-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 10/28/2023] [Indexed: 11/12/2023]
Abstract
BACKGROUND The deletions of azoospermic factor regions (AZF) are considered risk factor of spermatogenic failure. AZF duplications or complex copy number variants (CNVs) were rarely studied because STS-PCR could not always detect these changes. The application of multiplex ligation-dependent probe amplification (MLPA) as a valuable test for detection of the deletion and or duplication was introduced to investigate the AZF sub-region CNVs. The MLPA technique is still not applied on a large scale, and the publications in this area of research are limited. The aim of this work was to evaluate the efficacy of MLPA assay to detect AZF-linked CNVs in idiopathic spermatogenic failure patients and to evaluate its importance as a prognostic marker in the reproduction outcome. RESULTS Forty infertile men (37 with azoospermia and 3 with severe oligozoospermia) and 20 normal fertile men were subjected to thorough clinical, pathological, and laboratory assessment, chromosomal study, MLPA, STS-PCR assays, histopathology study, and testicular sperm retrieval (TESE). Out of the 40 patients, 7 patients have shown CNV in the AZFc region, 6 patients have partial deletion, and one patient has partial duplication. Only one of the normal control has AZFc duplication. STS-PCR was able to detect the deletion in only 4 out of the 7 positive patients and none of the control. CONCLUSION We concluded that MLPA should be applied on a larger scale for the detection of Y chromosome microdeletion as a rapid, efficient, and cheap test.
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Affiliation(s)
- Maha M Eid
- Human Cytogenetic Department, Human Genetics and Genome Research Institute, National Research Center, Bohouth Street, 12311 Dokki, Cairo, Egypt
| | - Ola M Eid
- Human Cytogenetic Department, Human Genetics and Genome Research Institute, National Research Center, Bohouth Street, 12311 Dokki, Cairo, Egypt.
| | - Amany H Abdelrahman
- Clinical and Chemical Pathology Department, Medical Research and Clinical Studies Institute, National Research Center, Cairo, Egypt
| | | | | | - Rania M A AbdelKader
- Human Cytogenetic Department, Human Genetics and Genome Research Institute, National Research Center, Bohouth Street, 12311 Dokki, Cairo, Egypt
| | - Mirhane Hassan
- Clinical and Chemical Pathology Department, Medical Research and Clinical Studies Institute, National Research Center, Cairo, Egypt
| | - Marwa Farid
- Human Cytogenetic Department, Human Genetics and Genome Research Institute, National Research Center, Bohouth Street, 12311 Dokki, Cairo, Egypt
| | - Alshaymaa A Ibrahim
- Clinical and Chemical Pathology Department, Medical Research and Clinical Studies Institute, National Research Center, Cairo, Egypt
| | - Safa N Abd El-Fattah
- Clinical and Chemical Pathology Department, Medical Research and Clinical Studies Institute, National Research Center, Cairo, Egypt
| | - Rana Mahrous
- Human Cytogenetic Department, Human Genetics and Genome Research Institute, National Research Center, Bohouth Street, 12311 Dokki, Cairo, Egypt
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Patel SKJK, Kabir R, Nayak R, Palo I, Banerjee B. A Rare Case of 45,X/46,X,del(Y)(q12→qter) Mosaicism in An Infertile Male with Y Chromosome Microdeletion. J Reprod Infertil 2023; 24:293-300. [PMID: 38164427 PMCID: PMC10757685 DOI: 10.18502/jri.v24i4.14157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 06/06/2023] [Indexed: 01/03/2024] Open
Abstract
Background Males with 45,X/46,XY karyotype have two different types of cells. This condition is associated with a wide range of clinical phenotypes. In infertile males, the mosaic 45,X/46,XY karyotype is a frequent sex chromosome defect and they might be able to conceive with the help of assisted reproductive technology; nevertheless, there is a potential risk of transmission of azoospermia factor (AZF) microdeletions in addition to 45,X to all the male progeny. In this case report, the purpose was to present a rare sex chromosomal mosaicism of an infertile man. Case Presentation Comprehensive molecular and cytogenetic analysis of an infertile male was performed in this case study. A 27-year-old male was presented with history of azoospermia and was unable to conceive after being involved in five years of marriage. Cytogenetic investigation revealed a rare mosaic karyotype pattern of 45,X/46,X,del(Y)(q12→qter). Y chromosome microdeletion (YMD) analysis revealed notable deletions of 06 loci. Comparative genomic hybridization (CGH) microarray was performed to investigate probable functional genetic associations. Conclusion Deletion of Y-linked genes leads to different testicular pathological conditions contributing to male infertility. Individuals with normal male phenotype harbor YMD, although size and location of the deletion do not always correspond well with quality of sperm. Therefore, in addition to semen analysis, identification of genetic variables is important which will play a crucial role in proper diagnosis and management of infertile couples. The present case study demonstrates the significance of comprehensive molecular testing and cytogenetic screening for individuals with idiopathic infertility.
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Affiliation(s)
| | - Rahul Kabir
- inDNA Center for Research and Innovation in Molecular Diagnostics, inDNA Life Sciences Private Limited, Odisha, India
| | - Ruchismita Nayak
- inDNA Center for Research and Innovation in Molecular Diagnostics, inDNA Life Sciences Private Limited, Odisha, India
| | - Indira Palo
- Department of Obstetrics and Gynecology, Amit Hospital, Odisha, India
| | - Birendranath Banerjee
- inDNA Center for Research and Innovation in Molecular Diagnostics, inDNA Life Sciences Private Limited, Odisha, India
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Gavilan M, Vivar C, Núñez V, Choque C, Guzmán M, Duarte C. First report of frequencies of Y chromosome microdeletions at a reproductive medicine center in Peru. Heliyon 2023; 9:e20221. [PMID: 37780786 PMCID: PMC10539958 DOI: 10.1016/j.heliyon.2023.e20221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 08/17/2023] [Accepted: 09/14/2023] [Indexed: 10/03/2023] Open
Abstract
Objective Y chromosome Microdeletions are the second genetic cause of infertility in men. Despite its importance for infertility treatment, there is no previous research in Peru. The aim of this study was to determine the frequencies and characteristics of Y chromosome microdeletions in a group of men who sought infertility consultation at a specialized reproductive medicine center in Peru. Methods In this study, 201 semen samples were analyzed. The samples were obtained from Niu Vida's fertility program. Each seminal sample was analyzed according to the recommendations of the Laboratory Manual of the World Health Organization (WHO) 2010. A buccal swab and a 500 μL aliquot of seminal sample were used for the molecular study of Y chromosome microdeletions in each patient. The frequencies and the type of Y chromosome microdeletion in the AZFa, AZFb and AZFc regions were evaluated. Results The prevalence of Y chromosome microdeletions in the AZF region was 6.45% in oligozoospermic and azoospermic patients, and a prevalence of 20% was observed specifically in azoospermic patients. No microdeletions of AZFb type were detected. A partial region microdeletion of AZFa was detected in a teratozoospermic patient with a normal sperm count. Conclusions The study represents the first report on the incidence of Y chromosome microdeletions in Peru. Our results indicate a high prevalence of microdeletions in azoospermic patients compared to similar studies. It is suggested to assess the presence of AZFa microdeletions and to evaluate additional genetic markers in this region to identify specific mutations that may cause impaired sperm production and male infertility in the Peruvian male population.
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Affiliation(s)
- M. Gavilan
- BIOLINKS Laboratories, Research & Development Lab, Lima, Peru
| | - C. Vivar
- Niu Vida. Specialized Center for Assisted Reproduction, Lima, Peru
| | - V. Núñez
- Niu Vida. Specialized Center for Assisted Reproduction, Lima, Peru
| | - C. Choque
- BIOLINKS Laboratories, Research & Development Lab, Lima, Peru
| | - M. Guzmán
- Niu Vida. Specialized Center for Assisted Reproduction, Lima, Peru
| | - C. Duarte
- Niu Vida. Specialized Center for Assisted Reproduction, Lima, Peru
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The Trinh S, Nguyen NN, Thi Thu Le H, Thi My Pham H, Tien Trieu S, Tran NTM, Sy Ho H, Van Tran D, Van Trinh T, Trong Hoang Nguyen H, Pham Minh N, Duc Dang T, Huu Dinh V, Thi Doan H. Screening Y Chromosome Microdeletion in 1121 Men with Low Sperm Concentration and the Outcomes of Microdissection Testicular Sperm Extraction (mTESE) for Sperm Retrieval from Azoospermic Patients. Appl Clin Genet 2023; 16:155-164. [PMID: 37663123 PMCID: PMC10473397 DOI: 10.2147/tacg.s420030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 08/04/2023] [Indexed: 09/05/2023] Open
Abstract
Background The Y chromosome has a specific region, namely the Azoospermia Factor (AZF) because azoospermia is typically reported in the microdeletion of the AZF region. This study aims to assess the characteristics of AZF microdeletion after screening a massive number of low sperm concentration men; and the Microdissection testicular sperm extraction (mTESE) outcomes for retrieving sperm from azoospermic patients. Materials and Methods This retrospective multiple-center study enrolled a total of 1121 men with azoospermia, cryptozoospermia, and severe oligozoospermia from December 2016 to June 2022. An extension analysis used a total of 17 STSs to detect the position-occurring microdeletion in the AZF region (AZFa, b, c, and/or d loci). Microdissection testicular sperm extraction (mTESE) was performed to retrieve sperm in azoospermic men diagnosed AZFc microdeletion. Results One hundred and fifty-three men carried AZF microdeletion were detected in the 1121 participants (13.64%). The incidences of AZF microdeletion were confined to AZF a, c, and d regions, both individual and concurrence, with the most common in the AZFc region accounting for 49.67%; There was no significant difference in clinical and paraclinical characteristics between the deleted regions, except FSH level (highest in AZFa microdeletion, p = 0.043). The AZFc region was the most common type of AZF microdeletion (49.67%), including complete microdeletion (4 patients) and gr/gr partial microdeletion (39 patients) with 50.00% and 63.63% in the success rate of mTESE, separately. Conclusion The absence of AZFa and/or AZFb regions often express the most severe phenotype - azoospermia and the increasing FSH level. The AZFc region played the most common microdeletion. Microdissection testicular sperm extraction (mTESE) was the possible therapy for sperm retrieval from the testis of azoospermia men having AZFc microdeletion.
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Affiliation(s)
- Son The Trinh
- Military Institute of Clinical Embryology and Histology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Nhat Ngoc Nguyen
- Military Institute of Clinical Embryology and Histology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Hien Thi Thu Le
- Department of Andrology, Andrology and Fertility Hospital of Hanoi, Hanoi, Vietnam
| | - Hanh Thi My Pham
- Department of Andrology, Andrology and Fertility Hospital of Hanoi, Hanoi, Vietnam
| | - Sang Tien Trieu
- Department of Biology and Genetics, Vietnam Military Medical University, Hanoi, Vietnam
| | - Ngoc Thao My Tran
- Department of Life Sciences, Biosciences Division, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, UK
| | - Hung Sy Ho
- Department of Obstetrics and Gynecology, Hanoi Medical University, Hanoi, Vietnam
| | - Danh Van Tran
- Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam
| | - Tam Van Trinh
- Department of Andrology, Andrology and Fertility Hospital of Hanoi, Hanoi, Vietnam
| | | | - Ngoc Pham Minh
- Department of Andrology, Andrology and Fertility Hospital of Hanoi, Hanoi, Vietnam
| | - Trinh Duc Dang
- Faculty of Mathematics and Computer Science, Vietnam Military Medical University, Hanoi, Vietnam
| | - Viet Huu Dinh
- Department of Andrology, Andrology and Fertility Hospital of Hanoi, Hanoi, Vietnam
| | - Hang Thi Doan
- Military Institute of Clinical Embryology and Histology, Vietnam Military Medical University, Hanoi, Vietnam
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Deng C, Mao J, Zhao L, Liu D, Lin H, Zhang Z, Yang Y, Zhang H, Hong K, Jiang H. Testicular sperm aspiration has a poor effect in predicting micro-TESE outcomes in NOA patients with AZFc deletion. Basic Clin Androl 2023; 33:28. [PMID: 37558984 PMCID: PMC10413523 DOI: 10.1186/s12610-023-00195-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 04/24/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND Testicular sperm aspiration (TESA) is widely used in the diagnosis and management of nonobstructive azoospermia. However, its ability for predicting microdissection testicular sperm extraction in nonobstructive azoospermia (NOA) patients with AZFc deletion remains uncertain. To investigate whether TESA affected the sperm retrieval rate (SRR) in NOA patients with AZFc deletion, a retrospective analysis of the clinical data of NOA patients with AZFc deletion who underwent microdissection testicular sperm extraction (micro-TESE) was conducted. The effects of age, testicular volume, follicle-stimulating hormone (FSH) levels, luteinizing hormone (LH) levels, testosterone (T) levels and TESA on the SRR were analyzed in this group of patients. RESULTS A total of 181 individuals had their sperm successfully collected and underwent micro-TESE, with an SRR of 67.4%. The patients were separated into two groups based on their micro-TESE results (sperm acquisition and nonsperm acquisition), with no significant variations in age, testicular volume, FSH levels, LH levels, or T levels between the two groups. There was no significant difference in the SRR between any of the groups into which patients were classified based on reproductive hormone reference value ranges. Binary logistic regression was used to explore the absence of significant effects of age, testicular volume, FSH levels, LH levels, and T levels on sperm acquisition in patients undergoing micro-TESE. In the preoperative testicular diagnostic biopsy group, the sperm acquisition and nonsperm acquisition groups had SRRs of 90.1% and 65.1%, respectively. More significantly, there was no significant difference in the SRR between the negative preoperative testicular diagnostic biopsy group and the nonpreoperative testicular diagnostic biopsy group (65.1 vs. 63.8%, p = 0.855). CONCLUSION There is a high probability of successful sperm acquisition in the testis of men undergoing micro-TESE. In this group of patients, age, testicular volume, FSH levels, LH levels, and T levels may have little bearing on the micro-TESE outcome. In patients whose preoperative TESA revealed the absence of sperm, the probability of obtaining sperm by micro-TESE remained high (65.1%); negative TESA results appeared to not influence the SRR (63.8%) in patients undergoing micro-TESE.
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Affiliation(s)
- Chenyao Deng
- Department of Urology, Peking University Third Hospital, Beijing, 100191, China
- Department of Andrology, Peking University Third Hospital, Beijing, 100191, China
| | - Jiaming Mao
- Department of Andrology, Peking University Third Hospital, Beijing, 100191, China
- Department of Reproductive Medicine Center, Peking University Third Hospital, Beijing, 100191, China
| | - Lianming Zhao
- Department of Urology, Peking University Third Hospital, Beijing, 100191, China
- Department of Andrology, Peking University Third Hospital, Beijing, 100191, China
- Department of Human Sperm Bank, Peking University Third Hospital, Haidian District, 49 North Garden Road, Beijing, 100191, China
| | - Defeng Liu
- Department of Andrology, Peking University Third Hospital, Beijing, 100191, China
- Department of Reproductive Medicine Center, Peking University Third Hospital, Beijing, 100191, China
| | - Haocheng Lin
- Department of Urology, Peking University Third Hospital, Beijing, 100191, China
- Department of Andrology, Peking University Third Hospital, Beijing, 100191, China
- Department of Human Sperm Bank, Peking University Third Hospital, Haidian District, 49 North Garden Road, Beijing, 100191, China
| | - Zhe Zhang
- Department of Urology, Peking University Third Hospital, Beijing, 100191, China
- Department of Andrology, Peking University Third Hospital, Beijing, 100191, China
| | - Yuzhuo Yang
- Department of Andrology, Peking University Third Hospital, Beijing, 100191, China
- Department of Reproductive Medicine Center, Peking University Third Hospital, Beijing, 100191, China
| | - Haitao Zhang
- Department of Urology, Peking University Third Hospital, Beijing, 100191, China
- Department of Andrology, Peking University Third Hospital, Beijing, 100191, China
- Department of Human Sperm Bank, Peking University Third Hospital, Haidian District, 49 North Garden Road, Beijing, 100191, China
| | - Kai Hong
- Department of Urology, Peking University Third Hospital, Beijing, 100191, China.
- Department of Andrology, Peking University Third Hospital, Beijing, 100191, China.
- Department of Human Sperm Bank, Peking University Third Hospital, Haidian District, 49 North Garden Road, Beijing, 100191, China.
| | - Hui Jiang
- Department of Urology, Peking University Third Hospital, Beijing, 100191, China.
- Department of Andrology, Peking University Third Hospital, Beijing, 100191, China.
- Department of Human Sperm Bank, Peking University Third Hospital, Haidian District, 49 North Garden Road, Beijing, 100191, China.
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Campbell K, Suarez Arbelaez MC, Ghomeshi A, Ibrahim E, Roy S, Singh P, Khodamoradi K, Miller A, Lundy SD, Ramasamy R. Next-generation sequencing analysis of semen microbiome taxonomy in men with nonobstructive azoospermia vs. fertile controls: a pilot study. F&S SCIENCE 2023; 4:257-264. [PMID: 37321541 PMCID: PMC10527663 DOI: 10.1016/j.xfss.2023.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 06/08/2023] [Accepted: 06/09/2023] [Indexed: 06/17/2023]
Abstract
OBJECTIVES To study how the semen microbiome profile in men with nonobstructive azoospermia (NOA) differs from that of fertile controls (FCs). DESIGN Using quantitative polymerase chain reaction and 16S ribosomal RNA, we sequenced semen samples from men with NOA (follicle-stimulating hormone >10 IU/mL, testis volume <10 mL) and FCs and performed a comprehensive taxonomic microbiome analysis. SETTING All patients were identified during evaluation at the outpatient male andrology clinic at the University of Miami. PATIENTS In total, 33 adult men, including 14 diagnosed with NOA and 19 with proven paternity undergoing vasectomy, were enrolled. MAIN OUTCOME MEASURES Bacterial species in the semen microbiome were identified. RESULTS Alpha-diversity was similar between the groups, suggesting similar diversity within samples, whereas beta-diversity was different, suggesting differences in taxa between samples. In the NOA men, the phyla Proteobacteria and Firmicutes were underrepresented, and Actinobacteriota were overrepresented compared with FC men. At the genus level, Enterococcus was the most common amplicon sequence variant in both groups, whereas 5 genera differed significantly between the groups, including Escherichia and Shigella, Sneathia, and Raoutella. CONCLUSION Our study showed significant differences in the seminal microbiome between men with NOA and fertile men. These results suggest a loss of functional symbiosis may be associated with NOA. Further research into the characterization and clinical utility of the semen microbiome and its causal role in male infertility is necessary.
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Affiliation(s)
- Katherine Campbell
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, Florida
| | | | - Armin Ghomeshi
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Emad Ibrahim
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, Florida
| | - Sabita Roy
- Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida
| | - Praveen Singh
- Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida
| | - Kajal Khodamoradi
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, Florida
| | - Aaron Miller
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
| | - Scott D Lundy
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio
| | - Ranjith Ramasamy
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, Florida.
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Lucotte EA, Guðmundsdóttir VB, Jensen JM, Skov L, Macià MC, Almstrup K, Schierup MH, Helgason A, Stefansson K. Characterizing the evolution and phenotypic impact of ampliconic Y chromosome regions. Nat Commun 2023; 14:3990. [PMID: 37414752 PMCID: PMC10326017 DOI: 10.1038/s41467-023-39644-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 06/22/2023] [Indexed: 07/08/2023] Open
Abstract
A major part of the human Y chromosome consists of palindromes with multiple copies of genes primarily expressed in testis, many of which have been claimed to affect male fertility. Here we examine copy number variation in these palindromes based on whole genome sequence data from 11,527 Icelandic men. Using a subset of 7947 men grouped into 1449 patrilineal genealogies, we infer 57 large scale de novo copy number mutations affecting palindrome 1. This corresponds to a mutation rate of 2.34 × 10-3 mutations per meiosis, which is 4.1 times larger than our phylogenetic estimate of the mutation rate (5.72 × 10-4), suggesting that de novo mutations on the Y are lost faster than expected under neutral evolution. Although simulations indicate a selection coefficient of 1.8% against non-reference copy number carriers, we do not observe differences in fertility among sequenced men associated with their copy number genotype, but we lack statistical power to detect differences resulting from weak negative selection. We also perform association testing of a diverse set of 341 traits to palindromic copy number without any significant associations. We conclude that large-scale palindrome copy number variation on the Y chromosome has little impact on human phenotype diversity.
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Affiliation(s)
- Elise A Lucotte
- Bioinformatics Research Centre, Aarhus University, Dk-8000, Aarhus C., Denmark.
- Ecologie Systematique et Evolution, CNRS, Université Paris-Saclay, AgroParisTech, 91198, Gif-sur-Yvette, France.
| | - Valdís Björt Guðmundsdóttir
- deCODE genetics/Amgen Inc., 101, Reykjavik, Iceland
- Department of Anthropology, University of Iceland, 101, Reykjavik, Iceland
| | - Jacob M Jensen
- Bioinformatics Research Centre, Aarhus University, Dk-8000, Aarhus C., Denmark
| | - Laurits Skov
- Bioinformatics Research Centre, Aarhus University, Dk-8000, Aarhus C., Denmark
| | - Moisès Coll Macià
- Bioinformatics Research Centre, Aarhus University, Dk-8000, Aarhus C., Denmark
| | - Kristian Almstrup
- Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark
| | - Mikkel H Schierup
- Bioinformatics Research Centre, Aarhus University, Dk-8000, Aarhus C., Denmark
| | - Agnar Helgason
- deCODE genetics/Amgen Inc., 101, Reykjavik, Iceland.
- Department of Anthropology, University of Iceland, 101, Reykjavik, Iceland.
| | - Kari Stefansson
- deCODE genetics/Amgen Inc., 101, Reykjavik, Iceland
- Faculty of Medicine, School of Health Sciences, University of Iceland, 101, Reykjavik, Iceland
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Emirdar V, Acet F. The effect of azoospermia factor microdeletions on intracytoplasmic sperm injection results in azoospermia patients. Pak J Med Sci 2023; 39:672-676. [PMID: 37250564 PMCID: PMC10214791 DOI: 10.12669/pjms.39.3.7003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 11/08/2022] [Accepted: 01/29/2023] [Indexed: 05/31/2023] Open
Abstract
Background &Objective Y chromosome abnormalities are common in male patients with severe oligo-azoospermia. In studies with karyotype analysis and cytogenetic methods, the importance of the Y chromosome in spermatogenesis has been well understood. Deletions in the azoospermia factor (AZF) localized at the distal end of the Y chromosome adversely affect the spermatogenesis process. Our objective was to determine the frequency of AZF microdeletion in azoospermia patients who underwent microTESE. Methods In this retrospective cohort study, 806 azoospermic men attending the In Vitro Fertilization (IVF) Center for infertility treatment between 2010 and 2022 were included. AZF deletion screening was conducted in all patients included in the study. Azoospermic patients with and without Y microdeletion were matched with the female's age, cause of infertility, number of oocytes retrieved and number of metaphase II (MII) oocytes produced and compared. The primary outcome was the live birth rate (LBR). Pregnancy rate (PR) and clinical pregnancy rates (CPR) were secondary outcomes. Results We detected Y microdeletion in 55 (6.82%) of 806 infertile azoospermic men and 35 of them included in the study. Although the required gonadotropin dose and the total number of retrieved oocytes were similar, clinical pregnancy rates and live birth rates were found to be significantly lower in the microdeletion patient group (21.6% vs. 43%, p<0.05; and 18.9% vs. 36%, p<0.05, respectively). Conclusions Poor sperm quality in AZF microdeletion patients complicates the selection of appropriate sperm for ICSI. Therefore, it leads to a decrease in embryonic development, fertilization and pregnancy results. In order to select the best sperm for the use in ICSI procedure in this patient population, intracytoplasmic morphologically selected sperm injection (IMSI) method can be preferred to improve the cycle outcomes.
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Affiliation(s)
- Volkan Emirdar
- Volkan Emirdar, MD, Department of Obstetrics and Gynecology, Izmir Economy University, Medicalpoint Hospital, Izmir, Turkey
| | - Ferruh Acet
- Ferruh Acet, MD, Department of IVF Research and Training Center, Ege University Faculty of Medicine, Izmir, Turkey
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41
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Wagner AO, Turk A, Kunej T. Towards a Multi-Omics of Male Infertility. World J Mens Health 2023; 41:272-288. [PMID: 36649926 PMCID: PMC10042660 DOI: 10.5534/wjmh.220186] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 10/15/2022] [Indexed: 01/17/2023] Open
Abstract
Infertility is a common problem affecting one in six couples and in 30% of infertile couples, the male factor is a major cause. A large number of genes are involved in spermatogenesis and a significant proportion of male infertility phenotypes are of genetic origin. Studies on infertility have so far primarily focused on chromosomal abnormalities and sequence variants in protein-coding genes and have identified a large number of disease-associated genes. However, it has been shown that a multitude of factors across various omics levels also contribute to infertility phenotypes. The complexity of male infertility has led to the understanding that an integrated, multi-omics analysis may be optimal for unravelling this disease. While there is a vast array of different factors across omics levels associated with infertility, the present review focuses on known factors from the genomics, epigenomics, transcriptomics, proteomics, metabolomics, glycomics, lipidomics, miRNomics, and integrated omics levels. These include: repeat expansions in AR, POLG, ATXN1, DMPK, and SHBG, multiple SNPs, copy number variants in the AZF region, disregulated miRNAs, altered H3K9 methylation, differential MTHFR, MEG3, PEG1, and LIT1 methylation, altered protamine ratios and protein hypo/hyperphosphorylation. This integrative review presents a step towards a multi-omics approach to understanding the complex etiology of male infertility. Currently only a few genetic factors, namely chromosomal abnormalities and Y chromosome microdeletions, are routinely tested in infertile men undergoing intracytoplasmic sperm injection. A multi-omics approach to understanding infertility phenotypes may yield a more holistic view of the disease and contribute to the development of improved screening methods and treatment options. Therefore, beside discovering as of yet unknown genetic causes of infertility, integrating multiple fields of study could yield valuable contributions to the understanding of disease development. Future multi-omics studies will enable to synthesise fragmented information and facilitate biomarker discovery and treatments in male infertility.
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Affiliation(s)
- Ana Ogrinc Wagner
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domžale, Slovenia
| | - Aleksander Turk
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domžale, Slovenia
| | - Tanja Kunej
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Domžale, Slovenia.
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Jafari L, Safinejad K, Nasiri M, Heidari M, Houshmand M. The relationship between common mutations in CFTR, AR genes, Y chromosome microdeletions and karyotyping abnormalities with very severe oligozoospermia in Iranian men. Genes Genomics 2023; 45:519-529. [PMID: 35982373 DOI: 10.1007/s13258-022-01300-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/26/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Male infertility due to very severe oligozoospermia has been associated with some genetic risk factors. OBJECTIVE To investigate the distribution of the mutations in the CFTR gene, the CAG-repeat expansion of the AR gene, also Y chromosome microdeletions and karyotyping abnormalities in very severe oligozoospermia patients. METHODS In the present case-control study, 200 patients and 200 fertile males were enrolled. All patients and control group were karyotyped. Microdeletions were evaluated using multiplex PCR. Five common CFTR mutations were genotyped using the ARMS-PCR technique. The CAG-repeat expansion in the AR gene was evaluated for each individual using sequencing. RESULTS Overall 4% of cases shows a numerical and structural abnormality. 7.5% of patients had a deletion in one of the AZF regions on Yq, and 3.5% had a deletion in two regions. F508del was the most common (4.5%) CFTR gene mutation; G542X, and W1282X were detected with 1.5% and 1% respectively. One patient was found to have AZFa microdeletion and F508del in heterozygote form; one patient had AZFb microdeletion with F508del. F508del was seen as compound heterozygous with G542X in one patient and with W1282X in the other patient. The difference in the mean of the CAG-repeats in the AR gene in patients and control groups was statistically significant (P = 0.04). CONCLUSION Our study shows the genetic mutations in men with severe oligozoospermia and given the possibility of transmission of these disorders to the next generation by fertilization, counseling and genetic testing are suggested for these couples before considering ICSI.
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Affiliation(s)
- Leyla Jafari
- Department of Biology, Arsanjan Branch, Islamic Azad University, Arsanjan, Iran
| | - Kyumars Safinejad
- Department of Biology, Borujerd Branch, Islamic Azad University, Borujerd, Iran.
| | - Mahboobeh Nasiri
- Department of Biology, Arsanjan Branch, Islamic Azad University, Arsanjan, Iran
| | - Mansour Heidari
- Department of Medical Genetics, Tehran University of Medical Sciences (TUMS), Poursina Ave, Tehran, Iran
| | - Massoud Houshmand
- Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran
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43
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Dicke AK, Pilatz A, Wyrwoll MJ, Punab M, Ruckert C, Nagirnaja L, Aston KI, Conrad DF, Di Persio S, Neuhaus N, Fietz D, Laan M, Stallmeyer B, Tüttelmann F. DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia. Commun Biol 2023; 6:350. [PMID: 36997603 PMCID: PMC10063662 DOI: 10.1038/s42003-023-04714-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Accepted: 03/15/2023] [Indexed: 04/01/2023] Open
Abstract
Non-obstructive azoospermia, the absence of sperm in the ejaculate due to disturbed spermatogenesis, represents the most severe form of male infertility. De novo microdeletions of the Y-chromosomal AZFa region are one of few well-established genetic causes for NOA and are routinely analysed in the diagnostic workup of affected men. So far, it is unclear which of the three genes located in the AZFa chromosomal region is indispensible for germ cell maturation. Here we present four different likely pathogenic loss-of-function variants in the AZFa gene DDX3Y identified by analysing exome sequencing data of more than 1,600 infertile men. Three of the patients underwent testicular sperm extraction and revealed the typical AZFa testicular Sertoli cell-only phenotype. One of the variants was proven to be de novo. Consequently, DDX3Y represents the AZFa key spermatogenic factor and screening for variants in DDX3Y should be included in the diagnostic workflow.
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Affiliation(s)
- Ann-Kristin Dicke
- Institute of Reproductive Genetics, University of Münster, 48149, Münster, Germany
| | - Adrian Pilatz
- Clinic for Urology, Paediatric Urology and Andrology, Justus Liebig University Gießen, 35390, Gießen, Germany
| | - Margot J Wyrwoll
- Institute of Reproductive Genetics, University of Münster, 48149, Münster, Germany
| | - Margus Punab
- Andrology Centre, Tartu University Hospital, 50406, Tartu, Estonia
- Institute of Clinical Medicine, University of Tartu, 50406, Tartu, Estonia
- Institute of Biomedicine and Translational Medicine, University of Tartu, 50411, Tartu, Estonia
| | - Christian Ruckert
- Institute of Human Genetics, University of Münster, 48149, Münster, Germany
| | - Liina Nagirnaja
- Division of Genetics, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA
| | - Kenneth I Aston
- Andrology and IVF Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Donald F Conrad
- Division of Genetics, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA
| | - Sara Di Persio
- Centre of Reproductive Medicine and Andrology, University Hospital Münster, 48149, Münster, Germany
| | - Nina Neuhaus
- Centre of Reproductive Medicine and Andrology, University Hospital Münster, 48149, Münster, Germany
| | - Daniela Fietz
- Institute of Veterinary Anatomy, Histology and Embryology, Justus Liebig University Gießen, 35392, Gießen, Germany
| | - Maris Laan
- Institute of Biomedicine and Translational Medicine, University of Tartu, 50411, Tartu, Estonia
| | - Birgit Stallmeyer
- Institute of Reproductive Genetics, University of Münster, 48149, Münster, Germany
| | - Frank Tüttelmann
- Institute of Reproductive Genetics, University of Münster, 48149, Münster, Germany.
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44
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Lahoz Alonso R, Sienes Bailo P, César Márquez MÁ, Sánchez Torres JC, Albericio Portero JI, Sánchez Parrilla M, Suárez Broto MÁ, Rello Varas L, Izquierdo Álvarez S. [AZF gene microdeletions in azoospermic-oligozoospermic males]. Med Clin (Barc) 2023; 160:151-155. [PMID: 35999075 DOI: 10.1016/j.medcli.2022.06.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 06/05/2022] [Accepted: 06/09/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND AND OBJECTIVE The presence of microdeletions in the Y-chromosome azoospermia factor (AZF) region (YCMs) is considered the most frequent genetic cause of male infertility along with Klinefelter syndrome. The objective of this study was to investigate the frequencies and type of YCMs in infertile men in Aragon and to analyze the relationship between sex hormones, sperm count and microdeletions in them. PATIENTS AND METHODS Retrospective descriptive study of 644 men who during 2006-2019 were screened for YCMs using YChromStrip (Operón, Spain) by PCR+reverse hybridization, spermiogram, karyotype and quantification of sex hormones. RESULTS The frequency of YCMs was 3.88% (25/644), not being detected in any patient with mild or normospermic oligozoospermia, that is, in sperm counts higher than 5×106/mL. The group of azoospermic patients was the one that presented a higher frequency of YCMs (14.58%, 14/96). Deletions in the AZFc region were the most frequent (68%). 20% (5/25) of patients with YCMs also presented some type of karyotype abnormality that included aneuploidies, deletions, duplications and/or translocations. Sperm count was significantly lower and FSH and LH concentrations significantly higher in the group of patients with YCMs. CONCLUSIONS YCMs screening is a key test in the diagnostic approach to male infertility. Obtaining an adequate result allows choosing suitable assisted reproduction techniques, preventing unnecessary treatments and the transmission of genetic defects to offspring.
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Affiliation(s)
- Raquel Lahoz Alonso
- Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, España
| | - Paula Sienes Bailo
- Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, España.
| | | | | | - Javier Ignacio Albericio Portero
- Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, España; Unidad de Reproducción Asistida. Hospital Materno-Infantil Universitario Miguel Servet, Zaragoza, España
| | - Marcelino Sánchez Parrilla
- Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, España; Unidad de Reproducción Asistida. Hospital Materno-Infantil Universitario Miguel Servet, Zaragoza, España
| | | | - Luis Rello Varas
- Servicio de Bioquímica Clínica, Hospital Universitario Miguel Servet, Zaragoza, España
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Sciorio R, Tramontano L, Rapalini E, Bellaminutti S, Bulletti FM, D'Amato A, Manna C, Palagiano A, Bulletti C, Esteves SC. Risk of genetic and epigenetic alteration in children conceived following ART: Is it time to return to nature whenever possible? Clin Genet 2023; 103:133-145. [PMID: 36109352 DOI: 10.1111/cge.14232] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 09/12/2022] [Accepted: 09/13/2022] [Indexed: 01/07/2023]
Abstract
Assisted reproductive technology may influence epigenetic signature as the procedures coincide with the extensive epigenetic modification occurring from fertilization to embryo implantation. However, it is still unclear to what extent ART alters the embryo epigenome. In vivo fertilization occurs in the fallopian tube, where a specific and natural environment enables the embryo's healthy development. During this dynamic period, major waves of epigenetic reprogramming, crucial for the normal fate of the embryo, take place. Over the past decade, concerns relating to the raised incidence of epigenetic anomalies and imprinting following ART have been raised by several authors. Epigenetic reprogramming is particularly susceptible to environmental conditions during the periconceptional period; therefore, unphysiological conditions, including ovarian stimulation, in vitro fertilization, embryo culture, cryopreservation of gametes and embryos, parental lifestyle, and underlying infertility, have the potential to contribute to epigenetic dysregulation independently or collectively. This review critically appraises the evidence relating to the association between ART and genetic and epigenetic modifications that may be transmitted to the offspring.
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Affiliation(s)
- Romualdo Sciorio
- Edinburgh Assisted Conception Programme, EFREC, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Luca Tramontano
- Department of Women, Infants and Adolescents, Division of Obstetrics, Geneva University Hospitals, Geneva, Switzerland
| | - Erika Rapalini
- IVF Department, Versilia Hospital Lido di Camaiore, Lucca, Italy
| | - Serena Bellaminutti
- Department of Gynaecology and Obstetrics, Ospedale Regionale di Lugano, Lugano, Switzerland
- Gynecology and Fertility Unit, Procrea Institute, Lugano, Switzerland
- Gynecology Unit, Centro Medico, Lugano, Switzerland
| | | | - Antonio D'Amato
- Obstetrics and Gynaecology Clinic, University of Bari, Bari, Italy
| | - Claudio Manna
- Biofertility IVF and Infertility Center, Rome, Italy
| | - Antonio Palagiano
- CFA Napoli, Italy, CFA: Centro Fecondazione Assistita Napoli, Naples, Italy
| | - Carlo Bulletti
- Ostetricia e Ginecologia, EXTRA OMNES Medicina e Salute Riproduttiva, Cattolica, Italy
| | - Sandro C Esteves
- Andrology and Human Reproduction Clinic, Campinas, Brazil
- Department of Surgery (Division of Urology), University of Campinas (UNICAMP), Campinas, Brazil
- Faculty of Health, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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46
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Micro-TESE strategy in patients with NOA caused by AZFc deletion: synchronous or asynchronous? ZYGOTE 2023; 31:25-30. [PMID: 36205231 DOI: 10.1017/s0967199422000466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
In the treatment of infertile patients with non-obstructive azoospermia (NOA) caused by the deletion of the azoospermia factor c region (AZFc) on the Y chromosome, synchronous and asynchronous surgical strategies are discussed. Clinical data from NOA patients with the AZFc deletion who underwent micro-TESE were analyzed retrospectively. The sperm retrieval rate (SRR) and sperm utilization rate of synchronous and asynchronous operation groups were followed up and compared. The fertilization rate, high-quality embryo rate, clinical pregnancy rate, abortion rate, and cumulative live birth rate of ICSI in patients with successful sperm retrieval were compared between the two groups. The two groups had sperm utilization rates of 98.9% (93/94) and 50.0% (14/28), respectively. The asynchronous group's sperm consumption rates were much lower than those of the synchronous operation group. Fertilization rate, high-quality embryo rate, clinical pregnancy rate of fresh transfer cycle, abortion rate, and cumulative live birth rate of patients in the synchronous operation group with fresh sperm, and the asynchronous operation group with thawed sperm, respectively, were 30.6% vs 33.8%, 33.8% vs 40.7%, 40.0% vs 12.5%, 30.4% vs 7.1%. Between the two groups, there was no significant difference. This suggests that individuals with NOA caused by the AZFc deletion have a high possibility of successfully acquiring sperm using micro-TESE and ICSI to conceive their own offspring. Synchronous micro-TESE is recommended to improve sperm utilization rate and the cumulative live birth rate.
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47
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Rudnik-Schöneborn S, Wyrwoll MJ, Tüttelmann F, Toth B, Pinggera GM, Zschocke J. Genetische Diagnostik bei ungewollt kinderlosen Paaren oder wiederholten Fehlgeburten. GYNAKOLOGISCHE ENDOKRINOLOGIE 2023. [DOI: 10.1007/s10304-022-00494-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
ZusammenfassungEtwa 10–15 % aller Paare sind ungewollt kinderlos, entweder durch das fehlende Eintreten einer Schwangerschaft oder durch rezidivierende Aborte. Nachweisbare Ursachen einer Fertilitätsstörung finden sich gleichermaßen bei Männern und bei Frauen, bei einem Drittel sind beide Partner beteiligt. Bei 5–10 % der weiblichen und 10–20 % der männlichen Patienten sind mit den derzeit etablierten diagnostischen Analysen genetische Ursachen erkennbar. Eine ätiologische Abklärung erlaubt eine fundierte Prognose und manchmal eine spezifische Therapie, sie kann auf ein erhöhtes Risiko des Auftretens kindlicher Erkrankungen hinweisen. Eine spezifische genetische Abklärung ist daher unabhängig von einer gegebenenfalls geplanten reproduktionsmedizinischen Behandlung bei allen Paaren indiziert, die länger als ein Jahr vergeblich versuchen, ein Kind zu bekommen, und bei denen keine andere Erklärung für eine Unfruchtbarkeit nachgewiesen wurde. Die genetische Diagnostik der Unfruchtbarkeit umfasst bei beiden Partnern in der Regel eine klassische Karyotypisierung zum Nachweis einer gegebenenfalls vorliegenden gonosomalen oder balancierten strukturellen Chromosomenveränderung. Dies ist insbesondere beim wiederholten Auftreten von Fehlgeburten bei beiden Partnern indiziert. Abhängig von hormonellen Befunden sollte bei Frauen ein attenuiertes adrenogenitales Syndrom bzw. bei Verdacht auf eine primäre Ovarialinsuffizienz eine FMR1-Prämutation ausgeschlossen werden. Die genetische Diagnostik des Mannes bei Azoospermie oder gegebenenfalls bei schwerer Oligozoospermie umfasst zusätzlich zur Karyotypisierung die Testung auf AZF-Mikrodeletionen (AZF Azoospermiefaktor) sowie in Abhängigkeit von den klinischen Parametern auf pathogene Varianten im CFTR-Gen als mögliche Ursache einer obstruktiven Azoospermie. Sequenzanalysen spezifischer Gene können bei Frauen und Männern mit hypogonadotropem Hypogonadismus oder bei Verdacht auf eine monogene Spermatogenesestörung in Betracht gezogen werden. Gemäß den Leitlinien und nationalen gesetzlichen Grundlagen sollten vor der genetischen Diagnostik sowie beim Nachweis genetischer Ursachen einer Infertilität mögliche Konsequenzen und die Bedeutung für zukünftige Kinder im Rahmen einer genetischen Beratung besprochen werden.
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48
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Chao HH, Zhang Y, Dong PY, Gurunathan S, Zhang XF. Comprehensive review on the positive and negative effects of various important regulators on male spermatogenesis and fertility. Front Nutr 2023; 9:1063510. [PMID: 36726821 PMCID: PMC9884832 DOI: 10.3389/fnut.2022.1063510] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 12/23/2022] [Indexed: 01/17/2023] Open
Abstract
With the increasing global incidence of infertility, the influence of environmental factors, lifestyle habits, and nutrients on reproductive health has gradually attracted the attention of researchers. The quantity and quality of sperm play vital roles in male fertility, and both characteristics can be affected by external and internal factors. In this review, the potential role of genetic, environmental, and endocrine factors; nutrients and trace elements in male reproductive health, spermatozoa function, and fertility potency and the underlying mechanisms are considered to provide a theoretical basis for clinical treatment of infertility.
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Affiliation(s)
- Hu-He Chao
- Development Center for Medical Science and Technology, National Health Commission of the People's Republic of China, Beijing, China
| | - Ye Zhang
- Advanced Medical Research Institute, Shandong University, Jinan, Shandong, China
| | - Pei-Yu Dong
- College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, China
| | | | - Xi-Feng Zhang
- College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, China,*Correspondence: Xi-Feng Zhang ✉ ; ✉
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49
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Microdeletions and microduplications linked to severe congenital disorders in infertile men. Sci Rep 2023; 13:574. [PMID: 36631630 PMCID: PMC9834233 DOI: 10.1038/s41598-023-27750-w] [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: 11/04/2022] [Accepted: 01/06/2023] [Indexed: 01/13/2023] Open
Abstract
Data on the clinical validity of DNA copy number variants (CNVs) in spermatogenic failure (SPGF) is limited. This study analyzed the genome-wide CNV profile in 215 men with idiopathic SPGF and 62 normozoospermic fertile men, recruited at the Andrology Clinic, Tartu University Hospital, Estonia. A two-fold higher representation of > 1 Mb CNVs was observed in men with SPGF (13%, n = 28) compared to controls (6.5%, n = 4). Seven patients with SPGF were identified as carriers of microdeletions (1q21.1; 2.4 Mb) or microduplications (3p26.3, 1.1 Mb; 7p22.3-p22.2, 1.56 Mb; 10q11.22, 1.42 Mb, three cases; Xp22.33; 2.3 Mb) linked to severe congenital conditions. Large autosomal CNV carriers had oligozoospermia, reduced or low-normal bitesticular volume (22-28 ml). The 7p22.3-p22.2 microduplication carrier presented mild intellectual disability, neuropsychiatric problems, and short stature. The Xp22.33 duplication at the PAR1/non-PAR boundary, previously linked to uterine agenesis, was detected in a patient with non-obstructive azoospermia. A novel recurrent intragenic deletion in testis-specific LRRC69 was significantly overrepresented in patients with SPGF compared to the general population (3.3% vs. 0.85%; χ2 test, OR = 3.9 [95% CI 1.8-8.4], P = 0.0001). Assessment of clinically valid CNVs in patients with SPGF will improve their management and counselling for general and reproductive health, including risk of miscarriage and congenital disorders in future offspring.
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50
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Kalantari H, Sabbaghian M, Vogiatzi P, Rambhatla A, Agarwal A, Colpi GM, Sadighi Gilani MA. Bridging the Gap between AZF Microdeletions and Karyotype: Twelve Years' Experience of an Infertility Center. World J Mens Health 2023:41.e7. [PMID: 36593709 DOI: 10.5534/wjmh.220089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 08/13/2022] [Accepted: 08/31/2022] [Indexed: 01/03/2023] Open
Abstract
PURPOSE Despite all past efforts, the current guidelines are not explicit enough regarding the indications for performing azoospermia factor (AZF) screening and karyotype, burdening clinicians with the decision to assess whether such tests are meaningful for the infertile male patient. These assessments can be costly and it is up to the healthcare practitioner to decide which are necessary and to weigh the benefits against economic/psychological harm. The aim of this study is to address such gaps and provide update on current management options for this group of patients. MATERIALS AND METHODS To address such gaps in male infertility management and to elucidate whether AZF screening is indicated in individuals who concomitantly harbor chromosomal abnormalities we conducted a retrospective cohort analysis of 10,388 consecutive patients with non-obstructive azoospermia (NOA) and severe oligozoospermia. RESULTS Previously, it has been suggested that all NOA cases with chromosomal defects, except males with 46,XY/45,X karyotype, have no indication for AZF screening. Our findings revealed that cases carrying the following chromosomal abnormalities inv(Y)(p11.2q12); idic(Y)(q11.2); 46,XY,r(Y); idic(Y)(p11.2) and der(Y;Autosome) (76/169; 44.9%; 95% CI, 37.7-52.5) should also be referred for AZF deletion screening. Here, we also report the correlation between sperm count and AZF deletions as a secondary outcome. In accordance with previously reported data from North America and Europe, our data revealed that only 1% of cases with >1×106 sperm/mL had Y chromosome microdeletions (YCMs). CONCLUSIONS In the era of assisted reproduction, finding cost-minimization strategies in infertility clinics without affecting the quality of diagnosis is becoming one of the top prioritized topics for future research. From a diagnostic viewpoint, the results reflect a need to reconsider the different karyotype presentations and the sperm count thresholds in male infertility guidelines as indicators for YCM screening during an infertility evaluation.
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Affiliation(s)
- Hamid Kalantari
- Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Marjan Sabbaghian
- Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
| | - Paraskevi Vogiatzi
- Andromed Health & Reproduction, Reproductive Health Diagnostic Center, Athens, Greece
| | - Amarnath Rambhatla
- Vattikuti Urology Institute, Department of Urology, Henry Ford Hospital, Detroit, MI, USA
| | - Ashok Agarwal
- American Center for Reproductive Medicine, Global Andrology Forum, Moreland Hills, OH, USA
| | - Giovanni M Colpi
- Andrology and IVF Unit, Next Fertility Procrea, Lugano, Switzerland
| | - Mohammad Ali Sadighi Gilani
- Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
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