Clinical, Hormonal, and Genetic Evaluation of Idiopathic Nonobstructive Azoospermia and Klinefelter Syndrome Patients

To investigate the clinical, hormonal, and genetic factors in infertile men with idiopathic nonobstructive azoospermia (NOA) or azoospermic Klinefelter syndrome (KFS), a total of 556 and 96 patients, respectively, were included in this study. All patient samples were analyzed cytogenetically. Serum reproductive hormone levels were measured. Microdeletions in the azoospermia factor (AZF) region of the Y chromosome were detected by multiplex PCR using 16 specific sequence-tagged sites. FSH and LH levels in both NOA and KFS patients were significantly higher than the normal range, and the testosterone level in KFS patients was significantly lower. Ninety-two (95.8%) of the KFS patients showed non-mosaic 47,XXY karyotypes and 47,XXY,inv(9)(p11.1q13); the other KFS patients had mosaic karyotypes of 47,XXY/46,XY, 47,XXY/46,XX, and 47,XXY/48,XXXY/46,XX. Among the 556 idiopathic NOA patients with normal karyotypes, 67 (12.05%) had microdeletions in the AZF region of the Y chromosome. Microdeletions were most frequently detected in the AZFc region, followed by AZFa, AZFb, AZFbc, and partial AZFc deletions. However, Y chromosome microdeletions were not found in any of the azoospermic KFS patients. In view of the hormonal and genetic abnormalities in infertile men with idiopathic NOA and with azoospermic KFS, genetic testing for karyotype, Y chromosome microdeletions, and hormonal parameters is advocated.

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Chromosomal abnormalities and Y chromosome microdeletions in infertile men with azoospermia and oligozoospermia in Eastern China

Journal of International Medical Research ◽

10.1177/0300060519896712 ◽

2019 ◽

Vol 48 (4) ◽

pp. 030006051989671

Author(s):

Jing Sha ◽

Guiping Huang ◽

Bei Zhang ◽

Xia Wang ◽

Zaochun Xu ◽

...

Keyword(s):

Y Chromosome ◽

Assisted Reproduction ◽

Sex Chromosome ◽

Chromosomal Abnormalities ◽

Eastern China ◽

Peripheral Blood Lymphocytes ◽

Specific Sequence ◽

Sequence Tagged Sites ◽

Infertile Men ◽

Y Chromosome Microdeletions

Objective The objective was to investigate the frequency and type of chromosomal abnormalities and Y chromosome microdeletions in infertile men with azoospermia and oligozoospermia to ensure appropriate genetic counseling before assisted reproduction in Eastern China. Methods A total of 201 infertile men (148 with azoospermia and 53 with oligozoospermia) were enrolled. Real-time PCR using six Y-specific sequence-tagged sites of the azoospermia factor (AZF) region was performed to screen for microdeletions. Karyotype analyses were performed on peripheral blood lymphocytes with standard G-banding. Results Out of 201 infertile patients, 22 (10.95%) had Y microdeletions [17/148 (11.49%) men with azoospermia and 5/53 (9.43%) men with oligozoospermia]. The most frequent microdeletions were in the AZFc region, followed by the AZFa+b + c, AZFb+c, AZFa, and AZFb regions. Chromosomal abnormalities were detected in 18.91% (38/201) of patients, 34 of which were sex chromosome abnormalities (16.92%) and 4 of which were autosomal abnormalities (1.99%). Chromosomal abnormalities were more prevalent in men with azoospermia (22.97%) than in those with oligozoospermia (7.55%). Conclusions We detected a high incidence of chromosomal abnormalities and Y chromosomal microdeletions in infertile Chinese men with azoospermia and oligozoospermia. These findings suggest the need for genetic testing before the use of assisted reproduction techniques.

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Evaluation of Y chromosome microdeletions and chromosomal anomalies in infertile men

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2021-0003 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Ozlem Oz

Keyword(s):

Y Chromosome ◽

Banding Technique ◽

Chromosomal Anomalies ◽

Specific Sequence ◽

Sequence Tagged Sites ◽

Infertile Men ◽

Y Chromosome Microdeletions ◽

Male Patients ◽

Patient Selection Criteria ◽

Methodological Aspects

Abstract Objectives Chromosome anomalies and Y chromosome microdeletions are one of the reasons that can be seen in infertile patients and affect fertility. In this study, it was aimed to determine the frequencies of chromosomal anomalies and Y chromosome microdeletions in primary infertile male patients. Methods We included 374 patients with primary infertility in this study. Cytogenetic analysis was performed with the GTG banding technique by using trypsin and Giemsa stain. Y microdeletion analysis was studied by multiplex polymerase chain reaction using 28 Y chromosome-specific sequence-tagged sites. Results Chromosomal irregularities were detected in 27 (7.22%) of infertile cases. It was observed that 7 (25.92%) of chromosomal irregularities detected in cases were in autosomal and 20 (%74.08) were in gonosomal chromosomes. The incidence of Y chromosome microdeletion was 1.07% (4/374) and the microdeletions were observed in AZFb, AZFc and AZFd regions. AZFc + AZFd deletion was detected in three patients (0.81%) and AZFb + AZFc + AZFd deletion in one patient (0.26%). Conclusions In conclusion, gonosomal chromosome irregularity was higher than autosomal chromosome irregularity in infertile men. The frequency of Y microdeletion has different rates according to some factors such as ethnic differences of patients, patient selection criteria, differences in the number of cases, and methodological aspects.

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Frequency of Y Chromosome Microdeletions in Azoospermic and Oligospermic Iranian Infertile Men

International Journal of Medical Laboratory ◽

10.18502/ijml.v7i2.2918 ◽

2020 ◽

Author(s):

Sepideh Gholami Yarahmadi ◽

Saeid Morovvati ◽

Monireh Raam ◽

Ziba Morovvati

Keyword(s):

Polymerase Chain Reaction ◽

Y Chromosome ◽

In Vitro Fertilisation ◽

Control Group ◽

Chain Reaction ◽

Azoospermia Factor ◽

Infertile Men ◽

Y Chromosome Microdeletions ◽

Polymerase Chain

Background and Aims: Azoospermia factor (AZF) region of the Ychromosome has several genes which are responsible for normal spermatogenesis. Microdeletions of these genes are associated with azoospermia and oligospermia. These microdeletions are too small to be detected by karyotyping. They can be easily identified using polymerase chain reaction. The aim of this study is to determine the frequencies of Ychromosome microdeletions in azoospermic and oligospermic Iranian infertile men and compare them with other studies in different ethnic groups. Materials and Methods: At first, karyotype analysis was performed in 80 infertile men and 30 healthy age-matched counterparts as control group using standard cytogenetic methods. Second, genomic DNA was extracted from all cases and genetic screening was conducted for Y chromosome microdeletions by multiplex polymerase chain reaction for AZF genes on both infertile and control men using 6 STS markers on the long arm of the Y chromosome. Results: Totally, 49 infertile men were azoospermic and 31 were oligospermic. Y-chromosome microdeletions in the AZFc region were detected in 4 of azoospermic patients. Y-chromosome microdeletions was not detected in any of the oligospermic patients and the control group. Conclusions: This finding recommends that genetic counseling and screening before starting assisted reproductive techniques such as in vitro fertilisation and intracytoplasmic sperm injection can prevent unnecessary treatment and transmission of genetic defects to offspring

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Frequency of Y chromosome microdeletions in Armenian infertile men

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.11.54-57 ◽

2020 ◽

pp. 54-57

Author(s):

Г.Р. Шахсуварян ◽

Р. Караханян ◽

Т.Ф. Саркисян ◽

В.Л. Ижевская

Keyword(s):

Male Infertility ◽

Ethnic Groups ◽

Y Chromosome ◽

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Azoospermia Factor ◽

Infertile Men ◽

Y Chromosome Microdeletions ◽

Therapeutic Measures

Микроделеции длинного плеча Y-хромосомы являются частой генетической причиной мужского бесплодия, связанного с азооспермией и олигозооспермией. В различных этнических группах частота встречаемости микроделеций Y-хромосомы может существенно варьировать, а их спектр иметь определенные особенности. Целью представленного исследования являлось определение частоты и структуры микроделеционных изменений локуса AZF у мужчин армянской национальности с бесплодием для оптимизации диагностических и лечебных мероприятий с применением вспомогательных репродуктивных технологий. The long arm of the Y chromosome microdeletions are common genetic cause of male infertility, related with azoospermia and oligozoospermia. The frequency of various Y-chromosome microdeletions can vary significantly in different ethnic groups and have certain features. The aim of the presented research is to determine the frequency and spectrum of AZF (azoospermia factor) microdeletions in infertile men of Armenian nationality, in order to optimize diagnostic and therapeutic measures using assisted reproductive technologies.

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High Frequency of 45,X/46,XY mosaicism carring a structurally abnormal Y chromosome in patients with Y chromosome microdeletions: a 8-year period retrospective study

10.21203/rs.3.rs-44357/v1 ◽

2020 ◽

Author(s):

Hong-Ge Li

Keyword(s):

Retrospective Study ◽

Cell Line ◽

Y Chromosome ◽

High Frequency ◽

Chromosomal Mosaicism ◽

Nonobstructive Azoospermia ◽

Infertile Men ◽

Y Chromosome Microdeletions ◽

Structural Abnormalities ◽

Almost All

Abstract Background: Structural abnormalities of Y chromosome are commonly described in associated with the occurrence of a 45,X/46,XY chromosomal mosaicism. In recent years, evidences of an association between Y chromosome microdeletions and 45,X/46,XY mosaicism had been investigated, and 45,X/46,XY mosaicism was found to be particularly common in patients with Y chromosome microdeletions. The aim of our study was to investigate the presence of 45,X/46,XY mosaicism carrying a structurally abnormal Y chromosome in patients with Y chromosome microdeletions.Results: A 8-year retrospective study was conducted on 6545 infertile men with nonobstructive azoospermia or oligozoospermia. A total of 19 patients with 45,X/46,XY mosaicism or its variants were found, of which 78.95% (15/19) had a structural Y chromosome abnormalities in 46,XY cell line. Thirteen of 19 (68.42%, 13/19) patients with 45,X/46,XY mosaicism had Y chromosome microdeletions, and 12/13 (92.31%) of them exhibited a structurally abnormal Y chromosome.Conclusions: Our results were consistent with previous studies that a high frequency of 45,X/46,XY mosaicism or its variants were detected in patients with Y chromosome microdeletions. Different from previous studies, we found that 45,X/46,XY mosaicism in patients with Y chromosome microdeletions almost all exhibited a structurally abnormal Y chromosome.

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The genetic causes of infertility in patients with oligozoospermia and azoospermia in Turkish population

Yeni Üroloji Dergisi ◽

10.33719/yud.2021;16-2-834672 ◽

2021 ◽

pp. 159-164

Author(s):

Yavuz Onur Danacıoglu ◽

Mustafa Gürkan Yenice ◽

Fatih Akkas ◽

Mustafa Soytas ◽

Serhat Seyhan ◽

...

Keyword(s):

Y Chromosome ◽

Sex Chromosome ◽

Klinefelter Syndrome ◽

Assisted Reproductive Techniques ◽

Obstructive Azoospermia ◽

Severe Oligozoospermia ◽

Genetic Causes ◽

Infertile Men ◽

Y Chromosome Microdeletions ◽

Reproductive Techniques

Objective: Advances in the science of genetics and the development of assisted reproductive techniques focus on the genetic causes of infertility. The aim of this research is to reveal genetic abnormalities in terms of sex chromosome aneuploidy and Y chromosome microdeletions. Material and Methods: A total of 350 patients with azoospermia or severe oligozoospermia were selected. After general examination of the patients and laboratory investigations were performed, cartoypes and Y chromosome microdeletions were examined. Results: A total of 225 infertile men with non-obstructive azoospermia (NOA) and 125 infertile men with oligozoospermia were enrolled into the study. The overall cytogenetic anomaly rate was 16%. Chromosomal changes were detected in 32 of 350 (9.1%) cases. The most common genetic anomaly was 47, XXY (Klinefelter syndrome) and the incidence was 11.5% in NOA group. This rate was 3.2% in oligozoospermia group. Y chromosome microdeletions were detected in 24 (6.8%) patients and similarly, it was observed more frequently in the NOA group than in the oligozoospermia group. Conclusion: The incidence of genetic causes have been increasing with the severity of infertility. As a result, genetic screening and appropriate genetic counseling are needed before the use of assisted reproductive techniques. Keywords: azospermia, chromosome, infertility, microdeletion, oligozoospermiaage

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O-165 Prevalence of microdeletions of azoospermia factor (AZF) region on Y chromosome and defects of DAZ and DAZH gene expression in infertile men with azoospermia and oligospermia

Fertility and Sterility ◽

10.1016/s0015-0282(97)90797-4 ◽

1997 ◽

Vol 68 ◽

pp. S81-S82

Author(s):

H.S Lee ◽

G.J Song ◽

J.H Kim ◽

J.T Seo ◽

Y.S Lee ◽

...

Keyword(s):

Gene Expression ◽

Y Chromosome ◽

Azoospermia Factor ◽

Infertile Men ◽

Azf Region

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Detection Y Chromosome Microdeletions Among Iraq Population in Infertile Patients with Azoospermia and Severe Oligospermia

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.9.2.23 ◽

2019 ◽

Vol 9 (02) ◽

Author(s):

Samah A Hammood ◽

Alaauldeen S M AL-Sallami ◽

Saleh M Al-Khafaji

Keyword(s):

Y Chromosome ◽

Karyotype Analysis ◽

Semen Analysis ◽

Obstructive Azoospermia ◽

Severe Oligozoospermia ◽

Infertile Men ◽

Y Chromosome Microdeletions ◽

Detailed Evaluation ◽

Health Organization ◽

Infertile Patients

Objective: To detection of microdeletions of Y chromosome and study the frequency of microdeletions in infertile men with non-obstructive azoospermia or severe oligozoospermia(Middle Euphrates center)in Iraq population. Material and methods: 153 males were included in the study, the casesweredivided into groups according to the infertility etiology and semen analysis according to Word health organization, the frequencies and the characteristicsof Y chromosome microdeletions were investigated in groups. Multiplex PCR was applied to detect the microdeletions. Results:Y chromosome microdeletion was detected in 42 (40.7%) of 153 cases ,Microdeletions in azoospermia showed more frequently detected 28 (52.8%), followed by severe oligospermia 14 (28 %),Microdeletions in the AZFc region were the most common 12 (22.64%), followed by AZFb 11(20.75%) and AZFa 5(9.43%) in azoospermia compared to severe oligospermisAZFc 6 (12%) AZFb 4 (8 %) and AZFa 4 (8%). Conclusion: Y chromosome microdeletions were detected quite frequently in certain infertility subgroups. Therefore, detailed evaluation of an infertile man by physical examination, semen analysis, hormonal evaluationsand when required, karyotype analysis may predict the patients for whom Y chromosome microdeletionanalysis is necessary and also prevent cost increases. Recommendation: This study emphasizes that analysis of microdeletions should be carried out for all patients with idiopathic azoospermia and severe oligospermia who are candidates for intracytoplasmic sperm injection

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Detection of AZF microdeletions and reproductive hormonal profile analysis of infertile sudanese men pursuing assisted reproductive approaches

BMC Urology ◽

10.1186/s12894-021-00834-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hassan Osman Alhassan Elsaid ◽

Tarteel Gadkareim ◽

Tagwa Abobakr ◽

Eiman Mubarak ◽

Mehad A. Abdelrhem ◽

...

Keyword(s):

Y Chromosome ◽

Klinefelter Syndrome ◽

Semen Analysis ◽

Control Group ◽

Male Factor ◽

Exact Test ◽

Fisher's Exact Test ◽

Infertile Men ◽

Significant Difference ◽

Fisher’S Exact Test

Abstract Background Male factor is the major contributor in roughly half of infertility cases. Genetic factors account for 10–15% of male infertility. Microdeletions of azoospermia factors (AZF) on the Yq region are the second most frequent spermatogenesis disorder among infertile men after Klinefelter syndrome. We detected in our previous study a frequency of 37.5% AZF microdeletions which investigated mainly the AZFb and AZFc. We attempted in this study for the first time to evaluate the frequencies of all AZF sub-regions microdeletions and to analyze reproductive hormonal profiles in idiopathic cases of azoospermic and oligozoospermic men from Sudan. Methods A group of 51 medically fit infertile men were subjected to semen analysis. Four couples have participated in this study as a control group. Semen analysis was performed according to WHO criteria by professionals at Elsir Abu-Elhassan Fertility Centre where samples have been collected. We detected 12 STSs markers of Y chromosome AZF microdeletions using a multiplex polymerase chain reaction. Analysis of reproductive hormone levels including Follicle Stimulating, Luteinizing, and Prolactin hormones was performed using ELISA. Comparisons between outcome groups were performed using Student’s t-test Chi-square test or Fisher’s exact test. Results AZF microdeletion was identified in 16 out of 25 Azoospermic and 14 out of 26 of the Oligozoospermic. Microdeletion in the AZFa region was the most frequent among the 30 patients (N = 11) followed by AZFc, AZFd (N = 4 for each) and AZFb (N = 3). Among the Oligozoospermic participants, the most frequent deletions detected were in the AZFa region (N = 10 out of 14) and was significantly associated with Oligozoospermic phenotype, Fisher's Exact Test (2-sided) p = 0.009. Among the Azoospermic patients, the deletion of the AZFc region was the most frequent (N = 9 out of 16) and was significantly associated with Azoospermia phenotype Fisher's Exact Test p = 0.026. There was a significant difference in Y chromosome microdeletion frequency between the two groups. The hormonal analysis showed that the mean levels of PRL, LH, and FSH in Azoospermic patients were slightly higher than those in oligozoospermic. A weak negative correlation between prolactin higher level and Azoospermic patients was detected. (AZFa r = 0.665 and 0.602, p = 0.000 and 0.0004, AZFb r = 0.636 and 0.409, p = 0.000 and 0.025, and AZFd r = 0.398 and 0.442, p = 0.029 and 0.015). The correlation was positive for AZFa and negative for AZFb and AZFd. Conclusions We concluded in this study that the incidences of microdeletions of the Y chromosome confined to AZF a, b, c and d regions is 58.8% in infertile subjects with 31.4% were Azoospermic and 27.5% were Oligozoospermic. This might provide a piece of evidence that these specified regions of the Y chromosome are essential for controlling spermatogenesis. These findings will be useful for genetic counseling within infertility clinics in Sudan and to adopt appropriate methods for assisted reproduction.

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