Chromosomal abnormalities in azoospermic and non-azoospermic infertile men: numbers needed to be screened to prevent adverse pregnancy outcomes (original) (raw)
Chromosomal abnormalities in 1663 infertile men with azoospermia: the clinical consequences
Human Reproduction, 2017
What is the prevalence of chromosomal abnormalities in azoospermic men and what are the clinical consequences in terms of increased risk for absent spermatogenesis, miscarriages and offspring with congenital malformations? SUMMARY ANSWER: The prevalence of chromosomal abnormalities in azoospermia was 14.4%, and the number of azoospermic men needed to be screened (NNS) to identify one man with a chromosomal abnormality with increased risk for absence of spermatogenesis was 72, to prevent one miscarriage 370-739 and to prevent one child with congenital malformations 4751-23 757. WHAT IS KNOWN ALREADY: Infertility guidelines worldwide advise screening of non-iatrogenic azoospermic men for chromosomal abnormalities, but only few data are available on the clinical consequences of this screening strategy.
The prevalence of chromosomal abnormalities in subgroups of infertile men
Human Reproduction, 2012
background: The prevalence of chromosomal abnormalities is assumed to be higher in infertile men and inversely correlated with sperm concentration. Although guidelines advise karyotyping infertile men, karyotyping is costly, therefore it would be of benefit to identify men with the highest risk of chromosomal abnormalities, possibly by using parameters other than sperm concentration. The aim of this study was to evaluate several clinical parameters in azoospermic and non-azoospermic men, in order to assess the prevalence of chromosomal abnormalities in different subgroups of infertile men. methods: In a retrospective cohort of 1223 azoospermic men and men eligible for ICSI treatment, we studied sperm parameters, hormone levels and medical history for an association with chromosomal abnormalities.
Chromosomal abnormalities in men with azoospermia
2021
Background: Infertility affects about 15 percent of all couples attempting pregnancy, with the man responsible in approximately half the cases. Azoospermia is detected in up to 8% of male infertility situations. The prevalence of chromosomal abnormalities is increased in azoospermic men. Material and methods: We performed cytogenetic analysis in a group of 128 infertile men with azoospermia from the Republic of Moldova during 2013-2018 period. Karyotyping was performed on peripheral blood lymphocytes according to standard methods of G-banding of metaphase chromosomes. For reporting the results, the 2016 International System of Cytogenetic Nomenclature was used. Results: Chromosomal variations were identified in 48 infertile men with azoospermia. In 38 cases were found abnormalities of gonosomes and in 10 cases abnormalities of autosomes. The most common sex chromosomal abnormality was Klinefelter syndrome: in 21 (55.3%, 95CI 47.23-63.37) cases homogeneous form 47,XXY and in 4 (10.5%, 95CI 5.52-15.48) cases mosaic form. Y-chromosome aberrations were also identified: in 7 (18.4%, 95CI 12.11-24.69) cases was noticed duplication of distal arm 46,XYqh+ and in 3 (7.9%, 95CI 3.53-12.27) cases deletion of the same arm 46,X,del(Y). Additionally, 45,X/46,XY and 46,XX karyotypes were found. Conclusions: 38% of the studied group have chromosomal variations that may explain the origin of infertility. All men with azoospermia should be offered cytogenetic screening followed by appropriate genetic counseling before infertility treatment.
2018
Introduction Approximately 15% to 20% of couples are infertile and suffer from inability to conceive after at least 1 year of frequent unprotected intercourse. In almost 50% of the couples with infertility, the causes are male-related (1-3). Male infertility is a multifactorial disorder in which the contribution of genetic abnormalities has been estimated to be 50% (4,5). Different factors including biological, clinical, environmental and other factors are known for their contribution to the severity of infertility, their role in worsening the effects of pre-existing genetic or medical factors and hence their effect on gamete and embryo development and reduced sperm quality leading to infertility (6-9). To date, sperm parameters are the most frequently investigated factor associated with the prevalence of chromosomal abnormalities in male infertility. But there have been few studies on the possible correlation between a special patient characteristics and lifestyle and chromosomal a...
Journal of Cancer Prevention & Current Research
Background: Infertility was found to affect approximately 10%-15% of the couples, worldwide. Male factors are responsible for at least 50% of the infertility cases. The chromosomal abnormality is more common in infertile men than in fertile men. However, the aim of this study was to evaluate the frequency and type of major chromosomal abnormalities in the infertile men with problems in their sperm count, who had been referred to cytogenetic center in Shiraz, the main referral center in southern Iran. Materials and Methods: A total of 433 infertile males, with azoospermia [169(31%)] and oligospermia [264(69%)], were included in this prospective observational study. Samples were retrospectively collected from the infertile males, and examined by karyotype analysis. Results: The findings revealed that there are 17.3% chromosomal problems, in which 14.3% and 3% of all cases exhibited numerical and structural abnormalities, respectively. Among the 433 infertile patients, 57(33%) exhibited a numerical sex chromosome abnormality, including 49 (11.3%) subjects with typical Klinefelter syndrome, 4 (2.95%) ones with structural sex chromosome and 11 (4.4%) ones with the autosomal chromosome abnormality. Conclusion: The results from this study demonstrated that chromosomal abnormalities are common in the infertile men with a higher frequency of sex chromosomal abnormality, especially those with the numerical type. This highlights the importance of karyotype findings to make appropriate decisions regarding the management of the patients in infertility clinics.
Chromosomal studies in infertile men
T͡Sitologii͡a i genetika
Prometaphase and metaphase chromosome analyses performed on 70 consecutive men with primary infertility (for a period of at least 2 years) revealed 8 (11.42%) men with some kind of chromosomal abnormality. The highest frequency of abnormal karyotypes (10%) was found among patients with azoospermia and the most frequent anomaly was 47, XXY chromosomal constitution, found in 6 (8.57%) patients. All the chromosomal aberrations found in this study, was sex chromosomal type and we did not find any autosomal aberration. All patients with numerical chromosomal anomalies had azoospermia. The incidence of structural aberration in our study was 1.42%. 15 patients had different chromosomal variants (21.38%). We suggest that men with azoospermia should be considered for cytogenetic investigation and we report that "variants of the Y chromosome" have no influence on the sperm count (Million/ml) and fertility of men.
International braz j …, 2011
Purpose: To determine the frequency of genetic alterations in a population of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia. Materials and Methods: Retrospective study of a group of 143 infertile men with severe oligozoospermia or non-obstructive azoospermia from the Andrology Outpatient Clinic of the Human Reproduction Service at the ABC School of Medicine. Of these patients, 100 had severe oligozoospermia, and 43 non-obstructive azoospermia. All patients underwent a genetic study which included karyotype analysis and Y-microdeletion investigation. Results: Genetic abnormalities were found in 18.8% of the studied patients. Chromosomal abnormalities were found in 6.2% of the patients, being more prevalent in the azoospermia group (11.6%) than in the oligozoospermia group (4%). Chromosomal variants were found in 8.3%, and Y-chromosome microdeletions in 4.2% of patients. Conclusion: The high frequency of genetic alterations (18.8%) in our series justified performing a genetic investigation in a population with idiopathic infertility, as results may help determine the prognosis, as well as the choice of an assisted reproduction technique. Moreover, a genetic investigation could minimize the risk of transmitting genetic abnormalities to future generations such as genetic male infertility, mental retardation, genital ambiguity and/or birth defects.
Introduction Our objective is to detect the frequency and types of major genetic abnormalities of idiopathic nonobstructive azoospermia (NOA) to give appropriate genetic counseling before assisted reproductive techniques (ART) in Middle East and to compare the frequencies with other regions of the world. Material and methods A total of 880 Middle Eastern patients with NOA were recruited in this multicenter study for genetic evaluation prior to use of ART. Karyotyping was performed on peripheral blood lymphocytes according to standard G-banding methods, polymerase chain reaction (PCR) was performed to screen the microdeletions in the AZF region of the Y chromosome Results The present study shows that the total prevalence of genetic abnormalities is 28.41 %, including 184 patients (20.91 %) with chromosome disorder and 66 patients (7.5 %) with Y chromosome microdeletions. The most prevalent chromosome abnormality is Klinefelter’s syndrome, which includes 161 patients (18.3 %), 7 patients had XX reversal male sex (0.8 %), 2 patients had 47XYY (0.23 %) and 2 patients had 45XO/46XY (0.23 %). Structural abnormalities occurred in 12 patients (1.36 %). Conclusions The high prevalence of genetic abnormalities (28.41 %) in our study strongly suggests the need for routine genetic testing and counseling prior to assisted reproduction in such population with idiopathic infertility, as a result may help determine the prognosis, as well as the choice of ART. Moreover it allows specific pre-implantation genetic testing to minimize the risk of transmitting genetic defects to offspring. Keywords Genetic abnormality . Non-obstructive Azoospermia . Microdeletion
International braz j urol, 2011
Purpose: To determine the frequency of genetic alterations in a population of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia. Materials and Methods: Retrospective study of a group of 143 infertile men with severe oligozoospermia or non-obstructive azoospermia from the Andrology Outpatient Clinic of the Human Reproduction Service at the ABC School of Medicine. Of these patients, 100 had severe oligozoospermia, and 43 non-obstructive azoospermia. All patients underwent a genetic study which included karyotype analysis and Y-microdeletion investigation. Results: Genetic abnormalities were found in 18.8% of the studied patients. Chromosomal abnormalities were found in 6.2% of the patients, being more prevalent in the azoospermia group (11.6%) than in the oligozoospermia group (4%). Chromosomal variants were found in 8.3%, and Y-chromosome microdeletions in 4.2% of patients. Conclusion: The high frequency of genetic alterations (18.8%) in our series justified performing a genetic investigation in a population with idiopathic infertility, as results may help determine the prognosis, as well as the choice of an assisted reproduction technique. Moreover, a genetic investigation could minimize the risk of transmitting genetic abnormalities to future generations such as genetic male infertility, mental retardation, genital ambiguity and/or birth defects.
Chromosomal defects in infertile men with poor semen quality
Journal of Assisted Reproduction and Genetics, 2012
Purpose To assess the incidence and the type of chromosomal aberrations in males with infertility we reviewed cytogenetic results in 76 Tunisian infertile men (54 nonobstructive azoospermia and 22 oligo-asthenospermia). Methods Karyotyping was performed on peripheral blood lymphocytes according to the standard methods. Molecular diagnosis of classical and partial Y-chromosomal microdeletions was performed by amplifying Y-specific STSs markers. Results Various numerical and structural chromosome abnormalities were identified in 15 patients (19.48%). The occurrence of chromosomal abnormality in the azoospermics and severe oligo-asthnospermic was 21.7% and 13.5%, respectively. The most common was Klinefelter syndrome, accounting for 10 of the 15 cytogenetic defects. The total frequency of Y chromosomal microdeletions was 17.1%, with respective frequencies in azoospermic and severe oligospermic groups, 11.1% and 31.8%. The most frequent of Y chromosomal deletions were the partial ones (11.1% in azoospermic and 27.2% in oligospermic). Conclusion The occurrence of chromosomal abnormalities among infertile males strongly suggests the need for routine genetic testing and counseling prior to the employment of assisted reproduction techniques. Keyword Male infertility. Chromosome abnormality. Klinefelter syndrome. Y microdeletions. Severe oligoasthenospermia. Azoospermia Capsule Cytogenetic results have been reviewed in 76 Tunisian infertile men in order to assess the incidence and the type of chromosomal aberrations in male with infertility.
Chromosomal abnormalities predisposing to infertility, testing, and management: a narrative review
Bulletin of the National Research Centre
Background Much interest has not been placed on the role of chromosomal abnormalities in the pathogenesis and rising prevalence of infertility in recent times. This review was conducted to renew public interest on the chromosomal basis of infertility, testing, and management. Main text Meiotic and post-zygotic mitotic errors may cause infertility-predisposing chromosomal abnormalities, including Klinefelter syndrome, Jacob syndrome, Triple X syndrome, Turner syndrome, and Down syndrome. Chromosomal abnormalities such as deletion, translocation, duplication, inversion, and ring chromosome may also predispose to infertility. Notable features of male chromosomal infertility include spermatogenic failure, characterized by azoospermia, oligospermia, and gonadal dysgenesis, while females include premature ovarian insufficiency, amenorrhea, spontaneous abortion, and gonadal dysgenesis. The risk of these abnormalities is influenced by maternal age and environmental factors such as chemical ...
Chromosomal Translocations in Men with Azoospermia
International Journal of Health Services Research and Policy
Male infertility is liable for half of the genetic infertility cases. Robertsonian and Reciprocal translocations are the major chromosomal rearrangements in the infertile population. In this study, we aimed to submit a Robertsonian and two Reciprocal translocations in three couples with a history of male infertility with azoospermia. Chromosomal analysis of the one couple in the male partner appeared with an abnormal karyotype with 45,XY,rob(13;14) chromosomal constitution, while the female partner revealed normal 46,XX karyotype. The other two couple revealed in the male partner with reciprocal translocations, while the female partners showed normal 46,XX karyotype; one of the infertile males has karyotype with 46,XY,rcp(19;10), and another infertile male with 46,XY,rcp(6;14) chromosomal constitution. The cytogenetic analysis is mandatory to identify any probable chromosomal anomalies for couples with primer infertility. Couples with repeated abortions should be offered a prenatal diagnosis in the case of future pregnancies. Chromosome translocation carriers should be counseled to use advanced technologies such as assisted reproductive technology such as PGD.
Chromosomal constitution of infertile men
Clinical Genetics, 2008
Mitotic chromosome analyses performed on 820 infertile men revealed 60 (7.3%) men with some kind of chromosomal abnormality. Sex chromosomal abnormalities were detected in 28 (3.4%) and autosomal translocations in 9 (1 .O%). Pericentric inversions of chromosome 9, with possible adverse effect on reproduction, was found in 23 (2.8%). Chromosome variants comprised a group of 77 (9.3%) subjects. We suggest that men with severe oligozoospermia and azoospermia should be considered for cytogenetical evaluation.
Comptes Rendus Biologies, 2014
Male infertility is the cause in half of all childless partnerships. Numerous factors contribute to male infertility, including chromosomal aberrations and gene defects. Few data exist regarding the association of these chromosomal aberrations with male infertility in Arab and North African populations. We therefore aimed to evaluate the frequency of chromosomal aberrations in a sample of 476 infertile men with nonobstructive azoospermia (n = 328) or severe oligozoospermia (n = 148) referred for routine cytogenetic analysis to the department of cytogenetics of the Pasteur Institute of Tunis. The overall incidence of chromosomal abnormalities was about 10.9%. Out of the 52 patients with abnormal cytogenetic findings, sex chromosome abnormalities were observed in 42 (80.7%) including Klinefelter syndrome in 37 (71%). Structural chromosome abnormalities involving autosomes (19.2%) and sex chromosomes were detected in 11 infertile men. Abnormal findings were more prevalent in the azoospermia group (14.02%) than in the severe oligozoospermia group (4.05%). The high frequency of chromosomal alterations in our series highlights the need for efficient genetic testing in infertile men, as results may help to determine the prognosis, as well as the choice of an assisted reproduction technique. Moreover, a genetic investigation could minimize the risk of transmitting genetic abnormalities to future generations.
Sao Paulo Medical Journal, 2023
Male infertility is defined as the biological inability of a man to induce pregnancy in a fertile woman after unprotected sexual intercourse for at least one year. 1 A study of a North American population revealed that 12% of male individuals aged 15-44 years are infertile. 2 The main factors related to infertility include obesity, infection, neoplasms, cryptorchidism, smoking, varicocele, chromosomal anomalies, sperm duct defects, scrotal exposure to high temperatures, hormonal imbalances, celiac disease, medications, heavy metal poisoning, and exposure to ionizing radiation. 3-5 Regarding the genetic causes of male infertility, approximately 15-20% of men with severe non-obstructive azoospermia or oligospermia have microdeletions on the long arm of the Y chromosome (AZFa, b, or c regions) where the spermatogenesis genes are located. 6,7 Some cases of male infertility may also be related to disorders of sex development (DSD), such as Klinefelter syndrome (KS), testicular 46,XX DSD, and disorders related to the synthesis or action of testicular hormones. 8 Currently available DSD cohorts in the literature mostly include pediatric patients, with genital ambiguity being the main reason for referral. 9,10 In contrast, studies of genetic causes of male infertility have mainly focused on chromosomal anomalies and Yq microdeletions. 11,12 In these studies, as well as in the guidelines on male infertility, 3 DSD are not specifically considered a cause. A recent study by our group of 84 men with non-obstructive infertility (azoospermia or severe oligospermia) showed that 10 (12%) had KS, 1 had testicular DSD 46,XX, and 1 had mild
Somatic cytogenetic and azoospermia factor gene microdeletion studies in infertile men
Brazilian Journal of Medical and Biological Research, 2006
The objective of the present study was to determine the frequency of somatic chromosomal anomalies and Y chromosomal microdeletions (azoospermia factor genes, AZF) in infertile males who seek assisted reproduction. These studies are very important because the assisted reproduction techniques (mainly intracytoplasmic sperm injection) bypass the natural selection process and some classical chromosomal abnormalities, microdeletions of AZF genes or some deleterious genic mutations could pass through generations. These genetic abnormalities can cause in the offspring of these patients male infertility, ambiguous external genitalia, mental retardation, and other birth defects. We studied 165 infertile men whose infertility was attributable to testicular problems (60 were azoospermic, 100 were oligospermic and 5 were asthenospermic). We studied 100 metaphases per patient with GTG banding obtained from temporary lymphocyte culture for chromosomal abnormality detection and performed a genomic DNA analysis using 28 Y chromosome-specific sequencetagged sites for Y AZF microdeletion detection. Karyotyping revealed somatic anomalies in 16 subjects (16/165 = 9.6%). Of these 16, 12 were in the azoospermic group (12/60 = 20%) and 4 were in the oligospermic group (4/100 = 4%). The most common chromosomal anomaly was Klinefelter syndrome (10/165 = 6%). Microdeletions of AZF genes were detected in 12 subjects (12/160 = 7.5%). The frequencies detected are similar to those described previously. These results show the importance of genetic evaluation of infertile males prior to assisted reproduction. Such evaluation can lead to genetic counseling and, consequently, to primary and secondary prevention of mental retardation and birth defects.
Genetic evaluation of infertile men
Human Reproduction, 1999
Recently, microdeletions in the azoospermic factor region of the Y chromosome, in addition to chromosomal anomalies, have been detected in men with azoospermia or severe oligozoospermia. In this study we evaluated the molecular and cytogenetic defects of infertile men. The frequency of Y microdeletions among 105 azoospermic, 28 oligozoospermic and 32 fertile men was tested on lymphocyte DNA using a series of 20 sequence-tagged sites. In addition, microdeletions were evaluated on testicular-derived DNA among 26 azoospermic patients who underwent testicular biopsy and in whom no sperm cells could be identified. Karyotype analysis was performed on 72 of the infertile patients. Deletions were detected in 6.7% azoospermic and 3.6% oligozoospermic men. No deletions were identified among the fertile men. Identical results were obtained with DNA derived either from lymphocytes or testicular tissue. The frequency of chromosomal aberrations in the 72 infertile patients tested (62 azoospermic, 10 oligozoospermic) was 16.6%, with a high percentage of gonosome anomalies. Additional andrological parameters (hormone values, cryptorchidism) failed to identify men at risk for having microdeletions before the test. Our findings support the recommendation to perform genetic defect screening among infertile men before their enrolment in an intracytoplasmic injection/in-vitro fertilization programme.
Chromosomal Abnormality in Men with Impaired Spermatogenesis
International Journal of Fertility & Sterility, 2014
Background: Chromosomal abnormalities and Y chromosome microdeletions are regarded as two most frequent genetic causes associated with failure of spermatogenesis in the Caucasian population. Materials and Methods: To investigate the distribution of genetic defects in the Romanian population with azoospermia or severe oligozoospermia, karyotype analysis by G-banding was carried out in 850 idiopathic infertile men and in 49 fertile men with one or more children. Screening for microdeletions in the azoospermia factor (AZF) region of Y chromosome was performed by multiplex polymerase chain reaction (PCR) on a group of 67 patients with no detectable chromosomal abnormality. The results of the two groups were compared by a two-tailed Fisher’s exact test. Results: In our study chromosomal abnormalities were observed in 12.70% and 8.16% of infertile and fertile individuals respectively. Conclusion: Our data suggests that infertile men with severe azoospermia have higher incidences of geneti...
Human Reproduction, 2001
BACKGROUND: An increased incidence of chromosome abnormalities has been reported in sperm samples of many infertile men by fluorescence in-situ hybridization (FISH). METHODS: Sperm aneuploidy and diploidy rates for chromosomes 13, 18, 21, X and Y were evaluated in 63 patients with normal karyotypes using dual and triplecolour FISH techniques. Indications for sperm FISH analysis were: recurrent miscarriages of unknown aetiology (RM, n ⍧ 40), repeated implantation failure after intracytoplasmic sperm injection (ICSI) (IF, n ⍧ 19), previous Down's syndrome pregnancies (n ⍧ 3), and meiotic abnormalities (MA, n ⍧ 1). Nine healthy normozoospermic donors were also evaluated as a control group. RESULTS: A significant increase in the incidence of sex chromosome disomies was found in the RM, IF and MA groups. Oligoasthenoteratozoospermic patients (n ⍧ 21) showed significantly higher rates of diploidy and disomies for sex chromosomes and chromosomes 18 and 21 than normozoospermic patients (n ⍧ 14). Thirty-one patients with normal and seven with abnormal FISH results had undergone several ICSI treatments (108 and 23 cycles respectively). Couples with abnormal sperm FISH results showed decreased pregnancy and implantation rates and increased miscarriage rates. CONCLUSIONS: Patients with a clinical background of recurrent miscarriages of unknown aetiology or implantation failure after ICSI are at risk of showing sperm chromosomal abnormalities, the incidence of which is higher in oligoasthenoteratozoospermic patients.
Comprehensive 5-Year Study of Cytogenetic Aberrations in 668 Infertile Men
Journal of Urology, 2010
Purpose-The causes of male infertility are heterogeneous but more than 50% of cases have a genetic basis. Specific genetic defects have been identified in less than 20% of infertile males and, thus, most causes remain to be elucidated. The most common cytogenetic defects associated with nonobstructive azoospermia are numerical and structural chromosome abnormalities, including Klinefelter syndrome (47,XXY) and Y chromosome microdeletions. To refine the incidence and nature of chromosomal aberrations in males with infertility we reviewed cytogenetic results in 668 infertile men with oligozoospermia and azoospermia. Materials and Methods-High resolution Giemsa banding chromosome analysis and/or fluorescence in situ hybridization were done in 668 infertile males referred for routine cytogenetic analysis between January 2004 and March 2009. Results-The overall incidence of chromosomal abnormalities was about 8.2%. Of the 55 patients with abnormal cytogenetic findings sex chromosome aneuploidies were observed in 29 (53%), including Klinefelter syndrome in 27 (49%). Structural chromosome abnormalities involving autosomes (29%) and sex chromosomes (18%) were detected in 26 infertile men. Abnormal cytogenetic findings were observed in 35 of 264 patients (13.3%) with azoospermia and 19 of 365 (5.2%) with oligozoospermia. Conclusions-Structural chromosomal defects and low level sex chromosome mosaicism are common in oligozoospermia cases. Extensive cytogenetic assessment and fluorescence in situ hybridization may improve the detection rate in males with oligozoospermia. These findings highlight the need for efficient genetic testing in infertile men so that couples may make informed decisions on assisted reproductive technologies to achieve parenthood.