Genetic Causes Of Male Infertility Research Articles

The outcomes of intracytoplasmic sperm injection (ICSI) using spermatozoa with Y chromosome microdeletion

AZF microdeletions are the leading genetic cause of male infertility and useful to obtain reliable genetic information for assisted reproductive techniques. Thus, the detection is clinically relevant for appropriate genetic counseling. However, there are only a few reports evaluating clinical course of the patients with AZF microdeletions. The aim of this study was to clarify the results of microdissection testicular sperm extraction (micro TESE) with Y chromosome microdeletion and ICSI outcomes using sperm from those men. A retrospective study in 18 Japanese reproductive center. This study was retrospectively examined a total of 1934 azoospermic or severe oligozoospermic patinets who undergone genetic testing for AZF deletions in 18 Japanese medical centers from April 2007 to June 2016. We examined genetic testing for AZF deletions by Promega Y Chromosome AZF Analysis System (version 2.0). We firstly investigated each type of AZF deletions frequencies, and sperm retrieval rate (SRR) by micro TESE of the azoospermic patients with AZF deletions. In addition, we analyzed the ICSI results using testicular or ejaculatory sperm of men with AZF deletions. AZF microdeletions were found in 189 cases (9.8%): 20 AZFa, 15 AZFb, 72 AZFc, 1 AZF a+b, 58 AZFb+c, and 23 AZFa+b+c. Of men with isolated AZFc deletion, spermatozoa were retrieved in 71.4% (30/42) by micro TESE. We could not find spermatozoa from patients with other AZF deletions. Twenty-nine couples underwent ICSI using testicular sperm retrieved by micro TESE, and 3 couples underwent ICSI using ejaculatory sperm. In totally, 572 metaphase 2 oocytes were retrieved by 62 oocyte retrieval cycles. Fertilization rate was 46.1% (220/477). We performed 62 embryo transfer (ET) cycles, mean replaced embryos were 1.39 per ET. Implantation rate per total transfer embryos were 19.8% (17/86), and clinical pregnancy rate per ET cycles were 27.4% (17/62). Abortion rate was 23.5% (4/17). Although we could not detect significant differences, the results of ICSI using ejaculatory sperm had better propensity in fertilization rate, implantation rate, and clinical pregnancy rate compared with the results of ICSI using testicular sperm (72.7% vs 44.1%, 50.0% vs 17.5%, 75.0% vs 24.1%, respectively). AZFc deletions are associated with severe dysregulations of spermatogenesis, however, sperm retrieval is possible in more than half by micro-TESE. It is useful to obtain reliable genetic information from azoospermic patients and to avoid unnecessary micro TESE. The results of this study provide useful actual clinical information for infertile couples with AZF deletions.

The Role of Protamine 1 Gene Polymorphism and Anti FSH Antibody in Infertile Couples

Background: Infertility is a worldwide problem which affects approximately 15% of all couples, and is defined as, inability to conceive after twelve months of contraceptive-free unprotected intercourse. Materials and methods: Optical density of anti follicle stimulation hormone antibody in the serum was detected by enzyme–linked immunosorbent assay technique and from which anti follicle stimulation hormone antibody concentrations were evaluated according to cut-off. One polymorphic sites of Protamine 1 Gene was genotyped on 72 couples suffering from infertility. Another group consist of 20 couples apparently healthy individuals. Genotypes were determined by the polymerase chain restriction fragment length polymorphism (PCR-RFLP) method. Results: Anti FSH antibody result demonstrated differences in antibody values between the patients and the control group with significant statistically, the frequency of the reported SNP was no significantly different compared to normal fertile males, which suggest that such SNP may not serve as a good molecular marker for genetic diagnosis of male infertility. Conclusion: The SNP G197T are completely absent and are not associated with male infertility with aforementioned, therefore these SNPs may not represent as a molecular marker for the diagnosis of genetic cause of male infertility in our studied population.

Cytogenetic analysis of 10,286 cases with male infertility

Chromosome analysis of 10,286 cases with male infertility and to discuss the genetic causes of male infertility. 10,286 patients with azoospermia and oligoasthenozoospermia were collected in the present center from January 2009 to January 2013.Peripheral blood lymphocyte culture and chromosome analysis were performed. In all the 10,286 cases with azoospermia and oligoasthenozoospermia, 8,401 cases showed normal karyotype, 538 cases had chromosome polymorphism, accounting for 5.2% and 1,378 cases had chromosomal abnormalities with a frequency of 13.4%; Conclusions: Genetic factors are closely related to the occurrence of azoospermia and oligoasthenozoospermia, and chromosome analysis in patients with male infertility is necessary.

MP35-09 SPERM ANEUPLOIDY IS ASSOCIATED WITH WORSE GENERAL HEALTH IN INFERTILE MEN

You have accessJournal of UrologyInfertility: Epidemiology & Evaluation II1 Apr 2017MP35-09 SPERM ANEUPLOIDY IS ASSOCIATED WITH WORSE GENERAL HEALTH IN INFERTILE MEN Taylor P. Kohn, Alexander W. Pastuszak, Katherine M. Rodriguez, Zachary J. Solomon, Matthew F. Cherches, Dolores J. Lamb, and Larry I. Lipshultz Taylor P. KohnTaylor P. Kohn More articles by this author , Alexander W. PastuszakAlexander W. Pastuszak More articles by this author , Katherine M. RodriguezKatherine M. Rodriguez More articles by this author , Zachary J. SolomonZachary J. Solomon More articles by this author , Matthew F. CherchesMatthew F. Cherches More articles by this author , Dolores J. LambDolores J. Lamb More articles by this author , and Larry I. LipshultzLarry I. Lipshultz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1099AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Numerous studies have examined the relationship between male infertility and men′s health but most have not investigated specific causes of infertility and their health impact. Here we examine the relationship between general male health and sperm aneuploidy. METHODS We used the Charlson Co-Morbidity Index (CCI) to assess and compare the health status of men with abnormal sperm aneuploidy to five groups of men who received care at an academic infertility clinic: men with normal sperm ploidy (normal FISH), men with genetic abnormalities that may cause infertility (genetic infertile), men presenting for infertility with varicocele (varicocele), men with idiopathic infertility (idiopathic) and proven-fertile men. Sperm ploidy was assessed using fluorescence in situ hybridization (FISH). Genetic infertile men had proven Y chromosome microdeletions or abnormal karyotype. CCI for men with sperm FISH results was completed via telephone survey and CCI for genetic infertile men was extracted from intake forms. Men who were diagnosed with a varicocele or idiopathic infertility had not conceived after 12 months. Men with varicoceles, men with idiopathic infertility, and fertile controls completed the CCI in clinic. Fertile controls included men who presented for vasectomy and had fathered a child in the past 5 years. RESULTS 402 men were included in this analysis: 92 with an abnormal sperm FISH results, 7 with a normal sperm FISH test, 49 genetic infertile men, 85 men with idiopathic infertility, 86 infertile men with varicocele, and 83 fertile controls. Mean age, semen density, and CCI of all groups are described in Table 1. Of note, malignancy was common in our cohort, exceeding rates in the SEER database for comparable age (Table 1). Controlling for age, we explored infertility groups as a predictor of elevated CCI score, and found that only men with abnormal sperm FISH (p=0.002) had increased risk of a higher CCI score. Age also increased the risk for a higher CCI score, with each additional year raising the CCI by 0.0117 points (p=0.009). CONCLUSIONS Men with elevated sperm aneuploidy have nearly double the prevalence of general health issues, particularly malignancy, when compared with men with infertility of other etiologies. These findings further support the relationship between genetic causes of male infertility and general health. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e460-e461 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Taylor P. Kohn More articles by this author Alexander W. Pastuszak More articles by this author Katherine M. Rodriguez More articles by this author Zachary J. Solomon More articles by this author Matthew F. Cherches More articles by this author Dolores J. Lamb More articles by this author Larry I. Lipshultz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Testis Transcriptome Modulation in Klinefelter Patients with Hypospermatogenesis

The main genetic cause of male infertility is represented by the Klinefelter Syndrome (KS), a condition accounting for 3% of all cases of infertility and up to15% of cases of azoospermia. KS is generally characterized by azoospermia; approximately 10% of cases have severe oligozoospermia. Among these, the 30–40% of patients show hypospermatogenesis. The mechanisms leading to adult testis dysfunctions are not completely understood. A microarray transcriptome analysis was performed on testis biopsies obtained from three KS patients with hypospermatogenesis and three control subjects. KS testis showed a differential up- and down-regulation of 303 and 747 transcripts, respectively, as compared to controls. The majority of down-regulated transcripts were involved in spermiogenesis failure and testis morphological defects, whereas up-regulated genes were responsible for testis apoptotic processes. Functional analysis of the transcriptionally altered genes indicated a deregulation in cell death, germ cell function and morphology as well as blood-testis-barrier maintenance and Leydig cells activity. These data support a complex scenario in which spermatogenic impairment is the result of functional and morphological alterations in both germinal and somatic components of KS testis. These findings could represent the basis for evaluating new markers of KS spermatogenesis and potential targets of therapeutic intervention to preserve residual spermatogenesis.

Klinefelter syndrome: cardiovascular abnormalities and metabolic disorders.

Klinefelter syndrome (KS) is one of the most common genetic causes of male infertility. This condition is associated with much comorbidity and with a lower life expectancy. The aim of this review is to explore more in depth cardiovascular and metabolic disorders associated to KS. KS patients have an increased risk of cerebrovascular disease (standardized mortality ratio, SMR, 2.2; 95% confidence interval, CI, 1.6-3.0), but it is not clear whether the cause of the death is of thrombotic or hemorrhagic nature. Cardiovascular congenital anomalies (SMR, 7.3; 95% CI, 2.4-17.1) and the development of thrombosis or leg ulcers (SMR, 7.9; 95% CI, 2.9-17.2) are also more frequent in these subjects. Moreover, cardiovascular abnormalities may be at least partially reversed by testosterone replacement therapy (TRT). KS patients have also an increased probability of endocrine and/or metabolic disease, especially obesity, metabolic syndrome and type 2 diabetes mellitus. The effects of TRT on these abnormalities are not entirely clear.

Partial and complete microdeletions of Y chromosome in infertile males from South of Iran.

Y chromosome microdeletions are the second genetic cause of male infertility. The incidence of Y chromosome microdeletions can vary considerably depending on several factors, including patient selection criteria, population composition, and diagnostic protocols. They are associated with spermatogenic failure and lead to azoospermia or oligozoospermia. The advance in assisted reproductive technology and intracytoplasmic sperm injection, and the possibility of genetic defect transmission to the next generation make it necessary to improve our knowledge about the various factors leading to spermatogenic impairment. This study was designed to determine the frequency of microdeletions of Y chromosome in a population from South of Iran. 81 infertile males with non-obstructive azoospermia or oligozoospermia were selected. Multiplex PCR using several STS markers was carried out to detect the complete or partial microdeletions. The frequency of both complete and partial microdeletions in men with azoospermia or severe oligozoospermia was 7.4%. All microdeletions were observed in AZFc region. There was 1.25% complete microdeletions and after excluding complete microdeletions, we detected 5% gr/gr and 1.25% b2/b3 microdeletions. In our control group of fertile males, 4% gr/gr microdeletions was detected while there was no b2/b3 microdeletions. We concluded that there is a low frequency of Y chromosome microdeletions in a population of infertile males from South of Iran. b2/b3 microdeletions was detected only in infertile males and not in the control group. Screening a population with larger sample size is necessary to determine the involvement of this partial microdeletion in infertility of this population.

Initiative for standardization of reporting genetics of male infertility

ABSTRACTThe number of publications on research of male infertility is increasing. Technologies used in research of male infertility generate complex results and various types of data that need to be appropriately managed, arranged, and made available to other researchers for further use. In our previous study, we collected over 800 candidate loci for male fertility in seven mammalian species. However, the continuation of the work towards a comprehensive database of candidate genes associated with different types of idiopathic human male infertility is challenging due to fragmented information, obtained from a variety of technologies and various omics approaches. Results are published in different forms and usually need to be excavated from the text, which hinders the gathering of information. Standardized reporting of genetic anomalies as well as causative and risk factors of male infertility therefore presents an important issue. The aim of the study was to collect examples of diverse genomic loci published in association with human male infertility and to propose a standardized format for reporting genetic causes of male infertility. From the currently available data we have selected 75 studies reporting 186 representative genomic loci which have been proposed as genetic risk factors for male infertility. Based on collected and formatted data, we suggested a first step towards unification of reporting the genetics of male infertility in original and review studies. The proposed initiative consists of five relevant data types: 1) genetic locus, 2) race/ethnicity, number of participants (infertile/controls), 3) methodology, 4) phenotype (clinical data, disease ontology, and disease comorbidity), and 5) reference. The proposed form for standardized reporting presents a baseline for further optimization with additional genetic and clinical information. This data standardization initiative will enable faster multi-omics data integration, database development and sharing, establishing more targeted hypotheses, and facilitating biomarker discovery.

Clinical consequences of microdeletions of Y chromosome in Japanese non-obstrctive azoospermic patients

AZF microdeletions are the leading genetic cause of male infertility and useful to obtain reliable genetic information for assisted reproductive techniques. Thus, the detection is clinically relevant for appropriate genetic counseling. However, there are only a few reports evaluating clinical course of the patients with AZF microdeletions. The aim of this study was to investigate the prevalence and the results of microdissection testicular extraction (micro TESE) outcome in Japanese azoospermic patients with AZF microdeletions. A retrospective study in a reproductive center. A total of 573 azoospermic patients and 15 relatives whose son and brother affect AZF microdeletion were examined genetic testing for AZF deletions by Promega Y Chromosome AZF Analysis System (version 2.0) in a Japanese medical center from September 2013 to March 2016. We analyzed sperm retrieval rate (SRR) of the patients with AZF microdeletion. In addition, we analyzed fertilization and clinical pregnancy rates of those in whom the sperm retrieval was successful. AZF microdeletions were found in 75 cases (13.1%) of men with azoospermia: 6 AZFa, 4 AZFb, 28 AZFc, 1 AZFa+b, 24 AZFb+c, and 12 AZFa+b+c. All of 12 fathers of affected son with AZF microdeletion were not observed AZF microdeletion. One of 3 brothers showed AZFb+c microdeletion (same pattern as sibling). No spermatozoa were found with micro TESE of the patients with AZFa, AZFb, AZFa+b, AZFb+c and AZFa+b+c deletions. Spermatozoa was only obtained from patients with AZFc microdeletions. Of men with isolated AZFc deletion, spermatozoa were found in 85.7% (24/28) by micro TESE. Patient age was 35.9 ± 5.4 years old. Testicular atrophy was seen in almost all men (mean testicular volume: 13.7 ± 4.0ml). Follicular stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels before surgery was 18.6 ± 9.3 mIU/ml, 5.7 ± 2.1 mIU/ml, and 383.1 ± 143.7 ng/dl, respectively. No correlation was found between serum FSH, LH, and T level with the success of sperm retrieval. Patients’ age and testicular volume and also did not affect the SRR for micro-TESE. Fertilization rate was 49.6% and clinical pregnancy rate per embryo transfer (ET) was 23.5%. Three children were safely delivered and 7 pregnancies were ongoing. Two of them had miscarriages. The frequency of AZF deletions in Japan is similar to in other countries. AZFc deletions are associated with severe dysregulations of spermatogenesis, however, sperm retrieval is possible in more than half by micro TESE. It is useful to obtain reliable genetic information from azoospermic patients and to avoid unnecessary micro TESE. Patients with those Y microdeletions does not seem to have ICSI outcomes comparable (lower 2PN rates and clinical pregnancy rates).

Recurrent Microdeletions at Xq27.3-Xq28 and Male Infertility: A Study in the Czech Population.

BackgroundGenetic causes of male infertility are hypothesized to involve multiple types of mutations, from single gene defects to complex chromosome rearrangements. Recently, several recurrent X-chromosome microdeletions (located in subtelomeric region of the long arm) were reported to be associated with male infertility in Spanish and Italian males. The aim of our study was to test their prevalence and infertility association in population of men from the Czech Republic.Methods107 males with pathological sperm evaluation resulting in nonobstructive infertility were compared to 131 males with normal fecundity. X-chromosome microdeletions were assessed by +/- PCR with three primer pairs for each region Xcnv64 (Xq27.3), Xcnv67 (Xq28) and Xcnv69 (Xq28). The latter microdeletion was further characterized by amplification across the deleted region, dividing the deletion into three types; A, B and C.ResultsWe detected presence of isolated Xcnv64 deletion in 3 patients and 14 controls, and Xcnv69 in 3 patients and 6 controls (1 and 1 patient vs.4 and 1 control for types A and B respectively). There was one control with combined Xcnv64 and Xcnv69 type B deletions, and one patient with combination of Xcnv64 and Xcnv69 type C deletions. The frequency of the deletions was thus not higher in patient compared to control group, Xcnv64 was marginally associated with controls (adjusted Fisher´s exact test P = 0.043), Xcnv69 was not associated (P = 0.452). We excluded presence of more extensive rearrangements in two subjects with combined Xcnv64 and Xcnv69 deletions. There was no Xcnv67 deletion in our cohort.ConclusionIn conclusion, the two previously reported X-linked microdeletions (Xcnv64 and Xcnv69) do not seem to confer a significant risk to impaired spermatogenesis in the Czech population. The potential clinical role of the previously reported patient-specific Xcnv67 remains to be determined in a larger study population.

AB024. Interpretation for Y chromosomal microdeletions of EAA/EMQN 2013 guideline

After the Klinefelter syndrome, Y chromosomal microdeletions are the second most frequent genetic cause of male infertility. The European Academy Andrology (EAA) and the European Molecular genetics Quality Network (EMQN) revised the new 2014 laboratory guidelines on Sep 2013 based on 1999 and 2004 editions according to 12 years clinical accumulation and specialist consensus. The new guideline emphasizes: (I) the Y chromosomal microdeletions region in azoospermic and severe oligozoospermic men mainly is azoospermia factor (AZF) region, include AZFa, AZFb, AZFbc, AZFc and AZFabc, only the microdeletions of relevant region have the specific clinical manifestation; (II) the guideline think the supposed AZFd region by some experts and recommended by some commercial diagnostic kits does not exist. The gr/gr deletion in AZFc region is a genetic risk factor for sperm production, but the clinical implications is not confirmed, not be recommended as the routine detection item; (III) the guideline still recommended the classical 6 sits detection, excessively high number of markers do not improve the sensitivity of the test, may even complicate the interpretation of the results, the method based on two multiplex polymerase chain reactions remains fully valid and appropriate for accurate diagnosis of AZF deletions; (IV) the performance of 12 years EQA scheme indicate that participating laboratories has demonstrated an improvement on reporting practice and decreasing diagnostic error rates by improve the performance. In Chinese infertility men, the frequency of Y chromosomal microdeletions occurrence is in high level, as 11.5%. We suggest the AZF diagnostic should be the routine detection item for azoospermic and severe oligozoospermic men, call on domestic AZF detection laboratory join the EQA scheme and complete the performance of Y chromosome microdeletions detection.

Analysis of partial azoospermia factor c deletion and DAZ copy number in azoospermia and severe oligozoospermia.

Microdeletions of the azoospermia factor (AZF) regions in the Y chromosome are a well-known genetic cause of male infertility, resulting in impairment of spermatogenesis. However, the partial deletions of AZFc region related to spermatogenetic impairment are controversial. We investigated partial deletion of AZFc region and DAZ copy number in a population of Iranian infertile men and normozoospermic controls. In total, 154 infertile men (113 patients with azoospermia, 41 with oligozoospermia) and 111 normozoospermic controls were analysed using PCR. Gene dosage analysis of the DAZ genes was performed by fragment analysis. Our results showed that the frequencies of gr/gr deletion in the azoospermic, severe oligozoospermic and normozoospermic men were 4.4% (5/113), 7.3% (3/41) and 1.8% (2/111) respectively. In the azoospermic patients, the frequency of b2/b3 was 1.8% (2/113). Partial AZFc deletions were not significantly different between the infertile and normozoospermic men. The frequencies of gr/gr deletions and b2/b3 were not significantly different between the azoospermic/severe oligozoospermic men and normozoospermic controls. Our data suggested that gr/gr deletion was not associated with azoospermia/oligozoospermia in an Iranian population.

Case Report: Y Chromosome Microdeletion in an Infertile Patient with Mosaic Klinefelter Synd

Among genetic factors which contribute about 10-15 percent of male infertility, the most common genetic causes of male infertility are Klinefelter’s Syndrome (KS) and Y chromosome microdeletions re...

Case Report: Y Chromosome Microdeletion in an Infertile Patient with Mosaic Klinefelter Syndrome

Among genetic factors which contribute about 10-15 percent of male infertility, the most common genetic causes of male infertility are Klinefelter’s Syndrome (KS) and Y chromosome microdeletions re...

Deregulation of sertoli and leydig cells function in patients with Klinefelter syndrome as evidenced by testis transcriptome analysis.

BackgroundKlinefelter Syndrome (KS) is the most common abnormality of sex chromosomes (47,XXY) and represents the first genetic cause of male infertility. Mechanisms leading to KS testis degeneration are still not completely defined but considered to be mainly the result of germ cells loss. In order to unravel the molecular basis of global testis dysfunction in KS patients, we performed a transcriptome analysis on testis biopsies obtained from 6 azoospermic non-mosaic KS patients and 3 control subjects.ResultsThe analysis found that, compared to controls, KS patients showed the differential up- and down-expression of 656 and 247 transcripts. The large majority of the deregulated transcripts were expressed by Sertoli cells (SCs) and Leydig cells (LCs). Functional analysis of the deregulated transcripts indicated changes of genes involved in cell death, inflammatory response, lipid metabolism, steroidogenesis, blood-testis-barrier formation and maintenance, as well as spermatogenesis failure.ConclusionsTaken together, present data highlight the modulation of hundreds of genes in the somatic components of KS patient testis. The increased LCs steroidogenic function together with the impairment of inflammatory pathways and BTB structure, result in increased apoptosis. These findings may represent a critical roadmap for therapeutic intervention and prevention of KS-related testis failure.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1356-0) contains supplementary material, which is available to authorized users.

Clinical characteristics of men with non-mosaic Klinefelter syndrome in northeastern China: implications for genetic counseling.

Klinefelter syndrome (KS) is the most common genetic cause of male infertility. Widespread development in assisted reproductive technology has provided non-mosaic KS patients with the opportunity of having biological children. Testosterone replacement therapy and micro-dissection testicular sperm extraction are effective sperm retrieval techniques for KS patients. Despite the success of sperm retrieval and intracytoplasmic sperm injection (ICSI), some areas of early aggressive hormonal spermatogenesis and appropriate management of KS remain controversial. Androgenotherapy, a common treatment for KS, carries a risk of decreasing focal spermatogenesis by lowering the gonadotropin content. Inadequately treated hypogonadism increases psychosocial morbidity in KS patients. Preventive care must be provided from the time of diagnosis, preferentially through a multidisciplinary approach. This indicates the need for improved genetic counseling of KS patients. The aim of this study was to report the prevalence of non-mosaic KS in a Chinese infertile male population. The rate of early diagnosis was lower in KS patients; most of these were diagnosed after rising concerns of reproductive capacity. The mean age of patients with sperm or germ cells was significantly lower, while the semen volume of these patients was significantly higher. However, the semen volume was negatively correlated with the age and ratio of luteinizing hormone/testosterone content in KS patients. Therefore, genetic counseling of KS patients should focus on early diagnosis and timely treatment, in addition to improving the quality of life of all KS patients. The use of testosterone replacement therapy and/ or micro-dissection testicular sperm extraction should be preferentially considered for fertility preservation.

Genetic screening and evaluation for chromosomal abnormalities of infertile males in Jilin Province, China.

Chromosomal abnormality is the most common genetic cause of male infertility, particularly in cases of azoospermia, oligozoospermia, and recurrent spontaneous abortion. Chromosomal rearrangement may interrupt an important gene or exert position effects. The functionality of genes at specific breakpoints, perhaps with a specific role in spermatogenesis, may be altered by such rearrangements. Structural chromosome abnormalities are furthermore known to increase the risk of pregnancy loss. In this study, we aimed to assess chromosomal defects in infertile men from Jilin Province, China, by genetic screening and to evaluate the relationship between structural chromosome abnormalities and male infertility. The prevalence of chromosomal abnormalities among the study participants (receiving genetic counseling in Jilin Province, China) was 10.55%. The most common chromosome abnormality was Klinefelter syndrome, and the study findings suggested that azoospermia and oligospermia may result from structural chromosomal abnormalities. Chromosome 1 was shown to be most commonly involved in male infertility and balanced chromosomal translocation was identified as one of the causes of recurrent spontaneous abortion. Chromosomes 4, 7, and 10 were the most commonly involved chromosomes in male partners of women experiencing repeated abortion.

Study of Three Single Nucleotide Polymorphisms in the SLC6A14 Gene in Association with Male Infertility.

Although several genetic causes of male infertility are known, the condition in around 60.0–75.0% of infertile male patients appears to be idiopathic. In some, genetic causes may be polygenic and require several low-penetrance genes to produce a phenotype outcome. In others, pleiotropy, when a gene can produce several phenotypic traits, may be involved. We have investigated whether single nucleotide polymorphisms (SNPs) in the SLC6A14 [solute carrier family 6 (amino acid transporter), member 14] gene are associated with male infertility. This gene has previously been linked with obesity and cystic fibrosis, which are associated with male infertility. It has a role in the transport of tryptophan and synthesis of serotonin that are important for normal spermatogenesis and testicular function. We have analyzed three SNPs (rs2312054, rs2071877 and rs2011162) in 370 infertile men and 241 fertile controls from two different populations (Macedonian and Slovenian). We found that the rs2011162(G) allele and rs2312054(A)-rs2071877(C)-rs2011162(G) haplotype are present at lower frequencies in the infertile rather than the fertile men (p = 0.044 and p = 0.0144, respectively).We concluded that the SLC6A14 gene may be a population-specific, low-penetrance locus which confers susceptibility to male infertility/subfertility. Additional follow-up studies of a large number of infertile men of different ethnic backgrounds are needed to confirm such a susceptibility.

Klinefelter's Syndrome in an Adolescent

Klinefelter’s syndrome is an important common sex chromosomal abnormality in humans and it remains an important genetic cause of male infertility. A 12-year-old student was referred to our hospital due to presence of small penis and testes since birth and progressive breast enlargement of five years duration. On examination, the height was 1.64 metres and weight was 75kg. Breasts and axillary hairs were well developed at Tanner stage IV and III respectively and hair distribution of external genitalia was at Tanner stage IV. The penis and testes were small but well developed. There was no hypospadias or epispadias. Transperineal and transrectal ultrasound showed no ovaries or uterus. Hormonal profile was normal except low Follicle stimulating hormone. Karyotype was 47 XXY. Parent was concerned with the gynecomastia and subsequently was referred to general surgeon for mastectomy. We reported a first case of Klinefelter’s syndrome in an adolescent presenting to our gynecology clinic. The various forms of differential diagnoses of gynecomastia were discussed.

Mutations of the aurora kinase C gene causing macrozoospermia are the most frequent genetic cause of male infertility in Algerian men.

Klinefelter syndrome and Y-chromosomal microdeletion analyses were once the only two genetic tests offered to infertile men. Analyses of aurora kinase C (AURKC) and DPY19L2 are now recommended for patients presenting macrozoospermia and globozoospermia, respectively, two rare forms of teratozoospermia particularly frequent among North African men. We carried out genetic analyses on Algerian patients, to evaluate the prevalence of these syndromes in this population and to compare it with the expected frequency of Klinefelter syndrome and Y-microdeletions. We carried out a retrospective study on 599 consecutive patients consulting for couple infertility at the assisted reproduction unit of the Ibn Rochd Clinique, Constantine, Algeria. Abnormal sperm parameters were observed in 404 men. Fourteen and seven men had typical macrozoospermia and globozoospermia profiles, respectively. Molecular diagnosis was carried out for these patients, for the AURKC and DPY19L2 genes. Eleven men with macrozoospermia had a homozygous AURKC mutation (79%), corresponding to 2.7% of all patients with abnormal spermograms. All the men with globozoospermia studied (n = 5), corresponding to 1.2% of all infertile men, presented a homozygous DPY19L2 deletion. By comparison, we would expect 1.6% of the patients in this cohort to have Klinefelter syndrome and 0.23% to have Y-microdeletion. Our findings thus indicate that AURKC mutations are more frequent than Klinefelter syndrome and constitute the leading genetic cause of infertility in North African men. Furthermore, we estimate that AURKC and DPY19L2 molecular defects are 10 and 5 times more frequent, respectively, than Y-microdeletions.