AZFc Deletions Research Articles

Investigation of genotype-phenotype correlation in patients with AZF microdeletion in a single-reference centre.

In this study, we aimed to elucidate the relationship between AZF deletion type and clinical information of azoospermic patients with AZF microdeletion in the Turkish population. Azoospermic patients with normal karyotype and AZF microdeletion were analysed retrospectively by collecting clinical data including hormone profile, demographic characteristics and micro-TESE results. As a result of the AZF microdeletion tests of 42 cases with 46 XY karyotype, AZFa deletion was detected in 3 cases, AZFb deletion in 2 cases, AZFc deletion in 31 cases, AZFb+AZFc deletion in 4 cases and AZFa+AZFb+AZFc deletion in 2 cases respectively. Spermatozoon was obtained in 16 cases with AZFc microdeletion with micro-TESE. Pregnancy was achieved in 2 cases. There was no statistically significant difference between the type of deletion and age, height, weight, body mass index, hormone profile and testicular volume. When AZF is evaluated according to the type of microdeletion, it will be appropriate to plan the medical and surgical options more carefully in a multidisciplinary manner in cases with deletions including AZFa, AZFb or their combinations. Also, genotype-phenotype correlation was found to be consistent with the literature; particularly patients having AZFc deletions were found to have a chance for pregnancy.

Study on clinical and genetic characteristics of male patients with non-obstructive azoospermia

We examined 501 patients with non - obstructive azoospermia to evaluate clinical, subclinical, and genetic characteristics. The results show that the average age of patients in the study was 29.8 ± 5.5 years. Primary infertility accounts for the majority, with a rate of 90.3%. There was 38.6% of patients had a history of mumps orchitis. The average levels of FSH, LH, testosterone were 31.6 ± 16.5 mIU/mL, 15.5 ± 10 mIU/mL and 12.8 ± 7.13 nmol/L, respectively. The prevalence of chromosomal abnormalities was 30.7%. Of these, the sex chromosome aneuploidy with 47,XXY karyotype (Klinefelter syndrome) accounted for 27.3%. The incidence of AZF microdeletion was 13.8%. Of these, AZFc deletion was the most common at the rate of 42.1%, AZFa deletion, which accounted for 2.6%, were the least prevalent, and the frequency of AZFd deletion was 5.3%. However, there was no solitary AZFb deletion, which combined with other AZF deletions with 34.2%. Our research shows that mumps orchitis and chromosomal abnormalities are the leading causes of azoospermia. Screening for genetic abnormalities plays an important role in infertile patients with non - obstructive azoospermia.

Effects of Y chromosome Microdeletions on Male Fertility

Background: In the process of human reproduction, spermatogenesis is one of the most important stages, which is controled by special genes on Y chromosome. Previous studies show that some infertile men have microdeletions on Y chromosome, which cause the reduction of sperm count. Three prominent spermatogenesis loci have been identified on the Y chromosome and entitled “azoospermia factors” (AZFa, b, and c). Hereby, this review article aimed to investigate the content of the Y chromosome microdeletions and their importance in male fertility. Methods: Data and information were collected on English-language articles from PubMed and MEDLINE databases. For Persian articles, Persian-language databases, including SID Scientific Database, IranMedex Medical Articles Database, IranDoc (Iran Scientific Information and Documents Research Institute), Magiran Publication Information, and MedLib were investigated. More than 50 articles on Y chromosome microdeletions and infertility published during 2000-2020 were studied. Results: Previous studies implicated that Y chromosome microdeletions in AZFa, AZFb, and AZFc regions are accompanied by defect in spermatogenesis, leading to oligo / azoospermia. Patients with AZFa and AZFb microdeletions present secretory azoospermia and do not have sperm in their seminiferous tubules. Complete AZFc deletion involves region b2/b4, which contains a total of 12 genes. Incomplete deletion of AZFc includes b1/b3, b2/b3 and gr/gr. The most common of which are gr/gr. In men with gr/gr deletion, sperm count and motility were lower than control group. Conclusion: Y chromosomal microdeletions emerged as the most frequent structural chromosome anomaly associated with the quantitative reduction of sperm. The development of assisted reproductive techniques (ART) like intra-cytoplasmic sperm injection (ICSI) and testicular sperm extraction (TESE) helps to bypass the natural barriers of fertilization.

Yq microdeletions and their current status in relation to Indian and Global scenario associated to male infertility: A mini appraisal

Background: Y chromosome microdeletions provide a pivotal role in the control of spermatogenesis. These are located on the q arm of it, specifically, the azoospermia factor (AZF) region, hence named as Yq microdeletions. The mutations in this region are related to testicular pathologies such as azoospermia, oligozoospermia, and other semen categories. Objectives: This study was undertaken to review these microdeletions, screening, and their correlation to semen categories in relation to the Indian and Global populations in context to male infertility, future strategies, and its implications. Methodology: These deletions are screened using sequence-tagged sites (STS) of the European Academy of Andrology (EAAs) and Non-EAAs with polymerase chain reaction technology. The data included were Indian and Global studies obtained from research articles, abstracts, and reviews (75) indexed in Google Scholar, PubMed, and Scopus. Results: A number of total 45,562 Y chromosomes were analyzed. In India, this frequency contributes to 8.33% (453/5435) against the average frequency of 6.96% (3170/ 45562) worldwide. Globally, this frequency was higher (9.1%) in the North American continent. Among all types of deletions, AZFc deletions are higher followed by b, a, b+c, and others as well as are related to azoospermia than oligospermia and other semen cases/categories globally including India. In India, the data on partial deletions are scanty. Further, cases with AZFc are better suitable for assisted reproductive technologies after counseling. Conclusion: Evaluation of correct deletion type to a specific testis pathologic phenotype is suggested for sperm retrieval to correct the male partner. This study is hence better suitable for azoospermia with AZFc deletion around the Global and Indian scenario in association with male infertility. Future strategies are thus called for successful treatment of a specific microdeletion clinically in the male.

Histology and sperm retrieval among men with Y chromosome microdeletions.

In this review of Y chromosome microdeletions, azoospermia factor (AZF) deletion subtypes, histological features and microTESE sperm retrieval rates are summarized after a systematic literature review. PubMed was searched and papers were identified using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Approximately half of infertile couples have a male factor contributing to their infertility. One of the most common genetic etiologies are Y chromosome microdeletions. Men with Y chromosome microdeletions may have rare sperm available in the ejaculate or undergo surgical sperm retrieval and subsequent intracytoplasmic sperm injection to produce offspring. Azoospermia or severe oligozoospermia are the most common semen analysis findings found in men with Y chromosome microdeletions, associated with impaired spermatogenesis. Men with complete deletions of azoospermia factor a, b, or a combination of any loci have severely impaired spermatogenesis and are nearly always azoospermic with no sperm retrievable from the testis. Deletions of the azoospermia factor c or d often have sperm production and the highest likelihood of a successful sperm retrieval. In men with AZFc deletions, histologically, 46% of men demonstrate Sertoli cell only syndrome on biopsy, whereas 38.2% have maturation arrest and 15.7% have hypospermatogenesis. The microTESE sperm retrieval rates in AZFc-deleted men range from 13-100% based on the 32 studies analyzed, with a mean sperm retrieval rate of 47%.

Current Status of Y Chromosome Microdeletions: Prevalence, Distribution, Implication and Association with Male Infertility in Indian Men- A Review

Introduction: Infertility affects about 15% of couples attempting pregnancy and in approximately 50% of these cases, male factors are responsible. Male infertility is clinically characterised by azoospermia and oligozoospermia depending on the amount of loss of genetic material and the size of the affected region on the Y Chromosome Microdeletions (YCM). The majority of genes located in the Y chromosome are involved in male related functions such as spermatogenesis in human, in addition to other endocrine and physiological factors. These microdeletions are located on q arm of Y chromosome, specifically Azoospermia Factor (AZF) region, hence called Yq microdeletions. These deletions are in form of complete/ incomplete, recombination; mutations and Copy Number Variations (CNV) and vary in frequency depending on region, ethnicity, lifestyles and other epigenetic factors. Hence, this study is well reviewed in Indian men with infertility caused by AZF a,b,c and other partial deletions. So, it is important to the one who is affected by these mutations and infertile couples who adopt Assisted Reproductive Technologies (ARTs) after counseling. It is further useful for prediction of testicular sperm retrieval chances. Aim: To review the current status of Yq microdeletion frequency in infertile Indian men with the available data and their correlation with testicular phenotypes as well as other factors. These would also reckon as a supportive to other clinical findings for diagnosis of specific deletion of infertility to adopt ARTs to the infertile couple. Materials and Methods: Various studies including our data were collected to European Molecular Genetics Quality Network (EMQN) as well as analyse these Yq microdeletions screened using specific Sequence Tagged Sites (STS) of available kit like European Academy of Andrology (EAA) and non-EAAs using Polymerase Chain Reaction (PCR) technology. Various researchers from various zones of India contributed to microdeletion screening of Y chromosome using various STS to AZF locus. These data from 30 study groups were compared to geographical areas/zones, Indian populations, environment, selection criteria and other factors in this review. Results: The data on thousands of Y chromosome analysis confirmed that the frequency of microdeletions are affected by sample size, selection criteria of subjects, different geographical regions, ethnicity, Oxidative Stress (OS), Deoxyribonucleic Acid (DNA) fragmentation and food styles in addition to genetic defects. In Indian subcontinent, these deletions contribute to 8.33% from screening of 5435 Y chromosomes (453/5435). Lower percent (5.37%) of Yq microdeletions in Western India than other parts was observed, being highest in South East (20.52%) and North East zones (17.77%) as mentioned in the present study. These variations in Yq microdeletions are attributed to geographic region, foodstyle, other environmental factors and others. AZFc deletions were more prevalent and correlated to azoospermia (referred/ selected, 66%; deleted 61%) from 30/15 citations respectively in present cohort over oligospermic and/or severe oligospermic men followed by b and a sub-regions including b+c, a+b and others in AZF locus. Amongst 30 study groups, 27 exhibited AZFc deletions at higher rate. Conclusion: From these data in India, it was hence noticed that screening of Yq microdeletion is an important criterion and its correlation with spermeograms is very necessary to infer degree of infertility in men. Such cases are strongly suggested to undergo genetic counselling before adoption of ARTS as deletions increase risk of genetic anomalies, low birth weight and congenital malformations in New Births (NB) of Intracytoplasmic Sperm Injection and Testicular Sperm Ejaculates (ICSI/TESE) adopted cases. Thus, Y deletion evaluation reckons the diagnosis of type of male infertility and its prevention in the next generation propagation through ARTs adopting infertile couples after counselling.

Cytogenetic and molecular study of 370 infertile men in South India highlighting the importance of copy number variations by multiplex ligation-dependent probe amplification.

Male infertility is a common and severe problem affecting 7% of population. The main objective of this study is to identify the chromosomal abnormalities, Y microdeletions in infertile men and also to access the frequency of abnormal sperm count. Based on the sperm count and viability, the infertile men were grouped as Azoospermia, Asthenospermia, Oligospermia and the remaining as Idiopathic infertility. A total of 370 infertile men and 60 normal control men were recruited. Chromosomal abnormalities were identified in 3 men (3/370). The prevalence of Y microdeletions in the infertile group is 8/370 in the Azoospermia factor (AZF) region with four AZFc deletion/duplication, two AZFa deletion, one AZF b & AZFc deletion and one case of total AZF a, AZFb & AZFc deletion. However, only five cases of Y microdeletions were identified by Multiplex PCR but an additional three cases by MLPA (Multiplex ligation-dependent probe amplification). Fluorescence in situ hybridisation also confirmed the deletions. Here, we performed MLPA post-multiplex PCR, and our study revealed good yield of the Y microdeletion identification. The partial duplications which are difficult to be identified can now be easily identified by MLPA, and hence, we recommend MLPA as the choice of investigation compared to multiplex PCR for infertile men.

Evaluation from a different perspective of 10-year results of infertile males with Y chromosome AZFc microdeletions compared with a control group.

AZFc microdeletions will be evaluated upon being divided into partial and complete subgroups. The association of deletions with reactive oxidative stress (ROS) and sperm DNA fragmentation (SDFI) and the impact of their coexistence on fertility starting from the pregnancy process until live birth will be presented. Semen analyses, microbiological results, hormones, ROS and sperm TUNEL tests were checked. Preimplantation genetic testing (PGT) was planned for relevant patients. Intracytoplasmic sperm injection (ICSI) was applied. Their embryo fragmentation was monitored via time lapse. Their results were compared with those with no AZF deletion and no other genetic problems. Azoospermia rate was 71.5%, m-TESE success rate was 25%, pregnancy rate was 26% and live child rate was 2.2%. No difference was detected between the partial and total groups in terms of ROS and SDFI rates and no difference was identified with the control group. Better results were obtained in terms of live child rate in patients with partial AZFc and low ROS/SDFI. Spermatozoon was retrieved in AZFc deletions and pregnancy, and live child was identified. No AZFc impact was observed on ROS and SDFI in the results compared with the control groups in terms of their coexistence.

Chromosomal microarray analysis of infertile men with azoospermia factor microdeletions

Azoospermia factors, located in the long arm of the Y chromosome, are critical for spermatogenesis, the microdeletions of AZF are considered to be associated with male infertility. In addition to complete deletion, several AZFc partial deletions were also detected in infertile men with wide phenotypic heterogeneity. In this study, we investigated the relevance of Y chromosome deletions, Y-linked CNVs and variable phenotypes in infertile men. To clarify the relationship between phenotypic heterogeneity and Y chromosome deletion in male infertility, we performed chromosomal microarray analysis (CMA) capable of analyzing thousands of loci simultaneously to investigate Y-linked copy number variations (CNVs). Firstly, we reviewed the results of Y chromosome screening in 554 infertile patients and then compared the results of CMA to routine Y chromosome screening in 29 patients with Y chromosomal microdeletions. Then, the Y-linked CNVs associated with oligoasthenospermia were identified according to ACMG standards and guidelines. The results indicated that the prevalence of Yq microdeletions was 5.23% (29/554), with 93% (27/29) of the deletions in the AZFc region among 554 infertile men recruited in this study. The results of CMA and multiplex-PCR-based AZFc deletion analysis were generally concordant, but CMA provided more details about location, size and OMIM genes involved in deletion fragments of the AZF region. Of 29 clinically infertile phenotype-related CNVs detected by CMA, nine were pathogenic and the remaining 20 CNVs were OVUS. Except for a 15.69 Mb loss CNV in AZFa + b + c and an 8.25 Mb loss CNV in AZFb + c, others were located in the AZFc region. Based on a combination of the clinical symptoms and loss CNVs, we concluded that the CNV size and the involvement of spermatogenesis critical genes are two important factors that determine the relevance of a CNV in the AZFc region to the presence or absence of a clinically infertile phenotype.

AZF deletions in Indian populations: original study and meta-analyses.

To identify the frequency of Y chromosome microdeletions in Indian populations and to quantitatively estimate the significance of association between these deletions and male infertility. A total of 379 infertile males (302 azoospermic and 77 oligozoospermic infertile males) and 265 normozoospermic fertile males were evaluated for Y chromosome microdeletions (YCD) using PCR amplification and gel electrophoresis. Meta-analyses were performed on AZFa (2079 cases and 1217 controls), AZFb (2212 cases and 1267 controls), AZFc (4131 cases and 2008 controls), and AZFb+c (1573 cases and 942 controls) deletions data to quantitatively estimate the significance of association between these deletions and male infertility in Indian populations. The results revealed that out of 379 infertile azoospermic and oligozoospermic males, 38 (10.02%) had AZF deletions. No deletion was found in control samples. The highest percentage of deletions was observed in the AZFc region, followed by AZFa and AZFb. Qualitative analysis showed that AZF deletions were present in 0.59 to 32.62% (average 13.48%) of infertile cases in Indian populations. Meta-analysis revealed a significant association of AZFa (OR = 6.74, p value = 0.001), AZFb (OR = 4.694, p value = 0.004), AZFc (OR = 13.575, p value = 0.000), and AZFb+c (OR = 5.946, p value = 0.018) deletions with male infertility. AZF deletions were seen in 10.02% of azoospermic and oligozoospermic cases with the highest frequency of AZFc deletions. Pooled analysis for all studies showed deletion frequency from 0.59 to 32.62% (average = 13.48%). Meta-analysis showed significant association of AZFa, AZFb, and AZFb+c deletions with male infertility. Analysis of Y chromosome microdeletions should be reckoned as an essential testing for diagnostic and therapeutic purposes.

High frequency of Y chromosome microdeletions in male infertility patients with 45,X/46,XY mosaicism.

The mosaic 45,X/46,XY karyotype is a common sex chromosomal abnormality in infertile men. Males with this mosaic karyotype can benefit from assisted reproductive therapies, but the transmitted abnormalities contain 45,X aneuploidy as well as Y chromosome microdeletions. The aim of this study was to investigate the clinical and genetic characteristics of infertile men diagnosed with 45,X/46,XY mosaicism in China. Of the 734 infertile men found to carry chromosomal abnormalities, 14 patients were carriers of 45,X/46,XY mosaicism or its variants, giving a prevalence of 0.27% (14/5269) and accounting for 1.91% (14/734) of patients with a chromosomal abnormality. There were ten cases (71.43%, 10/14) of 45,X mosaicism exhibiting AZF microdeletions. Case 1 and Case 4 had AZFc deletions, and the other eight cases had AZFb+c deletions. A high frequency of Y chromosome microdeletions were detected in male patients with 45,X/46,XY mosaicism. Preimplantation genetic diagnosis should be offered to men having intracytoplasmic sperm injection for hypospermatogenesis caused by 45,X/46,XY mosaicism, to avoid the risk of transfering AZF microdeletions in addition to X monosomy in male offspring.

Chromosomal and Y-chromosome microdeletion analysis in 1,300 infertile males and the fertility outcome of patients with AZFc microdeletions.

The present study investigated the frequency of chromosome aberrations and AZF microdeletions in infertile patients with nonobstructive azoospermia (NOA) or severe oligozoospermia. Additionally, the effect of the AZFc microdeletions on the success of microdissection testicular sperm extraction (microTESE) and intracytoplasmic sperm injection (ICSI) methods were evaluated. Peripheral blood samples were received from 1,300 infertile men with NOA and severe oligozoospermia. Karyotyping and FISH analysis were performed according to standard methods. AZF microdeletions were analysed using multiplex polymerase chain reaction or GML Y-chromosome Microdeletion Detection System consisting of 14 markers. The chromosomal aberrations and the AZF microdeletions frequency among 1,300 infertile men were 10.6% and 4.0% respectively. Either ejaculated spermatozoa or microTESE was performed on only in 19 out of 26 patients with AZFc deletions. Of the 19 patients, four had severe oligozoospermia and 15 had NOA. In eight out of 15 NOA patients, testicular mature spermatozoa were obtained (53.3%) and then ICSI was applied to mature oocytes. After undergoing ICSI treatment, clinical pregnancy and live birth outcome rates were found to be 37.5% and 25% respectively. These results suggest that infertile patients with AZFc microdeletion could achieve successful fertilisation pregnancies with the help of assisted reproductive technology.

Y chromosome microdeletion screening using a new molecular diagnostic method in 1030 Japanese males with infertility.

The azoospermia factor (AZF) region is important for spermatogenesis, and deletions within these regions are a common cause of oligozoospermia and azoospermia. Although several studies have reported this cause, the present research, to the best of our knowledge, is the first large-scale study assessing this factor in Japan. In this study, 1030 male patients with infertility who were examined for Y chromosome microdeletion using the polymerase chain reaction-reverse sequence-specific oligonucleotide (PCR-rSSO) method, a newly developed method for Y chromosome microdeletion screening, were included. The study enrolled 250 patients with severe oligospermia and 717 patients with azoospermia. Among the 1030 patients, 4, 4, 10, and 52 had AZFa, AZFb, AZFb+c, and AZFc deletions, respectively. The sperm recovery rate (SRR) of microdissection testicular sperm extraction in patients with AZFc deletions was significantly higher than that in those without AZF deletions (60.0% vs 28.7%, P = 0.04). In patients with gr/gr deletion, SRR was 18.7%, which was lower than that in those without gr/gr deletion, but was not statistically significant. In conclusion, our study showed that the frequency of Y chromosome microdeletion in male patients in Japan was similar to that reported in patients from other countries, and SRR was higher in patients with AZFc deletion.

Clinical and molecular characterization of Y microdeletions and X-linked CNV67 implications in male fertility: a 20-year experience.

Approximately 15% of couples worldwide are affected with infertility, attributed to a male co-factor in about half of the cases. Y chromosome microdeletions are the second most common genetic cause for male infertility, with a global prevalence of 2-10% in infertile men. Recently, CNV67, localized in X chromosome, has emerged as potential contributor to male infertility, with a described frequency of 1.1% in the oligo/azoospermic men. To investigate the prevalence of Y-linked CNVs in a cohort of Portuguese infertile men and correlate the patients' phenotypes with a genetic alteration; to investigate the CNV67 deletion in a subset of patients and corroborate the role of this CNV in male infertility. We retrospectively analysed a database of 4000 Portuguese infertile men for karyotype anomalies and Y microdeletions and selected a cohort of 400 for CNV67 screening analysis by quantitative PCR or single PCR plus/minus. Karyotype anomalies were present in 263 patients (6.6%), with Klinefelter syndrome representing the most frequent karyotype anomaly (2.8%). Among the 4000 patients, the prevalence of Yq microdeletions was 4.6%. Ninety microdeletions (10.0%) were found in the azoospermic group, 44 deletions (4.5%) in the severe oligozoospermic group, 1 AZFc partial deletion (0.3%) in the mild-moderate oligozoospermic group and 2 partial AZFc deletions (0.4%) in the normozoospermic group. Complete AZFc deletions represented 56.8% of the Yq microdeletions. The CNV67 deletion frequency was 1.2% in the studied sample. This study presents one of the largest samples of infertile men worldwide with the main purpose of correlating the Yq microdeletions with sperm count. Our findings are supported by previous reviews with large data and provide a reliable estimation of the prevalence of these anomalies in a Portuguese population. CNV67 was exclusively deleted in patients with spermatogenic impairment, showing a consistent genotype-phenotype correlation and a significant prevalence.

Gr/gr deletion predisposes to testicular germ cell tumour independently from altered spermatogenesis: results from the largest European study.

The association between impaired spermatogenesis and TGCT has stimulated research on shared genetic factors. Y chromosome-linked partial AZFc deletions predispose to oligozoospermia and were also studied in TGCT patients with controversial results. In the largest study reporting the association between gr/gr deletion and TGCT, sperm parameters were unknown. Hence, it remains to be established whether this genetic defect truly represents a common genetic link between TGCT and impaired sperm production. Our aim was to explore the role of the following Y chromosome-linked factors in the predisposition to TGCT: (i) gr/gr deletion in subjects with known sperm parameters; (ii) other partial AZFc deletions and, for the first time, the role of partial AZFc duplications; (iii) DAZ gene dosage variation. 497 TGCT patients and 2030 controls from two Mediterranean populations with full semen/andrological characterization were analyzed through a series of molecular genetic techniques. Our most interesting finding concerns the gr/gr deletion and DAZ gene dosage variation (i.e., DAZ copy number is different from the reference sequence), both conferring TGCT susceptibility. In particular, the highest risk was observed when normozoospermic TGCT and normozoospermic controls were compared (OR = 3.7; 95% CI = 1.5-9.1; p = 0.006 for gr/gr deletion and OR = 1.8; 95% CI = 1.1-3.0; p = 0.013 for DAZ gene dosage alteration). We report in the largest European study population the predisposing effect of gr/gr deletion to TGCT as an independent risk factor from impaired spermatogenesis. Our finding implies regular tumour screening/follow-up in male family members of TGCT patients with gr/gr deletion and in infertile gr/gr deletion carriers.

High frequencies of Non Allelic Homologous Recombination (NAHR) events at the AZF loci and male infertility risk in Indian men

Deletions in the AZoospermia Factor (AZF) regions (spermatogenesis loci) on the human Y chromosome are reported as one of the most common causes of severe testiculopathy and spermatogenic defects leading to male infertility, yet not much data is available for Indian infertile men. Therefore, we screened for AZF region deletions in 973 infertile men consisting of 771 azoospermia, 105 oligozoospermia and 97 oligoteratozoospermia cases, along with 587 fertile normozoospermic men. The deletion screening was carried out using AZF-specific markers: STSs (Sequence Tagged Sites), SNVs (Single Nucleotide Variations), PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) analysis of STS amplicons, DNA sequencing and Southern hybridization techniques. Our study revealed deletion events in a total of 29.4% of infertile Indian men. Of these, non-allelic homologous recombination (NAHR) events accounted for 25.8%, which included 3.5% AZFb deletions, 2.3% AZFbc deletions, 6.9% complete AZFc deletions, and 13.1% partial AZFc deletions. We observed 3.2% AZFa deletions and a rare long AZFabc region deletion in 0.5% azoospermic men. This study illustrates how the ethnicity, endogamy and long-time geographical isolation of Indian populations might have played a major role in the high frequencies of deletion events.

MP46-12 CAN SEMEN PARAMETERS PREDICT CHROMOSOMAL ANOMALY IN MALE FACTOR INFERTILITY?

INTRODUCTION AND OBJECTIVES:We aim to investigate the prevalence of chromosomal abnormalities, AZF microdeletions and partial AZFc deletions in male infertility patients, and also to determine clin...

The Association of Partial Azoospermia Factor C Deletions and Male Infertility in Northwestern China

Background: Male infertility is a major health issue worldwide. Y chromosome microdeletions are well-characterized genetic causes of male infertility. The association of partial AZFc deletions (gr/gr, b2/b3, and b1/b3) with male infertility is not well confirmed in diverse populations. The purpose of the present study was to investigate the frequency of partial AZFc deletions and their association with male infertility in a population from Northwestern China. Methods: Multiplex polymerase chain reaction was used to detect partial AZFc deletions in 228 infertile patients. We analyzed 141 cases of azoospermia (AS), 87 cases of oligozoospermia (OS), and 200 fertile controls. Results: Our data showed that the frequency of a b2/b3 deletion in infertile men, men with AS, men with OS, and controls was 3.51, 2.13, 5.75, and 0.00%, respectively. The frequency of this deletion was significantly different between the infertile group and the control group (3.51 vs. 0.00%, respectively, p = 0.021) and between the OS group and the control group (5.75 vs. 0.00%, respectively, p = 0.003). The frequency of a gr/gr deletion in each group was 11.84, 9.22, 16.09, and 7.50%, respectively. The frequency of a gr/gr deletion was significantly different between the OS group and the control group (16.09 vs. 7.50%, respectively, p = 0.026) but not between the infertile group and the control group (11.84 vs. 7.50%, p = 0.132) or the AS group and the control group (9.22 vs. 7.50%, p = 0.569). The frequency of a b1/b3 deletion was 0.44, 0.71, 0.00, and 3.00%, respectively. For this deletion, there was no significant difference between the infertile (0.44 vs. 3.00%, p = 0.089), AS (0.71 vs. 3.00%, p = 0.276), and OS groups (0.00 vs. 3.00%, p = 0.236) and the control group. Conclusions: Our results suggest that the b2/b3 deletion might be associated with male infertility and that the gr/gr deletion might be associated with spermatogenic failure in men with OS in Northwestern China (Ningxia).

GENETIC FACTORS OF MALE INFERTILITY, THEIR COMBINATIONS AND THE SPERMATOLOGICAL CHARACTERISTICS OF MEN WITH FERTILITY FAILURES

The objectiveis to study the occurrence of common genetic factors of male infertility in men with reproductive problems, their combinations and spermatological characteristics.Materials and methods. 393 men with infertility in marriage were examined. According to the results of the cytogenetic study, the sample is divided into 3 groups: 135 men with numerical sex chromosome abnormalities; 58 male patients with a balanced structural rearrangement; 200 men with normal karyotype. Y chromosome microdeletions, CFTR gene mutations and CAG-repeats polymorphism of AR gene were analyzed.Results. The Y-chromosome microdeletions partially AZFc deletions were detected in 13 % male patients with sex chromosome abnormalities. A combination of chromosomal abnormalities with AZF deletions and/or CFTR gene mutations and long CAG repeats of AR gene was found in 19 % infertile men with balanced chromosome rearrangements. Infertile men with normal male karyotype presented the frequency of common genetic factors of male infertility was almost 2 times higher than the combined frequency of these factors in groups of patients with chromosomes abnormalities. Azoospermia in men with normal karyotype and patients with chromosome abnormalities was diagnosed with the same frequency (58 %). In all men who have identified the presence of two or more genetic factors of male infertility, severe forms of pathozoospermia (azoospermia and severe oligozoospermia) were found.Conclusion. The combination of genetic factors of male infertility is accompanied by severe forms of pathozoospermia that indicates a possible additive effect of negative effect on spermatogenesis and male fertility.

Analysis of partial AZFc (gr/gr, b1/b3, and b2/b3) deletions in Iranian oligozoospermia candidates for intracytoplasmic sperm injection (ICSI)

Background/aim: Infertility is a main health issue. The human Y chromosome contains essential genes for spermatogenesis, especially those located on four major intervals defined as AZFa, AZFb, AZFc, and AZFd. A partial deletion of the AZFc region is reported as a significant risk factor for oligo-/azoospermia. The main purpose of this study was to investigate the prevalence of partial deletions in the AZFc region (gr/gr, b1/b3, and b2/b3) in Iranian oligozoospermic candidates for intracytoplasmic sperm injection. Materials and methods: Multiplex PCR was used to assess the micro and partial deletions in 60 oligozoospermia infertile and 80 fertile men. Results: Two cases (3.33%) showed AZFb deletion but no microdeletion was detected in the control samples. In the AZFc region, 20% of the patients showed deletions, in which 15% and 5% showed gr/gr and b2/b3 deletions, respectively. However, 10% of the healthy individuals also showed partial deletions, including gr/gr (7.5%) and b2/b3 (2.5%). No significant correlation was detected between the presence of gr/gr microdeletion in patients and controls (P > 0.05). Conclusion: Our study showed that the partial AZFc deletions are not associated with male infertility in Iranian subjects.