AZFc Region Research Articles

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

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

Evaluation of chromosomal abnormalities and Y-chromosome microdeletions in 1696 Turkish cases with primary male infertility: A single-center study.

The aim of this study was to determine the frequencies of chromosomal abnormalities and Y-chromosome microdeletions in Turkish cases with primary male infertility in a single center. Chromosomal abnormalities and Y-chromosome microdeletions were investigated in 1696 cases with primary male infertility between 2012 and 2017. Karyotype analyzes and Y-chromosome microdeletions analyzes [azoospermia factor (AZF) regions] were performed in all cases by using standard cytogenetic methods and the multiplex polymerase chain reaction method, respectively. Chromosomal abnormalities were found in 142 cases (8.4%; 142/1696). Y-chromosome microdeletions were detected in 46 cases (2.7%; 46/1696). Y-chromosome microdeletions in the AZFc region were found in 20 of 46 cases (43%). This study is one of the few were a large number of cases was studied in Turkey. It indicates that cytogenetic and Y-chromosome microdeletion studies should be conducted in cases with primary male infertility prior to selecting assisted reproductive techniques.

Prevalence of Y chromosome microdeletion in azoospermic infertile males of Iraqi population

In human gamete development, the important period is spermatogenesis, which is organized by specific genes on Y chromosome. In some cases, the infertile men have shown microdeletions on Y chromosome, which seemed as if the structural chromosome variance is linked to the reduction of sperm count. This study aimed to determine the frequency and patterns of Y chromosome microdeletions in azoospermia factor (AZF) of Iraqi infertile males. Here, 90 azoospermic infertile males as a study group and 95 normal fertile males as control group were investigated for the microdeletion of AZF loci using numerous sequence-tagged sites. Of these 90 infertile male patients, 43 (47.8%) demonstrated Y chromosome microdeletions, in which AZFb region was the most deleted section inazoospermia patients (33.3%) followed by deletions in the AZFc region (23%), while there were no microdeletion in the AZFa region. The largest microdeletion involved in both AZFb and AZFc was detected in six azoospermic patients (6.7%). The present study demonstrated a high frequency of Y chromosome microdeletions in the infertile Iraqi patients which is not reported previously. The high frequency of deletions may be due to the association of ethnic and genetic factors. PCR-based Y chromosome screening for microdeletions has a potential to be used in infertility clinics for genetic counselling and assisted reproduction.

The association of gr/gr deletion in the Y chromosome and impaired spermatogenesis in Bulgarian males: a pilot study

BackgroundThe microdeletions of the Y chromosome are associated with a decreased number of sperm cells in the ejaculate and male infertility. One such deletion is the gr/gr, which leads to reduction of the alleles in the DAZ gene. In order to evaluate its role, 30 patients with sperm count below 5 × 106/mL and 30 normal fertile men were genotyped for microdeletions in Azoospermia Factor (AZF) region, including gr/gr deletion.ResultsTwenty-one men (70.00%) from the males with impaired fertility had a normal genotype, seven men (23.33%) were carriers of a gr/gr deletion, and two men (6.67%) demonstrated a deletion of the AZFc region. From the control group, there were 22 men (73.33%) with no deletion, seven (23.33%) carried a gr/gr deletion, and one man (3.33%) carried a possible deletion in the b1-b4 region of the Y chromosome. The gr/gr deletion of the Y chromosome showed a statistically nonsignificant difference (p = 0.94, alpha < 0.05) with the control group (chi-square, degrees of freedom 0.006).ConclusionThe results from the research show no association between this deletion and male infertility in the studied population. Despite the small sample size, the high frequency of the gr/gr deletion, found in the control group, suggests that this variant may not be associated with impaired spermatogenesis.

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.

"Second-look" Micro Testicular Sperm Extraction (MicroTESE) in Patients with Non-obstructive Azoospermia Following Histopathological Analysis.

Introduction:Microdissection testicular sperm extraction (microTESE) is considered the gold standard method for surgical sperm retrieval among patients with non-obstructive azoospermia (NOA).Aim:This study aimed to evaluate the correlation between histopathological findings after failed microTESE procedure and outcomes of the „second-look“ procedure and to provide insight into the most common histopathological patterns after testicular biopsy within our population.Methods:The retrospective study included 33 selected patients with NOA, who had undergone unsuccessful sperm retrieval. The diagnosis of NOA was made after the assessment of the patient’s history data, a physical examination, semen analysis, the hormonal profile, and genetic studies. After negative sperm retrieval, histopathological report has been analyzed for „second-look“ microTESE attempt.Results:Five testicular histopathological patterns were found: hypospermatogenesis (9,1%), Sertoli cell-only syndrome (43%), germ cell maturation arrest (15%), seminiferous tubule hyalinization (15%), mixed pattern (21%). Y-microdeletions were detected in 5 patients, of which 3 patients showed AZFc region deletions. Only 3 patients (9,1%) underwent a „second-look“ procedure after the evaluation of histopathological reports. After the stimulation therapy and „second-look“ procedure, we had a positive outcome in a single patient (33,3%). Mean FSH value in patients with confirmed spermatogenesis was 17.26±3.11IU/l, while mean FSH value in patients without presence or germ cell statistically significantly exceeded and was 24.28±4.71IU/L (p=0.038).Conclusion:Histopathological reports following the microTESE procedure are obligatory for the proper selection of patients who are candidates for the „second-look“ microTESE attempt. Patients with Sertoli cell-only syndrome and hypospermatogenesis particularly can benefit from the “second-look” procedure.

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

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

Karyotypic abnormalities and molecular analysis of Y chromosome microdeletion in Iranian Azeri Turkish population infertile men

ABSTRACTInfertility is one of the major health-threatening problems in communities which may lead to psychological problems among couples. Y chromosome abnormalities and microdeletions have recently been considered as one of the male infertility factors. The aim of this study was to evaluate different chromosomal disorders and azoospermia factor b (AZFb), AZFc and AZFd microdeletions in idiopathic non-obstructive oligo or azoospermia infertile men. One hundred infertile (78 azoospermia and 22 oligospermia) and 100 fertile men were included in this study. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were evaluated by electrochemiluminescence. Karyotyping was performed according to standard methods and interpreted using the International System for Human Cytogenetic Nomenclature (ISHCN) recommendation. For Y chromosome microdeletion analysis, a multiplex polymerase chain reaction (PCR) was performed using STS primers. Higher FSH (24.32 ± 15.32 versus 8.02 ± 3.37, p < 0.0001) and LH (14.97 ± 8.26 versus 5.42 ± 2.73, p < 0.0001) were observed in infertile patients compared to their fertile counterpart. Additionally, 14% of infertile patients exhibited abnormal karyotype. The frequency of Y chromosome microdeletions in azoospermic and oligospermic patients was 32.05% (25/78) and 0% (0/22), respectively. Additionally, in azoospermic patients, the highest microdeletion frequency was related to the AZFc region (80%). Our data indicate the presence of chromosomal changes in the most infertile men, suggesting karyotype and molecular analysis of Y chromosome microdeletions for genetic counseling before assisted reproduction.Abbreviations: ART: assisted reproductive technology; AZF: azoospermia factor; DAZ: deleted in azoospermia; FCS: fetal calf serum; FSH: follicle stimulating hormone; LH: luteinizing hormone; PCR: polymerase chain reaction; SRY: sex-determining region Y; STS: sequence-tagged sites

Y chromosome microdeletions screening in Tunisian infertile men

The aim of this study was to establish the prevalence of chromosomal abnormalities and microdeletions on the Y chromosome in Tunisian infertile men with severe oligozoospermia or non-obstructive azoospermia. In cases of azoospermia, we aimed also to correlate histological results after negative testicular sperm extraction with the type of Y chromosome microdeletion. 84 infertile patients and 52 controls were screened for karyotypic abnormalities using G-banding and Yq chromosome microdeletions using multiplex PCR. 7 infertile males (8.3%) carried chromosomal abnormalities and 8 (9.5%) presented Y chromosome microdeletions. The frequency of chromosome abnormalities in azoospermic patients was 11.1% vs 3.3% in the severe oligozoospermic group. Klinefelter syndrome was the most frequent chromosomal abnormalities in 85.7% of cases. Only one patient had a 46,X,del Y/45,X karyotype. The frequency of microdeletions was 11.1% in the azoospermic group and 6.7% in the severe oligozoospermic group. Six out of 84 (7.14%) of the infertile patients had microdeletions in the AZFc region, one azoospermic male had microdeletion in the AZFbc regions and one in the AZFb region, no deletions in the AZFa region. Among the 6 azoospermic patients with microdeletions: 4 had Sertoly cell only syndrome (SCOS) and 2 had maturation arrest (MA). Genetic abnormalities in infertile Tunisian patients are similar to those reported in other countries. The knowledge of the existence of genetic abnormalities and microdeletions is useful to provide a correct diagnosis and it allows the clinician to refer the patient to adequate assisted reproduction technique and examine the value of testicular biopsy pertinence.

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

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

Cytogenetic and molecular characterization of an oligoasthenozoospermia male carrier of an unbalanced Y;22 translocation

Rationale:Y;autosome translocations are associated with male infertility and azoospermia. Some carriers with a Y:22 translocation can produce offspring and transmit the translocation through generations without phenotypic repercussion. Hence, the clinical features of carriers with certain Y chromosome abnormalities remain uncertain.Patient concerns:An apparently healthy 33-year-old man, 175 cm tall and weighing 60 kg had a 6-month history of primary infertility.Diagnoses:The patient was diagnosed with oligoasthenozoospermia. A series of examinations have been performed to evaluate possible genetic causes of this diagnosis. Several methods included semen analysis, hormone measurements, cytogenetic analysis, and high-throughput multiplex ligation-dependent probe amplification semiconductor sequencing.Interventions:The patient underwent detailed genetic counseling. Cytogenetic analysis was advised for his father. Preimplantation genetic diagnosis was performed to improve potential pregnancy success rate.Outcomes:Semen analysis revealed oligoasthenozoospermia. Hormone levels were within the normal limits. The karyotype of the patient and his father was 45,X,der(Y;22). Sequencing results indicated the presence of the sex-determining region on the Y chromosome gene. Y-chromosome microdeletion detection showed the presence of AZF (azoospermic factor)a, AZFb, and AZFc regions, but deletion of b2/b3 and duplication of b3/b4 regions.Lessons:A clinical karyotype report involving a Y chromosome abnormality should consider the results of semen analysis, which helps to identify the chromosomal breakpoint. Semiconductor sequencing technology was useful for clarifying AZF gene microdeletions.

Detection of Y-Chromosome microdeletions in Egyptian infertile males

The major genetic causes in male infertility are chromosomal abnormalities and Y chromosomal microdeletions (YCMs). YCMs occur in approximately 15% of azoospermic patients and 10% of severe oligospermic patients. These microdeletions lead to spermatogenic failure. This study aims to report the incidence of Azoospermia factor (AZF) microdeletions in Egyptian infertile males with severe oligoospermia & non obstructive azoospermia (NOA) using multiplex PCR. One hundred-fifty infertile males were included. Semen analysis, hormonal assay, karyotyping, testicular sperm extraction and testicular biopsy were performed.Y chromosome microdeletions were detected by using multiplex polymerase chain reaction (PCR). Among 150 infertile males; Considering Y chromosome; in severe oligospermic infertile males 3/36 (8.3%) had Y chromosome microdeletions in AZF subregions where; 1/3(33.3%) showed deletions in AZF-c and 2/3(66.7%) showed deletions in both AZF-b+c. However; no deletions were detected in AZF-a region in this group. In NOA group, 21/114(18.4%) had Y chromsome microdeletions in AZF subregions where; 1/21 (4.8%) showed deletions in AZF-b region, 2/21 (9.5%) showed deletion in both of AZF-a+b+c regions, 8/21 (38%) showed deletions in AZF-c region only and 10/21 (47.6%) showed deletions in both AZF-b+c regions. Conclusion: The frequency of Y chromosome microdeletions in our studied patients was similar to many ethnic reports. Detection of AZF microdeletions is necessary for proper genetic diagnosis in infertile males. AZFc can help informed decisions regarding positive testicular sperm extraction outcome.

Molecular and cytogenetic analysis of infertile Hakka men with azoospermia and severe oligozoospermia in southern China.

ObjectiveTo determine the prevalence of chromosome abnormalities and azoospermia factor (AZF) microdeletions in Hakka men with infertility in southern China.MethodsHakka male patients, who received clinical counselling for infertility between August 2016 and October 2017, and fertile male controls, were enrolled into this retrospective study. Patients diagnosed with infertility and controls underwent cytogenetic analysis by standard G-banding; AZF microdeletions were examined by multiplex polymerase chain reaction and capillary electrophoresis.ResultsOut of 918 male patients who received fertility counselling, 57 were diagnosed with infertility due to azoospermia or severe oligozoospermia. Of these infertile patients, 22.81% (13/57) carried chromosome abnormalities, with 47, XXY being the most common abnormal karyotype. In addition, 36.84% (21/57) presented with Y chromosome microdeletions, most frequently in the complete AZFc and partial AZFc region. Duplication of the AZFc region was found in three patients. No AZF microdeletions were found in 60 fertile male controls.ConclusionThe high AZF microdeletion frequency in the current Hakka population suggests that AZF microdeletion analysis is essential in fertility screening, and combined with cytogenetic analysis, may influence the choice of assisted reproductive techniques and reduce the risk of inherited genetic disease.

Incidence of Y chromosome microdeletions in patients with Klinefelter syndrome.

The aim of this study was to study the incidence of Y chromosome microdeletions in a Caucasian population of Klinefelter syndrome (KS) patients and to investigate the possible association between Y chromosome microdeletions and KS. We conducted a retrospective study on 118 KS patients, 429 patients with non-obstructive azoospermia (NOA), and 155 normozoospermic men. Eight of the 118 KS patients had undergone testicular sperm extraction (TESE). All patients underwent semen examination and Y chromosome microdeletions evaluated by PCR, using specific sequence tagged site (STS) primer sets, which spanned the azoospermia factor AZFa, AZFb, and AZFc regions of the Y chromosome. Semen analysis of the KS group revealed: 1 patient with oligozoospermia, 1 with severe oligoasthenoteratozoospermia, 2 with cryptozoospermia, and 114 with azoospermia. Eight of the 114 azoospermic KS patients underwent TESE, and spermatozoa were recovered from three of these, all of whom had non-mosaic karyotype 47, XXY. 10.7% of the NOA patients presented AZF microdeletions. In 429 cases with NOA, 8 cases had AZFa + b+c deletion, 6 cases had AZF b + c deletion, 4 cases had AZFa microdeletion, 8 cases had AZFb microdeletion, and 20 cases had AZFc microdeletion. Just one KS patient (0.8%) presented microdeletion in the AZFc region. The percentage of microdeletions in KS patients was lower than in NOA patients, suggesting that AZF microdeletions and KS do not have a causal relationship and that Y chromosome microdeletions are not a genetic factor linked to KS.

Detection of Partial AZFc Microdeletions in Azoospermic Infertile Men Is Not Informative of MicroTESE Outcome.

BackgroundMicrodeletions of the Yq chromosome are among the most frequent genetic etiological factor of male infertility which spans the azoospermia factor regions (AZFa, AZFb and AZFc). Microdeletions are mostly seen in the AZFc region and usually cover genes actively involved in spermatogenesis. Partial AZFc microdeletions may also occur with various spans, namely gr/gr, b2/b3 and b1/b3. It is known that the outcome of microtesticular sperm extraction (TESE), the surgical process for sperm retrieval from the testis in infertile azoospermic men, may be pre- dicted based on the type of AZF microdeletion. We therefore aimed to evaluate the correlation between partial AZFc microdeletions and microTESE results.Materials and MethodsIn this cross-sectional study, 200 infertile azoospermic men referred to the Royan Institute were examined for the presence of partial AZFc microdeletions before undergoing microTESE. Partial AZFc micro- deletions were detected by multiplex polymerase chain reaction (PCR) of seven different sequence-tagged site (STS) markers. The data were analyzed with the Chi-square test.ResultsAmong the 90 patients (45%) with a positive microTESE outcome, 9 (10%) showed a partial microdeletion in AZFc region. Of the 110 (55%) patients with a negative microTESE outcome, 7 (6.3%) had an AZFc partial micro- deletion. With respect to the span of the microdeletions, among the 200 patients, 11 (5.5%) were gr/gr and 5 (2.5%) were b2/b3. Statistical analysis showed no significant difference between the patients with and without partial AZFc microdeletions with respect to microTESE outcome.ConclusionPartial AZFc microdeletions is not a predictor of microTESE outcome in azoospermic men.

039 Y-chromosome abnormalities in men with sub-fertility. An analysis of the frequency of abnormalities and determination of a threshold sperm concentration for genetic analysis

Detection of microdeletions of the long arm of the Y chromosome (Yq) is common practice in men with azoospermia and severe oligozoospermia. Guidelines from the European Association of Urology recommend testing for Yq microdeletions in men with a semen concentration of <5 million/mL. We aim to describe the prevalence of Yq microdeletions in a multi-ethnic urban population in London, United Kingdom. We also aim to determine a threshold based on semen concentration (million/mL) for testing for Yq microdeletions. We performed a retrospective cohort study on 1473 men that underwent genetic evaluation between July 2004 and December 2016. Univariate logistic regression analyses were conducted with microdeletions vs no-microdeletions as the response variable. Semen concentration, combined testicular volume, FSH, LH and testosterone were all used as predictor variables. Microdeletions of the Y-chromosome were found in 4% of our population (n = 58). Microdeletion of the AZFc region occurred in 75% of these men followed by AZFb+c in 13.8%, followed by AZFb, then AZFa and partial AZFa. Semen count was a significant predictor of the presence of a microdeletion (p = 0.035). None of the men with an AZF microdeletion had a sperm count of greater than 0.5 million/mL. We propose a reduction in the current semen count threshold at which Yq microdeletions are tested. A threshold value of 0.5 million/mL (a 10-fold reduction compared to the current guidelines), would increase the specificity without adversely affecting the sensitivity (See table 1). The cost savings of this would be significant. The sperm retrieval rate (SSR) following microdissection testicular sperm extraction was 33.2%. This rate is lower than is described in the literature.

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.

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

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

Y chromosome microdeletions and varicocele as aetiological factors of male infertility: A cross-sectional study.

The pathogenic mechanisms by which varicocele disrupt spermatogenesis are not clearly understood. Over 30% of male infertility cases resulting from spermatogenic problems are associated with genetic abnormalities, and Y chromosome microdeletions are the second most frequent genetic cause. Here, we aimed to evaluate the frequency of Y chromosome microdeletion in infertile men with varicocele. A cross-sectional study comprising 51 infertile men with varicocele presenting spermatogenesis failures was performed. Y chromosome microdeletion research was made using polymerase chain reaction. Of the 51 men with infertility and varicocele, 35.3% (18/51) had nonobstructive azoospermia and 64.7% had severe oligozoospermia. Y chromosome microdeletion was found in two cases (3.9%): one patient had nonobstructive azoospermia and complete microdeletion of the AZFb and AZFc regions, and another patient had severe oligozoospermia and complete microdeletion of the AZFc region. Although in recent years, a genetic aetiology related to Y chromosome microdeletions has become a major cause of infertility in males with spermatogenesis failures, in this study, the varicocele was the clinical cause of seminal abnormalities that could lead to infertility, suggesting that both varicocele and Y chromosome microdeletion aetiologies can present, alone or combined, as factors of male infertility.