Partial AZFc Deletions Research Articles

Relationship between AZFc deletions and testicular histology in infertile South Chinese men with azoospermia and severe oligospermia.

BackgroundThe AZFc deletion has been associated with wide range of phenotypes including complete absence of germ cells in the testes (SCOS), reduction in germ cells hypospermatogenesis, and maturation arrest. The main objective of this study was to evaluate the relationship between AZFc microdeletions and testicular histology in South Chinese men with azoospermia or severe oligospermia.Findings338 men presenting with idiopathic non-obstructive azoospermia or severe oligospermia were evaluated between March 2012 and April 2015. Thirty-nine of the patients examined had an AZFc deletion (10.9 %). Testicular cytopathology was examined in 25 patients with an AZFc microdeletion and 14 with an AZFc deletion. There was no significant difference in the testicular histology of patients with partial or complete AZFc deletions (Mann–Whitney U = 152.500, p = 0.515). There was an association between testicular histology and gr/gr, b1/b3 or b2/b3 deletion (Fisher’s exact test, p = 0.013).ConclusionsMen with a gr/gr partial deletion were at higher risk of having hypospermatogenesis or maturation arrest. Men with a b1/b3 partial deletion were at higher risk of having maturation arrest. Men with a b2/b3 partial deletion were at higher risk of having maturation arrest or complete absence of germ cells in the testes.

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.

Y Chromosome Microdeletions and Partial AZFc Deletions in Infertile Men from South India

Aim: Yq microdeletions involving the azoospermia factor (AZF) region are the second most frequent genetic cause of spermatogenic failure next to Klinefelter syndrome. These deletions occur in about 10-15 percent of men with azoospermia and severe oligozoospermia. Molecular screening for AZF deletions has become mandatory in the work-up of infertile men. Further, partial AZFc deletions categorized as gr/gr, b2/b3, b1/b3 and b2/b4 deletions have also been known to affect spermatogenesis. This study aimed to screen for both classical AZF deletions in 250 karyotypically normal infertile men from south India and partial AZFc deletions as a case-control analysis involving 108 fertile men. Methods: PCR amplification involving two multiplex reactions was carried out using primers for six Original Research Article Suganya et al.; BJMMR, 13(12): 1-10, 2016; Article no.BJMMR.24208 2 STSs sY84, sY86 (AZFa), sY127, sY134 (AZFb), and sY254, sY255 (AZFc) with two internal controls (SRY, ZFY). Further, those men who showed deletions with one or both STSs sY1291 and sY1191 were subsequently tested with sY1189 and sY1192 to detect partial AZFc deletions. Results: One individual showed deletion of all the three AZF regions while two men had only AZFc deletion. Deletion of partial AZFb (sY127) was seen besides complete AZFc region in the fourth patient. The gr/gr, b2/b3 and b1/b3 deletions were detected in 24 (9.6%), one (0.4%) and nine (3.6%) infertile men in comparison with five, one and two fertile men respectively. The b2/b4 deletion was observed in a single azoospermic individual. Conclusion: Screening for AZF deletions would help in not only determining the cause for male infertility but also in its management and accurate genetic counselling.

Screening for AZFc partial deletions in Dravidian men with nonobstructive azoospermia and oligozoospermia.

Dravidians are the predominant population residing in South India with a diverse genetic structure. Considering various genetic discoveries taking place today, it is evident that deletions in the AZFc region are the most common cause of severe spermatogenic failure (SSF) in various populations studied. However, it is significant to note that there is a paucity of scientific literature on AZFc subdeletion screening among the Dravidian population. To investigate the prevalence and association of AZFc subdeletion patterns among Dravidian men with nonobstructive azoospermia (NOA) and oligozoospermia. A population of 354 subjects, including 120 patients with NOA, 109 with oligozoospermia, and 125 normal male controls, were screened using locus-specific sequence tag site markers. We found 21 (9.17%) patients with classical AZF deletion, while no deletions were observed in controls. After excluding the samples with AZF deletions, the remaining 208 infertile and 125 control samples were screened for partial AZFc deletions using a standardized multiplex polymerase chain reaction and on analysis revealed that 13 (6.25%) of the infertile samples possessed gr/gr subdeletions and 15 (7.21%) of the infertile samples possessed b2/b3 subdeletions. Six (4.8%) of the normal samples were found to carry gr/gr subdeletions and two (1.6%) had b2/b3 deletions. The b1/b3 deletion was not observed in any of the patient and control samples screened. Our finding shows that there is a strong association between b2/b3 subdeletion and SSF in the Dravidian population (odds ratio, 4.78; 95% confidence interval 1.07-21.26) (p=0.018). Further studies, including gene copy typing for DAZ and CDY genes and a comprehensive haplogrouping analysis, are recommended in a large and well-selected patient group to elude the genetic mechanism behind this association.

Investigation of AZF microdeletions in patients with Klinefelter syndrome.

We investigated azoospermia region microdeletions in male infertility patients with Klinefelter syndrome (KFS), as well as the association between azoospermia symptoms in patients with KFS and Y chromosome microdeletion polymorphisms. A total of 111 cases with male infertility confirmed to have KFS (47, XXY) and 94 fertile men were included in this study. Peripheral blood was drawn and DNA was extracted from these samples. Multiplex polymerase chain reaction was performed to screen the partial deletions of 25 sequence-tagged sites on the Y chromosome. In 111 cases with KFS, 1 case contained the AZFb+d+c deletion. The Gr/Gr deletion was identified in 12 KFS cases and 5 control cases. In addition, the b2/b3 deletion was identified in 13 KFS cases and 6 control cases. There were no significant differences in phenotype and genotype of the 2 partial AZFc deletions between patients and controls (P > 0.05). Our results suggest that patients with KFS may also have Y chromosome microdeletions to varying degrees and that the gr/gr deletion and b2/b3 deletion may not play a role in the susceptible genetic background of azoospermia in patients with KFS in the Sichuan population.

Greater prevalence of Y chromosome Q1a3a haplogroup in Y-microdeleted Chilean men: a case–control study

To determine the prevalence of South Amerindian Y chromosome in Chilean patients with spermatogenic failure and their association with classical and/or AZFc-partial Y chromosome deletions. We studied 400 men, 218 with secretory azo/oligozoospermia (cases) and 182 controls (116 fertile and/or normozoospermic, and 66 azoospermic with normal spermatogenesis). After a complete testicular characterization (physical evaluation, hormonal and/or biopsy) peripheral blood was drawn to obtain DNA for Y chromosome microdeletions, AZFc-partial deletions and biallelic analysis by allele specific polymerase chain reaction (PCR) of the M3 (rs3894) single nucleotide polymorphism (SNP). Classical AZF microdeletions were found in 23 cases (Y-microdeleted). AZFc-partial deletions were observed in 10 cases (6 "gr/gr", 3 "b2/b3" and 1 "b1/b3") and 4 controls (4 "gr/gr"). The AZFc-partial deletions were mainly associated with the absence of DAZ1/DAZ2 (64 %). No significant differences in the prevalence of AZFc-partial deletions were observed between cases and controls. We observed a significant higher proportion of the Q1a3a haplogroup in Y-microdeleted men compared to patients with spermatogenic failure without deletions and control men (P<0.01 and P<0.05, respectively by Bonferroni test). Among them, patients with AZFb deletions had an increased prevalence of the Q1a3a haplogroup compared to controls, cases without deletions and to those with complete or partial-AZFc deletions (P<0.01, Bonferroni test). The Q1a3a South Amerindian lineage seems to increase the susceptibility to non AZFc microdeletions. On the other hand, in Chilean population the AZFc-partial deletions ("gr/gr", "b1/b3" and/or "b2/b3") does not seem to predispose to severe spermatogenic impairment.

Analysis of partial AZFc deletions in Malaysian infertile male subjects

Complete deletions in the AZF (a, b, and c) sub-regions of the Y-chromosome have been shown to contribute to unexplained male infertility. However, the role of partial AZFc deletions in male infertility remains to be verified. Three types of partial AZFc deletions have been identified. They are gr/gr, b1/b3, and b2/b3 deletions. A recent meta-analysis showed that ethnic and geographical factors might contribute to the association of partial AZFc deletions with male infertility. This study analyzed the association of partial AZFc deletions in Malaysian infertile males. Fifty two oligozoospermic infertile males and 63 fertile controls were recruited to this study. Screening for partial AZFc deletions was done using the two sequence-tagged sites approach (SY1291 and SY1191) which were analyzed using both the conventional PCR gel-electrophoresis and the high resolution melt, HRM method. Gr/gr deletions were found in 11.53% of the cases and 9.52% of the controls (p = 0.725). A B2/b3 deletion was found in one of the cases (p = 0.269). No B1/b3 deletions were identified in this study. The results of HRM analysis were consistent with those obtained using the conventional PCR gel-electrophoresis method. The HRM analysis was highly repeatable (95% limit of agreement was -0.0879 to 0.0871 for SY1191 melting temperature readings). In conclusion, our study showed that partial AZFc deletions were not associated with male infertility in Malaysian subjects. HRM analysis was a reliable, repeatable, fast, cost-effective, and semi-automated method which can be used for screening of partial AZFc deletions.

Impaired spermatogenesis and GR/GR deletions related to Y chromosome haplogroups in Korean men

Microdeletion of the Azoospermia Factor (AZF) regions in Y chromosome is a well-known genetic cause of male infertility resulting from spermatogenetic impairment. However, the partial deletions of AZFc region related to spermatogenetic impairment are controversial. Therefore, this study was designed to characterize the partial AZFc deletion patterns and their clinical consequences in Korean population.

Impaired Spermatogenesis and gr/gr Deletions Related to Y Chromosome Haplogroups in Korean Men

Microdeletion of the Azoospermia Factor (AZF) regions in Y chromosome is a well-known genetic cause of male infertility resulting from spermatogenetic impairment. However, the partial deletions of AZFc region related to spermatogenetic impairment are controversial. In this study, we characterized partial deletion of AZFc region in Korean patients with spermatogenetic impairment and assessed whether the DAZ and CDY1 contributes to the phenotype in patients with gr/gr deletions. Total of 377 patients with azoo-/oligozoospermia and 217controls were analyzed using multiplex polymerase chain reaction (PCR), analysis of DAZ-CDY1 sequence family variants (SFVs), and quantitative fluorescent (QF)-PCR. Of the 377 men with impaired spermatogenesis, 59 cases (15.6%) had partial AZFc deletions, including 32 gr/gr (8.5%), 22 b2/b3 (5.8%), four b1/b3 (1.1%) and one b3/b4 (0.3%) deletion. In comparison, 14 of 217 normozoospermic controls (6.5%) had partial AZFc deletions, including five gr/gr (2.3%) and nine b2/b3 (4.1%) deletions. The frequency of gr/gr deletions was significantly higher in the azoo-/oligozoospermic group than in the normozoospermic control group (p = 0.003; OR = 3.933; 95% CI = 1.509–10.250). Concerning Y haplogroup, we observed no significant differences in the frequency of gr/gr deletions between the case and the control groups in the YAP+ lineages, while gr/gr deletion were significantly higher in azoo-/oligozoospermia than normozoospermia in the YAP− lineage (p = 0.004; OR = 6.341; 95% CI = 1.472–27.312). Our data suggested that gr/gr deletion is associated with impaired spermatogenesis in Koreans with YAP− lineage, regardless of the gr/gr subtypes.

Partial Microdeletions in the Y-Chromosome AZFc Region Are Not a Significant Risk Factor for Spermatogenic Impairment in Tunisian Infertile Men

Azoospermia factor (AZF) subdeletions were reported to be significant risk factors for spermatogenesis. In this study, we screened classical and partial microdeletions of the Y-chromosome AZF region in a group of 261 infertile men. Partial deletions were also screened in a control group of fertile men (n=124). In addition, Y haplogroups were analyzed in 24 gr/gr deleted patients. Among the 261 studied infertile men, seven subjects were found to have classical microdeletions. The most common partial deletion of AZFc (gr/gr) was observed in 13.02% of infertile men and in 12.90% of fertile men. The b1/b3 deletion was identified in 4.98% of infertile men and in 2.41% of fertile men. In addition, the b2/b3 deletion was identified in 1.53% of infertile patients but not in the control group. Our results suggest that partial AZFc deletions are not associated with spermatogenic failure in the Tunisian population.

Association of Spermatogenic Failure with the b2/b3 Partial AZFc Deletion

Infertility affects around 1 in 10 men and in most cases the cause is unknown. The Y chromosome plays an important role in spermatogenesis and specific deletions of this chromosome, the AZF deletions, are associated with spermatogenic failure. Recently partial AZF deletions have been described but their association with spermatogenic failure is unclear. Here we screened a total of 339 men with idiopathic spermatogenic failure, and 256 normozoospermic ancestry-matched men for chromosome microdeletions including AZFa, AZFb, AZFc, and the AZFc partial deletions (gr/gr, b1/b3 and b2/b3).AZFa and AZFc deletions were identified in men with severe spermatogenic failure at similar frequencies to those reported elsewhere. Gr/gr deletions were identified in case and control populations at 5.83% and 6.25% respectively suggesting that these deletions are not associated with spermatogenic failure. However, b2/b3 deletions were detected only in men with spermatogenic failure and not in the normospermic individuals. Combined with our previous data this shows an association of the b2/b3 deletion (p = 0.0318) with spermatogenic failure in some populations. We recommend screening for this deletion in men with unexplained spermatogenic failure.

High prevalence of GR/GR deletions in korean patients with oligozoospermia

To assess the association between partial AZFc deletions within the Azoospermia factor (AZF) c region and spermatogenetic impairment in Korean patients. Prospective study for partial AZFc deletions in Korean infertile men. The subjects selected comprise 46 men with normal spermatogenesis (> 20 X 106/ml) and 357 men with spermatogenic failure. The latter group included 232 patients with azoospermia (no spermatozoa in the ejaculates after centrifugation), 36 patients with cryptozoospermia (few sperm in the ejaculate that were only present after centrifugation, not during the initial evaluation), 53 patients with severe oligozoospermia (0.1 ≤ sperm count < 5 X 106/ml) and 36 patients with oligozoospermia (5 ≤ sperm count ≤ 20 X 106/ml). Partial AZFc deletion screening was performed with three plus/minus PCR assays (sY1191, sY1291, sY1206 and a control gene, SOHLH2). The absence of sY1191, sY1291, sY1191/sY1291, and sY1206 represents the b2/b3, gr/gr, b1/b3 and b3/b4 deletions, respectively. Totally, fifty eight out of 403 patients (14.4%) had subdeletions in AZFc region. Among the men with spermatogenic failure (n = 357), fifty four cases were partial AZFc deletions (15.1%); 31 of gr/gr (8.7%), 18 of b2/b3 (5.0%), 4 of b1/b3 (1.1%) and one of b3/b4 (0.3%) deletion. On the other hand, four out of 46 men with normal spermatogenesis (8.7%) showed partial AZFc deletions, including one gr/gr deletions (2.2%) and three b2/b3 deletions (6.5%). The frequency of gr/gr deletions was significantly higher in men with spermatogenic failure, especially patients with oligozoospermia (5/36, 13.9%), than in men with normal spermatogenesis (chi-square test, p = 0.04). Our data showed that a partial AZFc deletion, gr/gr deletion is associated with impaired spermatogenesis in Korean.

Associations of Y-chromosome subdeletion gr/gr with the prevalence of Y-chromosome haplogroups in infertile patients

Microdeletions in azoospermia factor (AZF) region on distal Yq are associated with male infertility and spermatogenic failure due to intra-chromosomal homologous recombination between large nearly identical repeat amplicons and are found in ∼10% of azoospermic and severe oligozoospermic cases. Although AZFc is deleted in azoospermia or oligozoospermia, no definitive conclusion has been drawn for the role of partial AZFc deletions to spermatogenic failure. Therefore, this study is planned to investigate the role of gr/gr subdeletions in individuals with spermatogenic failure and to find its relationship with Y chromosome haplogroups (HGs) in infertile men from Indian population. It is a case-control study involving 236 azoospermic, 182 oligospermic and 240 healthy normozoospermic men. We found 18 gr/gr, 11 b1/b3 and 2 b2/b3 subdeletions in azoospermic patients and 12 gr/gr, 5 b1/b3 and 4 b2/b3 subdeletions in oligospermic patients. However, we also found seven gr/gr deletions in normozoospermic men. Seven patients each with spermatogenic arrest and oligospermia who carry gr/gr subdeletions have deleted DAZ3/DAZ4 genes. A total of 11 patients with sertoli cell-only syndrome (SCOS) and 5 oligospermic patients with gr/gr subdeletions also have DAZ1/DAZ2 genes deleted indicating that deletions of DAZ genes contributed differently to damage to spermatogenic process. L1 HG is found in patients showing b1/b3 subdeletions, whereas HG H1a2 and H1b were found in normozoospermic individuals with gr/gr subdeletions. Our results provide evidence of association between the occurrence of subdeletions and male infertility as well as the severity of the spermatogenic failure.

Azoospermia factor and male infertility.

Recently, work has shown that azoospermia factor (AZF) microdeletions result from homologous recombination between almost identical blocks in this gene region. These microdeletions in the Y chromosome are a common molecular genetic cause of spermatogenetic failure leading to male infertility. After completion of the sequencing of the Y chromosome, the classical definition of AZFa, AZFb, and AZFc was modified to five regions, namely AZFa, P5/proximal-P1, P5/distal-P1, P4/distal-P1, and AZFc, as a result of the determination of Y chromosomal structure. Moreover, partial AZFc deletions have also been reported, resulting from recombination in their sub-ampliconic identical pair sequences. These deletions are also implicated in a possible association with Y chromosome haplogroups. In this review, we address Y chromosomal complexity and the modified categories of the AZF deletions. Recognition of the association of Y deletions with male infertility has implications for the diagnosis, treatment, and genetic counseling of infertile men, in particular candidates for intracytoplasmic sperm injection.

Y chromosome variations and male infertility

Male infertility is a common complex disease. Y-linked spermatogenic failure is an important cause for this disorder. Due to the presence of many repeat sequences and the frequent occurrence of non-allelic homologous recombination between the sequences in the male-specific region of the Y (MSY) region of the chromosome, Y chromosome possesses high variation rate. The variations may result in the dosage changes of spermatogenesis-related gene families and lead to male infertility. The present article reviews the recent progress of the study on Y chromosome variations, and its possible effect on spermatogenic function, in DNA level.

The AZFc region of the Y chromosome: at the crossroads between genetic diversity and male infertility

BACKGROUNDThe three azoospermia factor (AZF) regions of the Y chromosome represent genomic niches for spermatogenesis genes. Yet, the most distal region, AZFc, is a major generator of large-scale variation in the human genome. Determining to what extent this variability affects spermatogenesis is a highly contentious topic in human reproduction.METHODSIn this review, an extensive characterization of the molecular mechanisms responsible for AZFc genotypical variation is undertaken. Such data are complemented with the assessment of the clinical consequences for male fertility imputable to the different AZFc variants. For this, a critical re-evaluation of 23 association studies was performed in order to extract unifying conclusions by curtailing methodological heterogeneities.RESULTSIntrachromosomal homologous recombination mechanisms, either crossover or non-crossover based, are the main drivers for AZFc genetic diversity. In particular, rearrangements affecting gene dosage are the most likely to introduce phenotypical disruptions in the spermatogenic profile. In the specific cases of partial AZFc deletions, both the actual existence and the severity of the spermatogenic defect are dependent on the evolutionary background of the Y chromosome.CONCLUSIONSAZFc is one of the most genetically dynamic regions in the human genome. This property may serve as counter against the genetic degeneracy associated with the lack of a meiotic partner. However, such strategy comes at a price: some rearrangements represent a risk factor or a de-facto causative agent of spermatogenic disruption. Interestingly, this precarious balance is modulated, among other yet unknown factors, by the evolutionary history of the Y chromosome.

Phenotypic Expression of Partial AZFc Deletions Is Independent of the Variations in DAZL and BOULE in a Han Population

DAZ on the Y chromosome and 2 autosomal ancestral genes DAZL and BOULE are suggested to represent functional conservation in spermatogenesis. The partial AZFc deletion, a common mutation of the Y chromosome, always involves 2 DAZ copies and represents a different spermatogenic phenotype in the populations studied. To investigate whether the variations in DAZL and BOULE influence partial AZFc deletion phenotype, the genotyping of 15 loci variations, including 4 known mutations and 11 single-nucleotide polymorphisms (SNPs), was carried out in 157 azoo-/oligzoospermic men and 57 normozoospermic men, both groups with partial AZFc deletions. The frequencies of the alleles, genotypes, and haplotypes of the variations were compared between the 2 groups. As a result, for 9 exonic variations in DAZL and BOULE, only T12A was observed in both groups with similar frequency, and I71V was identified in an azoospermic man with b2/b3 deletion, whereas the rest were absent in the population. The distribution of DAZL haplotypes from 4 variations, including T12A, and of BOULE haplotypes from 2 SNPs was similar between men with normozoospermia and spermatogenic failure. Our findings indicate that the contribution of DAZL and BOULE variations to spermatogenic impairment in men with the DAZ defect is greatly limited, suggesting that expression of spermatogenic phenotypes of partial AZFc deletions is independent of the variations in DAZL and BOULE in the Han population.

The significance of Y chromosome microdeletion analysis in subfertile men with clinical variocele.

IntroductionThe aim of study is determining the cost-effectiveness of detection analysis in the presence of exceptional patients who have mild semen disorders, and beware of unnecessary varicocele repairs; and to ascertain whether patients with clinical varicocele should undergo Y chromosome (Yq) microdeletion analysis as a routine procedure.Material and methodsVaricocele with reflux was diagnosed in 51 male patients with subfertility symptoms upon physical examination (PE), confirmed by scrotal colour-Doppler ultrasound (CDU). After cytogenetic examination, Yq microdeletion analysis was performed on the peripheral blood samples using Promega Y Chromosome Deletion Detection System Version 2. Varicocele repair was performed under general anaesthesia with optical magnification (3-fold) through a subinguinal approach.ResultsThe mean age of the patients was 27.9. Values of semen concentration ranged from 0 to 72 million/ml, motility from 0 to 65% (A + B) and Kruger from 0% to 18%. The PE revealed normal size and consistency in the bilateral testicles. All patients were cytogenetically normal. However, Yq microdeletion was detected in 2 patients, 1 with mild oligoteratozoospermia and partial AZFb deletion (sY121) and the second patient with severe oligozoospermia and partial AZFc deletion (sY254 and sY255), and they were not subjected to varicocelectomy.ConclusionsThe routine performance of pre-operative Yq microdeletion analysis in patients with clinical varicocele does not seem to be cost-effective but the omission of patients with mild oligozoospermia would have subjected them to an unnecessary varicocelectomy and/or further ICSI applications and also would have caused the failure of referral for genetic counselling.

Genetic association between AZF region polymorphism and Klinefelter syndrome

Because of conflicting results about the association between azoospermic patients with Klinefelter syndrome (KFS) and azoospermia factor (AZF) polymorphism, and because nothing is known about the association of KFS with partial AZFc deletions, an association study was performed in Tunisian KFS patients. A total of 29 azoospermic patients and 13 fertile men were enrolled in this study. The classical microdeletions were found in six out of nine KFS patients (67%). Gr/Gr deletions and b2/b3 deletions are partial AZFc deletions. One KFS patient without classical microdeletions had a gr/gr deletion. This deletion (gr/gr) was observed in four out of 18 azoospermic patients without chromosomal abnormalities. In addition, two b2/b3 and one AZFc deletion were identified in this group. All KFS patients had elevated plasma FSH and LH concentrations, but normal plasma testosterone concentration. The testis biopsy of three samples with Y microdeletions revealed Sertoli cell-only syndrome. No Y microdeletions or partial AZFc deletions were found in the fertile group. It is concluded that in the patient population KFS patients may harbour Y microdeletions, and screening for these should be part of the diagnostic work-up, particularly in those considering assisted reproductive techniques. However, partial AZFc deletions might not play a role in predisposing genetic background for the phenotype of azoospermic KFS subjects.

Y chromosome gr/gr deletions are a risk factor for low semen quality

Subfertility affects one in eight couples. In up to 50% of cases, the male partner has low semen quality. Four Y chromosome deletions, i.e. Azoospermia factor a (AZFa), P5/proximal-P1 (AZFb), P5/distal-P1 and AZFc deletions, are established causes of low semen quality. Whether a recently identified partial AZFc deletion, the gr/gr deletion, also causes low semen quality is at present unclear. We used a dual approach to review the effect of the gr/gr deletion on semen quality. First, we conducted a systematic review and meta-analysis of previous association studies, to compare the prevalence of gr/gr deletions between azoo-/oligozoospermic men and normozoospermic men. Secondly, we studied a cohort of 1041 male partners of subfertile couples unselected for semen quality. We employed a cross-sectional design by screening all men for the gr/gr deletion and comparing the semen quality of men with and without the gr/gr deletion. Seven studies were included in the meta-analysis. The gr/gr deletion was significantly more prevalent among azoo-/oligozoospermic men than among normozoospermic men (OR 2.4, 95% CI 1.75-3.30). In our cohort, 25 men carried a gr/gr deletion. Men with this genotype had a lower sperm concentration (median 34 x 10(6)/ml versus 53 x 10(6)/ml, P = 0.017), total sperm count (median 108 x 10(6) versus 152 x 10(6), P = 0.006) and total motile sperm count (median 20 x 10(6) versus 50 x 10(6), P = 0.010) than men without the gr/gr deletion. Y chromosome gr/gr deletions significantly reduce sperm counts and are thus associated with low semen quality.