Genetic risk factors in infertile men with severe oligozoospermia and azoospermia

Özçelik

2010

J Assist Reprod Genet

Purpose To find the frequency and types of major chromosomal abnormalities with nonobstructive azoospermia and severe oligozoospermia to give appropriate genetic counseling before assisted reproduction techniques in Isparta (South of Turkey), and to investigate the general characteristics in this infertile male population. Methods and patients A total of 115 infertile males (92 were azoospermic, 23 severe oligospermic) were studied for the cytogenetic evaluation prior to use of assisted reproduction techniques. Also, 60 fertile males as a control group were studied. Karyotyping was performed on peripheral blood lymphocytes according to the standard methods. Levels of luteinising hormone, follicle-stimulating hormone (FSH), testosterone and prolactin were obtained and a testicular sonography examination was conducted. Results The total prevalence of chromosomal abnormalities was found to be 4.3% (5/115), including 4 patients with Klinefelter's Syndrome and 1 patient with gonadal dysygenesis (46XX). All of them were azoospermic males, corresponding to a frequency of 5.4% (5/92 patients). Oligozoospermic males and control males had no chromosomal abnormalities. There was a significant difference in serum FSH, LH, mean testicular volume and smoking when comparing patients (both azoospermic and oligozoospermic) and control groups (p<0.05). Also, there was a significant difference in serum FSH, LH and mean testicular volume when compared with azoospermic and oligozoospermic patients (p<0.05) Conclusions The occurrence of chromosomal abnormalities among infertile males strongly suggests the need for routine genetic testing and counseling prior to the employment of assisted reproduction techniques.

Section: Introductionmentioning

confidence: 99%

Cytogenetic abnormalities detected in patients with non-obstructive azoospermia and severe oligozoospermia

Özçelik

2010

J Assist Reprod Genet

European Urology Supplements

“…With no sperm found at multiple semen analyses, non-obstructive azoospermia (NOA) is the most severe form of infertility 1,5 . Despite genetic causes have been associated with male infertility 3,6,7 , genetic defects are found only in 17-20% of NOA individuals [7][8][9][10] . Except for a portion of patients with central endocrine disorders, the remaining 80% of NOA men having negative results on genetic testing are classified as idiopathic NOA (iNOA) 11 .…”

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confidence: 99%

Anti-Mullerian hormone-to-testosterone ratio is predictive of positive sperm retrieval in men with idiopathic non-obstructive azoospermia

Alfano¹,

Ventimiglia²,

Locatelli³

et al. 2018

The lack of clinically-reliable biomarkers makes impossible to predict sperm retrieval outcomes at testicular sperm extraction (TESE) in men with non-obstructive azoospermia (NOA), resulting in up to 50% of unnecessary surgical interventions. Clinical data, hormonal profile and histological classification of testis parenchyma from 47 white-Caucasian idiopathic NOA (iNOA) men submitted to microdissection TESE (microTESE) were analyzed. Logistic regression analyses tested potential clinical predictors of positive sperm retrieval. The predictive accuracy of all variables was evaluated using the receiver operating characteristic-derived area under the curve, and the clinical net benefit estimated by a decision-curve analysis (DCA). Overall, 23 (49%) and 24 (51%) patients were classified as positive and negative sperm retrievals at microTESE. While circulating hormones associated to a condition of primary hypogonadism did not predict sperm retrieval, levels of anti-Mullerian hormone (AMH) and the ratio AMH-to-total Testosterone (AMH/tT) achieved independent predictor status for sperm retrieval at microTESE, with a predictive accuracy of 93% and 95%. Using cutoff values of <4.62 ng/ml for AMH and <1.02 for AMH/tT, positive sperm retrieval was predicted in all individuals, with 19 men out of 47 potentially spared from surgery. DCA findings demonstrated clinical net benefit using AMH and AMH/tT for patient selection at microTESE.The relevance of male infertility has progressively grown in Western societies, with significant medical, psychological, and socio-economic implications. Seven out of 100 men are infertile, with up to 40% of infertile conditions still of unexplained or idiopathic origin [1][2][3] . Azoospermia affects about 1% among all men and 10-15% of infertile men 4,5 . With no sperm found at multiple semen analyses, non-obstructive azoospermia (NOA) is the most severe form of infertility 1,5 . Despite genetic causes have been associated with male infertility 3,6,7 , genetic defects are found only in 17-20% of NOA individuals [7][8][9][10] . Except for a portion of patients with central endocrine disorders, the remaining 80% of NOA men having negative results on genetic testing are classified as idiopathic NOA (iNOA) 11 .In patients with clinical evidence of NOA, testicular sperm extraction (TESE) is the technique of choice, which rationally has to be planned as a part of in vitro fertilization programs; in this context, microdissection TESE (microTESE) has been advocated as the gold-standard technique to improve sperm yield with minimal

“…A significant proportion of male infertility is accompanied by idiopathic azoospermia, most often presenting as non-obstructive azoospermia (NOA), which occurs in B1% of all adult men 3 . A few studies have reported that genetic factors including chromosome number defects, Y-chromosome microdeletions and autosomal mutations or polymorphisms in multiple biological pathways are involved in the development of NOA [4][5][6] .…”

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confidence: 99%

Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men

et al. 2014

Nat Commun

Male factor infertility affects one-sixth of couples worldwide, and non-obstructive azoospermia (NOA) is one of the most severe forms. Our previous genome-wide association study (GWAS) identified three susceptibility loci for NOA in Han Chinese men. Here we test promising associations in an extended three-stage validation using 3,608 NOA cases and 5,909 controls to identify additional risk loci. We find strong evidence of three NOA susceptibility loci (Po5.0 Â 10 À 8 ) at 6p21.32 (rs7194, P ¼ 3.76 Â 10 À 19 ), 10q25.3 (rs7099208, P ¼ 6.41 Â 10 À 14 ) and 6p12.2 (rs13206743, P ¼ 3.69 Â 10 À 8 ), as well as one locus approaching genome-wide significance at 1q42.13 (rs3000811, P ¼ 7.26 Â 10 À 8 ). In addition, we investigate the phenotypic effect of the related gene (gek, orthologous to CDC42BPA) at 1q42.13 on male fertility using a Drosophila model. These results advance our understanding of the genetic susceptibility to NOA and provide insights into its pathogenic mechanism.