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Artículos de revistas sobre el tema "Non-obstructive azoospermia"

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Publicado: 10 de marzo de 2023

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1

Schlegel, P. N. "Causes of azoospermia and their management". Reproduction, Fertility and Development 16, n.º 5 (2004): 561. http://dx.doi.org/10.1071/rd03087.

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Azoospermia may occur because of reproductive tract obstruction (obstructive azoospermia) or inadequate production of spermatozoa, such that spermatozoa do not appear in the ejaculate (non-obstructive azoospermia). Azoospermia is diagnosed based on the absence of spermatozoa after centrifugation of complete semen specimens using microscopic analysis. History and physical examination and hormonal analysis (FSH, testosterone) are undertaken to define the cause of azoospermia. Together, these factors provide a >90% prediction of the type of azoospermia (obstructive v. non-obstructive). Full definition of the type of azoospermia is provided based on diagnostic testicular biopsy. Obstructive azoospermia may be congenital (congenital absence of the vas deferens, idiopathic epididymal obstruction) or acquired (from infections, vasectomy, or other iatrogenic injuries to the male reproductive tract). Couples in whom the man has congenital reproductive tract obstruction should have cystic fibrosis (CF) gene mutation analysis for the female partner because of the high risk of the male being a CF carrier. Patients with acquired obstruction of the male reproductive tract may be treated using microsurgical reconstruction or transurethral resection of the ejaculatory ducts, depending on the level of obstruction. Alternatively, sperm retrieval with assisted reproduction may be used to effect pregnancies, with success rates of 25–65% reported by different centres. Non-obstructive azoospermia may be treated by defining the cause of low sperm production and initiating treatment. Genetic evaluation with Y-chromosome microdeletion analysis and karyotype testing provides prognostic information in these men. For men who have had any factors potentially affecting sperm production treated and remain azoospermic, sperm retrieval from the testis may be effective in 30–70% of cases. Once sperm are found, pregnancy rates of 20–50% may be obtained at different centres with in vitro fertilisation and intracytoplasmic sperm injection.
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2

Hooda, Ruchi, K. K. Gopinathan y Geeta Devi. "Fertility outcome after intracytoplasmic sperm injection with surgically retrieved sperm in obstructive and non-obstructive azoospermia". International Journal of Reproduction, Contraception, Obstetrics and Gynecology 11, n.º 10 (27 de septiembre de 2022): 2760. http://dx.doi.org/10.18203/2320-1770.ijrcog20222474.

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Background: Azoospermia is a highly upcoming subject in the last few decades. In the past, use of donor sperm was the only option providing a realistic chance of conception for couples affected by azoospermia. Introduction of sperm retrieval techniques and assisted reproductive technologies, especially intracytoplasmic sperm injection (ICSI), has provided these men a chance to father their genetically own child and changed the management approach significantly. The aim of this study was to compare the outcome of intracytoplasmic sperm injection (ICSI) of surgically retrieve sperms between couples with infertility due to male non-obstructive azoospermia (NOA) and obstructive azoospermia (OA).Methods: It was a retrospective observational study and data analysis was conducted at Centre for Infertility and Assisted Reproduction (CIMAR), Edappal, Kerala, India from January 2018 to December 2021. The selection of cases was based on detailed history, physical examination, husband’s semen analysis confirmed twice and hormone profile. During a period of four years, 754 azoospermic patients were diagnosed at our centre. In this study, female age <35 years considered as the inclusion criteria as female age plays a pivotal role for IVF/ICSI outcome, while patient in whom voluntary donor sperm used, patients in whom sperm retrieval failed, female age >35 years and female associated with any pathology which can alter the treatment outcome e.g., endometriosis, severe adenomyosis, diminished ovarian reserve, fibroid uterus were excluded from the study groups. On the basis of serum FSH, serum testosterone and testicular size and considering inclusion and exclusion criteria, patients were subdivided into two group as: group A (n=75) included patients with non-obstructive azoospermia and group B (n=75) included patients with obstructive azoospermia, underwent ICSI.Results: Clinical pregnancy rate, fertilization and implantation rate were found to be higher in OA cases in comparison to those of NOA cases. Grade A embryo formation rate and miscarriage rate showed no significant difference.Conclusions: As the cause of azoospermia is different in both the groups, the chances of achieving a successful outcome (fertilization rate, embryo formation rate, and clinical pregnancy rate) after ICSI are negatively affected by the type of azoospermia and are reduced in men with NOA in comparison to patients with OA.
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Chiba, Koji, Noritoshi Enatsu y Masato Fujisawa. "Management of non-obstructive azoospermia". Reproductive Medicine and Biology 15, n.º 3 (18 de enero de 2016): 165–73. http://dx.doi.org/10.1007/s12522-016-0234-z.

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4

Jin, Qi, Hong Pan, Binbin Wang, Jing Wang, Tao Liu, Xiaoying Yu, Chao Jia, Xiang Fang, Yifeng Peng y Xu Ma. "ThePGAM4gene in non-obstructive azoospermia". Systems Biology in Reproductive Medicine 59, n.º 4 (mayo de 2013): 179–83. http://dx.doi.org/10.3109/19396368.2013.783887.

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5

Cito, Gianmartin, Maria E. Coccia, Sara Dabizzi, Simone Morselli, Pier A. Della Camera, Andrea Cocci, Luciana Criscuoli et al. "Relevance of testicular histopathology on prediction of sperm retrieval rates in case of non-obstructive and obstructive azoospermia". Urologia Journal 85, n.º 2 (23 de marzo de 2018): 60–67. http://dx.doi.org/10.1177/0391560318758940.

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Introduction: The aim of our research was to establish the relevance of testicular histopathology on sperm retrieval after testicular sperm extraction in patients with non-obstructive azoospermia and in patients with obstructive azoospermia, who already underwent a previous failure testicular fine needle aspiration. Methods: We evaluated a total of 82 azoospermic men, underwent testicular sperm extraction, referring to the Assisted Reproductive Technology Centre of the University of Florence, Italy between January 2008 and March 2017. A general and genital physical examination, scrotal and trans-rectal ultrasound, semen analysis, hormone measurements, including follicle-stimulating hormone, luteinizing hormone and total testosterone, were collected. Results: Successful sperm retrieval was obtained in 36 men of total (43.9%). Successful sperm retrieval was 29.5% in non-obstructive azoospermia patients, while men with obstructive azoospermia, who, underwent a previous failure testicular fine needle aspiration, had sperm retrieval in 86% of cases. Mean luteinizing hormone was 6.55 IU/L, total testosterone 4.70 ng/mL, right testicular volume 13.7 mL and left testicular volume 13.6 mL. Mean Follicle-stimulating hormone was 13.45 IU/L in patients with negative sperm retrieval and 8.18 IU/L in men with successful sperm retrieval. According to histology, 20.7% had normal spermatogenesis, 35.3% hypospermatogenesis, 35.3% maturation arrest and 8.5% Sertoli cell-only syndrome. Successful sperm retrieval was 88.2% in patients with normal spermatogenesis, 24.1% in the maturation arrest group and 48.27% in patients with hypospermatogenesis, while negative sperm retrieval was reported in Sertoli cell-only syndrome patients. Seven cases with maturation arrest showed a successful sperm retrieval. Conclusion: Testicular histopathology after testicular sperm extraction offers important information on prediction of sperm retrieval and can guide the surgeon in choosing the more suitable therapeutic practice.
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6

Vorobets, M. Z., O. V. Melnyk, I. V. Kovalenko, R. V. Fafula, A. T. Borzhievsky y Z. D. Vorobets. "Сondition of urogenital tract microbiotes and pro- and antioxidant system in male azoospermia". Regulatory Mechanisms in Biosystems 12, n.º 4 (20 de octubre de 2021): 696–701. http://dx.doi.org/10.15421/022196.

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Over the past 20 years, there has been a clear trend to increase in the number of infertile men in Ukraine, their percentage reaches 50% in infertile couples. There is a significant percentage of male infertility caused by azoospermia – the lack of sperm in the ejaculate. In male infertility, azoospermia is found in 10–15% of patients, among other forms of pathospermia. Given the ambiguity of ideas about the etiology, pathogenesis and treatment and diagnostic approaches for various types of infertility, it remains important to clarify the relationship of urogenital infections with the regulatory systems of cells, including the state of the pro- and antioxidant system and the search for additional markers. 119 patients with various forms of azoospermia were examined. All patients underwent the following studies: spermogram, infectious screening, inhibin B, lipid peroxidation, activity of enzymes of the glutathione antioxidant system in sperm plasma and blood serum. Infectious screening included analysis of urethral secretions, bacteriological examination of sperm or prostate secretion, assessment of the species and quantitative composition of the microflora of the male urogenital tract. According to the results of spermogram and other diagnostic methods, a non-obstructive form of azoospermia was detected in 69 patients. In obstructive azoospermia, ejaculate as such was absent. It is suggested that inhibin B may be an important medical diagnostic test for azoospermia. As a result of the conducted researches the importance of determining the concentration of inhibin B as a marker of azoospermia was demonstrated and a negative correlation of moderate strength between the content of inhibin B and testosterone level in the plasma of men with non-obstructive azoospermia was revealed. It was found that Ureaplasma pervum and Ureaplasma urealyticum infect the male genitourinary system to the greatest extent among a number of microorganisms, both in non-obstructive and obstructive forms of azoospermia. Enterococcus faecalis is more pronounced in the sperm fluid in the non-obstructive form of azoospermia and prostate secreton in the obstructive form of azoospermia. In the non-obstructive form of azoospermia in the seminal plasma and serum, the processes of lipid peroxidation intensify, the concentration of reduced glutathione decreases and the activities of the enzymes of the glutathione antioxidant system (glutathione peroxidase and glutathione transferase) decrease. It can be considered that an important diagnostic test for the nonobstructive form of azoospermia is the ratio of reduced glutathione to oxidized glutathione in sperm plasma.
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7

Qi, Lin, Ya P. Liu, Nan N. Zhang y Ying C. Su. "Predictors of testicular sperm retrieval in patients with non-obstructive azoospermia: a review". Journal of International Medical Research 49, n.º 4 (abril de 2021): 030006052110027. http://dx.doi.org/10.1177/03000605211002703.

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Azoospermia is divided into two categories of obstructive azoospermia and non-obstructive azoospermia. Before 1995, couples with a male partner diagnosed with non-obstructive azoospermia had to choose sperm donation or adoption to have a child. Currently, testicular sperm aspiration or micro-dissection testicular sperm extraction combined with intracytoplasmic sperm injection allows patients with non-obstructive azoospermia to have biological offspring. The sperm retrieval rate is significantly higher in micro-dissection testicular sperm extraction compared with testicular sperm aspiration. Additionally, micro-dissection testicular sperm extraction has the advantages of minimal invasion, safety, limited disruption of testicular function, a low risk of postoperative intratesticular bleeding, and low serum testosterone concentrations. Failed micro-dissection testicular sperm extraction has significant emotional and financial implications on the involved couples. Testicular sperm aspiration and micro-dissection testicular sperm extraction have the possibility of failure. Therefore, predicting the sperm retrieval rate before surgery is important. This narrative review summarizes the existing data on testicular sperm aspiration and micro-dissection testicular sperm extraction to identify the possible factor(s) that can predict the presence of sperm to guide clinical practice. The predictors of surgical sperm retrieval in patients with non-obstructive azoospermia have been widely studied, but there is no consensus.
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Yarahmadi, Elham, Parnaz Borjian Boroujeni, Mehdi Totonchi y Hamid Gourabi. "Genotyping of the EIF1AY Gene in Iranian Patients with Non-Obstructive Azoospermia". Current Urology 13, n.º 1 (2019): 46–50. http://dx.doi.org/10.1159/000499295.

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Background: EIF1AY is one of the genes essential for normal spermatogenesis and is located in azoospermic factors region. Objective: The present study was designed to investigate the EIF1AY gene nucleotide variations, and correlate it with spermatogenic maturation arrest and azoospermia in Iranian population. Methods: A total number of 30 Iranian idiopathic non-obstructive azoospermic patients were selected as case group and 30 fertile men served as a control group who had at least 1 child. Nucleotide variation was analyzed in exon 3 and exon 5 in EIF1AY gene of both groups. DNA extraction from peripheral blood samples of selected individuals was done followed by amplification by PCR and sequencing with Sangar method. Results: Totally 3 single nucleotide variations were identified: one in the intronic region of exon 3, next one in non-coding transcript exon variant (rs13447352) and the third one in the exonic region of exon 5, all were registered in NCBI-Gene database. Conclusion: There was no statistically significant difference in the incidence of nucleotide variation between 2 study populations (p > 0.05). Further studies are required to specify the effects of Y: T20588295G variation on modification of protein structure, as well as the expression pattern of the gene and its association with azoospermia.
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9

Kumar, R. "Medical management of non-obstructive azoospermia". Clinics 68, S1 (5 de marzo de 2013): 75–79. http://dx.doi.org/10.6061/clinics/2013(sup01)08.

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10

Vij, Sarah C., Edmund Sabanegh y Ashok Agarwal. "Biological therapy for non-obstructive azoospermia". Expert Opinion on Biological Therapy 18, n.º 1 (19 de septiembre de 2017): 19–23. http://dx.doi.org/10.1080/14712598.2018.1380622.

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Ibrahim, Raditya, Cennikon Pakpahan y Pety Narulita. "Non-Obstructive Azoospermia with Hypergonadotropic Hypogonadism without a Significant Abnormalities in the Physical Examination". Indonesian Andrology and Biomedical Journal 3, n.º 1 (30 de junio de 2022): 18–21. http://dx.doi.org/10.20473/iabj.v3i1.35982.

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Background: Around 10 % of infertile men and 1 percent of all males have azoospermia. There are two types of azoospermia, which are obstructive and non-obstructive azoospermia. Non-obstructive azoospermia's main mechanism is because the testes fail to produce the sex hormone and induce spermatogenesis (primary testicular failure). Case: A patient is 28 years old and has a job as a car paint worker. He came with the chief complaint of infertility since two and a half years ago. He and his wife were having intercourse 3-4 times a week. Past medical history is unremarkable. His wife’s medical history is also unremarkable. Physical examination and ultrasound of the testes are normal. The semen analysis in this patient was azoospermia for 2 different times in the span of 2 weeks with no abnormalities in the accessory gland. Hormonal profiles results are testosterone level 2,32 ng/mL and FSH 15,03 mIU/mL, which indicatehypergonadotropic hypogonadism. The patient was suggested to evaluate further (complete hormonal profile, karyotyping analysis, and Y-Chromosome microdeletion) and educate about the possibility to conceive with assisted reproductive technology (ART). Discussion: Hypergonadotropic hypogonadism is a challenging case that needs a complete assessment such as complete hormonal profile, karyotyping analysis, Y-chromosome microdeletion analysis, and also, in this case, the paint thinner exposure in the workplace is needed to be considered. The chance of normal conception is very small, and the assisted reproductive procedure is necessary. Conclusion: Some abnormalities are usually present in the physical examination of azoospermia patients. This case convinces us of the importance of thorough history taking and other investigations. Managing this patient will be challenging, with the goal of the therapy is to achieve spermatogenesis to be able to use the spermatozoa available for ICSI.
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12

Yoshida, A., H. Onodera, K. Sakakibara, Y. Yamada y M. Tanaka. "Comparison of ART outcome between non-obstructive azoospermia and obstructive azoospermia: 15 years experiences". Fertility and Sterility 102, n.º 3 (septiembre de 2014): e68-e69. http://dx.doi.org/10.1016/j.fertnstert.2014.07.234.

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Hauptman, Dinko, Marta Himelreich Perić, Tihana Marić, Ana Katušić Bojanac, Nino Sinčić, Zoran Zimak, Željko Kaštelan y Davor Ježek. "Leydig Cells in Patients with Non-Obstructive Azoospermia: Do They Really Proliferate?" Life 11, n.º 11 (19 de noviembre de 2021): 1266. http://dx.doi.org/10.3390/life11111266.

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Background: Non-obstructive azoospermia (NOA) is a form of male infertility caused by disorders of the testicular parenchyma and impaired spermatogenesis. This study aimed to investigate the nature of Leydig cell changes in patients with NOA, especially whether their actual proliferation occurred. Methods: 48 testicular biopsies from infertile patients with NOA and 24 testicular biopsies originating from azoospermic patients suffering from obstructive azoospermia (OA) were included in the study. Leydig cells and their possible proliferative activity were analysed by immunohistochemistry and morphometry (stereology). Results: Unlike in the OA group, Leydig cells in NOA patients were sometimes organised into larger clusters and displayed an abundant cytoplasm/hypertrophy. Moreover, significant fibrosis of the interstitial compartment was demonstrated in some NOA samples, often accompanied by inflammatory cells. Stereological analysis showed no increase/proliferation of Leydig cells; on the contrary, these cells decreased in number in the NOA group. Conclusions: The decrease in the number of Leydig cells can be explained by previous inflammatory changes within the testicular interstitium and consequent interstitial fibrosis. The interstitial fibrosis might have a deteriorating effect on Leydig cells.
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Mansour, R. T., A. Kamal, I. Fahmy, N. Tawab, G. I. Serour y M. A. Aboulghar. "Intracytoplasmic sperm injection in obstructive and non-obstructive azoospermia". Human Reproduction 12, n.º 9 (1 de septiembre de 1997): 1974–79. http://dx.doi.org/10.1093/humrep/12.9.1974.

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Kutsenko, A. O. "The analysis of the efficiency of the program ІМSI at fertilization in vitro". HEALTH OF WOMAN, n.º 6(112) (29 de julio de 2016): 28–32. http://dx.doi.org/10.15574/hw.2016.112.28.

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The aim of the study: to analyze the results of the program ІМSI as one of the methods of VRT to ensure in vitro fertilization. Materials and methods. The basis of the study consisted of 100 couples with male factor infertility. Pair was examined and treated at the Institute of reproductive medicine (Kiev) in 2013-2015. The Diagnosis verified, assistance was provided in the framework of standard clinical protocols. The 51 men were diagnosed oligoasthenozoospermia, obstructive and non-obstructive azoospermia - in 28 and 21 men, respectively. Results. There were identified features according to the results of cycles. When native - biochemical pregnancy achieved almost equally often oligoasthenozoospermia and obstructive azoospermia (53.0±6.9% and 53.4±9.4%), whereas non-obstructive in two times less (28.6±9.8%). When critical the difference in results is not traced with obstructive and non-obstructive azoospermia and was 16% lower in cases of oligoasthenozoospermia. Biochemical pregnancies occurred in 63 of the 100 pairs (63.0±4.8%), with oligoasthenozoospermia and 37 of 51 (72.5 per cent), obstructive azoospermia – in 19 of 28 (67.8 per cent), non-obstructive – 7 of 21 (33.3 percent). After reproductive losses (5 of 63, 7.9% as) the end result was lower – 58.0±4.9 per cent. The number of births in total in the group with oligoasthenozoospermia was 35 of 51 (68.6%), obstructive and non-obstructive azoospermia - 17 of 28 (60.7 per cent) and 6 of 21 (28.6 per cent), respectively. Conclusion. The data motivate the need of finding opportunities to improve program performance ІМSI. Promising in this regard is the preparation of the pair to her conduct, which goes beyond the limits of the medical, carried out according to the protocols. An important point should be the identification and leveling of risk factors for general medicine and a social plan. Key words: male infertility, the program ІМSI, results.
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Gamidov, S. I., T. V. Shatylko, A. Kh Tambiev, N. G. Gasanov, A. Yu Popova y A. A. A. Alravashdeh. "Difficulties in differential diagnosis between obstructive and non-obstructive azoospermia". Urology Herald 10, n.º 2 (22 de junio de 2022): 19–31. http://dx.doi.org/10.21886/2308-6424-2022-10-2-19-31.

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Introduction. The difference between obstructive and non-obstructive azoospermia (OA and NOA) is important for the choice of treatment tactics and adequate counseling of a married couple.Objective. To describe, analyze, and classify possible challenges in differentiating between two types of azoospermiaMaterials and methods. The retrospective review of database on surgical sperm retrieval attempts performed our hospital (n = 754). A subpopulation of 216 patients who were preliminary diagnosed with OA, was selected for further analysis. All patients had testicular pathology data following sperm retrieval attempt. Rate of reclassification was assessed as a primary outcome. Reclassified cases were further analyzed to find a possible reason for incorrect differential diagnosis.Results. Among 216 patients with initially suspected OA, 131 (60.6%) had evidence of spermatogenic dysfunction on pathological examination of seminiferous tubules. Multivariate regression analysis showed that only regular exposure to high temperatures was an independent predictor of NOA detection in patients with normal endocrine and clinical parameters (OR = 1.989; 95% CI = 1.101 – 3.595). Analysis of the decision tree showed that patients with inhibin B levels below 93 pg/ml had the highest risk of an incorrect initial diagnosis (82.6%).Conclusions. Differential diagnosis of OA and NOA is not such a simple task. Any case of azoospermia against the background of normal semen volume by default should be considered as a case of NOA if there is no anamnestic or clinical data clearly indicating obstruction. Regular exposure to high temperature is likely to cause azoospermia in men with initially severe disorders of spermatogenesis. Finally, the reference values of inhibin B offered by most laboratories are not intended to assess reproductive function.
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Özer, Cevahir, Mehmet Reşit Gören, Ümit Gül, Tahsin Turunç y Sezgin Güvel. "Varicocelectomy in Patients with Non-obstructive Azoospermia". Journal of Urological Surgery 6, n.º 4 (1 de diciembre de 2019): 320–24. http://dx.doi.org/10.4274/jus.galenos.2019.2737.

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Salama, Nader y Saeed Blgozah. "Serum estradiol levels in infertile men with non-obstructive azoospermia". Therapeutic Advances in Reproductive Health 14 (enero de 2020): 263349412092834. http://dx.doi.org/10.1177/2633494120928342.

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Purpose: To report the different patterns of estradiol levels in infertile men with non-obstructive azoospermia and correlate these levels with their clinical and laboratory findings. Materials and methods: A retrospective study was launched, and a retrieval of data for infertile men with non-obstructive azoospermia ( n = 166) and fertile controls ( n = 40) was performed. The retrieved data included demographics, clinical findings, scrotal duplex, semen analysis, and hormonal assay (testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, and estradiol). Results: Our findings showed a wide spectrum of estradiol concentrations. The patients were arranged into three groups (high, normal, and low estradiol groups). The normal estradiol group was the most prevalent (71.1%). Testosterone, gonadotrophins, testicular volumes, and the number of patients with jobs in polluted workplaces showed significant differences among the study groups ( p = 0.001, <0.001, <0.001, and 0.004, respectively). Age, body mass index, varicocele prevalence, prolactin, and smoking habits did not show any significant differences among the groups. Obesity was lacking in the low estradiol group, but it had significantly higher prevalence in the normal ( p = 0.013) or high group ( p = 0.023) compared with the controls. Conclusion: Serum estradiol, in infertile men with non-obstructive azoospermia, may be present at different levels. It is recommended that estradiol be measured in infertile men with non-obstructive azoospermia when there is an alteration in testosterone concentration, obesity, a polluted workplace occupation, or before trying hormonal therapy. Extended studies are highly recommended to provide a clear clue whether alterations in estradiol concentrations in men with non-obstructive azoospermia are the cause or a consequence of the condition.
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Marialva Rodrigues, C., N. Ramos, V. Metrogos, J. P. Rosa, P. Ferreira, P. Sá E Melo y P. M. Simoes De Oliveira. "ICSI outcomes in patients with obstructive and non-obstructive azoospermia". European Urology Supplements 16, n.º 13 (diciembre de 2017): e2985-e2986. http://dx.doi.org/10.1016/s1569-9056(17)32121-8.

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Cioppi, Francesca, Viktoria Rosta y Csilla Krausz. "Genetics of Azoospermia". International Journal of Molecular Sciences 22, n.º 6 (23 de marzo de 2021): 3264. http://dx.doi.org/10.3390/ijms22063264.

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Azoospermia affects 1% of men, and it can be due to: (i) hypothalamic-pituitary dysfunction, (ii) primary quantitative spermatogenic disturbances, (iii) urogenital duct obstruction. Known genetic factors contribute to all these categories, and genetic testing is part of the routine diagnostic workup of azoospermic men. The diagnostic yield of genetic tests in azoospermia is different in the different etiological categories, with the highest in Congenital Bilateral Absence of Vas Deferens (90%) and the lowest in Non-Obstructive Azoospermia (NOA) due to primary testicular failure (~30%). Whole-Exome Sequencing allowed the discovery of an increasing number of monogenic defects of NOA with a current list of 38 candidate genes. These genes are of potential clinical relevance for future gene panel-based screening. We classified these genes according to the associated-testicular histology underlying the NOA phenotype. The validation and the discovery of novel NOA genes will radically improve patient management. Interestingly, approximately 37% of candidate genes are shared in human male and female gonadal failure, implying that genetic counselling should be extended also to female family members of NOA patients.
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Shatylko, T. V., S. I. Gamidov, N. P. Naumov, A. Al’ravashdekh, A. Y. Popova y R. I. Safiullin. "Imaging methods for seminal tract obstruction". Andrology and Genital Surgery 23, n.º 1 (17 de marzo de 2022): 13–20. http://dx.doi.org/10.17650/1726-9784-2022-23-1-13-20.

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Differential diagnosis between obstructive and non-obstructive azoospermia is an important task in clinical management of infertile patients. Chances of extracting sperm in obstructive azoospermia are high enough to inform the couple about favorable outcome of assisted reproductive technologies without resorting to donor sperm. Some forms of seminal tract obstruction can be corrected by microsurgical interventions or endoscopic resection of the ejaculatory ducts. Therefore, one of the objectives standing before imaging methods in reproductive andrology is the detection of these cases. In this literature review we present a detailed analysis of how to suspect and diagnose this form of azoospermia using imaging.
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Elia, Jlenia, Rossella Mazzilli, Michele Delfino, Maria Piane, Cristina Bozzao, Vincenzo Spinosa, Luciana Chessa y Fernando Mazzilli. "Impact of Cystic Fibrosis Transmembrane Regulator (CFTR) gene mutations on male infertility". Archivio Italiano di Urologia e Andrologia 86, n.º 3 (30 de septiembre de 2014): 171. http://dx.doi.org/10.4081/aiua.2014.3.171.

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Objective. The aim of this study was to evaluate the prevalence of most common mutations and intron 8 5T (IVS8-5T) polymorphism of CFTR gene in Italian: a) azoospermic males; b) non azoospermic subjects, male partners of infertile couples enrolled in assisted reproductive technology (ART) programs. Material and methods. We studied 242 subjects attending our Andrology Unit (44 azoospermic subjects and 198 non azoospermic subjects, male partners of infertile couples enrolled in ART programs). Semen analysis, molecular analysis for CFTR gene mutations and genomic variant of IVS8-5T polymorphic tract, karyotype and chromosome Y microdeletions, hormonal profile (LH, FSH, Testosterone) and seminal biochemical markers (fructose, citric acid and L-carnitine) were carried out. Results. The prevalence of the common CFTR mutations and/or the IVS8-5T polymorphism was 12.9% (4/31 cases) in secretory azoospermia, while in obstructive azoospermia was 84.6% (11/13 cases; in these, the most frequent mutations were the F508del, R117H and W1282X). Regarding the non azoospermic subjects, the prevalence of the CFTR and/or the IVS8-5T polymorphism was 11.1% (11/99 cases) in severe dyspermia, 8.1% (6/74 cases) in moderate dyspermia and finally 4.0% (1/25 cases) in normospermic subjects. Conclusions. This study confirms the highly significant prevalence of CFTR mutations in males with bilateral absence of the vas deferens or ejaculatory ducts obstruction compared with subjects with secretory azoospermia. Moreover, the significant prevalence of mutations in severely dyspermic subjects may suggest the possible involvement of CFTR even in the spermatogenic process. This could explain the unsatisfactory recovery of sperm from testicular fine needle aspiration in patients affected by genital tract blockage.
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23

Liu, B., S. Su, P. Wang, X. Niu, X. Yang, W. Zhang, Z. Wang y X. Wang. "The value of epididymal protease inhibitor in differential diagnosis between obstructive azoospermia and non-obstructive azoospermia". Andrologia 43, n.º 5 (23 de septiembre de 2011): 346–52. http://dx.doi.org/10.1111/j.1439-0272.2011.01085.x.

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24

Huang, I.-Shen, William J. Huang y Alex T. Lin. "Distinguishing non-obstructive azoospermia from obstructive azoospermia in Taiwanese patients by hormone profile and testis size". Journal of the Chinese Medical Association 81, n.º 6 (junio de 2018): 531–35. http://dx.doi.org/10.1016/j.jcma.2017.09.009.

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25

Popova, A. Yu, S. I. Gamidov, R. I. Ovchinnikov, N. P. Naumov y N. G. Gasanov. "Varicocele and non-obstructive azoospermia – where to start?" Andrology and Genital Surgery 18, n.º 4 (1 de enero de 2017): 77–80. http://dx.doi.org/10.17650/2070-9781-2017-18-4-77-80.

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26

Ishikawa, Tomomoto. "Surgical recovery of sperm in non-obstructive azoospermia". Asian Journal of Andrology 14, n.º 1 (28 de noviembre de 2011): 109–15. http://dx.doi.org/10.1038/aja.2011.61.

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27

Boitrelle, F., M. Bendayan y G. Robin. "Predicting sperm extraction in non-obstructive azoospermia patients". Human Reproduction 35, n.º 12 (9 de noviembre de 2020): 2871–72. http://dx.doi.org/10.1093/humrep/deaa258.

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28

Elzanaty, Saad. "Non-obstructive azoospermia and clinical varicocele: therapeutic options". International Urology and Nephrology 45, n.º 3 (20 de abril de 2013): 669–74. http://dx.doi.org/10.1007/s11255-013-0443-x.

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29

Hartaningsih, Ni Made Dian, I. Putu Yuda Prabawa, Benediktus Bosman Ariesta Gusti Putu, Dwijo Anargha Sindhughosa, Ida Bagus Amertha Putra Manuaba y I. Gusti Ngurah Pramesemara. "Potensi terapi kombinasi Liver Growth Factor (LGF) dan Adrenomedullin (ADM) sebagai harapan baru penatalaksanaan Azoospermia Non-Obstruktif (ANO): tinjauan pustaka". Intisari Sains Medis 13, n.º 1 (18 de abril de 2022): 202–9. http://dx.doi.org/10.15562/ism.v13i1.1363.

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Non-Obstructive Azoospermia (NOA) is caused by the failure of spermatogenesis process. This case becomes the highest prevalence, 95% of the total azoospermia. Therapeutic modalities in use today such as invasive techniques, hormonal therapy, and gene therapy are less effective in the treatment of azoospermia. In addition, the overall therapeutic modalities also have serious side effects such as infection, testicular atrophy, nerve damage and other side effects. Referring to the problems above, non-obstructive azoospermia is an urgent health issue and requires effective and efficient management with minimal side effects, as the combination of Liver Growth Factor (LGF) and Adrenomedullin (ADM). LGF is able to regenerate spermatogenesis after spermatogonia testicular stem cell damage. LGF also works specifically by stimulating germinal cells without changes in somatic cells. The motility of reactivation could be improved by combining the ADM into therapy, which bind to specific receptors, and the result of increasing the cAMP / PKA and NO that are important in the regulation of cilia’s movement. Combination LGF and ADM are potential to create new therapeutic candidates in the management of non-obstructive azoospermia, which can be immediately implemented as effective and efficient therapy. Azoospermia Non-Obstruktif (ANO) adalah azoospermia yang disebabkan kegagalan proses spermatogenesis dan merupakan kasus dengan prevalensi tertinggi (95% dari total azoospermia). Modalitas terapi yang digunakan sampai saat ini seperti teknik invasif, terapi hormonal, dan terapi gen terbukti belum efektif dalam tatalaksana azoospermia. Selain itu, keseluruhan modalitas terapi ini juga memiliki efek samping serius yang perlu diwaspadai seperti infeksi, testis atropi, kerusakan saraf, serta efek samping lainnya. Merujuk pada permasalahan diatas, azoospermia non-obstruktif merupakan masalah kesehatan yang mendesak dan membutuhkan tatalaksana yang efektif dan efisien dengan efek samping yang minimal seperti dengan kombinasi terapi LGF dan ADM. LGF mampu meregenerasi testis dan mereaktivasi spermatogenesis setelah kerusakan sel punca spermatogonia. LGF juga bekerja secara spesifik dengan menstimulasi sel-sel germinal tanpa menyebabkan perubahan pada sel-sel somatis. Motilitas sperma hasil reaktivasi spermatogenesis kemudian ditingkatkan dengan mengkombinasikan ADM kedalam terapi dimana berikatan pada reseptor-reseptor spesifik sehingga berefek pada peningkatan cAMP/PKA dan NO yang penting dalam pengaturan kibasan flagella. Perpaduan antara terapi LGF dan ADM ini sangat berpotensi menciptakan kandidat terapi baru dalam penatalaksanaan NOA yang efektif dan efisien.
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30

S. Ambulkar, Prafulla y Sunil S. Pande. "Study of Y-Chromosome Microdeletions in Azoospermic Infertile Males using Multiplex PCR Analysis". Biosciences, Biotechnology Research Asia 15, n.º 2 (27 de junio de 2018): 351–57. http://dx.doi.org/10.13005/bbra/2639.

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The infertility affects about 15% of couples and male factors being responsible about 40-50%. In male infertility, genetic abnormalities of Y chromosome play crucial role in spermatogenesis defect. Y chromosome q arm having Azoospermia factor region (AZFa, AZFb, and AZFc) are most important for spermatogenesis. Here, we investigated the frequencies of Y-chromosome microdeletions using three sets of multiplex PCR in idiopathic cases of azoospermia. We studied a total of 110 infertile male with non-obstructive azoospermia subjects & 50 fertile control subjects. All DNA samples were used for Y chromosome microdeletions analysis by using 11 STS markers in three different multiplex PCR of AZF regions. Out of 110 infertile azoospermic males, 14 (12.72%) infertile males showed partial deletion of AZF regions using three sets of multiplex PCR group. In the AZF microdeletions of infertile males, individually AZFc region was the most deletions sites (10%) followed by AZFb (6.36%) and AZFa (1.81%). The sites and sizes of microdeletions differ in all infertile azoospermic males who showed at least two or more STS markers microdeletions. The frequency of Y chromosome microdeletions in our azoospermic infertile males is 12.72%. We conclude that Y chromosome microdeletions frequency in azoospermic infertile males is higher than other infertile group due to severe impairment in spermatogenesis. Multiplex PCR screening of microdeletions is very useful and time saving technique when used more number of STS markers. It will be great help to infertility clinics for genetic counseling and assisted reproduction.
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31

S. Vishwekar, Pallavi, Nikita Lad, Mamta Shivtare y Pradnya Shetty. "ICSI outcome in surgically retrieved sperm compared with ejaculated sperm control". International Journal of Reproduction, Contraception, Obstetrics and Gynecology 8, n.º 3 (26 de febrero de 2019): 869. http://dx.doi.org/10.18203/2320-1770.ijrcog20190847.

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Background: Globally, the prevalence of infertility is around 10% of the total population. 30% of these have male factor infertility. Azoospermia is found in 1% of men, in 20% of which, the etiology is a bilateral obstruction of the male genital tract while others have non obstructive azoospermia. In azoospermic men sperms are microsurgically retrieved from epididymis and testes by TESA and PESA respectively. The aim of this study was to evaluate the outcomes of intracytoplasmic sperm injection ICSI using surgically retrieved sperm of azoospermic men either obstructive or nonobstructive and to compare it with ejaculated sperms in men having severe oligospermia.Methods: This was retrospective cohort study conducted based on the data collected from our reproductive endocrinology and infertility unit, 126 ICSI cycles performed during the period of 5 years were taken and divided into two groups, one with patients having ejaculated sperms with oligospermia and other group with patients who had surgically retrieved normal sperms due to azoospermia. Outcome of these ICSI cycles included fertilization, cleavage, biochemical and clinical pregnancy was assessed.Results: In present study it was found that ICSI outcome was comparable in both the groups with ejaculated sperm and surgically retrieved sperm as fertilization rate (72% vs 65%), Implantation Rate (58 vs 51%), clinical pregnancy rate (CPR) (51% vs 44.82%) observed with ejaculated or retrieved sperm group respectively showed no statistical difference.Conclusions: Present study shows that minimally invasive techniques of PESA and TESA can be successfully performed to retrieve sperm for ICSI in the treatment of azoospermic men which gives them the chance to father their biological child. The result of this study indicates that treatment outcomes of PESA/TESA-ICSI cycles compare favourably with that of ICSI using ejaculated sperm.
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32

Ma, Meng, Shi Yang, Zhenzhen Zhang, Peng Li, Yuehua Gong, Linhong Liu, Yong Zhu et al. "Sertoli cells from non-obstructive azoospermia and obstructive azoospermia patients show distinct morphology, Raman spectrum and biochemical phenotype". Human Reproduction 28, n.º 7 (15 de marzo de 2013): 1863–73. http://dx.doi.org/10.1093/humrep/det068.

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Panasovskii, M. L. "Hormonal Status and Sperm Parameters in Patients with Microsurgery for Non-Obstructive Azoospermia". Ukraïnsʹkij žurnal medicini, bìologìï ta sportu 5, n.º 5 (1 de noviembre de 2020): 180–84. http://dx.doi.org/10.26693/jmbs05.05.180.

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Azoospermia occurs in approximately 10% of men with infertility and can occur due to obstruction of the reproductive tract (obstructive azoospermia) or lack of sperm production. Assessing the hormonal status of men can provide prognostic information on the effectiveness of surgical sperm removal for their further use in assisted reproductive technology programs. Before performing a testicular biopsy to establish a histological diagnosis and search for sperm in patients with non-obstructive azoospermia, it is advisable to assess the chances of obtaining sperm. The purpose of the study was to assess hormonal levels and sperm parameters during microsurgery in men with non-obstructive azoospermia. Material and methods. We analyzed the medical records of 45 men with non-obstructive azoospermia who underwent micro-TESE in the period from 2016 to 2019. We noted the data on the age of patients, their hormonal profile (level of follicle-stimulating hormone, luteinizing hormone and testosterone) were analyzed and morphofunctional characteristics of the obtained spermatozoa. Results and discussion. In our study, testosterone levels were significantly higher in patients in group 1, which may be due to the fact that men in this group were significantly younger. Sperm were removed from 10 (22%) patients with non-obstructive azoospermia. The probability of sperm removal decreased with increasing age of patients. The average concentration of sperm in the samples was (2.3±0.8) million, of which active (18.0±0.3)%. Morphological analysis of sperm revealed that the frequency of abnormalities of the head was 19.9±2.45, neck – 13.69±1.49, tail – (5.96±1.52)%. Mixed pathology, which involved defects of the head, neck and middle part were at the level of (34.6±4.21)%. The frequency of sperm neck abnormalities was (13.7±1.5)%. The most numerous were abnormalities associated with the presence of cytoplasmic residues on the surface of the sperm. The number of sperm with tail pathology was at the level of (5.9±1.5)%. In general, the mixed pathology, in which defects of the head, neck and middle part were involved, was at the level of (34.6±4.2)%. Conclusion. In this study, the frequency of positive micro-TESE, i.e. surgical procedures after which sperm were removed, was 22.2%. Morphological analysis of the drugs revealed that among the identified pathologies, most of them were sperm with the presence of one large or several small vacuoles. The number of vacuoles, their size and shape reflect defects at the level of compaction of the sperm nucleus. It has been shown that embryos formed after fertilization of oocytes with such sperm do not undergo reproductive selection and can stop in the early stages of development
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34

Abuzeid, M. I., M. A. Sasy y H. H. Salem. "Intracytoplasmic sperm injection for treatment of non-obstructive azoospermia". Gynecological Endocrinology 11, n.º 5 (enero de 1997): 335–39. http://dx.doi.org/10.3109/09513599709152558.

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35

Glina, S. y M. Vieira. "Prognostic factors for sperm retrieval in non-obstructive azoospermia". Clinics 68, S1 (5 de marzo de 2013): 121–24. http://dx.doi.org/10.6061/clinics/2013(sup01)13.

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36

Akhvlediani, N. D. Akhvlediani, I. A. Reva Reva, A. S. Chernushenko Chernushenko y D. Yu Pushkar Pushkar. "Sperm retrieval techniques in patients with non-obstructive azoospermia". Urologiia 4_2021 (3 de septiembre de 2021): 106–13. http://dx.doi.org/10.18565/urology.2021.4.106-113.

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37

Alkandari, Mohammad H. y Armand Zini. "Medical management of non-obstructive azoospermia: A systematic review". Arab Journal of Urology 19, n.º 3 (3 de julio de 2021): 215–20. http://dx.doi.org/10.1080/2090598x.2021.1956233.

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38

Jensen, Stephanie y Edmund Y. Ko. "Varicocele treatment in non-obstructive azoospermia: a systematic review". Arab Journal of Urology 19, n.º 3 (3 de julio de 2021): 221–26. http://dx.doi.org/10.1080/2090598x.2021.1956838.

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39

El-Haggar, S., T. Mostafa, T. Abdel Nasser, R. Hany y A. Abdel Hadi. "Fine needle aspiration vs. mTESE in non-obstructive azoospermia". International Journal of Andrology 31, n.º 6 (diciembre de 2008): 595–601. http://dx.doi.org/10.1111/j.1365-2605.2007.00814.x.

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40

Sofikitis, Nikolaos, Themis Mantzavinos, Dimitrios Loutradis, Yasuhisa Yamamoto, Vasilios Tarlatzis y Ikou Miyagawa. "Ooplasmic injections of secondary spermatocytes for non-obstructive azoospermia". Lancet 351, n.º 9110 (abril de 1998): 1177–78. http://dx.doi.org/10.1016/s0140-6736(05)79121-2.

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41

Lian, Jie, Xiansheng Zhang, Hui Tian, Ning Liang, Yong Wang, Chaozhao Liang, Xin Li y Fei Sun. "Altered microRNA expression in patients with non-obstructive azoospermia". Reproductive Biology and Endocrinology 7, n.º 1 (2009): 13. http://dx.doi.org/10.1186/1477-7827-7-13.

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42

Schlegel, Peter N., Cigdem Tanrikut y Philip S. Li. "V1534: Microdissection Testicular Sperm Extraction in Non-obstructive Azoospermia". Journal of Urology 177, n.º 4S (abril de 2007): 507. http://dx.doi.org/10.1016/s0022-5347(18)32196-7.

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43

Pook, C., N. Karunanithy, M. Shabbir y T. Yap. "Should clinical varicoceles in non-obstructive azoospermia be treated?" European Urology Open Science 19 (julio de 2020): e547. http://dx.doi.org/10.1016/s2666-1683(20)32931-1.

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44

Hibi, Hatsuki, Tomohiro Taki, Yoshiaki Yamada, Nobuaki Honda, Hidetoshi Fukatsu, Masanori Yamamoto y Yoshimasa Asada. "Testicular sperm extraction using microdissection for non-obstructive azoospermia". Reproductive Medicine and Biology 1, n.º 1 (marzo de 2002): 31–34. http://dx.doi.org/10.1046/j.1445-5781.2002.00006.x.

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45

Topping, Daniel, Petrice Brown, LuAnn Judis, Stuart Schwartz, Allen Seftel, Anthony Thomas y Terry Hassold. "Synaptic defects at meiosis I and non-obstructive azoospermia". Human Reproduction 21, n.º 12 (22 de julio de 2006): 3171–77. http://dx.doi.org/10.1093/humrep/del281.

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46

Atia, T., M. Abbas y A.-F. Ahmed. "Azoospermia factor microdeletion in infertile men with idiopathic severe oligozoospermia or non-obstructive azoospermia". African Journal of Urology 21, n.º 4 (diciembre de 2015): 246–53. http://dx.doi.org/10.1016/j.afju.2015.02.004.

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47

SOLE, Sally, Elissa WILLATS, Mark GREEN, Luk ROMBAUTS, Darren KATZ, Deirdre ZANDER-FOX y Fabrizzio HORTA. "Is There an Increased Incidence of Aneuploid Embryos in Cases of Obstructive and Non-Obstructive Azoospermia?" Fertility & Reproduction 04, n.º 03n04 (septiembre de 2022): 210. http://dx.doi.org/10.1142/s2661318222741212.

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Background: Current evidence supports that males with low spermatozoa concentrations, as well as obstructive azoospermia (OA) or non-obstructive azoospermia (NOA), present with high rates of aneuploid spermatozoa. This issue could potentially lead to an increased number of aneuploid embryos in subsequent ICSI cycles using surgically retrieved spermatozoa, however, azoospermia is not routinely considered to be a clinical indication for pre-implantation genetic testing for aneuploidies (PGT-A). Aim: To identify the incidence of aneuploid embryos in PGT-A cycles that used testicular spermatozoa extracted through surgical sperm retrieval (SSR). In addition, whether aneuploidy rates differed between embryos fertilised with SSR compared with ejaculated spermatozoa. Method: A retrospective study of OA and NOA patients who underwent SSR between March 2017 and September 2020 and had PGT-A cycles. Next-generation sequencing was employed to detect embryo aneuploidies. Data were compared and analysed using a chi-square test with PGT-A cycles using ejaculated spermatozoa within the same time-period. Results: A total of 57 males underwent SSR, leading to 68 cycles that included the use of PGT-A. A total of 152 embryos with conclusive results identified there to be 57.2% euploid embryos (87/152) and 38.2% aneuploid embryos (58/152) in the SSR group. In comparison, the ejaculated spermatozoa group resulted in 59.2% (2115/3677) euploid embryos and 35.7% (1312/3677) aneuploid embryos. The incidence of aneuploid embryos (38.2%) in the SSR group was not statistically significant [Odds ratio: 1.11 (0.79-1.56) p=0.53]. Importantly, there were no differences for mean maternal age for both study groups (SSR female partners: 36.7 years; ejaculated spermatozoa female partners: 37.1 years; p>0.1). Conclusion: The current outcomes indicate there is not an increased incidence of aneuploid embryos in PGT-A cycles of men who underwent to SSR compared with men using ejaculated spermatozoa.
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48

Kumar, Anupam, Rajesh Verma y N. K. Agrawal. "A study of urinary Bisphenol A levels in endocrine disorders". International Journal of Research in Medical Sciences 6, n.º 2 (24 de enero de 2018): 696. http://dx.doi.org/10.18203/2320-6012.ijrms20180323.

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Background: Bisphenol A (BPA) is a very common endocrine disruptor. Traditionally high doses of BPA showed adverse effects with respect to organ failure and cancer. However, evidence now shows that doses well below the traditional toxicological threshold have metabolic effects. This observational study was aimed to measure the urinary levels of BPA among patients with endocrine disorders namely type 2 diabetes mellitus, hypothyroidism, non-obstructive azoospermia, polycystic ovarian syndrome (PCOS) and simple obesity, and to correlate urinary BPA levels with different clinical, biochemical and hormonal parameters. Methods: 30 newly diagnosed cases each of Type 2 diabetes mellitus, primary hypothyroidism, polycystic ovarian syndrome (PCOS), non-obstructive azoospermia and simple obesity were selected for study (single disorder in one patient). Age and sex matched healthy relatives of patients (n=30) were recruited as controls. All cases and controls were subjected to spot urinary BPA level estimation.Results: There were significant differences obtained in the median values of BPA in urine between cases of azoospermia, and simple obesity as compared to controls whereas no correlation was obtained between urinary BPA levels and BMI or waist hip ratio, in patients of type 2 DM and primary hypothyroidism. Urinary BPA was significantly lower than controls in cases of PCOS.Conclusions: Urinary levels of BPA are an indicator of its toxic effects especially in patients of non-obstructive azoospermia and simple obesity. The values of BPA in urine were widely distributed showing variability of exposure from the environment.
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49

Bac, Nguyen Hoai y Hoang Long. "Study on clinical and genetic characteristics of male patients with non-obstructive azoospermia". Tạp chí Nghiên cứu Y học 141, n.º 5 (30 de junio de 2021): 39–45. http://dx.doi.org/10.52852/tcncyh.v141i5.211.

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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.
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50

Finocchi, Federica, Marianna Pelloni, Giancarlo Balercia, Francesco Pallotti, Antonio F. Radicioni, Andrea Lenzi, Francesco Lombardo y Donatella Paoli. "Seminal plasma miRNAs in Klinefelter syndrome and in obstructive and non-obstructive azoospermia". Molecular Biology Reports 47, n.º 6 (junio de 2020): 4373–82. http://dx.doi.org/10.1007/s11033-020-05552-x.

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