DOCSLIB.ORG

Molecular Analysis for Azoospermia Factor Microdeletions in the Y Chromosome for Azoospermic and Severe Oligospermic Infertile Iraqi Patients

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Molecular Analysis for Azoospermia Factor Microdeletions in the Y Chromosome for Azoospermic and Severe Oligospermic Infertile Iraqi Patients Sys Rev Pharm 2020;11(8):562-570 A multifaceted review journal in the field of pharmacy Molecular Analysis for Azoospermia Factor Microdeletions in the Y chromosome for Azoospermic and Severe Oligospermic Infertile Iraqi Patients 1Mohammed. N Al-Qaisi, B.Sc., 2Mushtak. T Al-Ouqaili, Ph.D.*, 3Duraid. T Al-Hadithi, M.D. 1Ramadi Teaching Hospital for Women and Children, Al-Anbar Health Office, Ramadi, Iraq 2Department of Microbiology, College of Medicine, University of Anbar, Ramadi, Iraq 3Department of Surgery, College of Medicine, University of Anbar, Ramadi, Iraq Corresponding Author E-mail: [email protected] ABSTRACT Defined infertility as incapability of a married couple tᴏ have children for the Keywords: AZF//microdeletion, male infertility, non- one-year ᴏf unprotected intercourse. Y chromosomal microdeletions are the obstructive/azoospermia and severe oligospermia, second greatest common genetic reason of men sterility. This research aims to Y/Chromosome//microdeletions. find the prevalence of AZF Y chromosome microdeletions in azoospermic and severe oligospermia patients. Further, to evaluate the prevalence types of Correspondence: AZF/c sub-region microdeletions in patients with AZF/c deletion in Iraq. A Mushtak. T Al-Ouqaili, Ph.D total of 75 infertile Iraqi males and 25 control were included in this study. The 2Department of Microbiology, College of Medicine, University of Anbar, DNA samples were extracted, and they were analysed for AZF microdeletions Ramadi, Iraq by utilizing eight sequence-tagged sites through a q/real-time PCR system. Corresponding Author E-mail: [email protected] After that, partial AZF/c deletion sub-region was investigated using four specific primers. These markers were chosen according to the EAA/ EMGQ recommendations. Out of 75 infertile patients, 46 patients (61.33%) revealed AZF microdeletions in the Y chromosomal with at least one STS deletion for one or more AZF regions. (32.6%) of patients with microdeletions observed in three regions AZFabc. Out of 24 patients who have AZF/c microdeletions (37.5%) were exhibited b2/b4 deletion (complete AZF/c deletions), (58.3%) were showed gr/gr microdeletion (partial AZF/c deletions. and (4.1%) with b2/b4 deletion continues the terminal heterochromatin region. The incidence of classical AZF microdeletions in our study subjects is high. In our study population, gr/gr partial AZF/c microdeletions were higher than b2/b4 complete AZF/c deletion. The mean levels of sex hormones in azoospermic sterile patients with AZF microdeletion were higher than the mean of azoospermic sterile men without deletion of AZF. INTRODUCTION intracytᴏplasmic sperm injection (ICSI) assists infertile The Y chromosome in human is important for sex males with Y chromosome microdeletions to become determination and male germ cell progress and fathers, the risk of infertility that may be transmitting from maintenance[1]. The /azoospermia factor (AZF) area infertile fathers to their offspring should be a note[9]. located on the long arm of the Y chromosome Y/q and There are few data on the occurrence of testicular tumors show a main role in the genetics/of male sterility and is in males with Y q micro-deletions, especially males born to dividing into three sections: AZF a, AZF b, and AZF c. These fathers with deletion. The recent documents on the higher sections contain genes that are involved in occurrence of neurological problems in infertile males spermatogenesis and the development of tests. Their with Y/q deletions are reported[10]. failure or loss is commonly associated with AZF microdeletions are toᴏ/small to be noticed by spermatogenetic defects and male infertility. However, karyotyping. but, with the advance of molecular biology Microdeletions at AZF are the most common structural technology, now AZF microdeletions can be recognized by chromosomal defects and the leading induce of male multiplex polymerase chain reaction (PCR) technique within infertility[2]. a short time[11]. According to the European Academy of The microdeletion of AZF a results in sertoli/cell/only Andrology /European Molecular Genetics guidelines, Six syndrome, and whole removal of AZFb[3] is associating sites were selected for preliminary screening of AZF absence, with spermatogenic arrest. Also, the microdeletion of AZF including SY84/SY86 (AZFa), SY127/SY134 (AZFb), and c induces variable clinical and histologic phenotypes, SY254/SY255 (AZF c for the identification of microdeletions ranging from Sertoli. Cell. only syndrome to in the Y chromosome)[12]. oligospermia[4]. While Partial deletions of AZF/c classify as Our study has been undertaken for analyzing the 1.6Mb gr/gr, 1.8Mb b2/b3, 1.6Mb b1/b3, and 3.5Mb prevalence and types of microdeletions in the AZF region b2/b4 (complete AZF/c deletions) were also known to of a Y chromosome in patients with azoospermia and influence spermatogenesis[5]. Among these, gr/gr sub- severe oligospermia from Al-Anbar Governorate west of deletions with occurrence varying from 2.1% to 12.5% in Iraq by using six sequence-tagged sites (STSs) as follow: infertile people and zero to 10.2% infertile males are sY84 and sY86 for AZF/a; sY127 and sY134 for AZF/b; frequently reported[6]. The gr/gr deletion, the common sY254 and sY255 for AZF/c according to the partial deletion of AZF/c, deletes about half of the b2/b4 recommendations by European Academy of Andrology/ area and can be described by different phenotypes European Molecular Genetics Quality Network EAA/ depending on the ethnic and geopolitical origin[7]. EMQN. Also, to determine the types of partial AZF/c sub- AZF microdeletions are causing by mistakes in the region deletion. and to determine the association between intrachromosomal recombination route[8]. While hormonal imbalance levels in the Luteinizing hormone, 562 Systematic Reviews in Pharmacy Vol 11, Issue 8, Aug-Sep 2020 Al-Ouqaili et al. /Molecular Analysis for Azoospermia Factor Microdeletions in the Y Chromosome for Azoospermic and Severe Oligospermic Infertile Iraqi Patients Follicle stimulating hormone, Prolactin hormone in addition to testosterone, and the occurrence of Y Hormonal study chromosome microdeletions. All participants have submitted for evaluation for hormonal studies including LH, FSH and prolactin in Patients and methods addition to testosterone hormone, in human serum on Study patients and ethics approval TOSOH Automated Immunoassay System (TOSOH This study has been approved by the Medical Ethics Bioscience, Japan). Committee at the University of Anbar, College of Medicine, according to the Scientific Research Ethics Committee, Molecular part Book No. 113 validated on 4/11/2019. We have studied 75 DNA extraction Iraqi infertile patients with impairment of Genomic/DNA was extracted frᴏm 400-µL bӏood samples spermatogenesis, 40 non-obstructive azoospermia/35 with the SaMag-12Automated Nucӏeic Acids Extraction severe oligozoospermia men who have been seeking System (Sacace biotechnologies/Italy), according to the consultation for infertility at the private infertility clinics. Al-Ouqaili, and Al-Qaysi protocols respectively[14,15]. The The study included 25 Health controls with normal quantity of nucleic acid has been detected by using the spermatogenesis, and their fertility status was assumed by Quantus™ Fluorometer with QuantiFluor® dsDNA System the reports that they were fathers for a child or more. (promega/ USA) provides a fast, easy and sensitive method for determining DNA concentration. DNA purity Semen analysis was also estimated by OD260/OD280 UV Semen analysis was done accᴏrding to normal standard spectrophotometer (Unico/ USA). criteria laid down by World Health Organization[13]. The identification of azoospermia depended on the lack of Molecular investigation using qReal-Time PCR sperm in at least two separate semen analyses and after technique centrifugation. The chosen infertile males were This part was achieved using two reactions in RT-PCR categorised as azoospermic or severe oligospermic (Sacace biotechnologies, Italy). Reaction A consisted of patients with less than five million/mL of sperm count. sY86, sY127, sY254, and ZFY/X STSs, and the other Moreover, the volume of semen, the concentration of reaction, B consisted of sY84, sY134, sY255, and SRY STSs. sperms, the sperms morphology, and the movement type Hydrolysis probes within a reaction were labelled using of the sperms, whether it was progressive, sluggish or channels of FAM, HEX, ROX, and CY5, and the STSs immobile were evaluated. information were listed in the table 1. Table 1. The information about the study sequence tag site (STS) locus STS Sequence (5′to 3′) Size Base pair MIX A ZFX/Y ZFX/Y-F 5′- ACC RCT GTA CTG ACT GTG ATT ACA C-3′ 495 ZFX/Y-R 5′- GCA CYT CTT TGG TAT CYG AGA AAG T-3′ AZF a sY86-F 5′- GTG ACA CAC AGA CTA TGC TTC-3′ 318 sY86-R 5′ - ACA CAC AGA GGG ACA ACC CT - 3′ AZF b sY127-F 5′- GGC TCA CAA ACG AAA AGA AA-3′ 274 sY127-R 5′- CTG CAG GCA GTA ATA AGG GA-3′ AZF c sY254-F 5′- GGG TGT TAC CAG AAG GCA AA-3′ 380 sY254-R 5′ - GAA CCG TAT CTA CCA AAG CAG C-3′ MIX B SRY sY14-F 5′ - GAA TAT TCC CGC TCT CCG GA-3′ 472 sY14-R 5′ - GCT GGT GCT CCA TTC TTG AG-3′ AZF a sY84-F 5′- AGA AGG GTC CTG AAA GCA GGT-3′ 326 sY84-R 5′ - GCC TAC TAC CTG GAG GCT TC-3′ AZF b sY134-F 5′- GTC TGC CTC ACC ATC AAC CG-3′ 301 sY134-R 5′- ACC ACT GCC AAA ACT TTC AA-3′ AZF c sY255-F 5′- GTT ACA GGA TTC GGC GTG AT-3′ 123 sY255-R 5′- CTC GTC ATG TGC AGC CAC-3′ The whole reaction amount was 35 μӏ; the amount of DNA The screening for AZF/c sub-region microdeletions by sample was seven μӏ.
Load more

Recommended publications
  • Genetics of Azoospermia
    International Journal of Molecular Sciences Review Genetics of Azoospermia Francesca Cioppi , Viktoria Rosta and Csilla Krausz * Department of Biochemical, Experimental and Clinical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy; francesca.cioppi@unifi.it (F.C.); viktoria.rosta@unifi.it (V.R.) * Correspondence: csilla.krausz@unifi.it Abstract: 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. Keywords: azoospermia; infertility; genetics; exome; NGS; NOA; Klinefelter syndrome; Y chromosome microdeletions; CBAVD; congenital hypogonadotropic hypogonadism Citation: Cioppi, F.; Rosta, V.; Krausz, C. Genetics of Azoospermia. 1. Introduction Int. J. Mol. Sci.
    [Show full text]
  • Hypomethylation of the DAZ3 Promoter in Idiopathic Asthenospermia: a Screening Tool for Liquid Biopsy Shichang Zhang1,3, Li Xu2,3, Mengyao Yu1 & Jiexin Zhang1*
    www.nature.com/scientificreports OPEN Hypomethylation of the DAZ3 promoter in idiopathic asthenospermia: a screening tool for liquid biopsy Shichang Zhang1,3, Li Xu2,3, Mengyao Yu1 & Jiexin Zhang1* Given the role of the deleted in azoospermia gene in male infertility, whether the somatic deleted in azoospermia methylation status is associated with idiopathic asthenospermia should be determined. To investigate the methylation levels of the deleted in azoospermia promoter in peripheral white blood cells from idiopathic asthenospermia patients relative to those in normozoospermia controls, 61 ethylene diamine tetraacetic acid anticoagulant blood samples were drawn from all participants for DNA isolation. The deleted in azoospermia promoter methylation ratio was detected by MassARRAY-based methylation quantifcation and confrmed by quantitative methylation-specifc polymerase chain reaction. A MassARRAY-based methylation analysis showed that the deleted in azoospermia 3 promoter (0 to − 2 kbp) was signifcantly hypomethylated in peripheral white blood cells from idiopathic asthenospermia males, specifcally one CpG site (− 246 to − 247). Quantitative methylation-specifc polymerase chain reaction data further confrmed that the methylation level of the deleted in azoospermia 3 promoter region in idiopathic asthenospermia patients was signifcantly lower than that in normozoospermia males. The area under the receiver operating characteristic curve determined by quantitative methylation-specifc polymerase chain reaction was 0.737 (95% confdence interval: 0.552 to 0.924), with a sensitivity of 53.9% and a specifcity of 88.2% at a cut- of level of 74.7%. Therefore, our results suggested that methylation ratio detection of the deleted in azoospermia 3 promoter region by real-time polymerase chain reaction assay is a promising and feasible tool for liquid biopsy in the clinical laboratories.
    [Show full text]
  • Genetic Landscape of Nonobstructive Azoospermia and New Perspectives for the Clinic
    Journal of Clinical Medicine Review Genetic Landscape of Nonobstructive Azoospermia and New Perspectives for the Clinic Miriam Cerván-Martín 1,2, José A. Castilla 2,3,4, Rogelio J. Palomino-Morales 2,5 and F. David Carmona 1,2,* 1 Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, Centro de Investigación Biomédica (CIBM), Parque Tecnológico Ciencias de la Salud, Av. del Conocimiento, s/n, 18016 Granada, Spain; [email protected] 2 Instituto de Investigación Biosanitaria ibs.GRANADA, Av. de Madrid, 15, Pabellón de Consultas Externas 2, 2ª Planta, 18012 Granada, Spain; [email protected] (J.A.C.); [email protected] (R.J.P.-M.) 3 Unidad de Reproducción, UGC Obstetricia y Ginecología, HU Virgen de las Nieves, Av. de las Fuerzas Armadas 2, 18014 Granada, Spain 4 CEIFER Biobanco—NextClinics, Calle Maestro Bretón 1, 18004 Granada, Spain 5 Departamento de Bioquímica y Biología Molecular I, Universidad de Granada, Facultad de Ciencias, Av. de Fuente Nueva s/n, 18071 Granada, Spain * Correspondence: [email protected]; Tel.: +34-958-241-000 (ext 20170) Received: 29 December 2019; Accepted: 16 January 2020; Published: 21 January 2020 Abstract: Nonobstructive azoospermia (NOA) represents the most severe expression of male infertility, involving around 1% of the male population and 10% of infertile men. This condition is characterised by the inability of the testis to produce sperm cells, and it is considered to have an important genetic component. During the last two decades, different genetic anomalies, including microdeletions of the Y chromosome, karyotype defects, and missense mutations in genes involved in the reproductive function, have been described as the primary cause of NOA in many infertile men.
    [Show full text]
  • Reproductive Chances of Men with Azoospermia Due to Spermatogenic Dysfunction
    Journal of Clinical Medicine Review Reproductive Chances of Men with Azoospermia Due to Spermatogenic Dysfunction Caroline Kang † , Nahid Punjani † and Peter N. Schlegel * Department of Urology, Weill Cornell Medical College, New York, NY 10021, USA; [email protected] (C.K.); [email protected] (N.P.) * Correspondence: [email protected] † Equal contribution. Abstract: Non-obstructive azoospermia (NOA), or lack of sperm in the ejaculate due to spermato- genic dysfunction, is the most severe form of infertility. Men with this form of infertility should be evaluated prior to treatment, as there are various underlying etiologies for NOA. While a significant proportion of NOA men have idiopathic spermatogenic dysfunction, known etiologies including ge- netic disorders, hormonal anomalies, structural abnormalities, chemotherapy or radiation treatment, infection and inflammation may substantively affect the prognosis for successful treatment. Despite the underlying etiology for NOA, most of these infertile men are candidates for surgical sperm retrieval and subsequent use in intracytoplasmic sperm injection (ICSI). In this review, we describe common etiologies of NOA and clinical outcomes following surgical sperm retrieval and ICSI. Keywords: non-obstructive azoospermia; infertility; intracytoplasmic sperm injection Citation: Kang, C.; Punjani, N.; 1. Introduction Schlegel, P.N. Reproductive Chances of Men with Azoospermia Due to Infertility affects up to 15% of couples worldwide, with up to 50% of cases attributable Spermatogenic Dysfunction. J. Clin. to male factor infertility [1]. In a majority of cases, the precise etiology underlying infertility Med. 2021, 10, 1400. https://doi.org/ in the male partner remains unclear. A subset of men with infertility have no sperm in 10.3390/jcm10071400 the ejaculate, known as azoospermia, which may further be classified into obstructive (OA) or non-obstructive azoospermia (NOA).
    [Show full text]
  • Microdeletion of Y‑Chromosome and Their High Impact on Male Infertility
    Commentary Microdeletion of Y‑chromosome and Their High Impact on Male Infertility INTRODUCTION known to interfere with spermatogenesis. Undoubtedly, among the genetic factors associated deletion of Male infertility is a multifactorial genetic disorder. WHO azoospermic factor (AZF) are known to play a crucial role in defined infertility as an inability to conceive naturally after regulating infertility. Y‑chromosomal imbalance contributes at least 1‑year of unprotected intercourse. It is expected about 14% of azoospermic and 5% of oligozoospermia that 15% of couples worldwide who seeks children have and plays a significant role in infertility with abnormal infertility while male factor alone contributes about 50% seminograms.[7] The expected phenotype ranges from in childless couples. In more than half of infertile male are oligozoospermia to azoospermia, and have a variable unknown idiopathic causes. Semen analysis shows abnormal impact because of the same karyotype within the same conditions such as azoospermia, oligozoospermia, family has been reported earlier.[8] In most of the cases, the teratozoospermia, asthenozoospermia, necrospermia, and distal region of Y‑chromosome is translocated to the short pyospermia.[1‑6] The prevalence of primary and secondary arm of an acrocentric chromosome and can be visualized by infertility varies between 29% and 71%, but about 30% fluorescence in situ hybridization This seems to be relevant of cases of reduced infertility are still unknown. The for diagnosing of microdeletion of Y‑chromosome in Y‑chromosomes play a significant role in maintaining fertility karyotypes of 47, XXY or mosaic 46, XY/47, XXY cases with in human. Hence, it is essential to understand the molecular clinical features characterized by testicular hypotrophy, structure of Y‑chromosome and their regions associated azoospermia and increased FSH levels.
    [Show full text]
  • A Comprehensive Review of Genetics and Genetic Testing in Azoospermia
    REVIEW A comprehensive review of genetics and genetic testing in azoospermia Alaa J. Hamada,I Sandro C. Esteves,II Ashok AgarwalI I Center for Reproductive Medicine, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA. II ANDROFERT – Andrology & Human Reproduction Clinic, Campinas, Sa˜ o Paulo, Brazil. Azoospermia due to obstructive and non-obstructive mechanisms is a common manifestation of male infertility accounting for 10-15% of such cases. Known genetic factors are responsible for approximately 1/3 of cases of azoospermia. Nonetheless, at least 40% of cases are currently categorized as idiopathic and may be linked to unknown genetic abnormalities. It is recommended that various genetic screening tests are performed in azoospermic men, given that their results may play vital role in not only identifying the etiology but also in preventing the iatrogenic transmission of genetic defects to offspring via advanced assisted conception techniques. In the present review, we examine the current genetic information associated with azoospermia based on results from search engines, such as PUBMED, OVID, SCIENCE DIRECT and SCOPUS. We also present a critical appraisal of use of genetic testing in this subset of infertile patients. KEYWORDS: Azoospermia; Male Infertility; Genetic Testing; Genetic Diseases; Klinefelter Syndrome; Y Chromosome. Hamada AJ, Esteves SC, Agarwal A. A comprehensive review of genetics and genetic testing in azoospermia. Clinics. 2013;68(S1):39-60. Received for publication on September 5, 2012; Accepted for publication on September 6, 2012 E-mail: [email protected] Tel.: 1 216 444-9485 & INTRODUCTION assisted reproduction therapeutic tools, clinical pregnancy and live birth rates were reported to range from 26-57% and Infertility refers to failure of a couple to conceive 18-55% for NOA and OA, respectively (10-16).
    [Show full text]
  • Y-Microdeletions: a Review of the Genetic Basis for This Common Cause of Male Infertility
    1390 Review Article on Genetic Causes and Management of Male Infertility Y-microdeletions: a review of the genetic basis for this common cause of male infertility Luke Witherspoon1^, Ali Dergham2, Ryan Flannigan3,4 1Division of Urology, Department of Surgery, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada; 2School of Medicine, Faculty of Health Sciences, Queen’s University, Kingston, ON, Canada; 3Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada; 4Department of Urology, Weill Cornell Medicine, New York, NY, USA Contributions: (I) Conception and design: All authors; (II) Administrative support: All authors; (III) Provision of study materials or patients: All authors; (IV) Collection and assembly of data: L Witherspoon, A Dergham; (V) Data analysis and interpretation: L Witherspoon, A Dergham; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Ryan Flannigan, MD. Department of Urologic Sciences, University of British Columbia, Gordon & Leslie Diamond Health Care Centre, Level 6, 2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada. Email: [email protected]. Abstract: The human Y-chromosome contains genetic material responsible for normal testis development and spermatogenesis. The long arm (Yq) of the Y-chromosome has been found to be susceptible to self- recombination during spermatogenesis predisposing this area to deletions. The incidence of these deletions is estimated to be 1/4,000 in the general population but has been found to be much higher in infertile men. Currently, Y-microdeletions are the second most commonly identified genetic cause of male infertility after Klinefelter syndrome. This has led to testing for these deletions becoming standard practice in men with azoospermia and severe oligospermia.
    [Show full text]
  • Current Status of Y Chromosome Microdeletions: Prevalence, Distribution, Implication Genetics Section and Association with Male Infertility in Indian Men- a Review
    DOI: 10.7860/JCDR/2021/46154.14604 Review Article Current Status of Y Chromosome Microdeletions: Prevalence, Distribution, Implication Genetics Section and Association with Male Infertility in Indian Men- A Review MANDAVA V RAO1, NIDHI P SHAH2, RUTVIK J RavaL3, POOJA P SOLANKI4, PARTH S SHAH5, SANDIP C SHAH6 ABSTRACT microdeletion screening of Y chromosome using various STS Introduction: Infertility affects about 15% of couples attempting to AZF locus. These data from 30 study groups were compared pregnancy and in approximately 50% of these cases, male to geographical areas/zones, Indian populations, environment, factors are responsible. Male infertility is clinically characterised selection criteria and other factors in this review. by azoospermia and oligozoospermia depending on the amount Results: The data on thousands of Y chromosome analysis of loss of genetic material and the size of the affected region confirmed that the frequency of microdeletions are affected by on the Y Chromosome Microdeletions (YCM). The majority of sample size, selection criteria of subjects, different geographical genes located in the Y chromosome are involved in male related regions, ethnicity, Oxidative Stress (OS), Deoxyribonucleic Acid functions such as spermatogenesis in human, in addition to other (DNA) fragmentation and food styles in addition to genetic defects. endocrine and physiological factors. These microdeletions are In Indian subcontinent, these deletions contribute to 8.33% from located on q arm of Y chromosome, specifically Azoospermia screening of 5435 Y chromosomes (453/5435). Lower percent Factor (AZF) region, hence called Yq microdeletions. These (5.37%) of Yq microdeletions in Western India than other parts deletions are in form of complete/incomplete, recombination; was observed, being highest in South East (20.52%) and North mutations and Copy Number Variations (CNV) and vary in East zones (17.77%) as mentioned in the present study.
    [Show full text]
  • The Epidemiology and Etiology of Azoospermia
    REVIEW The epidemiology and etiology of azoospermia Marcello Cocuzza, Conrado Alvarenga, Rodrigo Pagani Universidade de Sa˜ o Paulo, Faculdade de Medicina, Department of Urology, Sa˜ o Paulo/SP, Brazil. The misconception that infertility is typically associated with the female is commonly faced in the management of infertile men. It is uncommon for a patient to present for an infertility evaluation with an abnormal semen analysis report before an extensive female partner workup has been performed. Additionally, a man is usually considered fertile based only on seminal parameters without a physical exam. This behavior may lead to a delay in both the exact diagnosis and in possible specific infertility treatment. Moreover, male factor infertility can result from an underlying medical condition that is often treatable but could possibly be life-threatening. The responsibility of male factor in couple’s infertility has been exponentially rising in recent years due to a comprehensive evaluation of reproductive male function and improved diagnostic tools. Despite this improvement in diagnosis, azoospermia is always the most challenging topic associated with infertility treatment. Several conditions that interfere with spermatogenesis and reduce sperm production and quality can lead to azoospermia. Azoospermia may also occur because of a reproductive tract obstruction. Optimal management of patients with azoospermia requires a full understanding of the disease etiology. This review will discuss in detail the epidemiology and etiology of azoospermia. A thorough literature survey was performed using the Medline, EMBASE, BIOSIS, and Cochrane databases. We restricted the survey to clinical publications that were relevant to male infertility and azoospermia. Many of the recommendations included are not based on controlled studies.
    [Show full text]
  • Diagnosis and Treatment of Infertility in Men: AUA/ Tions Appear at the End of ASRM Guideline the Article
    1 Approved by the AUA Board of Directors AUA/ASRM Guideline October 2020 Authors’ disclosure of po- tential conflicts of interest and author/staff contribu- Diagnosis and Treatment of Infertility in Men: AUA/ tions appear at the end of ASRM Guideline the article. © 2020 by the American Urological Association and American Society for Re- Peter N. Schlegel, MD; Mark Sigman, MD; Barbara Collura; Christopher J. De productive Medicine Jonge, PhD, HCLD(ABB); Michael L. Eisenberg, MD; Dolores J. Lamb, PhD, HCLD (ABB); John P. Mulhall, MD; Craig Niederberger MD, FACS; Jay I. Sandlow, MD; Rebecca Z. Sokol, MD, MPH; Steven D. Spandorfer, MD; Cigdem Tanrikut, MD, FACS; Jonathan R. Treadwell, PhD; Jeffrey T. Oristaglio, PhD; Armand Zini, MD Purpose Failure to conceive within 12 months of attempted conception is due in whole or in part to the male in approximately one-half of all infertile couples. Although many couples can achieve a pregnancy with assisted reproductive technologies (ART), evaluation of the male is important to most appropriately direct therapy. Some male factor conditions are treatable with medical or surgical therapy, and others may only be managed with donor sperm or adoption. Some conditions are life threatening, while others have health and genetic implications for the patient and potential offspring. Without a male evaluation it is not possible to adequately design management of the patient and the couple. The purpose of this guideline is to outline the appropriate evaluation and management of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated.
    [Show full text]
  • Causes Male Infertility
    RESEARCH ARTICLE 227 Croat Med J. 2021;62:227-32 https://doi.org/10.3325/cmj.2021.62.227 A novel mutation in FK506 Derya Akyuz Sengun1, Esra Guzel Tanoglu2, Hakan binding protein-like (FKBPL) Ulucan1 1Department of Medical Genetics, causes male infertility Istanbul University Cerrahpasa Medical School, Istanbul, Turkey 2Department of Molecular Biology and Genetics, University of Health Sciences, Istanbul, Turkey Aim To perform a mutation analysis of FK506 binding pro- tein-like (FKBPL) in patients with azoospermia. Methods DNA samples were isolated from the peripheral blood of 30 azoospermic male patients with normal 46 XY karyotype and 10 healthy controls. Multiplex polymerase chain reaction assays were used to evaluate Y microdele- tions, and the patients without deletions were further an- alyzed. Sanger sequencing was used for mutation analysis. Results A heterozygous adenine to guanine substitution was observed at position c.28 (c.28A>G) (one patient), gua- nine to adenine substitution at c.90 (c.90G>A) (three pa- tients), and a novel insertion mutation of TCTCATAAGTCT at c. 229_240dup (two patients), all in FKBPL exon 2. Fur- thermore, four different benign variants were observed in the same gene. Conclusion Our study supports the literature on the eti- ologic effects of changes on autosomal chromosomes and highlights the importance of molecular analysis of all known and unknown genes that could be involved in male sexual development and function. Received: July 19, 2020 Accepted: May 5, 2021 Correspondence to: Hakan Ulucan University of Istanbul, Cerrahpasa Department of Medical Genetics Fatih, Istanbul [email protected] www.cmj.hr 228 RESEARCH ARTICLE Croat Med J.
    [Show full text]
  • Histology and Sperm Retrieval Among Men with Y Chromosome Microdeletions
    1456 Review Article on Genetic Causes and Management of Male Infertility Histology and sperm retrieval among men with Y chromosome microdeletions Wallace Yuen1#, Andrew P. Golin1#, Ryan Flannigan1,2, Peter N. Schlegel2 1Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada; 2Department of Urology, Weill Cornell Medicine, New York, NY, USA Contributions: (I) Conception and design: R Flannigan, W Yuen, AP Golin; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: W Yuen, AP Golin; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. #These authors contributed equally to this work. Correspondence to: Dr. Peter N. Schlegel. Weill Cornell Medicine, 525 East 68th Street, Starr 946, New York, NY, USA. Email: [email protected]. Abstract: In this review of Y chromosome microdeletions, azoospermia factor (AZF) deletion subtypes, histological features and microTESE sperm retrieval rates are summarized after a systematic literature review. PubMed was searched and papers were identified using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Approximately half of infertile couples have a male factor contributing to their infertility. One of the most common genetic etiologies are Y chromosome microdeletions. Men with Y chromosome microdeletions may have rare sperm available in the ejaculate or undergo surgical sperm retrieval and subsequent intracytoplasmic sperm injection to produce offspring. Azoospermia or severe oligozoospermia are the most common semen analysis findings found in men with Y chromosome microdeletions, associated with impaired spermatogenesis. Men with complete deletions of azoospermia factor a, b, or a combination of any loci have severely impaired spermatogenesis and are nearly always azoospermic with no sperm retrievable from the testis.
    [Show full text]