Population variation in Y-chromosome microdeletion and its role in the evaluation of male infertility management: a systematic review

Background: Infertility has been a significantly growing problem worldwide, affecting approximately 10-15% of couples within reproductive age. Among the many causes of male infertility, Y-chromosome microdeletion is considered one of the most frequent genetic causes. Thus, this systematic review was constructed to determine the prevalence of Y-chromosome microdeletion and the population variations in the different types of Y-chromosome microdeletions. Methods: We searched the PubMed, Scielo, and Science Direct databases to obtain articles that addressed the frequency of Y-chromosome microdeletion and male infertility. We identified 14 articles that originated from China, India, Iran, Brazil, Indonesia, North America, South Korea, and Slovakia, and the vital information collected included the year of publication, authors, number of patients with different types of Y-chromosome microdeletions, and the proportion of microdeletion in the major affected sub-regions of the Y-chromosome. Results: In this review, we attempted to highlight the variation in the frequency of Y-chromosome microdeletion in different geographical populations. The highest and lowest frequencies of Y-chromosome microdeletion were found in Indonesian (23.94%) and Slovakian (3.5%) populations, respectively. Conclusion: In conclusion, Y-chromosome microdeletion was undeniably found to be one of the leading genetic causes of male infertility. Azoospermic factor c (AZFc) microdeletion was the most frequent type of Y-chromosome microdeletion, typically presenting in patients with various clinical manifestations that ranged from oligozoospermia to azoospermia and exhibiting the highest chance for sperm retrieval. This review will undoubtedly help clinicians in providing a more accurate consultation to their patients and determining the success rates of assisted reproductive technology.

Observational study of Y chromosome microdeletion, EAA markers and non EAA markers in Chhattishgarh

Genetic factors contribute to 15% of all causes of male infertility. Y chromosome microdeletion is the second most common genetic cause of male infertility. Screening is important for Yq microdeletion as the defect can be transferred to offspring. Aim of our study is to detect the frequency of Y chromosome microdeletion in idiopathic infertile men using both EAA and non EAA markers in central region of India. Forty men from infertility clinic, seeking treatment of infertility were recruited in the study as cases. Thirty normal fertile men of same origin were recruited as controls. Semen analysis was done and cytogenetic normal infertile men were included in the study. Simplex and multiplex PCR methods were used to detect Yq microdeletions. Frequency of deletion was 11/40 (27.5%). Single deletion of AZF a,b,c were 12.5%, 7.5%, 2.5% respectively (). Double deletions of AZF a+c and b+c were 2.5% each (). Two subjects showed deletion for more than one loci. Overall frequency of deletion depends on sample size, no of markers used, inclusion criteria of subjects and geographic location. So, the screening is important for Yq microdeletion as the defect may be inherited to offspring.

Cytogenetics and Y Chromosome Microdeletion in Azoospermic Males - A Retrospective Cohort Study from a Tertiary Care Hospital in Kerala

BACKGROUND Infertility is the inability to become a parent of a child even after one year of intercourse involving male and female partner without any contraceptives. There are many causes for infertility, Y chromosome microdeletion is one among that. Partial or complete deletion of the proximal Yq region, which contains azoospermic factor (AZF) locus, leads to infertility. Along with genetic and biochemical factors the ethno-geographical reasons also play an important role in infertility. The present study was done to identify the association of genetic and hormonal factors in the development of infertility in azoospermic males of southern Kerala. METHODS Retrospectively screened the medical records of 2100 infertile males of the Department of Reproductive Medicine of Sree Avittom Tirunal Hospital, Government Medical College, Thiruvananthapuram for a period from January 2017 to December 2019. Stringent inclusion criterias were taken to select patients for the molecular study and finally 46 were selected. Structural and numerical chromosome abnormalities were detected using karyotyping and microdeletion was identified using polymerase chain reaction. Electro-chemiluminescence immunoassay method was used for the quantification of reproductive hormones. Demographic data of selected patients were collected from the medical records. RESULTS The cytogenetic results showed that among the selected patients, 10.86 % had Klinefelter syndrome and one person had De la Chapelle syndrome. Partial microdeletion in AZFa, b or c regions have been observed in 13.63 % of the patients. The hormonal analysis showed significant change in concentration of reproductive hormones irrespective of genetic defects. Demographic data showed that the majority of participated patients are unskilled/skilled laborers, economically poor and are from urban areas. CONCLUSIONS The study concludes that among the selected patients, 24.49 % have clinically significant chromosomal abnormalities like Klinefelter syndrome, De la Chappelle syndrome and partial microdeletion on the AZF region. Irrespective of genetic defects, significant changes in the concentration of reproductive hormones are also observed. KEYWORDS Azoospermia, Infertility, Karyotyping, Y Chromosome Microdeletion

Y chromosome microdeletion and cytogenetic findings in male infertility: A cross-sectional descriptive study

Background: Infertility affects about 15% of couples worldwide, and the male factor alone is responsible for approximately 50% of the cases. Genetic factors have been found to play important roles in the etiology of azoospermia and severe oligospermia conditions that affect 30% of individuals seeking treatment at infertility clinics. Objective: To determine the frequency of chromosomal abnormalities and Y chromosome microdeletion in infertile men. Materials and Methods: A total of 100 infertile men with abnormal semen parameters were included in this study from 2014 to 2018. Chromosomal analysis was carried out using standard G-banding using Trypsin Giemsa protocol. Multiplex polymerase chain reaction was used to determine the Y microdeletion frequency. Results: All participants were aged between 22 and 48 yr with a mean and standard deviation of 35.5 ± 5.1. Of the 100 subjects included in the study, three had Klinefelter syndrome-47,XXY, one had balanced carrier translocation- 46,XY,t(2;7)(q21;p12), one with the balanced carrier translocation with inversion of Y chromosome 45,XY,der(13;14)(q10;q10),inv(Y), one had polymorphic variant of chromosome 15, one had Yqh-, and another had an inversion of chromosome 9. Y chromosome microdeletion of Azoospermia factor c region was observed in 2% of the cases. To the best of our knowledge, the current study is the first reported case with unique, balanced carrier translocation of chromosome 2q21 and 7p21. Conclusion: The present study emphasizes the importance of routine cytogenetic screening and Y microdeletion assessment for infertile men, which can provide specific and better treatment options before undergoing assisted reproductive technology during genetic counseling. Key words: Chromosome aberrations, Infertility, Chromosome deletion, Polymerase chain reaction, Sequence tagged sites.

Prevalence of Y Chromosome Microdeletion Among Mongolian Infertile Men With Azoospermia and Severe Oligozoospermia

Backgound: Y chromosome microdeletions are the second most common genetic causes in male infertility. The aim of the present study was to reveal the patterns of Y chromosome microdeletions among Mongolian infertile men. Method: A descriptive study was performed to 75 infertile men during February 2017 to December 2018. Y chromosome microdeletions were identified by PCR. Semen parameters, hormonal levels, testis biopsy were determined. All collected data were evaluated with Statistical Package for Social Sciences (SPSS, version 22.0).Results: Among 75 infertile men, 2 cases of Y chromosome microdeletions were determined (2.66%). The first case had AZFa complete deletion and the other one had AZFc partial deletion. The azoospermia patient with AZFa complete deletion had Sertoli cell only syndrome in the testis biopsy, FSH 58.0 mIU/ml and LH 12.0 mIU/ml. The azoospermia patient with AZFc partial deletion showed FSH 23.85 mIU/ml and LH 13.01 mIU/ml. Serum FSH level was significantly higher in the Y chromosome microdeletion patients (p value 0.016). Conclusion: This study determined Y chromosome microdeletion among Mongolian infertile men to be at 2.66%. Our results showed FSH level is the best predictor of a successful TESE. However, best cut off value for FSH was 9.69 mIU/ml with a sensitivity and specificity 85.6% and 83.3% respectively. There is a possibility that sperm retrieval will be difficult from the TESE since the testicular tissue is severely damaged. The findings can be applied to IVF and Assisted Reproductive Techonology, and our results will help clinicians improve treatment management for Mongolian infertile couples.

Whole-genome sequencing analysis of Y chromosome microdeletion: a case report

The mechanisms by which Y chromosome microdeletions cause infertility have been well described; however, the therapeutic targets remain a challenge. Here, we used whole-genome sequencing to explore the mechanism of Y chromosome deletion and potential therapeutic targets in a patient with infertility. There were no abnormalities in the patient’s medical history. Routine semen analysis showed immotile sperm and only two motile spermatozoa were occasionally see after centrifugation, indicating that the direct cause of infertility was an abnormal sperm count and motility. A Y chromosome microdeletion test revealed partial deletion of the AZFc region, including AZFc1, AZFc2, AZFc3, and AZFc4. Whole-genome sequencing showed that the patient had seven harmful mutations, with only one significant epigenetic mutation, SH3KBP1. Gene Ontology analysis of these meaningful mutations indicated involvement of cAMP signaling pathways. The patient’s wife became pregnant following in vitro fertilization, and no significant abnormalities were found during prenatal examination. This case suggests that Y chromosome microdeletion and gene mutation may affect the cAMP signaling pathway, leading to reduced sperm quality and male infertility.