Chromosomal abnormalities and clinical conditions associated with the male infertility among Emirati: 10-year retrospective research study

Ferdos Ebrahim; Ihsan Ali Mahasneh

doi:10.4103/abhs.abhs_38_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 1 | Issue : 4 | Page : 228-236

Chromosomal abnormalities and clinical conditions associated with the male infertility among Emirati: 10-year retrospective research study

Ferdos Ebrahim, Ihsan Ali Mahasneh
Department of Applied Biology—Biotechnology Program, Faculty of Science, University of Sharjah, Sharjah, UAE

Date of Submission	05-Jun-2022
Date of Decision	13-Sep-2022
Date of Acceptance	21-Sep-2022
Date of Web Publication	31-Oct-2022

Correspondence Address:
Prof. Ihsan Ali Mahasneh
Department of Applied Biology—Biotechnology Program, Faculty of Science, University of Sharjah, Sharjah
UAE

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/abhs.abhs_38_22

Abstract

Background: Male infertility is a global health issue that is poorly described in United Arab Emirates. Methods: In this 10-year retrospective cross-sectional study, we retrieved data of 312 male patients attending Dubai Fertility Center in United Arab Emirates between January 2011 and January 2021. We identified the type and prevalence of chromosomal abnormalities and hormonal and semen abnormalities among Emirati infertile males as compared with regional and global populations. Results: Total chromosomal abnormalities accounted for 13.9% and 8% among azoospermic Emiratis and total Emirati infertile males, respectively. Numerical chromosomal abnormalities causing male infertility were Klinefelter syndrome, 47,XXY (4.0%); Jacob syndrome, 47,XYY (0.8%); mosaic, 48,XXXY/47,XXY/46,XY (0.4%); and mosaic 47,XXY/46,XY (0.4%). Structural chromosomal abnormalities causing male infertility were Y chromosome microdeletion (1.2%), 46,XX/46,XY (0.4%), 46,XY,inv(5)(p15.1q11.2) (0.4%), and 45,XY,der(13;15)(q10;q10) (0.4%). About 59.0% of the Emirati cohort had azoospermia, whereas 28.46% were diagnosed with other conditions of spermatogenic failure as severe oligoasthenoteratozoospermia (7.63%), severe oligoasthenospermia (5.22%), severe oligozoospermia (4.41%), oligoasthenoteratozoospermia (3.6%), asthenozoospermia (2.4%), oligoasthenospermia (1.6%), oligozoospermia (2%), teratozoospermia (0.8%), asthenoteratozoospermia (0.4%), and aspermia (0.4%). As for male hormonal profile of the Emiratis, azoospermic males with chromosomal defects had higher testosterone abnormality (72.2% vs. 45.4%), interstitial-cell stimulating hormone abnormality (66.6% vs. 42.6%), follicle-stimulating hormone abnormality (72.2% vs. 41.5%), and inhibin B hormone abnormality (100% vs. 83.8%) as compared to azoospermic males without chromosomal abnormalities. Conclusion: This is the first study to report conclusively the profiling of chromosomal abnormality among Emirati infertile males, which falls within the regional and global range, and to highlight the critical role of genetic testing and counseling for evaluating male infertility.

Keywords: Azoospermia, chromosomal abnormalities, Klinefelter syndrome, male infertility, Y chromosome microdeletion

How to cite this article:
Ebrahim F, Mahasneh IA. Chromosomal abnormalities and clinical conditions associated with the male infertility among Emirati: 10-year retrospective research study. Adv Biomed Health Sci 2022;1:228-36

How to cite this URL:
Ebrahim F, Mahasneh IA. Chromosomal abnormalities and clinical conditions associated with the male infertility among Emirati: 10-year retrospective research study. Adv Biomed Health Sci [serial online] 2022 [cited 2023 Jun 9];1:228-36. Available from: http://www.abhsjournal.net/text.asp?2022/1/4/228/359982

Background

Infertility is defined as the inability of couple to conceive after 12 months or more of regular unprotected intercourse [1]. This health condition affects ~48.5 million couples worldwide with male factors solely attributing to 20%–30% of total infertility cases [2]. Male infertility is categorized as a multifactorial health issue as it includes the collection of various health complications with different etiologies. The known causes influencing male reproductive health could be either acquired or congenital, which include chromosomal and genetic factors, hormonal abnormalities, physical defects, sexually transmitted diseases, environmental factors, and lifestyle [3],[4],[5].

Chromosomal abnormalities is a term defining any defect in the genetic material of a chromosome in terms of structure or number, which contributes to 15%–30% of male infertility cases with various degrees of spermatogenic failure [2]. Infertile males have higher chances by 10 times to carry chromosomal abnormalities compared with the general male population [5]. The most common chromosomal abnormality among males with fertility complications is Klinefelter syndrome (47,XXY), which is a collection of symptoms linked with extra X chromosome and could be found as various subclasses such as 47,XXY, 48,XXXY, and 49,XXXXY [6]. Following Klinefelter syndrome, Y chromosome microdeletion is the second most common chromosomal abnormality triggering spermatogenic failure. Using the latest diagnostic platform of the multiplex-polymerase chain reaction (PCR), the Y chromosome microdeletion (YCMD) is detected for the loss of azoospermia factor (AZF) interval (AZFa AZFb, AZFc, and possible AZFd subintervals) that is located on the long arm of the Y chromosome. This interval harbors unique gene families controlling spermatogenesis in males [5,7]. Despite the availability of updated advanced diagnostic gene tests, the male reproductive health is still being evaluated based on descriptive semen parameters and hormone profile. As a result, the genetic cause driving male factor infertility remains unidentified around the globe, which shows global heterogeneity as associated with different genealogical lineages of different populations.

The production of healthy sperm is an essential phase in the reproduction and continuity of species. Spermatogenesis is an extraordinary complex process that involves a series of steps for spermatogonia to develop into spermatozoa in the seminiferous tubules of the testes. According to the latest edition of World Health Organization (WHO) criteria and guidelines (5th edition, 2009) of the male infertility [8], the most severe form of spermatogenic failure is characterized by a complete lack of mature sperm in semen, termed as azoospermia. Other forms of spermatogenic abnormalities include aspermia (a complete lack of semen), oligozoospermia (reduced sperm count), asthenozoospermia (abnormal sperm motility), and teratozoospermia (abnormal sperm morphology). Some males present a combination of impairments in semen parameters as oligoasthenoteratozoospermia (abnormal sperm number, motility, and morphology), asthenoteratozoospermia (abnormal sperm motility and morphology), and oligoasthenospermia (abnormal sperm number and motility) [8].

A range of hormones are used as a diagnostic marker for evaluating male fertility as gonadotrophin-releasing hormone, testosterone hormone, interstitial-cell stimulating hormone, follicle-stimulating hormone, and inhibin B hormone. In general, the hormonal imbalance influences the health of a male reproductive system. Elevated or reduced quantity of these hormones can cause defects in semen parameters and eventually lead to problems concerning male infertility [3].

In comparison with other parts of the world and as far as concerned, there is no detailed study on the chromosomal abnormalities as associated with any microdeletion on the AZF gene of the Y chromosome among males of the UAE population. For instance, a study by Al-Gazali et al. [9] was the first study on the presence of high rates of consanguineous and intratribal marriages (50.5%), which has been reported that these ethnic-driven practices provoke chromosomal and genetic defects as more than 270 genetic disorders were reported among Emirati population [9],[10],[11],[12],[13]. Furthermore, as yet, no data concerning genetic causes of male infertility in United Arab Emirates (UAE) have been reported despite its clinical implications. Therefore, the aim of this study is to determine the prevalence of numerical and structural chromosomal abnormalities among Emirati infertile males as compared to other regional as well as global profile, in which we have determined, for the first time, the chromosomal, hormonal, and semen abnormality profile associated with male factor infertility among the Emirati male population.

Materials and methods

Subjects and ethics

We have planned our study to cover up all the available and accessible data recorded for the 10-year retrospective cross-sectional study through examining medical records of patients’ semen and hormonal analysis reports in addition to chromosomal and genetic investigation reports. This included a total file of 312 male patients, who visited Dubai Fertility Center in UAE between January 2011 and January 2021. The established inclusion criteria concerned collecting the corresponding medical data for all males that are having infertility problems including males with primary and secondary infertility through the 10 years. The 312 patients were furthermore classified as 271 Emiratis and 41 non-Emiratis. No exclusion criteria were established as to cover all the accessible data in relevance with male infertility on full scale for all of the male patients.

The present study was conducted in accordance with the Declaration of University Student and Resident Research Committee, Dubai Health Authority (Reference USRRC09-29/PG/2020). Additionally, the research study was approved by Postgraduate Committee, University of Sharjah (session 9; dated February 3, 2020), and Dubai Scientific Research Ethics Committee, Dubai Health Authority (Reference DSREC-SR-09/2020_03).

Retrospective chart review of semen abnormalities

Medical records of the Dubai Fertility Center (DFC) for the 10-year retrospective period of study (2011–2021) were examined to identify the prevalence and type of semen abnormalities among the Emirati and non-Emirati male patients that performed semen analysis. This was conducted depending on the available reports of the male patients who performed semen analysis according to the normal reference range as set in the latest edition of WHO criteria and guidelines (5th edition, 2009) for the examination and processing of human semen [8].

Retrospective chart review of chromosomal abnormalities

Medical records of the DFC for the 10-year retrospective period of the study (2011–2021) were examined for the prevalence of the numerical and structural chromosomal abnormalities among the Emirati and non-Emirati male patients. This was conducted depending on the available reports of the male patients who performed cytogenetic analysis tests that included karyotyping and Y chromosome microdeletion screening according to the standard method of the International System of Cytogenetic Nomenclature and the recommendations of European Academy of Andrology (EAA) and the European Molecular Genetics Quality Network, respectively [14,15].

Retrospective chart review of hormonal abnormalities

Medical records of the DFC for the 10-year retrospective period of study (2011–2021) were examined to determine hormonal abnormalities among azoospermic males with chromosomal abnormalities compared to azoospermic males without chromosomal abnormalities and across the whole sample of Emirati cohort only. This was conducted depending on the available reports of the Emirati male patients that performed hormonal evaluations using blood tests for the following hormones: testosterone (350.0–865.0 ng/dL), interstitial-cell stimulating hormone (ICSH) (1.7–8.6 mIU/mL), follicle-stimulating hormone (FSH) (1.5–12.4 mIU/mL), and inhibin B (120–400 pg/mL) according to the normal reference ranges of human hormonal profiling stated by American Urological Association (AUA).

Results

This retrospective cross-sectional study compromised a sample of 312 infertile males of which 271 were Emirati nationals and 41 were non-Emiratis consisting of Arabs and non-Arabs. The Emirati patients were from different geographical regions across the UAE. The ethnic origin of the patients was not assessed. The average age of Emirati infertile males was 38.1 years old as it ranged from 24 to 66 years old with a median of 37 years [Table 1].

Table 1: Basic demographic and clinical characteristics of the study population during 10-year retrospective cross-sectional study (2011–2021).

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Across the Emirati cohort, a total of 249 patients performed semen analysis [Table 2], of which 147 males (59%) had azoospermia and 71 males (28.46%) were diagnosed with other conditions of spermatogenic failure, whereas 31 males (12.4%) were normozoospermic. Other conditions of spermatogenic failure detected among Emirati infertile males included severe oligoasthenoteratozoospermia (OAT) (n = 19; 7.63%), severe oligoasthenospermia (n = 13; 5.22%), severe oligozoospermia (n = 11; 4.41%), OAT (n = 9; 3.6%), asthenozoospermia (n = 6; 2.4%), oligoasthenospermia (n = 4; 1.6%), oligozoospermia (n = 5; 2%), teratozoospermia (n = 2; 0.8%), asthenoteratozoospermia (n = 1; 0.4%), and aspermia (n = 1; 0.4%). The range of the clinical conditions varies between minimum of 0.4% for asthenoteratozoospermia and aspermia, and the maximum of 59% for azoospermia [Table 2].

Table 2: Prevalence of semen profile among Emirati infertile males during 10-year retrospective cross-sectional study (2011–2021).

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Cytogenetic analysis showed that among 250 Emirati infertile males that performed chromosomal and genetic screening, 230 males (92%) had a normal karyotype of 46,XY and intact Y chromosome, whereas 20 males (8%) had various chromosomal abnormalities distinguished as numerical (n = 14; 70%) and structural (n = 6; 30%) aberrations. Among the Emirati infertile males carrying numerical and structural chromosomal abnormalities, 19 out of 20 patients showed semen profile of azoospermia except for one patient with XYY Jacobs syndrome who had OAT. The prevalence of total chromosomal abnormality resulting in azoospermic infertility was 13.9% (n = 19/136).

[Table 3] shows the prevalence of medical conditions caused by numerical chromosomal abnormalities among azoospermic males and total infertile males that involve 10 cases of Klinefelter syndrome (47,XXY), two cases of Jacobs syndrome (47,XYY), one case of mosaic (48,XXXY/47,XXY/46,XY), and one case of mosaic (47,XXY/46,XY). The prevalence of the numerical chromosomal abnormalities causing male infertility among total male population of Emirati was 4.0%, 0.8%, 0.4%, and 0.4% for Klinefelter syndrome (47,XXY), Jacobs syndrome (47, XYY), mosaic (48,XXXY/47,XXY/46,XY), and mosaic (47,XXY/46,XY), respectively. The range varies between the minimum of 0.4% for the last two conditions and the maximum of 4.0% for the first condition.

Table 3: Prevalence of the numerical chromosomal abnormalities during 10-year retrospective cross-sectional study (2011–2021) for the Emirati males.

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[Table 4] shows the prevalence of medical conditions caused by structural chromosomal abnormalities among azoospermic males and total infertile males, which involve three cases of YCMD, one case of 46,XY,inv(5)(p15.1q11.2), one case of 45,XY,der(13;15)(q10;q10), and one case of 46,XX/46,XY. The prevalence of the medical conditions causing male infertility among total male population of Emirati was 1.2%, 0.4%, 0.4%, and 0.4% for YCMD, 46,XY,inv(5)(p15.1q11.2), 45,XY,der(13;15)(q10;q10), and 46,XX/46,XY, respectively. The range varies between the minimum of 0.4% for the last three medical conditions and the maximum of 1.2% for the first condition. In a further conducted study, the azoospermic Emirati males were selected for further investigation to determine the types of genetic microdeletions on the AZFa,b,c,d gene cluster.

Table 4: Prevalence of the structural chromosomal abnormalities during 10-year retrospective cross-sectional study (2011–2021) for the Emirati males.

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[Table 5] shows the prevalence of hormonal abnormalities of azoospermic males with chromosomal abnormalities compared to azoospermic males without chromosomal abnormalities and across the whole sample of Emirati cohort. Upon comparing the hormonal profiles of azoospermic males with and without chromosomal abnormalities, azoospermic males with chromosomal abnormalities had a higher incidence of abnormalities in levels of testosterone, ICSH, FSH, and inhibin B hormones. The prevalence of hormonal abnormality among total Emirati infertile males was 47.6%, 37.5%, 37.0%, and 80% for testosterone, ICSH, FSH, and inhibin B, respectively. The range varies between the minimum of 37.0% for FSH abnormality and the maximum of 80% for inhibin B abnormality.

Table 5: Prevalence of testosterone, ICSH, FSH, and inhibin B abnormalities during 10-year retrospective cross-sectional study (2011–2021) for the Emirati males.

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The non-Emirati sample compromised of 41 infertile males, which included Arabs and non-Arabs from different geographical populations that lived in the UAE. The average age of non-Emirati infertile males was 41.53 years old as it ranged from 28 to 67 years old with a median of 41 years [Table 1].

Across the non-Emirati cohort, 35 patients performed semen analysis of which 28 males (80%) were diagnosed with azoospermia and four males (11.42%) were diagnosed with severe OAT, whereas only three males (8.57%) were normozoospermic. Cytogenetic analysis showed that among 41 non-Emirati infertile males that performed chromosomal and genetic screening, 36 males (87.8%) had a normal karyotype of 46,XY and intact Y chromosome, whereas five males (12.1%) had various chromosomal abnormalities distinguished as numerical (n = 3; 60%) and structural (n = 2; 40%) aberrations.

[Table 6] shows the detected chromosomal abnormalities among five non-Emirati patients as it included one case of mosaic 47,XXY/46,XY, one case of mosaic 47,XXY/45,X/ 46,XY, one case of mosaic 45X/46,XY, 45,XY,der (14;21)(q10;q10), and one case of 46,XY,t(inv)(3)(p11.2q13.2);13;6(q13.2;q12;q21). The prevalence of the chromosomal abnormalities causing male infertility among the male population of non-Emirati cohort was 2.43% for each condition. The patient with mosaic 45X/46,XY showed a semen profile of severe OAT, whereas the rest of four non-Emirati patients with chromosomal abnormalities showed azoospermia.

Table 6: Prevalence of the chromosomal abnormalities among non-Emirati infertile males during 10-year retrospective cross-sectional study (2011–2021).

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Discussion

In this retrospective cross-sectional study, we examined all accessible correlated data of samples of 312 infertile males in which 271 were Emirati nationals and 41 were non-Emiratis. We assessed the types and prevalence of chromosomal abnormalities among azoospermic infertile males and across total Emirati infertile males. So far, numerous types of numerical and structural chromosomal abnormalities have been reported. Among the Emirati society, at least 270 genetic diseases were reported as over 240 of these diseases were caused by single-gene defects [10],[11],[12]. Despite the fact that most genetic defects could be noticed in early stages of life due to the phenotypic outcome, in some cases, the genetic abnormality is not detected prior to adulthood. As such, chromosomal abnormalities inducing male infertility are identified later in life when the patient decides to become a father. Chromosomal abnormalities occur more frequently in males with spermatogenetic failure, particularly azoospermic male as compared to the general male population [5]. Likewise, in our Emirati cohort, the prevalence of total chromosomal abnormalities was 13.9% and 8% among azoospermic males and total infertile males, respectively. The most frequent chromosomal abnormality observed among total infertile males was Klinefelter syndrome (4.0%) followed by YCMD (1.2%) and then Jacob syndrome (0.8%). Among azoospermic infertile males, the most frequent chromosomal abnormality observed was Klinefelter syndrome (7.35%). Our observed a prevalence of chromosomal aberration among infertile males is in consistence with previously reported regional data. A retrospective study of 625 patients attending academic tertiary medical center in Qatar reported an overall prevalence of chromosomal abnormalities reaching 10.6% as Klinefelter syndrome (3.7%) was the most frequent abnormality followed by YCMD (2.5%) [16]. Likewise in Morocco, Naasse et al. [17] screened 573 infertile males for the detection of chromosomal abnormalities and reported a prevalence of 10.47% for total chromosomal abnormalities as Klinefelter syndrome (7.1%) was reported as the most common chromosomal defect followed by YCMD (2.7%). On the other hand, in southern China, Zhao et al. [18] reported a higher prevalence of total chromosomal abnormalities (22.81%) among 57 male patients with azoospermia and severe oligozoospermia as 36.64% of the patients had YCMD followed by Klinefelter syndrome (14.03%).

Klinefelter syndrome is more frequently reported among males with azoospermia compared to males with oligozoospermia. This reduced fertility in men with Klinefelter syndrome would clearly reduce the chances of fathering their own biological children naturally. Moreover, it is challenging for males with Klinefelter syndrome to benefit from testicular sperm extraction (TESE), intravascular embolization (IVE), and intracytoplasmic sperm injection (ICSI) procedures as no sperm could be retrieved [6]. In the present study, we found that all of our patients with Klinefelter syndrome (47,XXY) belonged to the azoospermia subgroup. Another numerical chromosomal abnormality associated with male infertility is Jacobs syndrome (47,XYY) in which two cases were detected among our Emirati cohort of infertile males. Similarly, Beg et al. [19] reported two cases of XYY males among 88 infertile males with azoospermia and severe oligozoospermia in western Saudi Arabia. Furthermore, Naasse et al. [17] reported one case of XYY male with azoospermia among 573 infertile males of Morocco. The clinical significance of XYY males encounters varying degrees of spermatogenetic failure ranging from reduced sperm to a complete lack of sperm in semen [20]. Similarly in our cohort, one patient with 47,XYY had azoospermia, whereas the other patient had OAT indicating the varying degree among males with this abnormality.

Chromosomal inversions are structural chromosomal defects that are defined as rearrangements occurring within same chromosome. Chromosomal inversion is classified as paracentric and pericentric inversion. In general, pericentric inversions do not seem to have a direct health implication on male fertility status as approximately 12% of pericentric inversion cases lead to complications of male reproductive health [21]. On another note, inversions within different chromosomes are associated with different clinical outcomes. Among our Emirati infertile male cohort, we identified an extremely rare case of an azoospermic male with a pericentric inversion of chromosome 5. The patient showed a karyotype of 46, XY,inv(5)(p15.1q11.2), which could be the first reported case among Emirati males since it is poorly described in the literature.

Besides chromosomal inversions, chromosomal translocations are classified as structural chromosomal abnormalities that exist as two types: reciprocal translocation and Robertsonian translocation. The clinical significance of males with Robertsonian translocation shows variations in semen quality as some may present abnormalities, whereas others may show normal semen profile [22,23]. Furthermore, in 2%–5% of the recurrent miscarriage cases, chromosomal translocations were carried by either the father or the mother [24]. Patients with Robertsonian translocation carry 45 chromosomes as a result of translocations that occur between two acrocentric chromosomes (13; 14; 15; 21; or 22). Robertsonian translocations commonly take place between chromosome 13 and chromosome 14 and between chromosome 14 and chromosome 21, whereas it is less frequent to take place between the rest of acrocentric chromosomes. In this report, we observed an extremely rare case of Robertsonian translocation that occurred between chromosomes 13 and 15. The patient showed a karyotype of 45,XY,der(13;15)(q10;q10) and severe phenotype of azoospermia. This chromosomal abnormality is poorly described in the literature, yet a case of female with this chromosomal abnormality was reported with severe infertility problems [25]. Furthermore, it is more likely that our patient is possibly the first Emirati male reported in the literature with such rare karyotype.

Numerical and structural chromosomal abnormalities have an obvious impact on male reproductive health through influencing spermatogenesis process and male hormonal status. Accordingly, identifying the genetic aberration as driving force for male infertility is crucial for appropriate fertility counseling. Our present study reported significantly a higher prevalence of abnormalities in the following hormones levels: testosterone, ICSH, FSH, and inhibin B, among azoospermic males with chromosomal abnormalities in comparison to azoospermic males without chromosomal abnormalities. In general, our results suggest consistency with other reports as a majority of patients with chromosomal anomalies showed hormonal imbalance and abnormal semen parameters [16,26]. In accordance with our findings and reported data in the literature, we noticed that inhibin B could be used as a marker for impaired spermatogenesis in infertile males, yet further studies are required [27],[28],[29].

In the present study, azoospermia was the most common type of semen abnormality with the highest prevalence of 59% compared with other semen abnormalities among Emirati infertile males. Our results are similar to that reported earlier for Saudi Arabia (sharing similar genetic pool of the Arabian origin of genealogy) where Al-Turki [30] reported a high prevalence of azoospermia among 475 Saudi infertile males reaching 68.5%. Comparing with our study, the prevalence of azoospermia was reported in lower rates among global populations such as that reported by Makwe et al. [31] as a low prevalence of azoospermia (10.2%) was observed, whereas asthenozoospermia (55.8%) was reported as the most common semen abnormality among the examination of 604 infertile males in Nigeria. Likewise, Öztekin et al. [32] reported a reduced prevalence of azoospermia (10.3%) among a total of 406 male patients visiting fertility clinic in Turkey. Additionally, Rodprasert et al. [33] evaluated a semen profile of 287 Finnish and 873 Dannish males in a cross-sectional study in which reported the prevalence of azoospermia to be 1% and 0.8% among Finnish and Dannish males, respectively. These variations may be due to the size of sample population, geographic location, cultural issues, or ethnic origin of the studied population.

Our observed finding regarding the high prevalence of azoospermia among males in UAE would possibly indicate the existence of other unknown or novel genetic, epigenetic, nutritional, or local environmental factors that trigger this clinical condition, and therefore, a further study is recommended to determine the AZFa,b,c,d gene cluster as it will shed light on a better understanding for management and may be gene therapy treatment of male infertility in the future. Furthermore, several studies reported a significant association between azoospermia and consanguinity [34],[35],[36]. Consanguinity is socially favored practice and is referred to the marriage of closely related relatives. Consanguinity increases the chances of recessive genes transmission inherited from the same ancestors, which as a result increases the chances of genetic disorders, congenital physical disabilities, and mental health problems [10,37]. In fact, the Emirati society is characterized by increasing rates of consanguineous marriages as the incidence increased from 39% to 50.5% within one generation [9, 10, 12], which falls within a similar profile rate of consanguinity reported for the Arabian Gulf Council countries that are characterized by high rates of consanguinity [12]. Studies on the association of consanguinity with male reproductive health are poorly reported in the Middle East, as some studies showed a negative impact of consanguinity on fertility status and reproductive health of males [34],[35], [36,38]. Baccetti et al. [39] reported an association of consanguinity with rare genetic sperm-defect syndromes as a result of detecting structural deformity in sperm head and tail among a group of infertile males born to consanguineous families. Structural deformity in sperm head and tail leads in altered forms of sperm within ejaculate that would thus reduce male’s fertility. These kinds of sperm alterations have shown to be higher among males born to consanguineous families compared with males born to nonconsanguineous families as it is assumed to get inherited over generations as a result of being clustered within consanguineous populations [36, 39, 40]. Other studies suggest that consanguineous marriages may produce infertile male offsprings, as more of infertile males than fertile males were the offspring of prior consanguineous unions [36, 41, 42, 43]. However, it is important to note that very few researches on the association of consanguinity and male infertility have been conducted; thus more studies are required to be conducted in this field.

Conclusions

In conclusion, the prevalence of chromosomal and genetic defects as a driving factor for male infertility among Emirati males falls within the regional and the global ranges. Chromosomal abnormalities are more common among consanguineous populations and have deleterious impact on the spermatogenesis and hormonal profile of males as reflected in our study. It has become clear to conclude that the high prevalence of azoospermia among males in UAE suggests the presence of some unique genealogical-genotypic profile causing such a high rate of infertility among UAE males as also seen with males of the same genealogy in Gulf countries. This shows the importance of further investigation to determine the AZFa,b,c,d gene cluster and to determine the microdeletion, which appeared to be associated with the genetic pool of UAE males genealogy. This, hopefully, will shed light on a better understanding and the management of infertility as may be toward gene therapy treatment of male infertility in the future. In fact, genetic counseling as karyotyping and YCMD screening is highly recommended to evaluate the etiology of infertility and to direct for appropriate treatment in addition to significantly reduce the vertical transmission of genetic abnormalities to the next generations. Further studies are required to identify other genetic factors as point mutations, smaller microdeletions, and duplications, which cannot be detected using conventional karyotyping.

Study limitations

The findings of this study have to be seen in lights of some limitations concerning a low number of sampling compromising of 312 male patients of the National Fertility Center during 10 years. Our explanation for the low turnover during 10 years is due to the reasons related to social and cultural limitations, patients–privacy requirements, and legal limitations. The first main reason is due to social concerns of which being linked with culture and privacy impact on the male infertility as many male patients prefer to travel abroad for examination and treatments. This is explained due to men’s preference in conserving their privacy as infertility is considered a sensitive topic in the Middle East Arab countries, making it challenging to approach males with infertility problems. Another concern is due to legal limitations as it is challenging to access clinical data from private fertility sectors. In fact, another main reason is due to Emirati population size as compared to regional and international high-populated countries. The following concerns are reflected in this study as we encountered limitations in data collection and accessibility.

Acknowledgments

The authors would like to express sincere appreciation to the Faculty of Dubai Fertility Center with sincere gratitude to all staff for their practical suggestions and kind cooperation.

Authors’ contributions

FE: investigation, methodology, article writing, review, and editing; IAM: conceptualization, investigation, methodology, project administration, supervision, article review, and editing.

Ethical statement

The present study was ethically approved by the University Student and Resident Research Committee (Reference USRRC09-29/PG/2020) on September 21, 2020, and Dubai Scientific Research Ethics Committee (DSREC; Reference DSREC-SR-09/2020_03) on September 22, 2020, of Dubai Health Authority, in addition to Postgraduate Committee, University of Sharjah (session 9) on February 3, 2020.

Financial support and sponsorship

Not applicable.

Conflicts of interest

There are no conflicts of interest.

Data availability statement

The data that support the findings of this study are available with the authors upon reasonable request.

Declaration of patient consent

Not applicable.

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