Journal Information
Journal ID (publisher-id): JRI
ISSN: 2228-5482
ISSN: 2251-676X
Publisher: Avicenna Research Institute
Article Information
Copyright © 2010 Avicenna Research Institute
open-access: This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.
ReceivedDay: 14Month: 04Year: 2010
AcceptedDay: 14Month: 07Year: 2010
Print publication date: Season: Oct-DecYear: 2010
Volume: 11Issue: 3
First Page: 179Last Page: 181
Publisher Id: JRI-11-179

Cytogenetic Results of Patients with Infertility in Middle Anatolia, Turkey: Do Heterochromatin Polymorphisms Affect Fertility?
Ahmet OkayCaglayan1*
1Department of Medical Genetics, Kayseri Education and Research Hospital, Kayseri, Turkey
2Department of Medical Genetics, Faculty of Medicine, Erciyes University, Kayseri, Turkey
*Corresponding Author: Dr. Ahmet Okay Caglayan, Department of Medical Genetics, Kayseri Education and Research Hospital, Kayseri, Turkey.


Infertility is a significant multifactorial disorder that can be caused by chromosomal abnormalities. In this study, we aimed to cytogenetically investigate male and female patients admitted to the Genetic Diagnostic Laboratory of Kayseri Educational Hospital in Kayseri, Turkey with varied clinical prediagnoses of infertility.

Materials and Methods

Chromosomes from cultured peripheral blood lymphocytes of 274 patients and 427 individuals as the controls were analyzed using GiemsaTrypsin-Giemsa (GTG) banding. The individuals with sex chromosome aneuploidy or mosaicism were classified as carriers and with chromosomal polymorphism, respectively. The results of the two groups were compared statistically.


Pure sex chromosome aneuploidy was found in 29 (10.5%) patients and mosaic sex chromosome aneuploidy in 15 (5.5%) cases and the total rate of abnormalities was 16%. Karyotypes were composed of an overall polymorphism rate of 8% in the patient and 4% in the control groups with no statistically significant difference (p = 0.2 and p > 0.05, respectively).


The present study shows that chromosomal polymorphisms are common among infertile patients. Chromosomal abnormalities and even heteromorphisms are significant etiologic factors leading to fertility problems.

The overall high prevalence of chromosomal polymorphisms in infertile couples, compared to the normal population, needs to be confirmed with further investigations and larger study populations to delineate the role of “harmless” chromosomal aberrations in the etiology of infertility.


Infertility is a significant marital problem, affecting up to 15% of couples of reproductive age (1). Infertility can be caused by defects in the development of the urogenital system or its function by genetic defects of the endocrine system, including the hypothalamic-pituitarygonadal axis, or by defects in gametogenesis, sexual function, fertilization or early embryonic development.

Secondary or acquired infertility, such as after-tubal diseases, vasectomy or exposure to gonadotoxins, may occur (2). Cytogenetic abnormalities (both somatic and meiotic) are a major cause of male infertility (3). Cytogenetic studies have been reported to determine the contribution of chromosomal abnormalities in parents with reproductive failure from various countries (46). The aim of the present study was to evaluate the prevalence and nature of chromosomal aberrations in Turkish couples with infertility in middle Anatolia, Turkey, as there seemed to be an inadequate number of studies done in this region.

Materials and Methods

In a period between January 1998 to January 2009, 151 female and 123 male patients (n = 274) were referred to the Department of Medical Genetics for chromosome analysis as part of their infertility work up. In addition, 427 individuals who were undergoing different work ups other than infertility and had one or more children were simultaneously analyzed for polymorphisms. All the patients were evaluated by a skilled medical specialist and tested for antiphospholipid antibodies and relevant hormones. Ultrasouography was done to rule out other causes of infertility.

Cytogenetic Analysis

Chromosome preparations were obtained from routine peripheral blood lymphocyte cultures. A minimum of twenty GTG banded metaphases (minimally, 500-band level) were analyzed for each person. Karyotypes were recorded according to the recommendations of the International Standing Committee on Human Cytogenetic Nomenclature 1995 (7).

The purpose of the study was explained to the patients, and informed consent forms were signed by them. The institutional ethics committee approval was obtained before beginning the study.

Statistical Analyses

The results of the two groups were compared by two-tailed Fisher's exact test, and calculated online at GraphPad Software website (8).


We classified the individuals with sex chromosome aneuploidy or mosaicism as carriers and individuals with chromosomal polymorphism (Table 1). Pure sex chromosome aneuploidy was found in 29 (10.5%) and mosaic sex chromosome aneuploidy in 14 (6.5%) patients, putting the total rate of abnormalities at 16.1%. The karyotypes were composed of an overall polymorphisms rate of 8% in the patient and 4% in the control groups which were not statistically different, (respectively, p = 0.2 and p > 0.05, confidence level: 87.4%).


Reproductive disorders are closely associated with cytogenetic abnormalities. Studies have demonstrated that 2 – 14% of infertile men have constitutional chromosomal abnormalities. The prevalence of chromosomal aberrations is dependent on the definition of ‘infertility’, and is approximately 2% in males with combined indications of infertility (9), 5% in men with oligozoospermia and 14% with azoospermia (10).

The most common types of karyotypic abnormality include sex chromosomal abnormalities and Robertsonian translocations. The frequency of somatic chromosomal abnormalities in infertile men varies from 3% – 19%: that is 3% in the cases of mild infertility and 19% in men with nonobstructive azoospermia (NOA).

In the present study, we did not find any structural mutations in the patients, perhaps due to our strictly selected study population, but a high frequency of Klinefelter's karyotype was detected. Earlier studies had not investigated polymorphism and chromosomal aberrations as a determining factor in infertility in Kayseri, Turkey, therefore, this study could be of importance in this regard (11, 12).

Morphological variations of constitutive heterochromatin are frequently detected during routine cytogenetic analysis. Most often, chromosomes vary in size and position of heterochromatin in 1qh, 9qh, and 16qh regions. Although inherited variants have been reported not to be associated with any risk for phenotypic abnormalities, chromosomal heteromorphisms have been found to have a higher frequency relative to the normal population and have been regarded as abnormalities in some studies (5, 8, 13, 14). Recent studies suggest that classical euchromatic variants of 9q12/qh+ and heteromorphism on chromosome 6q may be responsible for recurrent abortions (15, 16). However, no statistical association was found between heteromorphism and infertility.

In recent years, reproductive problems have been associated not only with somatic chromosomal abnormalities but also with cytogenetic ones in the germ cells of infertile individuals with a normal constitutional karyotype (3). Research in this area has become more clinically relevant in the past few years with the advent of intracytoplasmic sperm injection (ICSI). Sperm chromosome complements in infertile men with normal 46,XY karyotype have been studied to determine whether meiosis in these men is prone to errors of nondisjunction, leading to aneuploidy. Unfortunately, the laboratory was not provided with semen samples for cytogenetic examination. Thus, we were not able to directly confirm seminal abnormalities or the direct influence of these chromosomes on spermatogenesis.


The way chromosomal abnormalities affect gametogenesis or embryogenesis is not explicitly evident and reaching a common conclusion demands further investigation in this field.

1. de KretserDM. Male infertilityLancet1997;349(9054):787–90.Review
2. KamelRM. Management of the infertile couple: an evidence-based protocolReprod Biol Endocrinol.2010;8:21.
3. ShahK, SivapalanG, GibbonsN, TempestH, GriffinDK. The genetic basis of infertilityReproduction.2003;126(1):13–25.
4. Cortés-GutiérrezEI, Cerda-FloresRM, Dávila-RodríguezMI, Hernández-HerreraR, Vargas-VillarrealJ, Leal-GarzaCH. Chromosomal abnormalities and polymorphisms in Mexican infertile menArch Androl.2004;50(4):261–5.
5. NakamuraY, KitamuraM, NishimuraK, KogaM, KondohN, TakeyamaM, et al.Chromosomal variants among 1790 infertile menInt J Urol.2001;8(2):49–52.
6. LissitsinaJ, MikelsaarR, PunabM. Cytogenetic analyses in infertile menArch Androl.2006;52(2):91–5.
7. 1st ed. Basel: Karger Publishers; 2005. International Standing Committee on Human Cyto-genetic Nomenclature; Shaffer LG, Tommerup N. ISCN 2005: an international system for human cytogenetic nomenclature.
8. CaglayanAO, OzyazganI, DemiryilmazF, OzgunMT. Are heterochromatin polymorphisms associated with recurrent miscarriage?J Obstet Gynaecol Res.2010;36(4):774–6.
9. MeschedeD, LouwenF, EibenB, HorstJ. Intra-cytoplasmic sperm injection pregnancy with fetal trisomy 9p resulting from a balanced paternal translocationHum Reprod.1997;12(9):1913–4.
10. JohnsonMD. Genetic risks of intracytoplasmic sperm injection in the treatment of male infertility: recommendations for genetic counseling and screeningFertil Steril.1998;70(3):397–411.
11. KumtepeY, BeyazyurekC, CinarC, OzbeyI, OzkanS, CetinkayaK, et al.A genetic survey of 1935 Turkish men with severe male factor infertilityReprod Biomed Online.2009;18(4):465–74.
12. VicdanA, VicdanK, GünalpS, KenceA, AkarsuC, IşikAZ, et al.Genetic aspects of human male infertility: the frequency of chromosomal abnormalities and Y chromosome microdeletions in severe male factor infertilityEur J Obstet Gynecol Reprod Biol.2004;117(1):49–54.
13. YakinK, BalabanB, UrmanB. Is there a possible correlation between chromosomal variants and spermatogenesis?Int J Urol.2005;12(11):984–9.
14. MadonPF, AthalyeAS, ParikhFR. Polymorphic variants on chromosomes probably play a significant role in infertilityReprod Biomed Online2005;11(6):726–32.Review
15. DundarM, CaglayanAO, SaatciC, BatukanC, BasbugM, OzkulY. Can the classical euchromatic variants of 9q12/qh+ cause recurrent abortions?Genet Couns.2008;19(3):281–6.
16. CaglayanAO, OzgunMT, DemiryilmazF, OzyazganI. Can heterochromatin polymorphism of chromosome 6 affect fertility?Genet Couns.2009;20(2):203–6.

[TableWrap ID: T0001] Table 1 

The patients’ karyotypes and their relevant frequencies

Karyotype Frequency Percentage (%)
46,XX 145 53
46,XY 73 26,7
Sex Chromosome Aneuploidies
  mos 45,X / 46,XY 4 1,5
  mos 45,X / 47,XXX / 46,XX 1 0,4
  mos 45,X / 47,XXX / 46,XX 1 0,4
  mos 47 XXY / 48 XXXY / 46 XX / 46 XY 1 0,4
  47,XXY 29 10,5
  mos 47,XXY/46,XY 8 2,9
  46,XX 16 qh+ 4 1,5
  46,XY Yqh+ 5 1,82
  46,XYqh- 2 0,9
  46,XY inv (9) (p11q12) yqh+ 1 0,5
  46,XY 1qh+ 1 0,5

Article Categories:
  • Original Article

Keywords: Chromosomal aberration, Cytogenetics, Infertility, Karyotype, Polymorphism, Sex chromosome aneuploidy.