Document Type : Original Research


1 Cancer Molecular Pathology Research Center, Ghaem Medical Center Mashhad University of Medical Sciences, Mashhad, Iran

2 Medical Genetic Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Background & Objective: Primary amenorrhea refers to the absence of menstruation in females of reproductive by age 16 when the development of secondary sexual characteristics is evident (breast development, pubic hair) or by age 14 when there are no secondary sexual characteristics are present. Primary amenorrhea can occur in several quite different reasons. Common hormonal causes of primary amenorrhea include constitutional delay, hypothalamic or pituitary disorders, chronic systemic disease, and primary ovarian insufficiency, some endocrine gland disorders, and other causes. Previous studies suggested that chromosomal abnormality is the second most common cause of amenorrhea. This report aims to measure the prevalence of the chromosomal abnormality in primary amenorrhea (PA) patients in the northeast of Iran.
Methods: Chromosomal study was carried out on 200 patients with clinical features. The standard method for culturing peripheral venous blood lymphocyte was to prepare metaphase chromosomes and perform routine GTG band analysis.
Results: The results revealed that 71% of PA had normal female karyotype (46,XX) and 29% showed different chromosomal abnormalities. The chromosomal abnormalities can be categorized into seven primary groups with or without mosaicism. 1- The most common karyotype was X chromosome aneuploidy (10.5%, n=21), 2- Male karyotype with or without structural abnormality of Y chromosome (5.5 %, n=11), 3- Mosaicism of turner karyotype and structural anomalies of X chromosome (4%, n=8), 4- Structural anomalies of the X chromosome (3.5%, n=7), 5- Mosaicism of turner karyotype and normal karyotype (3%, n=6), 6- Mosaicism of turner karyotype and male karyotype (1.5%, n=3) and 7- Super female karyotype (1%, n=2).
Conclusion: The present study has emphasized that early cytogenetic and timely investigation can be necessary for the evaluation of primary amenorrhea.


Main Subjects

Berek JS, Hillard PJA. Berek & Novak's Gynecology 14th: Ed. Lippincott Williams & Wilkins; 2007.

Schorge JO, Hoffman BL, Bradshaw KD, Halvorson LM, Schaffer JI, Corton MM. Williams gynecology: McGraw-Hill Medical New York; 2008.

Ghosh S, Roy S, Pal P, Dutta A, Halder A. IS THERE ANY ROLE OF METAL TOXICITY IN AMENORRHEA? Malays J Med Res. 2017;1(4):40-4.

Pal AK, Ambulkar PS, Sontakke BR, Talhar SS, Bokariya P, Gujar VK. A Study on Chromosomal Analysis of Patients with Primary Amenorrhea. J Hum Reprod Sci. 2019;12(1):29-34. [DOI:10.4103/jhrs.JHRS_125_17] [PMID] [PMCID]

Rajangam S, Nanjappa L. Cytogenetic studies in amenorrhea. Saudi Med J. 2007;28(2):187-92.

Ayatollahi H, Safaei A, Vasei M. Cytogenetic analysis of patients with primary amenorrhea in Southwest of Iran. Iran J Pathol. 2010;5(3):121-6.

Asoke K. Pal, Prafulla S. Ambulkar, [...], and Vijay K. Gujar. A Study on Chromosomal Analysis of Patients with Primary Amenorrhea. J Hum Reprod Sci. 2019 Jan-Mar; 12(1): 29-34. [DOI:10.4103/jhrs.JHRS_125_17] [PMID] [PMCID]

Migeon BR, Lee CH, Chowdhury AK, Carpenter H. Species differences in TSIX/Tsix reveal the roles of these genes in X-chromosome inactivation. Am J Hum Genet. 2002;71(2):286-93. [DOI:10.1086/341605] [PMID] [PMCID]

Ghosh S, Roy S, Pal P, Dutta A, Halder A. Cytogenetic analysis of patients with primary amenorrhea in Eastern India. J Obstet Gynaecol. 2018;38(2):270-5. [DOI:10.1080/01443615.2017.1353595] [PMID]

Goswami R, Goswami D, Kabra M, Gupta N, Dubey S, Dadhwal V. Prevalence of the triple X syndrome in phenotypically normal women with premature ovarian failure and its association with autoimmune thyroid disorders. Fertil Steril. 2003;80(4):1052-4. [DOI:10.1016/S0015-0282(03)01121-X]

Gersen S, Keagle M. The principles of clinical cytogenetics. Gersen SL, Keagle MB, editors. New York: Springer; 2013 Mar 26.Roy S, Pal P, Dutta A, Ghosh S, Halder A. Isochromosome Xq: Not a rare finding in short stature females with amenorrhoea. Int J Curr Res. 2015;7(6):16876-80.

Ibarra-Ramírez M, Martínez-de-Villarreal LE. Clinical and genetic aspects of Turner's syndrome. Medicina universitaria. 2016;18(70):42-8. [DOI:10.1016/j.rmu.2016.03.003]

Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, et al. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature. 1990;346(6281):240. [DOI:10.1038/346240a0] [PMID]

Behtash N, Zarchi MK. Dysgerminoma in three patients with Swyer syndrome. World J Surg Oncol. 2007;5(1):71. [DOI:10.1186/1477-7819-5-71] [PMID] [PMCID]

Dumic M, Lin-Su K, Leibel NI, Ciglar S, Vinci G, Lasan R, et al. Report of fertility in a woman with a predominantly 46, XY karyotype in a family with multiple disorders of sexual development. J Clin Endocrinol Metab. 2008;93(1):182-9. [DOI:10.1210/jc.2007-2155] [PMID] [PMCID]

Roy A, Banerjee D. Cytogenetic study of primary amenorrhoea. J Indian Med Assoc. 1995;93(8):291-2.

Wong M, Lam S. Cytogenetic analysis of patients with primary and secondary amenorrhoea in Hong Kong: retrospective study. Hong Kong Med J. 2005;11(4):267.

Kalavathi V, Chandra N, Nambiar GR, Shanker J, Sugunashankari P, Meena J, et al. Chromosomal abnormalities in 979 cases of amenorrhea: a review. Int J Hum Genet. 2010;10(1-3):65-9. [DOI:10.1080/09723757.2010.11886086]

Vijayalakshmi J, Koshy T, Kaur H, Mary FA, Selvi R, Parvathi VD, et al. Cytogenetic analysis of patients with primary amenorrhea. Int J Hum Genet. 2010;10(1-3):71-6. [DOI:10.1080/09723757.2010.11886087]

Pidugu VK. Chromosomal abnormalities in amenorrhea: a retrospective study and review of 637 patients in South India. Arch Iran Med. 2013;16(5):267.

Bhuyan AK, Sarma D, Saikia UK. Contemporary issues in primary amenorrhea: an experience from a tertiary care center. Indian J Endocr Metab. 2012;16(Suppl 2):S387.

Agacayak E, Icen MS, Tunc SY, EVSEN M, Kalkanli S, Basaranoglu S. The frequency and the type of different etiological factors in primary amenorrhea. Acta Medica. 2014;30:383.

Malla TM, Dar FA, Pandith AA, Zargar MH. Frequency and pattern of cytogenetic alterations in primary amenorrhea cases of Kashmir, North India. Egypt J Med Hum. 2016;17(1):25-31. [DOI:10.1016/j.ejmhg.2015.07.005]

Turner Syndrome Society. (2017). Clinical practice guidelines for the care of women and girls with Turner syndrome. European Society of Endocrinology, 117:3, G1-G70. Retrieved 11/29/2017 from

Bondy CA. Turner syndrome 2008. Hormone Research in Paediatrics. 2009;71(Suppl. 1):52-6.Güzel Erdal G, Balkan M. Turner Syndrome with Isochromosome Xq. J Pediatr Genet. 2020 Dec;9(4):243-245. doi: 10.1055/s-0039-3399496. Epub 2019 Nov 6. PMID: 32765927; PMCID: PMC7396462.

Razavi, Z., Tabatabaei, S., Ansari, N., Shahbazi, M. Chromosomal Patterns, Demographics, Clinical Features, and Karyotype-Phenotype Correlation in Patients with Turner Syndrome. J Iran Med Council, 2019; 2(6): 192-200.

Peter James Ellis, Robert P. Erickson, in Fetal and Neonatal Physiology (Fifth Edition), 2017

King TF, Conway GS. Swyer syndrome. Current Opinion in Endocrinology, Diab Obes. 2014 Dec 1;21(6):504-10. [DOI:10.1097/MED.0000000000000113] [PMID]