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Mohammad Khalaj Kondori
Reihaneh Amiri
Mehdi Haghi




Objective: premature ovarian insufficiency (POI) is defined as the loss of ovarian function before the age of 40 and affects approximately 1 percent of women. the disorder is clinically manifested by increased levels of follicle-stimulating hormone(FSH) (>40 IU/I), decreased levels of estradiol E2 (<20 IU/I) and secondary amenorrhea lasting for at least four months in women under 40 years of age. Numerous factors are involved in recurrent miscarriages, the most important of which are genetic factors like as chromosomal abnormalities and premutation in FMR1 gene in women. The present study aimed at investigating the relationship between the women s chromosomal abnormalities and premutation of FMR1 gene in women with premature ovarian insufficiency in the northwest of Iran.

Materials and methods: in the present applied research,50 women referring for POI were subjected to cytogenetic experiments via using the high resolution of GTG banding. Analysis of fragile x premutation were also conducted on the women based on PCR method.

Results: fifty patients were included, with a median age at menopause of 29 years. 15 out of 50 studied women (30 percent) were diagnosed with chromosomal abnormalities. 6 of these abnormalities were numerical one and nine of them were structural one. Out of 50 women subjected to FMR1 gene premutation,non of them show premutation.

conclusion: The rate of chromosome abnormalities in our sample was higher than in other populations while the prevalence of FMR1 premutation was lower than in other populations.

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1. Webber L, Davies M, Anderson R, Bartlett J, Braat D, Cartwright B, et al. management of women with premature ovarian insufficiency. European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI. Hum Reprod. 2016;31:926-37
2. Nelson L, Covington S, Rebar R. An update: spontaneous premature ovarian insufficiency is not an early menopause. Fertil Steril 2005;83:1327–32.
3. Nouha Bouali , Dorra Hmida , Soumaya Mougou , Jérôme Bouligand , Besma Lakhal , Sarra Dimessi , Bruno Francou , Ghada Saad , Saoussen Trabelsi , Monia Zaouali , Moez Gribaa , Molka Chaieb , Mouhamed Bibi , Anne Guiochon-Mantel , Ali Saad . Analysis of FMR1 gene premutation and X chromosome cytogenetic abnormalities in 100 Tunisian patients presenting premature ovarian failure. Ann Endocrinol (Paris). 2015 Dec;76(6):671-8.
4. Goswami D, Conway GS. Premature ovarian failure. Horm Res Pediatr 2007;68:196–202.
5. Simpson JL, Rajkovic A. Ovarian differentiation and gonadal failure. Am J Med Genet 1999;89:186–200
6. Qin Y, Jiao X, Simpson JL, Chen ZJ. Genetics of primary ovarian insufficiency: New developments and opportunities. Hum Reprod Update. 2015;21:787- 808
7. Liu J, Cox L. Primary ovarian insufficiency: an update. Int J Womens Health. 2014;6:235
8. Ana Raquel Neves , Ana Sofia Pais , Susana Isabel Ferreira , Vera Ramos , Maria João Carvalho , Alexandra Estevinho , Eunice Matoso , Fernanda Geraldes , Isabel Marques Carreira , Fernanda Águas . Prevalence of cytogenetic abnormalities and FMR1 gene premutation in a Portuguese population with premature ovarian insufficiency. Acta Med Port. 2021 Aug 31;34(9):580-585
9 Sarto G, Therman E, Patau K. X inactivation in man: a woman with t(Xq--;12q+). Am J Hum Genet. 1973;3:262–70.
10 . Greene AD, Patounakis G, Segars JH. Genetic associations with diminished ovarian reserve: A systematic review of the literature. J Assist Reprod Genet. 2014;31:935-46
11 . Utine GE, Şimşek-Kiper PÖ, Akgün-Doğan Ö, Ürel-Demir G, Alanay Y, Aktaş D, et al. Fragile x-associated premature ovarian failure in a large Turkish cohort: Findings of Hacettepe Fragile X Registry. Eur J Obstet Gynecol Reprod Biol. 2018;221:76-80.
12 . Wittenberger MD, Hagerman RJ, Sherman SL, McConckie-Rosell A, Welt C, Rebar RW, et al. The FMR1 premutation and reproduction. Fertil Steril. 2007;87:456-65.
13 Persani L, Rossetti R, Cacciatore C. Genes involved in human premature ovarian failure. J Mol Endocrinol 2010;45:257–79
14 Zinn AR, Page DC, Fisher EM. Turner syndrome: the case of the missing sex chromosome. Trends Genet 1993;9:90–3.
15 Zinn AR, Ross JL. Turner syndrome and haploinsufficiency. Curr Opin Genet Dev 1998;8:322-7.
16 Wittenberger MD, Hagerman RJ, Sherman SL, McConkie-Rosell A, Welt CK, Rebar RW, et al. The FMR1 premutation and reproduction. Fertil Steril 2007;87:456–65.
17 Bardoni B, Mandel JL. Advances in understanding of fragile X pathogenesis and FMRP function, and in identification of X linked mental retardation genes. Curr Opin Genet Dev 2002;12:284–93.
18 Murray A. Premature ovarian failure and the FMR1 gene. Semin Reprod Med 2000;18:59–66.
19 Allen EG, Sullivan AK, Marcus M, Small C, Dominguez C, Epstein MP, et al. Examination of reproductive aging milestones among women who carry the FMR1 premutation. Hum Reprod 2007;22:2142–52.
20 Coulam CB, Adamson SC, Annegers JF. Incidence of ovarian failure. Obstet Gynecol 1986;67:604–6.
21 Goswami D, Conway GS. Premature ovarian failure. Horm Res Pediatr 2007;68:196–202.
22 Jacquemont S, Hagerman RJ, Hagerman PJ, Leehey MA. Fragile-X syndrome and fragile X-associated tremor / ataxia syndrome : two faces of FMR1. Lancet Neurol. 2007;6:45-55.
23 Yrigollen C, Durbin-Johnson B, Gane L, Nelson DL, Hagerman R, Hagerman PJ, et al. AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome. Genet Med. 2012;14:729-36.