Analysis of mutations of the MEFV gene in women with infertility and familial Mediterranean fever

The study of the relationship between mutations in the MEFV (MEditerranean FeVer) gene and infertility creates opportunity for optimizing the diagnosis and prevention of reproductive disorders in women with familial Mediterranean fever (FMF). Data were collected from the patients registered in 1998- 2018 at the Center for Medical Genetics and Primary Health Care. From the cohort of 32000 patients analyzed for mutations in the MEFV gene, only women (4577) of reproductive age (18-49 years old) were selected, with clinical diagnosis FMF according to the International Tel-Hashomer criteria and confirmed by genetic testing. Comprehensive monitoring of reproductive function was performed in 373 women - 211 FMF patients and 162 non FMF women with reproductive disorders. Homozygous genotype M694V/M694V (11.5%) is associated with severe disease and renal amyloidosis (1.5%) (p=0.028). Infertility was revealed in 90.9% patients homozygous for M694V and 100% for M680I mutations (p<0.009). M694V mutation in population of women of reproductive age was more common in FMF patients with infertility (68.8%) compare to fertile women (31.2%) (p<0.009). A clear correlation between irregular uptakes or a low dose of colchicine and infertility among investigated FMF patients (88.4%) (p <0.001) was revealed. A delayed diagnosis of over 10 years was observed in 80.7% of infertile patients with FMF compared with 19.3% in fertile women (p<0.007). Infertility is largely associated with homozygous M694V or M680I genotypes of MEFV gene. Patients with FMF have a comparable prior-reproductive system with healthy controls. Infertility is formed under the influence of modifying factors such as social status, irregular intake of colchicine, and delayed diagnosis for more than 10 years.

familial Mediterranean fever, mutations of the MEFVgene, homozygous, heterozygous, infertility, colchicine, in vitro fertilisation (IVF)

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