FMR1 gene alleles in infertile women with primary ovarian insufficiency, diminished ovarian reserve and poor response to ovarian stimulation

Abstract

Expansions in the number of CGG repeats in the fragile X mental retardation 1 (FMR1) gene are associated with increased mRNA levels that exert a toxic effect on ovarian follicles. Our aim is to determine whether expansions of the FMR1 gene between 35 – 54 repeats are more frequent in infertile women with an alteration of the ovarian function (primary ovarian insufficiency (POI), diminished ovarian reserve (DOR) and poor response (PR) to controlled ovarian stimulation (COS). Observational study. We analyzed the files of 101 infertile women referred from the Infertility Unit to the genetic Unit of the Cochin Hospital for FMR1 gene testing and karyotpe between 01/08 and 08/11. We classified 85 women in whom FMR1 testing was performed in 5 groups according to the motive for genetic testing: 1) POI (FSH>11 IU/L with amenorrhea/irregular cycles) 2) DOR (regular cycles and FSH>11 UI/L, AMH<1ng/ml and/or antral follicle count<6), 3) PR (cancellation during COS or<6 follicles retrieved), 4) PR associated with DOR 5) family history only. Ten of the 85 (11.8%) women with an FMR1 testing had alleles between 35 - 54 repeats, and two women (2.4%) had alleles in the premutation range.Table 1FMR1 alleles in infertile women according to the motive of genetic testingAllele 1/Allele 2 §AllPOIDORPRDOR+PRFamily historyN=85N=17N=33N=14N=17N=4Normal/Normal73152811154Normal/Upper normal722210Normal/Intermediate3011∗1 woman had 2 intermediate range alleles § Definition of CGG repeats: Normal<35, upper normal 35-44, intermediate 45-54, premutation 55-199.10Normal/Premutation202000∗ 1 woman had 2 intermediate range alleles § Definition of CGG repeats: Normal<35, upper normal 35-44, intermediate 45-54, premutation 55-199. Open table in a new tab In infertile women tested for an ovarian function alteration, alleles between 35 – 54 repeats are more frequent (11.8%) than in the general population in which the reported frequency of these alleles is approximately 6% (Bretherick et al. 2005). In infertile women, FMR1 testing can provide an explanation for the alteration of the ovarian function.