Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Dec 16;5(12):e15303.
doi: 10.1371/journal.pone.0015303.

FMR1 genotype with autoimmunity-associated polycystic ovary-like phenotype and decreased pregnancy chance

Norbert Gleicher  1 , Andrea Weghofer, Irene H Lee, David H Barad
Affiliations

FMR1 genotype with autoimmunity-associated polycystic ovary-like phenotype and decreased pregnancy chance

Norbert Gleicher et al. PLoS One. .

Abstract

The FMR1 gene partially appears to control ovarian reserve, with a specific ovarian sub-genotype statistically associated with a polycystic ovary (PCO)- like phenotype. Some forms of PCO have been associated with autoimmunity. We, therefore, investigated in multiple regression analyses associations of ovary-specific FMR1 genotypes with autoimmunity and pregnancy chances (with in vitro fertilization, IVF) in 339 consecutive infertile women (455 IVF cycles), 75 with PCO-like phenotype, adjusted for age, race/ethnicity, medication dosage and number of oocytes retrieved. Patients included 183 (54.0%) with normal (norm) and 156 (46%) with heterozygous (het) FMR1 genotypes; 133 (39.2%) demonstrated laboratory evidence of autoimmunity: 51.1% of het-norm/low, 38.3% of norm and 24.2% het-norm/high genotype and sub-genotypes demonstrated autoimmunity (p=0.003). Prevalence of autoimmunity increased further in PCO-like phenotype patients with het-norm/low genotype (83.3%), remained unchanged with norm (34.0%) and decreased in het-norm/high women (10.0%; P<0.0001). Pregnancy rates were significantly higher with norm (38.6%) than het-norm/low (22.2%, p=0.001). FMR1 sub-genotype het-norm/low is strongly associated with autoimmunity and decreased pregnancy chances in IVF, reaffirming the importance of the distal long arm of the X chromosome (FMR1 maps at Xq27.3) for autoimmunity, ovarian function and, likely, pregnancy chance with IVF.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts: NG and DHB are listed as co-inventors on a number of pending United States patents and one already granted patent, which, peripherally, relate to this manuscript. Those patents claim: (1) Therapeutic benefits from supplementation of women with DOR with dehydroepiandrosterone (DHEA). Since some patients in this study were DHEA supplemented, this may have relevance. (2) Diagnostic benefits from determining triple CGG nucleotide repeats on the FMR1 gene in attempts to assess and predict ovarian reserve. NG is owner of the Center for Human Reproduction (CHR), where this study was conducted. The authors confirm that these conflicts do not alter our adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Prevalence of autoimmunity in reference to FMR1 genotype.
The prevalence of autoimmunity was in both patient groups the highest with het-norm/low FMR1 genotype and the lowest with het-norm/high genotype. This pattern, however, intensified in women with PCO-like phenotype. Gray bars represent women with normal ovarian reserve; white bars represent the PCO-like phenotype.
Figure 2
Figure 2. Pregnancy rates in IVF based on FMR1 genotype.
Pregnancy rates were the highest with norm FMR1 genotype and the lowest with het-norm/low genotype.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hundscheid RDL, Braat DDM, Kiemaney LALM, Smits APT, Thomas CMG. Increased serum FSH in female fragile X premutation carriers with either regular menstrual cycles or on oral contraceptives. Hum Reprod. 2001;16:457–462. - PubMed
    1. Welt CK, Smith PC, Taylor AE. Evidence of early ovarian aging in fragile X premutation carriers. J Clin Endocrinol Metab. 2004;89:4569–4574. - PubMed
    1. Bretherick KL, Fluker MR, Robinson WP. FMR1 repeat sizes in the gray zone and high end of normal range are associated with premature ovarian failure. Hum Genet. 2005;117:376–382. - PubMed
    1. Bodega B, Bione S, Dalprà L, Toniolo D, Ornaghi F, et al. Influence of intermediate and uninterrupted FMR1 CGG expansionsin premature ovarian failure manifestations. Hum Reprod. 2006;21:952–957. - PubMed
    1. Gleicher N, Weghofer A, Barad DH. A pilot study of premature ovarian senescence. I. Correlation of triple CGG repeats on the FMR1 gene to ovarian reserve parameters FSH and anti-Müllerian hormone. Fertil Steril. 2009;91:1700–1706. - PubMed

Publication types

Substances