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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.

FMR1 Genotype with Autoimmunity-Associated Polycystic Ovary-Like Phenotype and Decreased Pregnancy Chance