A pilot study of premature ovarian senescence: II. Different genotype and phenotype for genetic and autoimmune etiologies.

OBJECTIVE: To assess whether abnormal autoimmune function and number of triple CGG repeats on the FMR1 (fragile X) gene, both historically associated with risk toward premature ovarian senescence, represent independent risk factors.
DESIGN: Retrospective cohort study.
SETTING: Academically affiliated, private fertility center. PATIENT(S): Forty consecutive, new infertility patients, of which 11 presented with a primary diagnosis of repeat pregnancy loss, 23 with prematurely elevated, age-specific baseline follicle stimulating hormone (FSH) levels (i.e., premature ovarian aging) and 6 with premature ovarian failure. INTERVENTION(S): Determination of triple CGG repeats on both alleles of the FMR1 gene, assessment of ovarian reserve via FSH and anti-Müllerian hormone levels, and evaluation of autoimmune status by antiphospholipid antibody panel, antinuclear antibody panel, total immunoglobulin levels (IgG, IgM, IgA), thyroid antibodies (antiglobulin and antimicrosomal), antiovarian, and antiadrenal antibodies. RESULT(S): Twenty-two of 40 patients (55%) demonstrated autoimmune abnormalities. Women with and without autoimmune abnormalities did not differ in age. Patients with autoimmune abnormalities, however, demonstrated significantly lower FSH levels and higher anti-Mullerian hormone levels. Although triple repeats on the lower count allele (allele-1) of the FMR1 gene did not differ statistically, autoimmune patients demonstrated in the higher count allele (allele-2) significantly fewer triple repeats, significantly fewer triple repeats >or=30, and, in contrast to nonautoimmune patients, a normal mean level of triple repeats. CONCLUSION(S): Abnormal autoimmune function and expansions in triple CGG repeats on the FMR1 gene represent distinctively different etiologies for premature ovarian senescence in infertile patients and may, indeed, constitute its two principal causes.