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Background  Hypothesizing that redundant functional ovarian reserve (FOR) at young ages may clinically obfuscate prematurely diminished FOR (PDFOR), we investigated in young oocyte donors genotypes and sub-genotypes of the  FMR1  gene, in prior studies associated with specific ovarian aging patterns, and determined whether they already at such young age were associated with variations in ovarian reserve (OR). We also investigated racial as well as  FMR1  associations with menarcheal age in these donors.    Methods  In a cohort study we investigated 157 oocyte donor candidates and, based on the 95% CI of AMH, divided them into normal age-specific (AMH greater or equal to 2.1 ng/mL; n = 121) and PDFOR (AMH < 2.1 ng/mL; n = 36). We then assessed associations between numbers of trinucleotide repeat (CGGn) on the  FMR1  gene and FOR (based on anti-Müllerian hormone, AMH).    Results   FMR1  did not associate with AMH overall. Amongst 36 donors with PDFOR, 17 (42%) presented with at least one  low  (CGGn < 26 ) allele. Remaining donors with normal FOR presented with significantly more CGGn greater or equal to 26 (73.6% vs. 26.4%; P = 0.024) and higher AMH (P = 0.012). This finding was mostly the consequence of interaction between  FMR1  (CGGn < 26 vs. CGGn greater or equal to 26) and race (P = 0.013), with Asians most responsible (P = 0.009). Menarcheal age was in donors with normal FOR neither associated with race nor with  FMR1  status. In donors with PDFOR race was statistically associated with CGGn (P = 0.018), an association primarily based on significantly delayed age of menarche in African donors with CGGn < 26 in comparison to African donors with CGGn greater or equal to 26 (P = 0.019), and Caucasian (P = 0.017) and Asian donors (P = 0.025) with CGGn < 26.    Conclusions  CGGn on  FMR1  already at young ages affects FOR, but is clinically apparent only in cases of PDFOR. Screening for  low FMR1  CGGn < 26 at young age, thus, appears predictive of later PDFOR.

FMR1-dependent variability of ovarian aging patterns is already apparent in young oocyte donors