The Frequency of the Fragile X Syndrome Intermediate Allele and Premutation in Women with Diminished Oocyte Reserve (Dor) vs Normal Oocyte Reserve (NOR)
Naomi S Ganpo-Nkwenkwa, Sarah Deigan, and Jerome H Check*
ABSTRACT
Fragile X is a genetic disorder that causes developmental and behavioral issues. It is well known that patients who are carriers of the Fragile X gene have a higher frequency of diminished ovarian reserve (DOR). The purpose of this study was to determine the frequency of the Fragile X intermediate allele and premutation in women with DOR versus NOR. A Beacon Carrier Expanded Gene 436 sequencing test with deletion and duplication analysis was performed on 350 consecutive females with a history of infertility. Patients found to have the Fragile X Intermediate Allele or a Fragile X premutation were identified. DOR was defined as having a serum antimullerian hormone (AMH) level of less than 1 ng/mL, compared to those women with NOR with a serum AMH > 1 ng/mL. Finally, the portion of women with the Fragile X intermediate allele or premutation who also had DOR were evaluated. For those with DOR who had carrier screening for the first time, the frequency of either Fragile X intermediate alleles or the Fragile X premutations was 7 of 142 (4.3%). Six of those individuals had the intermediate alleles, while one had the premutation. For those with NOR on the first screening, there were 207 women. 3 (1.5%) were positive for the Fragile X intermediate alleles, and none had the premutation. Thus, of 9 women with the Fragile X intermediate alleles, 6 (66.7%) had DOR. 96% of cases of DOR were not associated with the Fragile X intermediate allele or premutation. Women with the Fragile X premutation are known to be at risk for gonadotoxicity and DOR. The converse is not true, women with DOR do not have a high frequency of Fragile X premutation or even the less clinically important intermediate allele. Therefore, in patients attempting to conceive, routine Fragile X carrier screening may not be necessary in women with DOR any more than in those with NOR.
