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

Reproductive Biology and Endocrinology

Andrea Weghofer²  Vitaly A Kushnir¹  Ho-Joon Lee¹  Tamar Michaeli¹  Emanuela Lazzaroni¹  Aya Shohat-Tal¹  David H Barad³  Ann Kim¹  Norbert Gleicher³ 

[1] Center for Human Reproduction, 10021, New York, NY, USA;Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University Vienna, 1090, Vienna, Austria;Foundation for Reproductive Medicine, 10021, New York, NY, USA

关键词: Oocyte donor;    Anti-müllerian hormone (AMH);    Ovarian reserve;    FMR1 gene;    Fragile X gene;   

Others  :  810816
DOI  :  10.1186/1477-7827-11-80

 received in 2013-06-06, accepted in 2013-08-08,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Gleicher et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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