ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Reproduction
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1609471
The association of CGG repeat length and AGG interruption patterns on FMR1 alleles with female infertility
Provisionally accepted
- 1Fudan University, Shanghai, Shanghai Municipality, China
- 2Peking Union Medical College Hospital (CAMS), Beijing, Beijing Municipality, China
- 3Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
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The aim of the present study was to investigate whether the CGG repeat length and AGG interruption patterns on the FMR1 gene affect female fecundity.Methods: A total of 266 infertile patients and 276 fertile controls were included in the study. All participants received FMR1 testing using triplet repeat primed PCR and capillary electrophoresis.The allele with the smaller number of CGG repeats was defined as "allele 1", and the allele with the larger number of CGG repeats was defined as "allele 2".The mean number of CGG repeat length at allele 2 in the secondary infertility group was higher than that in the control group (33.1 ± 6.7 vs 30.9 ± 3.3, Bonferroni corrected p=0.003). The proportion of 35-44 CGG repeat at both FMR1 alleles showed a higher trend in the secondary infertility group as compared to the control group after adjusting for age, education, smoking status, cohort and the CGG repeats of the other FMR1 allele (aOR=7.812, 95% CI 0.884-69.001; p=0.064 for allele 1; aOR=3.657, 95% CI 2.193-6.098; p<0.001 for allele 2, respectively). Lower AMH levels were associated with increased CGG repeat length at allele 1 in infertile patients (Adjusted R 2 =0.178, p=0.003) after adjusting for age, education, smoking status, infertility type and the CGG repeats of FMR1 allele 2. However, no significant correlation was found between the number of CGG repeats at allele 2 and AMH levels (Adjusted R 2 =0.150, p=0.086). Although the difference was not statistically significant, there was a higher proportion of 3 AGG interruptions at both alleles in the secondary infertility group as compared to the control group (6.1% vs 0%, p=0.146 for allele 1, 30.6% vs 11.3%, p=0.099 for allele 2). Patients with 35-44 CGG repeat length showed a higher carrier rate of 3 AGG interruptions at both alleles (p<0.001 for both).Conclusions: Overall, the high normal sized (35-44 CGG) repeat length at both FMR1 alleles may serve a promoting role in the development of secondary infertility in Asian women. In addition, the CGG repeat length at allele 1 appears to have a mild correlation with AMH levels in infertile patients.
Keywords: Allele 1, FMR1 gene, Female fecundity, AGG interruption, fragile X screening
Received: 10 Apr 2025; Accepted: 21 May 2025.
Copyright: © 2025 xuanyou, naixin, xianling, weihui, Shuyaun, Songchang and Chenming. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chen Songchang, Fudan University, Shanghai, 200433, Shanghai Municipality, China
Xu Chenming, Fudan University, Shanghai, 200433, Shanghai Municipality, China
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