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The association between a carrier state of FMR1 premutation and numeric sex chromosome variations

  • Genetics
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Abstract

Purpose

Women carriers of FMR1 premutation are at increased risk of early ovarian dysfunction and even premature ovarian insufficiency. The aim of this study was to examine a possible association between FMR1 permutation and numeric sex chromosome variations.

Methods

A retrospective case-control study conducted in the reproductive center of a university-affiliated medical center. The primary outcome measure was the rate of sex chromosomal numerical aberrations, as demonstrated by haplotype analyses, in FMR1 premutation carriers compared to X-linked preimplantation genetic testing for monogenic/single gene defect (PGT-M) cycles for other indications that do not affect the ovarian follicles and oocytes.

Results

A total of 2790 embryos with a final genetic analysis from 577 IVF PGT-M cycles were included in the final analysis. Mean age was similar between the groups, however, FMR1 carriers required more gonadotropins, and more women were poor responders with three or less oocytes collected. The ratio of embryos carrying a numeric sex chromosome variation was similar: 8.3% (138/1668) of embryos in the FMR1 group compared to 7.1% (80/1122) in the controls. A subgroup analysis based on age and response to stimulation has not demonstrated a significant difference either.

Conclusions

Although carriers of FMR1 premutation exhibit signs of reduced ovarian response, it does not seem to affect the rate of numeric sex chromosomal variation compared to women undergoing PGT-M for other indications. This suggests that the mechanism for chromosomal number aberrations in women at advanced maternal age are different to those FMR1 premutation carriers with poor ovarian reserve.

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Funding

No funding was received for conducting this study.

Author information

Author notes

  1. Mira Malcov and Ophir Blickstein equally contributed to this work.

Authors and Affiliations

  1. IVF Unit, Lis Maternity Hospital, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Mira Malcov, Ophir Blickstein, Adi Reches, Yael Kalma, Yuval Fouks, Foad Azem & Yoni Cohen

  2. Genetic Institute at Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Dana Brabbing-Goldstein & Adi Reches

  3. Boston IVF-The Eugin Group, Waltham, MA, USA

    Yuval Fouks

Authors
  1. Mira Malcov
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  2. Ophir Blickstein
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Corresponding author

Correspondence to Yoni Cohen.

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Ethics approval and consent to participate

The institution review board (IRB) of Tel Aviv Sourasky Medical Center approved the study (Approval number: 0149-20-TLV).

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The authors declare that they have no conflicts of interest.

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Supplementary information

Supplemental Table 1

Indication for PGT-M in the control group (DOCX 30.2 kb)

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Malcov, M., Blickstein, O., Brabbing-Goldstein, D. et al. The association between a carrier state of FMR1 premutation and numeric sex chromosome variations. J Assist Reprod Genet 40, 683–688 (2023). https://doi.org/10.1007/s10815-023-02730-1

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  • DOI: https://doi.org/10.1007/s10815-023-02730-1

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