Do FMR1 Premutation Carriers Experience Different Performance during IVF-PGT-M Cycles? A Comparison versus Autosomal Dominant Disorder Carriers

Aims:
To compare the performance of Fragile X mental retardation -1 (FMR1) premutation carriers (PM) vs. those with autosomal dominant (AD) diseases during IVF PGT-M cycles.

M & M:
A cohort historical study of all patients with FMR1 PM and AD diseases undergoing their first IVF, PGT-M cycle during a 13 years` period.

Results:
As premutation carriers with < 200 CGG repeats have increased risk of diminished ovarian reserve they were evaluated separately from carriers with ≥ 200 repeats. FMR1 PM (55-199 CGG repeats, n=90) had more cycles with no oocytes retrieved (5.6% vs. 1.5%, respectively p=0.04), yielded less oocytes (7.9±6.4 vs 10.8±5.8, respectively p<0.001) and lower 2PN zygotes (5.3±4.3 vs 7.2±4.7, respectively p=0.001) compared to women with AD disease. In addition, there was a trend toward more cycles with no available embryos suitable for biopsy (18.9% vs 10.8%, respectively, p=0.07) in FMR1 PM. Nevertheless, FMR1 PM demonstrated comparable fertilization rate (57.8% vs. 66.5% respectively, NS) and higher proportion of healthy embryos per biopsy (38.4% vs 30%, respectively, p=0.001). Although clinical pregnancy (CPR), implantation and live birth rates (LBR) per fresh transfer were comparable (18.2%,11.4% and 12.7% vs 20.7%, 15.5% and 19.1, NS), CPR and LBR per started cycle were significantly lower (12.2% and 8.8% vs 20.5% and 17.5%, respectively p=0.04 and 0.01) in the FMR1 PM group compared to women with AD diseases.

Conclusion:
FMR1 PM (55-199 CGG repeats) carriers demonstrate lower success rate during IVF PGT-M cycle probably due to diminished ovarian reserve resulting in less available healthy embryos.