IVF outcomes and aneuploidy rates in BRCA pathogenic variant carriers undergoing preimplantation genetic testing.

Objective

To evaluate in-vitro fertilization (IVF) outcomes and aneuploidy rates among women undergoing preimplantation genetic testing (PGT) for BRCA, compared with women undergoing PGT for other monogenic disorders (PGT-M).

Design

Retrospective cohort study. SUBJECTS Cases included 76 BRCA1 and 55 BRCA2 PVCs. Controls included 162 women undergoing PGT-M. EXPOSURE PGT-M at a tertiary IVF unit (2012-2025); combined PGT-M and PGT for aneuploidy (PGT-A) (2022-2025). MAIN OUTCOME MEASURES The primary outcome was the number of retrieved oocytes. Secondary outcomes included ovarian reserve parameters and PGT outcomes, including aneuploidy rate. Additionally, rates were compared between mutant and wild-type blastocysts to assess embryo-level effects.

Results

Ovarian reserve markers and oocyte yield were similar between groups (median 13 [IQR 8-18] vs. 13 [IQR 8-19], p=0.9), despite higher prevalence of infertility and lower gonadotropin doses among BRCA PVCs (p<0.01) vs. controls. Fertilization rates were higher in BRCA PVCs (77.6% vs. 70.7%, p<0.01), although multivariable analysis showed no differences in key IVF outcomes. In women undergoing combined PGT-M and PGT-A, aneuploidy rates were 46.9% in BRCA1 PVCs, 25.3% in BRCA2 PVCs, and 40.7% in controls (p=0.006). In adjusted analyses, BRCA2 PV status was associated with lower aneuploidy compared with controls (aOR 0.42, 95% CI 0.22-0.80), whereas BRCA1 PVCs did not differ.

Conclusion

BRCA PVs were not associated with impaired ovarian response or IVF outcomes. Aneuploidy rates were comparable in BRCA1 PVCs and lower in BRCA2 PVCs compared with controls. These findings provide reassurance regarding reproductive outcomes in BRCA carriers. To our knowledge, this is the largest study of BRCA PVCs undergoing PGT and among the first to examine the association between BRCA PVs and aneuploidy. Larger studies are needed to confirm these findings, given their important clinical implications.