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

BRCA1

Germline pathogenic BRCA1 and BRCA2 variants, assessed for their effect on ovarian reserve and embryo aneuploidy during preimplantation genetic testing

This retrospective cohort from a tertiary in-vitro fertilisation unit compared 76 carriers of a pathogenic BRCA1 variant and 55 carriers of a BRCA2 variant with 162 women undergoing preimplantation genetic testing for another monogenic disorder, between 2012 and 2025. Ovarian reserve markers and oocyte yield were comparable (median 13 [IQR 8-18] versus 13 [IQR 8-19]; p = 0.9), despite a higher prevalence of infertility and lower gonadotropin doses among carriers (p < 0.01). Fertilisation rates were higher in carriers (77.6% versus 70.7%; p < 0.01), with no difference in key in-vitro fertilisation outcomes on multivariable analysis. Among women undergoing combined preimplantation testing for a monogenic disorder and for aneuploidy, aneuploidy rates were 46.9% in BRCA1 carriers, 25.3% in BRCA2 carriers and 40.7% in controls (p = 0.006); after adjustment, BRCA2 status was associated with lower aneuploidy (adjusted OR 0.42; 95% CI 0.22-0.80), with no difference for BRCA1.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This directly answers a question raised at every consultation with a young carrier: ovarian reserve and stimulation yield do not differ, which allows genuine reassurance and argues against rushing fertility preservation on genetic status alone. The lower aneuploidy rate in BRCA2 carriers is counter-intuitive and rests on the subgroup recruited since 2022 only: I would not mention it in clinic before replication. The control group, made up of couples undergoing preimplantation testing for another monogenic disorder, is the right comparator but remains a selected population, and the single-centre design limits how far the small differences in fertilisation rates can be taken.

Analysis by Dr Thibaut Benquey