Should Preimplantation Genetic Testing (PGT) Systematically Be Proposed to BRCA Pathogenic Variant Carriers?

SIMPLE SUMMARY: Preimplantation genetic testing (PGT) has been developed to avoid the transmission of a critical hereditary disease, by selecting embryos for uterine transfer using a genetic analysis. BRCA mutated patients can undergo PGT and also be offered fertility preservation (FP) when diagnosed, with cancer or even preventively before a malignancy occurs. However, PGT but also FP success rates are closely related to ovarian reserve parameters, which are known to be potentially lower for BRCA pathogenic variant carriers. To this day, although BRCA pathogenic variants are related to reproductive issues, there are no international guidelines for the application of PGT and FP in this subgroup of patients. The aim of this article is to review the published real-life data regarding BRCA carriers’ ovarian reserve and PGT success rates in oncologic and non-oncologic contexts, to determine the actual indication of PGT and further to improve patients’ care pathway. ABSTRACT: Over the past years, BRCA genes pathogenic variants have been associated to reproductive issues. Indeed, evidence indicate that BRCA-mutated patients are not only at higher risk of developing malignancies, but may also present a reduction of the follicular stockpile. Given these characteristics, BRCA patients may be candidates to fertility preservation (FP) techniques or preimplantation genetic testing (PGT) to avoid the transmission of this inherited situation. Since the success rates of both procedures are highly related to the number of oocytes that could be recovered after ovarian stimulation, predicted by ovarian reserve tests, they are ideally performed before the diagnosis of cancer and its treatment. Despite the specific reproductive challenges related to BRCA status, no international guidelines for the application of PGT and FP in this subgroup of patients is currently available. The present article aims to review the available data regarding BRCA carriers’ ovarian reserve and PGT success rates in oncologic and non-oncologic contexts, to determine the actual indication of PGT and further to improve patients’ care pathway.