P-536 Preimplantation Genetic Testing for hereditary breast and ovarian cancer syndrome due to BRCA pathogenic variant : the parisian center experience
Authors: Borghese R , Steffann J , Lassartesse O , Souare F , Achour N , Mayeur A , Benachi A , Stoppa Lyonnet D , Grynberg M , Sonigo C 
Published: July 2024

Study question

What are the outcomes of Preimplantation genetic testing for monogenic disease (PGT-M) for BRCA pathogenic variants?

Summary answer

Among couples entering a PGT-M program for BRCA pathogenic variants, 23.5% achieved a live-birth.

What is known already

BRCA pathogenic variants are associated with an oncologic predisposition with variable penetrance and are accessible to screening and preventive procedures to avoid or early detect the development of cancer. Transmission of BRCAmutations to offspring poses a significant reproductive concern for BRCA mutation carriers. PGT-M offers a solution to prevent this mutation transmission. Despite reproductive challenges related to BRCA status, there are no existing international guidelines for applying PGT-M in these situations. In France, authorization for BRCA related PGT-M is case-specific, considering the personal and familial severity of the disease and submitted to a multidisciplinary prenatal diagnosis center (CPDPN).

Study design, size, duration

This retrospective observational study, is a single-center analysis of 46 requests for PGT-M related to BRCA pathogenic variants at our PGT center from January 2015 to December 2022.

Participants/materials, setting, methods

Forty-six couples asked for PGT-M for BRCA pathogenic variant carried by one of the partner. The present study involves the examination of data encompassing referrals, decisions as well as clinical outcomes associated with PGT-M.

Main results and the role of chance

Forty-six requests for PGT-M due to the risk of hereditary predisposition to breast and ovarian cancer have been received: 36 for a pathogenic variant in the BRCA1 gene and 10 for BRCA2. Nine couples ultimately did not proceed and dropped out. Eight requests were declined, either due to the refusal of the multidisciplinary prenatal diagnosis center (CPDPN) based on family history (n = 4) or alteration of ovarian reserve (n = 4), the 2 latter requests are still under investigation. In total, requests from 27 couples (55%) were considered eligible and feasible. Among them, 17 (63%) underwent at least one PGT-M cycles (5 dropped out before the beginning and 5 are still pending).

Overall, 33 ovarian stimulation cycles for in vitro fertilization were initiated, resulting in the retrieval of 192 mature oocytes and the formation of 145 embryos. Of these, 97 were biopsied, and 38 did not carried the BRCA pathogenic variant. A total of 21 fresh or frozen embryo transfers were performed and 8 pregnancies were achieved, leading to 4 deliveries and 5 live births (23.5% of couples who started a PGT-M cycle).

Limitations, reasons for caution

In the absence of established guidelines, there is variability in information regarding PGT-M among oncogeneticists. Thus, only selected carriers of BRCA pathogenic variants are addressed to our PGT centers. Additionally, women participating in a fresh PGT cycle were selected on several criteria including ovarian reserve parameters.

Wider implications of the findings

PGT-M provides a viable alternative for couples seeking to prevent the transmission of BRCA mutations. To increase the PGT-M cumulative live birth rate, the transfer of male embryos carrying the variant, assumed to have lower tumor risks, should be considered and discussed with patients.

Trial registration number

Not applicable