Vivianne C. G. Tjan-Heijnen, Herman Tournaye, I.A.P. Derks-Smeets, Pieter Verdyck, Willem Verpoest, Shari Mackens, Jos Dreesen, Ron J. T. van Golde, Christine E. M. de Die-Smulders, Maryse Bonduelle, Joep P.M. Geraedts, Martine De Rycke, Aimee D C Paulussen, M. Meijer-Hoogeveen, Jacques De Greve, Biology of the Testis, Gyneacology-Urology, Reproductive immunology and implantation, Surgical clinical sciences, Medical Genetics, Reproduction and Genetics, Laboratory for Medical and Molecular Oncology, Department of Embryology and Genetics, RS: GROW - Developmental Biology, Promovendi ODB, Genetica & Celbiologie, Klinische Genetica, Interne Geneeskunde, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and RS: GROW - R4 - Reproductive and Perinatal Medicine
Preimplantation genetic diagnosis (PGD) is a reproductive option for BRCA1/2 mutation carriers wishing to avoid transmission of the predisposition for hereditary breast and ovarian cancer (HBOC) to their offspring. Embryos obtained by in vitro fertilisation (IVF/ICSI) are tested for the presence of the mutation. Only BRCA-negative embryos are transferred into the uterus. The suitability and outcome of PGD for HBOC are evaluated in an observational cohort study on treatments carried out in two of Western-Europe's largest PGD centres from 2006 until 2012. Male carriers, asymptomatic female carriers and breast cancer survivors were eligible. If available, PGD on embryos cryopreserved before chemotherapy was possible. Generic PGD-PCR tests were developed based on haplotyping, if necessary combined with mutation detection. 70 Couples underwent PGD for BRCA1/2. 42/71 carriers (59.2 %) were female, six (14.3 %) of whom have had breast cancer prior to PGD. In total, 145 PGD cycles were performed. 720 embryos were tested, identifying 294 (40.8 %) as BRCA-negative. Of fresh IVF/PGD cycles, 23.9 % resulted in a clinical pregnancy. Three cycles involved PGD on embryos cryopreserved before chemotherapy; two of these women delivered a healthy child. Overall, 38 children were liveborn. Two BRCA1 carriers were diagnosed with breast cancer shortly after PGD treatment, despite negative screening prior to PGD. PGD for HBOC proved to be suitable, yielding good pregnancy rates for asymptomatic carriers as well as breast cancer survivors. Because of two cases of breast cancer shortly after treatment, maternal safety of IVF(PGD) in female carriers needs further evaluation.