INTRODUCTION: Preimplantation genetic testing for monogenic diseases (PGT-M) is a reproductive option for couples at high risk of transmitting inherited disorders. We report a ten-year single-centre PGT-M experience in families at risk of hemophilia. METHODS: A pre-clinical PGT-M work-up was performed for couples in which the female was a carrier of hemophilia A or B, following multidisciplinary counselling. Intracytoplasmic sperm injection (ICSI) was used to generate embryos. Blastocysts on days 5-7 were biopsied for genetic testing and cryopreserved by vitrification. Short tandem repeat markers were used for linkage analysis, alone or in combination with the pathogenic variant using a multiplex PCR. Embryos with conclusive results were transferred one at a time. RESULTS: 23 couples contacted the center seeking information on the PGT-M program, of which 19 underwent multidisciplinary counselling and pre-clinical PGT work-up. After ICSI, 69 embryos were biopsied and genetically characterized. A conclusive diagnosis was achieved for 58 embryos (84%): 42 unaffected embryos were suitable for transfer of whom 26 were transferred, resulting in 13 pregnancies (50% implantation rate per transfer), leading to eight live births, four miscarriages and one therapeutic termination. Prenatal diagnosis, performed in three cases, confirmed PGT-M results. Amplification failure occurred in nine cases, eight of which were successfully re-biopsied. Allele drop-out occurred in two embryos and recombination in one. CONCLUSIONS: Our experience shows that PGT-M is a valid and reliable option for couples at risk of transmitting severe genetic diseases, enabling prevention of affected pregnancies and reducing the emotional burden linked to therapeutic abortion.
Mortarino et al. (Wed,) studied this question.