Preimplantation Genetic Testing for Families at Risk of Haemophilia: Ten-Year Single-Centre Experience

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.

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.

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.

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.