Blastocyst biopsy and vitrification are effective for preimplantation genetic diagnosis of monogenic diseases

Study question What is the value of a new strategy for preimplantation genetic diagnosis (PGD) of monogenic diseases: blastocyst biopsy, cryopreservation and thawed embryo transfer? Summary answer This strategy is highly effective for PGD of monogenic diseases and merits wide use. What is known already PGD of monogenic diseases is conventionally performed on 6- to 8-cell embryos with fresh transfer. The diagnostic time is restricted and is subjected to amplification failure and allele drop-out (ADO). Study design, size, duration This is a prospective observational cohort study. A total of 33 couples were included from November 2008 to January 2012. Participants/materials, setting, methods A cohort of 33 couples who were carriers of monogenic diseases underwent a total of 40 oocyte pick-up (OPU) cycles, with subsequent blastocyst biopsy, vitrification and thawed embryo transfer. DNA analysis was performed by whole genome amplification using multiple displacement amplification followed by real-time PCR and mini-sequencing. Main results and the role of chance The diagnostic rate was 90% with 5% amplification failure and 5% ADO. The survival rate of vitrified blastocysts was 94%. Amongst 33 couples, 24 ongoing pregnancies were achieved (60% per OPU cycle) with an implantation rate of 50%. All of the genotyping results of prenatal diagnosis were consistent with those of PGD. There was no severe or late ovarian hyperstimulation syndrome (OHSS) and no hospitalization. Limitations, reasons for caution The participants are limited to the carriers of monogenic diseases. Wider implications of the findings This strategy achieves high rates of genotyping success, survival after warming and pregnancy. Cryopreservation of blastocysts after biopsy permits sufficient time for transportation of specimens and molecular diagnosis. In particular, cryopreservation of biopsied embryos without fresh transfer is an important strategy to prevent OHSS and circumvent a suboptimal endometrium in high responders. Study funding/competing interest(s) This study is financially supported by the National Science Council of Taiwan (grants NSC 96-2628-B-002-063-MY3, NSC 98-2314-B-002-088-MY3 and 98-FTN13). No competing interests are declared.