Pathogenic variant in (19q13.42) associated with recurrent gestational trophoblastic disease: Data from early embryo development observed during fertilization.

Objective: To describe development of human embryos derived from an individual with a homozygous pathogenic variant in (19q13.42) and recurrent hydatidiform mole (HM), an autosomal recessive condition thought to occur secondary to an oocyte defect.

Methods: A patient with five consecutive HM pregnancies was genomically evaluated via next generation sequencing followed by controlled ovarian hyperstimulation, fertilization (IVF) with intracytoplasmic sperm injection, embryo culture, and preimplantation genetic screening. Findings in were recorded and embryo culture and biopsy data were tabulated as a function of parental origin for any identified ploidy error.

Results: The patient was found to have a pathogenic variant in (c.2810+2T>G) in a homozygous state. Fifteen oocytes were retrieved and 10 embryos were available after fertilization via intracytoplasmic sperm injection. Developmental arrest was noted for all 10 embryos after 144 hours in culture, thus no transfer was possible. These non-viable embryos were evaluated by karyomapping and all were diploid biparental; two were euploid and eight had various aneuploidies all of maternal origin.

Conclusion: This is the first report of early human embryo development from a patient with any mutation. The pathogenic variant identified here resulted in global developmental arrest at or before blastocyst stage. Standard IVF should therefore be discouraged for such patients, who instead need to consider oocyte (or embryo) donation with IVF as preferred clinical methods to treat infertility.