Preimplantation genetic testing for monogenic disorders (PGT-M) for monogenic nephropathy: a single-center retrospective cohort analysis.

Background: Hereditary nephropathy is an important cause of renal insufficiency and end-stage renal disease. Therefore, for couples with monogenic nephropathy, preventing transmission of the disease to offspring is urgent. Preimplantation genetic testing for monogenic disorders (PGT-M) is a means to prevent intergenerational inheritance by screening and transplanting normal embryos. We provide a clinical overview of patients with monogenic nephropathy who underwent PGT-M.

Methods: The single-center retrospective cohort study was conducted at the Center for Reproductive Medicine, Shandong University from January 2014 to December 2022. A total of 352 couples with nephropathy-related disease were included in the cohort totally.

Results: Of the 352 couples with nephropathy-related disease, 180 accepted genetic screening. A total of 104 couples with monogenic nephropathy indications underwent PGT-M, including 90 of autosomal dominant inheritance, 10 of autosomal recessive inheritance, 4 of X-linked inheritance. 498 blastocysts were biopsied prior to testing, and 394 embryos underwent genetic testing, of which 76 were transferable, 247 were non-transferable and 71 were recommended for genetic counseling. Finally, 80 vitrified-thawed single blastocyst transfer cycles were performed in the cohort. Live births occurred in 38 women, of which 37 transferred embryos with non-pathogenic genotypes. The invasive prenatal diagnosis results of 18 women with live birth were obtained through follow-up, consistent with the PGT-M results of transferred embryos.

Conclusions: PGT-M is an effective means of preventing intergenerational inheritance of monogenic nephropathy. The absence of genetic abnormalities detected by prenatal diagnosis in healthy newborns without monogenic nephropathy also underscore its validity.