Combined Preimplantation Genetic Testing for Genetic Kidney Disease: Genetic Risk Identification, Assisted Reproductive Cycle, and Pregnancy Outcome Analysis

Abstract

BackgroundGenetic kidney disease is a major cause of morbidity and mortality in neonates and end-stage renal disease (ESRD) in children and adolescents. Genetic diagnosis provides key information for early identification of congenital kidney disease and reproductive risk counseling. Preimplantation genetic testing for monogenic disease (PGT-M) as a reproductive technology helps prospective parents to prevent passing on disease-causing mutations to their offspring.Materials and MethodsA retrospective cohort of couples counseled on PGT who had a risk to given birth to a child with genetic kidney disease or had a history of prenatal fetal kidney and urinary system development abnormalities from 2011 to 2021. Through a combination of simultaneously screening for aneuploidy and monogenic kidney disease, we achieved reproductive genetic intervention.ResultsA total of 64 couples counseled on PGT for monogenic kidney disease in a single reproductive center during the past 10 years, of whom 38 different genetic kidney diseases were identified. The most frequent indications for referral were autosomal recessive disease (54.7%), then autosomal dominant disease (29.7%), and X-linked disease (15.6%). Polycystic kidney disease was the most common diseases counted for 34.4%. After oocyte-retrieval in all of 64 females, a total of 339 embryos were diagnosed and 63 embryos were transferred in succession. Among 61 cycles of frozen-embryo transfer (FET), ongoing pregnancy/live birth rate (OP/LBR) reached 57.38%. The cumulative OP/LBR in our cohort for the 64 couples was 54.69%. In addition, we have carried out expanded carrier screening (ECS) in all the in vitro fertilization (IVF) couples performed PGT covering 7,311 individuals. The carrier frequency of the candidate genes for monogenic kidney diseases accounted for 12.19%.ConclusionOverall, the customization PGT-M plan in our IVF center is pivotal to decreasing the morbidity and implementing reproductive genetic intervention of genetic kidney disease.

State of the Science and Ethical Considerations for Preimplantation Genetic Testing for Monogenic Cystic Kidney Diseases and Ciliopathies

“…In a single reproductive center, ARPKD and ADPKD were the most common monogenic kidney diseases for which PGT was performed over a 10-year period, with referrals for AR diseases being more common (54.7%) than AD (29.7%). 6 In another center, AR disorders accounted for approximately 50% of the 389 patients with PGT-M kidney disease, whereas ADPKD was the most common single disease for which PGT-M was performed (16.5%), and ARPKD accounted for 6.68% of patients. 7…”

“…In a single reproductive center, ARPKD and ADPKD were the most common monogenic kidney diseases for which PGT was performed over a 10-year period, with referrals for AR diseases being more common (54.7%) than AD (29.7%). 6 In another center, AR disorders accounted for approximately 50% of the 389 patients with PGT-M kidney disease, whereas ADPKD was the most common single disease for which PGT-M was performed (16.5%), and ARPKD accounted for 6.68% of patients. 7 In a retrospective cohort of 43 couples (33 PKD1, two PKD2, and eight ARPKD), a total of 91 PGT cycles were conducted, resulting in a 36.8% rate of transferable embryos and a cumulative delivery rate of 57.8% per couple after five treatment cycles.…”

“…8 When PGT success for the monogenic disease is stratified by inheritance pattern, AR demonstrated a higher rate of embryos appropriate for transfer (69%) compared with both AD (46%) and X-linked conditions (48%), and adding aneuploidy screening decreased the rate for each variant type to 29%, 41%, and 22%, respectively. 9 However, there are more reported cases of successful PGT-M for ADPKD than ARPKD, 6–8,10 likely due to the higher prevalence of ADPKD.…”

“…5 Preimplantation genetic testing for monogenic (PGT-M) PKD has emerged as a viable option for couples at risk of passing these conditions to their children. 6–10 Despite the growing interest in PGT-M, the feasibility and ethical considerations remain subject to debate. This review provides an overview of the genetic basis of monogenic PKD and ciliopathies, focusing on the most common and most severe phenotypes where PGT-M may be most relevant.…”