Application of Combined PGT-A and PGT-M for Reproductive Management in a Couple Carrying GCDH Mutations with Prior Affected Offspring: A Rare Case Report

Abstract Case A 31-year-old woman with secondary subfertility, four recurrent pregnancy losses, and one previous live-born child affected with glutaric acidemia type I (GA-I) was evaluated. Genetic testing confirmed that both partners were heterozygous carriers of pathogenic GCDH variants (c.769C>T in exon 8 and c.1204C>T in exon 11, NM_000159.4). Given the high recurrence risk, the couple underwent in vitro fertilization with intracytoplasmic sperm injection, blastocyst culture, trophectoderm biopsy, and combined preimplantation genetic testing for aneuploidy (PGT-A) and monogenic disease (PGT-M). Outcome Three blastocysts were biopsied. One embryo exhibited segmental aneuploidy of chromosome 16 and was excluded. A second embryo was euploid and wild-type for both GCDH variants, classified as genetically normal. The third was euploid but heterozygous for c.769C>T, consistent with carrier status. The genetically normal embryo was selected for frozen embryo transfer, resulting in a singleton intrauterine pregnancy. Non-invasive prenatal testing at 12 weeks showed a normal chromosomal profile. At the time of report, the pregnancy is ongoing at 20 weeks without complications. Conclusion This case demonstrates that combined PGT-A and PGT-M can effectively prevent recurrence of GA-I, improve reproductive outcomes, and provide a valuable option for couples with monogenic disorders and recurrent pregnancy loss.