Clinical application of polar-body based preimplantation genetic testing for maternal mutations in females with a limited number of oocytes

Background Trophectoderm (TE) cell biopsy at the blastocyst stage is currently the predominant method used in preimplantation genetic testing for monogenic disorders (PGT-M). However, this approach may result in the discarding of genetically unaffected embryos due to the fact that not all embryos progress to the blastocyst stage. This study aimed to investigate the advantages of utilizing polar body (PB) biopsy in females with disease-causing mutations and a limited number of oocytes undergoing PGT-M. Methods Three couples with females carrying autosomal dominant or X-linked mutations in IRF6, FMR1, and EDA were recruited. The number of retrieved oocytes was no more than six per cycle. The first and second PBs (PB1 and PB2) of each oocyte were individually biopsied and subjected to multiple displacement amplification (MDA). The genotype of each embryo was deduced by analyzing the MDA products of corresponding PB1 and PB2 using a novel strategy that combined direct mutation testing and single nucleotide polymorphism linkage analysis. Mutation-free embryos cryopreserved before the blastocyst stage were selected to transfer. Results In total, four cycles were conducted resulting in the retrieval of 15 oocytes for the three couples. The genotype of each embryo was successfully determined. Seven mutation-free embryos were identified. Three of them were transferred and resulted in two clinical pregnancies, culminating in the birth of two healthy babies. The accuracy of the embryo genotypes was validated through genetic testing of the fetuses in the second trimester or at birth. Conclusions The PB-based strategy is feasible and effective to detect the mutation carrier statuses of embryos in PGT-M for maternal mutations. Compared with blastocyst stage detection, this method may preserve a higher number of genetically unaffected embryos for the patients. Further clinic trials are warranted to verify whether PB biopsy offers greater benefits than TE cell biopsy for females with disease-causing mutations and a limited number of oocytes in PGT-M.