Mosaic embryo transfer versus euploid embryo transfer after PGT-A: a systematic review and meta-analysis

Mosaic embryos detected by preimplantation genetic testing for aneuploidy (PGT-A) are increasingly transferred when no euploid alternatives exist, yet their reproductive potential relative to euploid embryos remains contested. A preferred reporting items for systematic reviews and meta-analyses (PRISMA) systematic review and meta-analysis of eight studies was conducted (1904 mosaic and 9332 euploid transfers). Overlapping cohorts were resolved a priori, and pre-specified subgroup analyses were conducted by mosaicism level, aneuploidy type, chromosomal complexity and dosage direction (trisomy versus monosomy). Pooled live birth and ongoing pregnancy rate was lower for mosaic transfers (RR 0.74, 95% CI 0.64 to 0.85; I² = 78%; 95% prediction interval: 0.41 to 1.34). The only prospective double-blind trial in which embryo classification was concealed from clinicians and patients found equivalent outcomes across all mosaic grades (RR 0.98; non-inferiority confirmed), suggesting that confounding by indication substantially explained the observed difference. Miscarriage rate was higher in the pooled analysis (RR 1.57, 95% CI 1.05 to 2.35; I² = 72%). Aneuploidy type was the most consistent prognostic modifier: segmentary mosaicism approached euploid outcomes (RR 0.90, 95% CI 0.81 to 1.00; I² = 28%), whereas whole-chromosome mosaicism was significantly worse (RR 0.60, 95% CI 0.53 to 0.68; I² = 22%; interaction P < 0.001). A complexity dose-response was observed (ongoing pregnancy and live birth rate: segmental mosaic 43.1% > single whole chromosome mosaic 32.5% > double whole chromosome mosaic 27.2% > complex ≥3 chromosomes 20.8% versus euploid 52.3%, P < 0.0001). Obstetric and perinatal outcomes were reassuring but of low or very low certainty. An evidence-based prioritization hierarchy is supported; prospective registries with obstetric follow-up are urgently needed.