Preimplantation genetic testing for aneuploidy in unexplained recurrent pregnancy loss: a systematic review and meta-analysis

Importance: Preimplantation genetic testing for aneuploidy (PGT-A) to deselect aneuploid embryos in assisted reproductive technology (ART) treatment cycles may hold promise by augmenting pregnancy rates per transfer and reducing pregnancy loss rates for patients with unexplained recurrent pregnancy loss (RPL). Objective: To explore effectiveness of PGT-A in managing unexplained RPL by evaluating several key aspects: the likelihood of live birth in a subsequent spontaneous pregnancy, whether women with unexplained RPL have a higher rate of aneuploidy, whether euploid blastocysts offer comparable live birth rate (LBR) in patients with unexplained RPL, whether the endometrium is less selective in unexplained RPL loss, and whether PGT-A increases the LBR or reduces pregnancy losses until delivery. Data sources: PubMed and Cochrane Library databases were searched from inception until June 2024. Study selection and synthesis: Studies involving patients with >= 2 unexplained RPL who underwent ART with or without PGT-A or expectant management were included. Main Outcome Measures: The primary outcome measure was the LBR. Secondary outcome measures were aneuploidy rate, clinical pregnancy rate, and clinical pregnancy loss rate. Results: Whether couples with unexplained RPL have higher embryo aneuploidy rates remains equivocal. Euploid blastocyst transfers yielded comparable clinical pregnancy loss rate (odds ratio [OR], 1.10; 95% confidence interval [CI], 0.57-2.13) and LBR (OR, 1.04; 95% CI, 0.74-1.44) in patients with and without unexplained RPL. Comprehensive chromosome analysis of products of conception shows similar aneuploidy rates between patients with and without RPL and does not support the less selective endometrium hypothesis. Preimplantation genetic testing for aneuploidy decreased clinical pregnancy loss rate (OR, 0.42; 95% CI, 0.27-0.67) and enhanced LBR per transfer (OR, 2.17; 95% CI, 1.77-2.65) and LBR per patient (OR, 1.85; 95% CI, 1.18-2.91) in patients with unexplained RPL. Conclusion and relevance: Current low-quality evidence suggests that PGT-A enhances LBR per transfer and per patient in unexplained RPL. Well-designed randomized controlled trials comparing ART with PGT-A vs. expectant management for unexplained RPL are warranted. Registration Number: CRD42021291546. (Fertil Steril (R) 2025;123:121-36. (c) 2024 by American Society for Reproductive Medicine.) El resumen est & aacute; disponible en Espa & ntilde;ol al final del art & iacute;culo.