Cumulative live birth following preimplantation genetic testing for aneuploidy versus conventional IVF/ICSI in unexplained recurrent pregnancy loss: a retrospective cohort study with intention-to-treat and per-protocol analyses

Objective To compare cumulative live birth rates (CLBR) between preimplantation genetic testing for aneuploidy (PGT-A) and conventional IVF/ICSI in women with unexplained recurrent pregnancy loss (uRPL) using intention-to-treat (ITT) and per-protocol (PP) analyses, and to assess effect modification by maternal age and prior miscarriage number. Methods This single-center retrospective cohort (2018–2024) included women with uRPL undergoing their first oocyte retrieval with planned single-blastocyst transfer. The ITT population included 589 patients (342 PGT-A vs 247 IVF/ICSI); after excluding patients who never underwent transfer and 47 patients (16 PGT-A, 31 IVF/ICSI) with remaining cryopreserved embryos and no live birth at the follow-up cutoff, the PP population included 389 patients (221 vs 168) who completed at least one transfer. Stabilized inverse probability of treatment weighting with doubly robust adjustment and robust variance estimation was applied. The primary outcome was CLBR per oocyte retrieval. Results In the ITT population, unadjusted CLBR was comparable (48.5% vs 47.4%, P = 0.779) and remained non-significant after adjustment (aOR 0.862, 95% CI 0.591–1.255, P = 0.437). In the PP population, neither first-transfer live birth (63.8% vs 58.3%, P = 0.272; aOR 0.942, P = 0.814) nor CLBR (75.1% vs 69.6%, P = 0.230; aOR 0.858, P = 0.595) differed significantly. Age and prior miscarriage number did not significantly modify the treatment–CLBR association (age: ITT P = 0.871, PP P = 0.071; miscarriage number: ITT P = 0.695, PP P = 0.289; both miscarriage-number tests were exploratory owing to limited propensity-score overlap in the >2-miscarriage stratum). Among women aged ≥35 years, ITT CLBR did not differ (33.6% vs 29.7%, P = 0.534; aOR 0.846, 95% CI 0.447–1.603, P = 0.608). Unadjusted PP outcomes favored PGT-A among women aged ≥35 years and those with exactly two prior miscarriages, but no adjusted differences remained significant after Bonferroni correction, except first-transfer clinical pregnancy in the ≥35-year stratum, which requires cautious interpretation. Miscarriage rates did not differ significantly between groups; no statistically significant perinatal differences were observed in this sample (166 vs 117 deliveries). Conclusions PGT-A did not improve CLBR per oocyte retrieval in women with uRPL and should not be routinely recommended. Unadjusted PP subgroup advantages are more plausibly attributable to embryo attrition and residual confounding than true benefit and require prospective confirmation.