Comparative Outcomes of In Vitro Fertilization and Frozen Embryo Transfer Cycles in Non-Major Thalassemia Spectrum and Non-Thalassemia Patients: A Propensity Score-Matched Cohort Study.

OBJECTIVE To assess whether oocyte yield, embryo development and pregnancy rates differ between the non-major thalassemia spectrum (NMTS) and non-thalassemia (NT) patients undergoing in vitro fertilization (IVF) or frozen embryo transfer (FET) cycles. DESIGN A propensity score-matched retrospective cohort study. SUBJECTS A total of 41,804 patients who underwent IVF (18,215 cycles) or FET (23,589 cycles) between January 2013 and December 2022 were included in the study. Patients were matched 1:2 for the NT (n = 5,816 IVF, n = 8,004 FET) and NMTS (n = 2,908 IVF, n = 4,002 FET) groups. Within the NMTS group, thalassemia carriers (TC) accounted for 80.7% of IVF cases and 74.9% of FET cases, while non-transfusion-dependent thalassemia (NTDT) patients represented 19.3% and 25.1%, respectively. EXPOSURE Standard ovarian stimulation protocols (GnRH agonist, GnRH antagonist, and minimal stimulation) were used for all patients. Clinical outcomes, including embryo development, clinical pregnancy, live birth, and miscarriage rates, were compared between the groups. MAIN OUTCOME MEASURES IVF cycle outcome (e.g., oocyte retrieval rate, fertilization rate, and blastocyst formation rate) and pregnancy outcomes (e.g., clinical pregnancy rate, live birth rate, and miscarriage rate). RESULTS After matching, the baseline characteristics, including age and body mass index, were comparable between the NT and NMTS groups. No significant differences were observed in oocyte yield and embryo development, including blastocyst formation (NT: 0.54 vs. NMTS: 0.56). In IVF cycles, the clinical pregnancy rate (adjust relative risk [aRR] = 1.03, 95% confidence interval [CI] = 0.96-1.09), live birth rate (aRR = 1.02, 95% CI = 0.95-1.09), and miscarriage rate (aRR = 1.07, 95% CI = 0.92-1.25) were similar. In FET cycles, the clinical pregnancy rate (aRR = 1.01, 95% CI = 0.96-1.07), live birth rate (aRR = 1.03, 95% CI = 0.97-1.10), and miscarriage rate (aRR = 0.92, 95% CI = 0.81-1.04) were comparable. Interaction analysis showed that baseline hormonal levels and ovarian stimulation protocols significantly influenced embryo development but did not affect pregnancy outcomes. CONCLUSION No significant differences in embryo development or pregnancy outcomes were found between NMTS and NT patients undergoing IVF or FET cycles. These findings suggest that NMTS patients do not face additional reproductive challenges in assisted reproductive technology. This study may help reduce reproductive anxiety in NMTS patients and has important public health relevance in resource-limited and high-prevalence regions, where it can support clinical decisions and inform equitable ART care delivery.