Comparative outcomes of in vitro fertilization and frozen embryo transfer cycles in patients with nonmajor thalassemia spectrum and nonthalassemia: a propensity score-matched cohort study.

OBJECTIVE

To assess whether oocyte yield, embryo development, and pregnancy rates differ between patients with nonmajor thalassemia spectrum (NMTS) and nonthalassemia (NT) 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 accounted for 80.7% of IVF cases and 74.9% of FET cases, whereas patients with nontransfusion-dependent thalassemia represented 19.3% and 25.1%, respectively.

EXPOSURE: Standard ovarian stimulation protocols (gonadotropin-releasing hormone agonist, gonadotropin-releasing hormone 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: The 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 (adjusted 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 patients with NMTS and NT undergoing IVF or FET cycles. These findings suggest that patients with NMTS do not face additional reproductive challenges in assisted reproductive technology. This study may help reduce reproductive anxiety in patients with NMTS and has important public health relevance in resource-limited and high-prevalence regions, where it can support clinical decisions and inform equitable assisted reproductive technology care delivery.