Association Between Blood Transfusion for Postpartum Haemorrhage and the Risk of Premature Ovarian Failure: A Nationwide Population-Based Cohort Study.

OBJECTIVE:To investigate the association between postpartum haemorrhage (PPH) severity and the subsequent risk of premature ovarian failure (POF), with blood transfusion used as a marker of severe PPH: DESIGN: Nationwide population-based retrospective cohort study. SETTING:Korean National Health Insurance Service (KNHIS) database. POPULATION:Women who delivered in Korea between 2015 and 2016. METHODS:Women were followed from delivery until diagnosis of POF, attainment of 40 years of age, or 31 December 2021. PPH was identified using International Classification of Diseases, 10th Revision (ICD-10) codes. Red blood cell (RBC) transfusion during the delivery hospitalization was used as the primary indicator of PPH severity. POF was defined as ovarian failure before 40 years of age. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). MAIN OUTCOME MEASURES:Incident premature ovarian failure. RESULTS:Among 745 125 women, 78 225 (10.5%) experienced PPH and 3552 (0.48%) developed POF during follow-up. When stratified by transfusion status, women with PPH requiring RBC transfusion had a markedly higher risk of POF (adjusted HR 2.058, 95% CI 1.668-2.539, p < 0.0001), whereas PPH without transfusion was associated with only a borderline association (adjusted HR 1.108, 95% CI 0.993-1.237, p = 0.066). A significant dose-response relationship was observed between RBC transfusion volume and POF risk, with adjusted HRs increasing progressively from 1.749 (95% CI 1.314-2.329) for 1 unit to 2.507 (95% CI 1.792-3.507) for 2-3 units and 2.894 (95% CI 1.439-5.820) for ≥ 4 units (p < 0.0001). CONCLUSIONS:Severe PPH requiring blood transfusion is associated with a substantially increased risk of premature ovarian failure in this nationwide population-based cohort. These findings support the importance of long-term endocrine surveillance and reproductive counselling for women who experience transfusion-requiring PPH.