Abstract Study question What are the assisted reproductive technology-associated risk factors for retained products of conception (RPOC) following delivery? Summary answer Frozen embryo transfer (FET) with hormone replacement cycles (HRC) constitutes the largest risk factor for RPOC. What is known already RPOC is a key cause of secondary postpartum hemorrhage. Previous studies have shown that the use of ART increases the risk of RPOC and subsequent transfusion following delivery. However, the relationships between specific ART-treatment factors and the risk of RPOC have not been elucidated. Study design, size, duration We performed a registry-based retrospective cohort study using the Japanese national ART registry, in which all the ART cycles performed in Japan are recorded including the perinatal outcomes. Participants/materials, setting, methods Singleton live births between 2007 and 2017 were studied (n = 306,411). Odds ratios (ORs) and 95% confidence intervals (CIs) for the potential risk factors for RPOC associated with fresh and frozen cycles were obtained from multiple logistic regression analysis, incorporating adjustment for maternal age, infertility, and calendar year. Because information regarding assisted hatching (AH) and HRC for endometrial preparation only became available in 2012, these factors were analysed using the data collected between 2012 and 2017. Main results and the role of chance RPOC was diagnosed for 132 deliveries (0.04%), of which 122 (92.4%) followed FET cycles and only 10 (0.01%) followed fresh embryo transfer (ET). No significant risk factors for RPOC were identified using the fresh ET data. For FET cycles, the use of HRC as an endometrial preparation method represented the largest risk factor (adjusted OR, 4.9; 95% CI, 2.0 to 12.3), with RPOC occurring in 0.05% of deliveries following HRC (51/97, 958 deliveries) but in only 0.01% following natural cycles (5/47, 79 deliveries). AH was also associated with a significantly higher risk of RPOC (adjusted OR, 1.9; 95% CI, 1.2 to 3.1), although the risk was lower than that associated with HRC). Subgroup analysis showed that these significant associations of HRC and AH with RPOC were present for transvaginal deliveries, but not deliveries by caesarean section. Limitations, reasons for caution The registry lacks important information regarding risk factors for RPOC, such as parity, body mass index, and history of previous uterine surgery. Furthermore, the lower prevalence of RPOC in the present study (0.04%) than in other studies (approximately 1%) suggests the possibility of non-differential misclassification for the outcomes of RPOC. Wider implications of the findings Although the possibility of residual confounding factors remains, the present findings suggest that additional care should be taken in the management of patients undergoing vaginal deliveries following FET who have HRC or AH. Trial registration number Not applicable
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