Ovarian stimulation increases the risk of ectopic pregnancy for fresh embryo transfers: an analysis of 68,851 clinical pregnancies from the Japanese Assisted Reproductive Technology registry.

OBJECTIVE: To evaluate the risk of ectopic pregnancies (EPs) for fresh cycles according to different ovarian stimulation protocols. DESIGN: Registry-based retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 68,851 clinical pregnancies after fresh single embryo transfer between 2007 and 2015. INTERVENTION (S): None MAIN OUTCOME MEASURE(S): Ectopic pregnancies. Odds ratios and 95% confidence intervals for EPs were calculated by using generalized estimating equations adjusted for potential maternal and treatment characteristics. RESULT(S): Among 68,851 clinical pregnancies, 1,049 (1.46%) cases of EP were reported. Compared with natural cycles, all ovarian stimulation protocols were associated with a significantly increased risk of EP. Ovarian stimulation with clomiphene (CC) demonstrated the highest odds ratios for EPs. Significant associations between ovarian stimulation protocols and EP compared with natural cycles were prominent when the number of retrieved oocytes was low (1-3) to moderate (4-7), but there were no significant associations when the number of retrieved oocytes was high (≥8). CONCLUSION(S): Ovarian stimulation protocols were significantly associated with an increased risk of EP. In particular, ovarian stimulation with CC had the highest risk of EP compared with other stimulation protocols. Further studies are essential to investigate possible confounding factors for different ovarian stimulation protocols, especially CC, and the risk of EP.