Abstract
BACKGROUND: Endometriosis is a common cause of infertility in women of reproductive age, and many affected women require assisted reproductive technology (ART) to conceive. It is also associated with increased risks of adverse obstetric complications. However, the impact of different frozen embryo transfer (FET) protocols on outcomes in this population remains unclear. This study aimed to evaluate obstetric outcomes after FET, comparing endometrial preparation methods in women with and without endometriosis using a nationwide cohort from the Republic of Korea. METHODS: We analyzed data from the National Health Insurance Service database (October 2017 to December 2021), including 44,118 singleton pregnancies following in vitro fertilization. The the artificial cycle (AC)-FET and the natural cycle (NC)-FET groups were distinguished based on prescription records, and patients were further categorized into endometriosis and non-endometriosis groups using the ICD-10 code N80. Logistic regression models were used to compare pregnancy and obstetric outcomes between AC-FET and NC-FET, and interaction analyses were conducted to assess whether the effects of FET protocols differed between patients with and without endometriosis. RESULTS: In endometriosis patients, AC-FET did not differ from NC-FET in miscarriage or term birth rates. In non-endometriosis patients, however, AC-FET was associated with higher miscarriage risk and lower term birth rate. For obstetric outcomes, AC-FET increased the risks of threatened abortion, HDP, and placenta previa in endometriosis patients. There was an interaction effect between endometrial preparation methods (AC-FET and NC-FET) and with or without endometriosis on the risks of threatened abortion (P = 0.046), suggesting a stronger association between threatened abortion and AC-FET in women with endometriosis. CONCLUSIONS: AC-FET was associated with an increased risk of adverse obstetric outcomes, including threatened abortion, HDP, and placenta previa in endometriosis patients. The additive effect observed for threatened abortion underscores the need for careful monitoring during early pregnancy in this population and supports considering NC-FET for those at high risk of miscarriage.